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Erythropoietin regulates immune/inflammatory reaction and improves neurological function outcomes in traumatic brain injury. | Traumatic brain injury (TBI) remains a leading cause of disability and death among young people in China. Unfortunately, no specific pharmacological agents to block the progression of secondary brain injury have been approved for clinical treatment. Recently, neuroprotective effects of erythropoietin (EPO) have been demonstrated in addition to its principal function in erythropoiesis, and hence it is viewed as a potential drug for TBI. In this study, we have investigated the neuroprotective effects of EPO associated with immune/inflammatory modulation in a mouse experimental TBI model. EPO (5000 U/kg body weight, i.p.) was injected at 1 hr, 1, 2, and 3 days after TBI, and its effect on cognitive function, brain edema, immune/inflammatory cells including regulatory T cells (Tregs), neutrophils, CD3<sup>+</sup> T cells, and microglia, cytokines including interleukin-10 (IL-10), transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were evaluated at different time points after treatment. EPO treatment significantly decreased brain edema and improved cognitive function when compared to Saline-treated mice (<i>p </i><<i> </i>.05). EPO treatment also significantly increased Tregs level in spleen and injured brain tissue as well as significantly reduced the infiltration and activation of immune/inflammatory cells (neutrophils, CD3<sup>+</sup>T cells, and microglia) in the injured hemisphere compared to Saline-treated control animals (<i>p </i><<i> </i>.05). In addition, ELISA analysis demonstrated that EPO treatment increased the expression of anti-inflammatory cytokine IL-10, but decreased the expression of proinflammatory cytokine IL-1β and TNF-α in the injured brain tissue (<i>p </i><<i> </i>.05). These findings suggest that EPO could improve neurological and cognitive functional outcomes as well as regulate immune/inflammatory reaction in TBI. | erythropoietin;neuroimmune;neuroinflammation;regulatory T cell (Treg);traumatic brain injury | pubmed |
Application of semiempirical electronic structure theory to compute the force generated by a single surface-mounted switchable rotaxane. | Herein we report a study of the switchable [3]rotaxane reported by Huang et al. (Appl Phys Lett 85(22):5391-5393, 1) that can be mounted to a surface to form a nanomechanical, linear, molecular motor. We demonstrate the application of semiempirical electronic structure theory to predict the average and instantaneous force generated by redox-induced ring shuttling. Detailed analysis of the geometric and electronic structure of the system reveals technical considerations essential to success of the approach. The force is found to be in the 100-200 pN range, consistent with published experimental estimates. Graphical Abstract A single surface-mounted switchable rotaxane. | Molecular machine;Rotaxane;Semiempirical;Theory | pubmed |
Repeated restraint stress increases seizure susceptibility by activation of hippocampal endoplasmic reticulum stress. | A growing body of evidence suggests that stress triggers a variety of pathophysiological responses. Recent studies show that stress produces enduring effects on structure and function of hippocampus, which is one of the most important structures involved in epilepsy. In the present study, we determined the effect of repeated restraint stress exposure on the susceptibility of pentylenetetrazole (PTZ)-induced seizures and the possible mechanisms involved using a rodent model. Our results show that mice subjected to repeated restraint stress exhibited shorter latency to PTZ-induced tonic-clonic seizures and higher seizure severity, suggesting chronic restraint stress increases seizure susceptibility. Following repeated restraint stress, we observed an increased level of endoplasmic reticulum (ER) stress as well as oxidative stress in the hippocampus. Moreover, our results show that chronic restraint stress exposure causes neuron loss in the hippocampus. Inhibition of ER stress with chemical chaperone, tauroursodeoxycholic acid (TUDCA), however, protects against chronic restraint stress-induced neuron loss, suggesting repeated restraint stress-induced neuronal degeneration is dependent on ER stress activation. On the other hand, inhibition of ER stress with TUDCA suppresses restraint stress-induced seizure susceptibility. Taken together, these results indicate that repeated restraint stress increases seizure susceptibility by activation of hippocampal ER stress and ER stress mediated oxidative stress and neurodegeneration. Thus, attenuating ER stress may serve as a potential therapeutic strategy targeted to block stress-induced seizure activities. | ER stress;Hippocampus;Oxidative stress;Restraint stress;Seizure susceptibility | pubmed |
Characterization and function analysis of a novel gene, Hc-maoc-1, in the parasitic nematode Haemonochus contortus. | Enoyl-CoA hydratase (MAOC) is required for the biosynthesis of the fatty acid-derive side chains of the ascaroside via peroxisome β-oxidation in the free-living nematode Caenorhabditis elegans. The derivative of dideoxy-sugar, ascarylose is used as dauer pheromones or daumones to induce development of the stress-resistant dauer larvae stage. Hc-maoc-1 gene was obtained by searching the Wellcome Trusts Sanger Institute's H. contortus genomic database. qRT-PCR was performed to analyse the transcriptional levels of Hc-maoc-1 with different developmental stages as templates. IFA was carried out to determine the expression pattern in L3 larvae and micro-injection was used to verify the promoter activity of 5'-flanking region of Hc-maoc-1. Overexpression and RNAi experiments were applied in N<sub>2</sub> strain to ascertain the gene function of Hc-maoc-1. The full-length cDNA of Hc-maoc-1 was 900 bp in length, which contained eight exons separated by seven introns and possessed the Hotdog domain and the MaoC-like domain, together with several other residues and a hydratase 2 motif. It was transcribed throughout the lifecycle and peaked in the fourth-stage larvae (L4) of H. contortus; however, its transcription level decreased in diapausing L4. The protein expression and location of Hc-MAOC-1 were mainly in the intestine of L3 larvae. Overexpression of Ce-maoc-1 and Hc-maoc-1 in C. elegans showed extended lifespan and increased body size. The protein Ce-MAOC-1 and Hc-MAOC-1 were localized in the intestine with a punctate pattern. In C. elegans, knockdown of Ce-maoc-1 conferred shortened lifespan and body lengths, decreased brood size and increased lipid storage. Caenorhabditis elegans was used as a model organism to ascertain the function of Hc-maoc-1 in H. contortus. Our results showed the similar characteristics and functions with Ce-maoc-1 and provided evidences of the potential functions of Hc-maoc-1 in biosynthesis of daumones in H. contortus. | Caenorhabditis elegans;Ce-maoc-1;Diapause;Haemonchus contortus;Hc-maoc-1 | pubmed |
Development and evaluation of consolidated bioprocessing yeast for ethanol production from ionic liquid-pretreated bagasse. | This work aimed to study the use of consolidated bioprocess (CBP) yeast expressing five cellulase genes (BGL, XYNII, EGII, CBHI and CBHII) for ethanol production from ionic liquid-pretreated bagasse and Laubholz unbleached Kraft pulp (LUKP). A proposed screening method shows that the optimal cellulase ratio varies for each biomass substrate, and thus it is essential to breed CBP yeast having optimal cellulase-displaying ratio for the target biomass. CBP yeast specialized towards bagasse produced 0.93g/l ethanol whiles that for LUKP produced 0.71g/l ethanol, which is approximately 4 and 2-fold, respectively, higher than that of the wild type. The cell-surface displayed enzymes synergistically contributed to the degradation of the biomass. The developed CBP yeast is a potential cheap source for consolidated bioprocessing of ethanol and the proposed screening method can be used for matching CBP yeast to a target biomass. | Bioethanol;Cell surface display;Cocktail δ-integration;Enzyme activity;Lignocellulose | pubmed |
Spontaneous Preterm Birth Is Associated with Differential Expression of Vaginal Metabolites by Lactobacilli-Dominated Microflora. | A major challenge in preventing preterm birth (PTB) is identifying women at greatest risk. This pilot study prospectively examined the differences in vaginal microbiota and metabolite profiles of women who delivered prematurely compared to their term counterparts in a cohort of asymptomatic (studied at 20-22, <i>n</i> = 80; and 26-28 weeks, <i>n</i> = 41) and symptomatic women (studied at 24-36 weeks, <i>n</i> = 37). Using 16S rRNA sequencing, the vaginal microbiota from cervicovaginal fluid samples was characterized into five Community State Types (CST) dominated by <i>Lactobacillus</i> spp.: CSTI (<i>Lactobacillus crispatus</i>), CSTII (<i>Lactobacillus gasseri</i>), CSTIII (<i>Lactobacillus iners)</i>, CSTV (<i>Lactobacillus jensenii</i>); and mixed anaerobes-CSTIV. This was then related to the vaginal metabolite profile and pH determined by <sup>1</sup>H-Nuclear Magnetic Resonance spectroscopy and pH indicator paper, respectively. At 20-22 weeks, the term-delivered women (TDW) indicated a proportion of CSTI-dominated microbiota >2-fold higher compared to the preterm-delivered women (PTDW) (40.3 vs. 16.7%, <i>P</i> = 0.0002), and a slightly higher proportion at 26-28 weeks (20.7 vs. 16.7%, <i>P</i> = 0.03). CSTV was >2-fold higher in the PTDW compared to TDW at 20-22 (22.2 vs. 9.7%, <i>P</i> = 0.0002) and 26-28 weeks (25.0 vs. 10.3%, <i>P</i> = 0.03). Furthermore, at 26-28 weeks no PTDW had a CSTII-dominated microbiome, in contrast to 28% of TDW (<i>P</i> < 0.0001). CSTI-dominated samples showed higher lactate levels than CSTV at 20-22 weeks (<i>P</i> < 0.01), and 26-28 weeks (<i>P</i> < 0.05), while CSTII-dominated samples indicated raised succinate levels over CSTV at 26-28 weeks (<i>P</i> < 0.05). These were supported by Principal coordinates analysis, which revealed strong clustering of metabolites according to CST. In addition, the CSTI-dominated samples had an average pH of 3.8, which was lower than those of CSTII-4.4, and CSTV-4.2 (<i>P</i> < 0.05). Elevated vaginal lactate and succinate were associated with predominance of CSTI and II over CSTV in women who delivered at term compared with their preterm counterparts. This suggests that <i>L. jensenii-</i>dominance and decreased lactate and/or succinate could increase the risk of PTB, while <i>L. crispatus/gasseri</i> may confer some protection against inflammation-associated PTB and highlight the need for further study in this area. | community state types;lactate;lactobacilli;metabolites;preterm birth;succinate;vaginal microbiome | pubmed |
Vitamin E supplementation in chronically hemodialyzed patients - influence on blood hemoglobin and plasma (anti)oxidant status. | <b></b><i>Background:</i> Disturbed oxidant/antioxidant status is involved in pathogenesis of anemia in end stage renal disease. There is evidence that vitamin E supplementation can increase blood hemoglobin in chronically hemodialyzed patients. However, the interindividual variation in response to the supplementation has not been fully addressed. <i>Methods:</i> 24 chronically hemodialyzed patients were supplemented with vitamin E (400 IU/day) in a period of two months. They had already been treated with erythropoiesis stimulating agents (ESA) and iron on a long-term basis, which was continued during the study period. A group of 20 healthy volunteers served as control subjects. Complete blood count, general biochemistry assays, the redox status by total thiols, oxidative stress by reactive oxygen metabolites, antioxidant status by biological antioxidant potential, and vitamin E (α- and γ- tocopherol) were measured before the start of supplementation, one month and two months later. <i>Results:</i> Overall, the vitamin E supplementation did not cause an increase of blood hemoglobin, hematocrit or red blood cells. However, 50 % of the patients with basal blood hemoglobin below 12.0 g/dL (N = 10) responded to the supplementation with its continuous increase. In addition, vitamin E exhibited a slight prooxidant effect only in the subgroup of patients with basal blood hemoglobin of ≥ 12.0 g/dL, two months after the start of supplementation (decreased total thiols: 300 ± 31 vs. 277 ± 36 µmol/L, p < 0.05; increased reactive oxygen metabolites: 183 ± 140 vs. 287 ± 112 CARR U, p > 0.05; decreased biological antioxidant potential: 2278 ± 150 vs. 2171 ± 126 µEq/L, p < 0.025), which coincided with their significantly increased serum α-tocopherol concentrations in comparison to the patients with basal blood hemoglobin below 12.0 g/dL (41.3 ± 7.2 vs. 59.9 ± 19.2 µmol/L, p < 0.025). <i>Conclusions:</i> When treated with ESA and iron on a long-term basis, the response to the vitamin E supplementation in chronically hemodialyzed patients is largely dependent on their basal blood hemoglobin and serum vitamin E concentrations. | Anemia;Hemodialysis;Hemoglobin ;Oxidative stress;Vitamin E | pubmed |
Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid-Induced AKI. | AKI is histologically characterized by necrotic cell death and inflammation. Diverse pathways of regulated necrosis have been reported to contribute to AKI, but the molecular regulators involved remain unclear. We explored the relative contributions of ferroptosis and necroptosis to folic acid (FA)-induced AKI in mice. FA-AKI in mice associates with lipid peroxidation and downregulation of glutathione metabolism proteins, features that are typical of ferroptotic cell death. We show that ferrostatin-1 (Fer-1), an inhibitor of ferroptosis, preserved renal function and decreased histologic injury, oxidative stress, and tubular cell death in this model. With respect to the immunogenicity of ferroptosis, Fer-1 prevented the upregulation of IL-33, an alarmin linked to necroptosis, and other chemokines and cytokines and prevented macrophage infiltration and Klotho downregulation. In contrast, the pancaspase inhibitor zVAD-fmk did not protect against FA-AKI. Additionally, although FA-AKI resulted in increased protein expression of the necroptosis mediators receptor-interacting protein kinase 3 (RIPK3) and mixed lineage domain-like protein (MLKL), targeting necroptosis with the RIPK1 inhibitor necrostatin-1 or genetic deficiency of RIPK3 or MLKL did not preserve renal function. Indeed, compared with wild-type mice, MLKL knockout mice displayed more severe AKI. However, RIPK3 knockout mice with AKI had less inflammation than their wild-type counterparts, and this effect associated with higher IL-10 concentration and regulatory T cell-to-leukocyte ratio in RIPK3 knockout mice. These data suggest that ferroptosis is the primary cause of FA-AKI and that immunogenicity secondary to ferroptosis may further worsen the damage, although necroptosis-related proteins may have additional roles in AKI. | IL-33;acute renal failure;cell death;ferroptosis;inflammation;renal proximal tubule cell | pubmed |
Anisometropia of spherical equivalent and astigmatism among myopes: a 23-year follow-up study of prevalence and changes from childhood to adulthood. | To study anisometropia of spherical equivalent and astigmatism from the onset of myopia at school age to adulthood. A total of 240 myopic schoolchildren (mean age 10.9 years), with no previous spectacles, were recruited during 1983-1984 to a randomized 3-year clinical trial of bifocal treatment of myopia. Examinations with subjective cyclopedic refraction were repeated 3 years later (follow-up 1) for 238 subjects and thereafter at the mean ages of 23.2 (follow-up 2) and 33.9 years (follow-up 3) for 178 and 134 subjects. After exclusions, the 102 subjects who attended all three follow-ups were included in the analyses. Corneal refractive power and astigmatism and anterior chamber depth was measured with Pentacam topography and axial length with IOL master at study end. Prevalence and changes in anisometropia of spherical equivalent (AnisoSE) and astigmatism (AnisoAST) and their relationships with refractive and axial measures were studied. Mean (±SD) of spherical equivalent (SE), AnisoSE and AnisoAST increased from baseline to follow-up end from -1.44 ± 0.57 D to -5.11 ± 2.23 D, from 0.28 ± 0.30 D to 0.68 ± 0.69 D and from 0.14 ± 0.18 D to 0.37 ± 0.36 D, respectively. Prevalence of AnioSE, ≥1 D, increased from 5% to 22.6% throughout follow-up. Higher AnisoSE was associated with SE in the less myopic eye at baseline and at follow-up 1, and with SE in the more myopic eye in follow-ups 2 and 3 in adulthood. At study end, AnisoSE was associated with the interocular difference in axial length (AL) (r = 0.612, p < 0.001) but not with the interocular difference in corneal refraction (CR) (r = -0.122, p = 0.266). In cases of low AnisoSE(≤1.00 D), the negative correlation between the real interocular differences (value of right eye minus value of left eye) in CR and AL (r = -0.427, p < 0.001) decreased the influence of the interocular difference in AL on AnisoSE, causing emmetropization in AnisoSE. The interocular difference in corneal astigmatism was the main factor associated with AnisoAST (r = 0.231, p = 0.020). No significant relationship was found between AnisoAST and level of SE. Anisometropia of the spherical equivalent (AnisoSE) increased along with the myopic progression and at study end was mainly associated with the interocular difference in AL. AnisoAST was mainly explained by the interocular difference in corneal astigmatism. In cases with low AnisoSE (≤1.0 D), the interrelationship between CR and AL decreased AnisoSE causing emmetropization in AnisoSE. | anisoastigmatism;anisometropia;astigmatism;axial length;cornea;emmetropization;myopia;refraction | pubmed |
Virtual surgery for patients with nasal obstruction: Use of computational fluid dynamics (MeComLand<sup>®</sup>, Digbody<sup>®</sup> & Noseland<sup>®</sup>) to document objective flow parameters and optimise surgical results. | Computational fluid dynamics (CFD) is a mathematical tool to analyse airflow. We present a novel CFD software package to improve results following nasal surgery for obstruction. A group of engineers in collaboration with otolaryngologists have developed a very intuitive CFD software package called MeComLand®, which uses the patient's cross-sectional (tomographic) images, thus showing in detail results originated by CFD such as airflow distributions, velocity profiles, pressure, or wall shear stress. NOSELAND® helps medical evaluation with dynamic reports by using a 3D endoscopic view. Using this CFD-based software a patient underwent virtual surgery (septoplasty, turbinoplasty, spreader grafts, lateral crural J-flap and combinations) to choose the best improvement in nasal flow. To present a novel software package to improve nasal surgery results. To apply the software on CT slices from a patient affected by septal deviation. To evaluate several surgical procedures (septoplasty, turbinectomy, spreader-grafts, J-flap and combination among them) to find the best alternative with less morbidity. The combination of all the procedures does not provide the best nasal flow improvement. Septoplasty plus turbinoplasty obtained the best results. Turbinoplasty alone rendered almost similar results to septoplasty in our simulation. CFD provides useful complementary information to cover diagnosis, prognosis, and follow-up of nasal pathologies based on quantitative magnitudes linked to fluid flow. MeComLand®, DigBody® and NoseLand® represent a non-invasive, low-cost alternative for the functional study of patients with nasal obstruction. | Computational fluid dynamics;DigBody;Dinámica de fluidos computacional;Flujo nasal;Función nasal;MeComLand;Nasal flow;Nasal physiology;NoseLand;Septoplastia;Septoplasty;Turbinoplastia;Turbinoplasty | pubmed |
Challenges During Implementation of a Patient-Facing Mobile App for Surgical Rehabilitation: Feasibility Study. | Translating research into practice, especially the implementation of digital health technologies in routine care, is increasingly important. Yet, there are few studies examining the challenges of implementing patient-facing digital technologies in health care settings. The aim of this study was to report challenges experienced when implementing mobile apps for patients to support their postsurgical rehabilitation in an orthopedic setting. A mobile app was tailored to the needs of patients undergoing rotator cuff repair. A 30-min usability session and a 12-week feasibility study were conducted with patients to evaluate the app in routine care. Implementation records (observation reports, issues log, and email correspondence) explored factors that hindered or facilitated patient acceptance. Interviews with clinicians explored factors that influenced app integration in routine care. Participant completion was low (47%, 9/19). Factors that affected patient acceptance included digital literacy, health status, information technology (IT) infrastructure at home, privacy concerns, time limitations, the role of a caregiver, inconsistencies in instruction received from clinicians and the app, and app advice not reflective of patient progress over time. Factors that negatively influenced app integration in routine care included competing demands among clinicians, IT infrastructure in health care settings, identifying the right time to introduce the app to patients, user interface complexity for older patients, lack of coordination among multidisciplinary clinicians, and technical issues with app installation. Three insights were identified for mobile app implementation in routine care: (1) apps for patients need to reflect their journey over time and in particular, postoperative apps ought to be introduced as part of preoperative care with opportunities for patients to learn and adopt the app during their postoperative journey; (2) strategies to address digital literacy issues among patients and clinicians are essential; and (3) impact of the app on patient outcomes and clinician workflow needs to be communicated, monitored, and reviewed. Lastly, digital health interventions should supplement but not replace patient interaction with clinicians. | health services;medical informatics;mobile application;mobile health;orthopedics;patients;personal health record;rehabilitation;rotator cuff;shoulder;surgery | pubmed |
Extrusion - back to the future: Using an established technique to reform automated chemical synthesis. | Herein, the benefits which extrusion can provide for the automated continuous synthesis of organic compounds are highlighted. Extrusion is a well-established technique that has a vital role in the manufacturing processes of polymers, pharmaceuticals and food products. Furthermore, this technique has recently been applied to the solvent-free continuous synthesis of co-crystals and coordination compounds including metal-organic frameworks (MOFs). To date, a vast amount of research has already been conducted into reactive extrusion (REX), particularly in the polymer industry, which in many cases has involved organic transformations, however, it has not received significant recognition for this. This review highlights these transformations and discusses how this previous research can be applied to the future of organic compound manufacture. | continuous;extrusion;industry;organic;synthesis | pubmed |
The influence of the subarcuate artery in the superior semicircular canal dehiscence and its frequency on stillbirths: illustrative cases and systematic review. | Literature describes that on the 25th gestational week the labyrinth is fully formed and with adult size. However, recent studies have shown that the cranial and labyrinth development continues until 3 years of age. To demonstrate through tomographic study the frequency of semicircular canal dehiscence on nine specimens of stillbirths between 32 and 40 weeks and, through literature review, present another possible etiology for its cause. Tomographic study of the temporal bone of 9 specimens of stillbirths between 32 and 40 weeks. A frequency of 88.89% of alterations were found in our study, with 44% presenting bilateral alterations and 44% unilateral alteration; 11.11% had no dehiscence. The tomographic study showed superior semicircular canal dehiscence (SSCD) in 88% of the specimens studied, protrusion of the superior semicircular canal (SSC) in all fetuses, and an enlarged SSC that may be caused by the expansion process provoked by the subarcuate artery entering the subarcuate canaliculus, leading to SSCD. | Semicircular canal;subarcuate artery;superior semicircular canal dehiscence;tinnitus;vertigo | pubmed |
Rethinking balance and impartiality in journalism? How the BBC attempted and failed to change the paradigm. | This article reconsiders the concepts of balance and impartiality in journalism, in the context of a quantitative content analysis of sourcing patterns in BBC news programming on radio, television and online in 2007 and 2012. Impartiality is the cornerstone of principles of public service broadcasting at the BBC and other broadcasters modelled on it. However, the article suggests that in the case of the BBC, it is principally put into practice through juxtaposing the positions of the two main political parties - Conservative and Labour. On this basis, the article develops the idea of the 'paradigm of impartiality-as-balance.' This paradigm prevails despite the news organisation's commitment to representing a broader range of opinion. The paradigm of impartiality-as-balance means that only a narrow range of views and voices are heard on the most contentious and important issues. Further, it results in reporting that focuses on party-political conflict, to the detriment of a journalism which provides much-needed context. | BBC;European Union;immigration;impartiality;journalism practice;objectivity;public service broadcasting;religion | pubmed |
Does Breast-feeding Relate to Development of Atopic Dermatitis in Young Korean Children?: Based on the Fourth and Fifth Korea National Health and Nutrition Examination Survey 2007-2012. | There have been conflicting reports concerning the relationship between breast-feeding and the development of atopic dermatitis (AD) in early childhood. The objective of this study was to investigate the associations between breast-feeding and the risk of AD in early childhood in Korea. We combined the fourth and fifth Korea National Health and Nutrition Examination Survey data collected from 2007 to 2012 and analyzed 2,015 children at 1 to 3 years old. Regression analysis was used to determine the association of the following variables: AD, feeding types, duration of breast-feeding, and others. The annual prevalence of exclusive breast-feeding and AD decreased. Parents with allergic diseases preferred breast-feeding and extended duration of feeding compared with those without. In multiple logistic regression analyses, exclusive breast-feeding in feeding type I (P=0.070; adjusted odds ratio [OR]=1.990), exclusive breast-feeding in feeding type II (P=0.095; adjusted OR=1.495) and breast-feeding duration (P=0.430; adjusted OR=1.013) were not significantly related to AD. Breast-feeding was not found to be associated with an occurrence of AD in young children. Rather, parents with histories of allergic diseases tended to prefer breast-feeding and extend its duration. To clarify the role of breast-feeding in the development of AD, a nation-wide prospective study is needed. | Atopic dermatitis;Korea;breast-feeding;children;prevention | pubmed |
Surveying immigrants without sampling frames - evaluating the success of alternative field methods. | This paper evaluates the sampling methods of an international survey, the Immigrant Citizens Survey, which aimed at surveying immigrants from outside the European Union (EU) in 15 cities in seven EU countries. In five countries, no sample frame was available for the target population. Consequently, alternative ways to obtain a representative sample had to be found. In three countries 'location sampling' was employed, while in two countries traditional methods were used with adaptations to reach the target population. The paper assesses the main methodological challenges of carrying out a survey among a group of immigrants for whom no sampling frame exists. The samples of the survey in these five countries are compared to results of official statistics in order to assess the accuracy of the samples obtained through the different sampling methods. It can be shown that alternative sampling methods can provide meaningful results in terms of core demographic characteristics although some estimates differ to some extent from the census results. | Hard-to-reach groups;Immigrants;Sampling;Survey | pubmed |
Gene expression and activity of antioxidant enzymes in rice plants, cv. BRS AG, under saline stress. | The rice cultivar (<i>Oryza sativa</i> L.) BRS AG, developed by Embrapa Clima Temperado, is the first cultivar designed for purposes other than human consumption. It may be used in ethanol production and animal feed. Different abiotic stresses negatively affect plant growth. Soil salinity is responsible for a serious reduction in productivity. Therefore, the objective of this study was to evaluate the gene expression and the activity of antioxidant enzymes (SOD, CAT, APX and GR) and identify their functions in controlling ROS levels in rice plants, cultivar BRS AG, after a saline stress period. The plants were grown in vitro with two NaCl concentrations (0 and 136 mM), collected at 10, 15 and 20 days of cultivation. The results indicated that the activity of the enzymes evaluated promotes protection against oxidative stress. Although, there was an increase of reactive oxygen species, there was no increase in MDA levels. Regarding genes encoding isoforms of antioxidant enzymes, it was observed that <i>OsSOD3</i>-<i>CU/Zn</i>, <i>OsSOD2</i>-<i>Cu/Zn</i>, <i>OsSOD</i>-<i>Cu/Zn</i>, <i>OsSOD4</i>-<i>Cu/Zn</i>, <i>OsSODCc1</i>-<i>Cu/Zn</i>, <i>OsSOD</i>-<i>Fe</i>, <i>OsAPX1</i>, <i>OsCATB</i> and <i>OsGR2</i> were the most responsive. The increase in the transcription of all genes among evaluated isoforms, except for <i>OsAPX6</i>, which remained stable, contributed to the increase or the maintenance of enzyme activity. Thus, it is possible to infer that the cv. BRS AG has defense mechanisms against salt stress. | Oryza sativa L.;Oxidative stress;Reactive oxygen species;Salinity | pubmed |
Evaluation of Plaque pH Changes Following Consumption of Health Drinks by Children: A Pilot Study. | With increased trend among people to choose a healthy diet, there is an increased consumption of health drinks by children. Thus, it is important to know their cariogenicity. To evaluate the effect of consumption of health drinks viz., Horlicks, Boost and Complan on plaque pH in children. The study consisted of four groups: Group I (control)- 10% sucrose solution, Group II- Horlicks, Group III- Boost, Group IV- Complan. Samples of plaque from representative teeth were collected and pH was measured using an electrode outside the mouth. After baseline pH was recorded, children were given their respective drinks and were asked to consume slowly over a period of three to five minutes following swish with 20 ml of the test drink for one minute. The pH was then recorded after 10, 20, 30, 40 and 60 minutes of the post consumption period. Obtained values were subjected to one-way ANOVA test for multiple group comparison followed by Post-Hoc Tukey's test for group wise comparison. Twenty minutes after consumption of Complan and Boost, pH was decreased, but not to the critical pH value as in case of sucrose. The pH was found to be slightly increased, 20 minutes post Horlicks consumption. Post 60 minutes consumption of all the drinks including sucrose solution, the pH was increased in comparison to post 20 minutes. However, 60 minutes post consumption of Boost and Horlicks, pH increased above the baseline. Consumption of health drinks viz., Complan and Boost did not lower the plaque pH to the level of critical pH. Consumption of Horlicks increased the plaque pH. | Beverages;Cariogenic;Sucrose | pubmed |
Factors affecting peri-implant fracture following locking plate for osteoporotic distal femur fractures. | The purpose of this study is to evaluate the outcomes and to analyze the risk factors for the occurrence of peri-implant fracture after treatment of osteoporotic distal femoral fractures using a locking plate. Risk factors affecting peri-implant fracture exist after locking plate fixation in osteoporotic distal femur fracture. Eighty-nine cases (88 patients) with osteoporotic distal femoral fractures were evaluated between January 2006 and January 2014. The cohort included 13 men and 76 women with a mean age of 70.4 (50-91). Mean duration of follow-up was 47.9 months (12 to 106). All patients with distal femoral fracture were treated with a locking compression plate. Bone mineralized densitometry measurement was obtained from all patients. Risk factors including sex, age, rheumatoid arthritis (RA), taking of bisphosphonate, primary or periprosthetic fracture after total knee arthroplasty (TKA), open or closed fracture, types of the most proximal screw (locking/cortical), and number of proximal screws were analyzed. Complication, union, time to union, and range of motion of knee were also evaluated. All patients had osteoporosis with the mean BMD of -3.16 (-2.5∼-5.4). The mean range of motion of knee was 126 degrees (90-145). Eighty-four cases (94.4%) showed union, the mean time to union was 14 weeks (10-42). Peri-implant fractures occurred in four patients (4.5%) after bone union at mean 37.5 months (14-62) postoperatively. Eight patients had angular deformities of over 5 degrees. Nonunion was observed in 5 cases and superficial wound infection in 2 cases. There were eight patients with RA, two of whom had suffered a peri-implant fracture. In statistical analysis, rheumatoid arthritis or periprosthetic fracture in TKA patients was a risk factor for peri-implant fracture (P=0.039, 0.019, respectively), and other factors showed no statistical differences. Treatment using a locking plate showed favorable outcomes in osteoporotic distal femoral fractures. However, peri-implant fracture could occur in patients with RA or periprosthetic fracture after TKA. Therefore, cautious consideration is required for management of osteoporotic distal femur fracture in patients with RA or periprosthetic fracture after TKA. Analysis of more cases will be needed in order to achieve conclusive results. Therapeutic study, level IV (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence. | Distal femoral fracture;Locking plate;Osteoporosis;Peri-implant fracture | pubmed |
Anti-hyperglycemic and antioxidant potential of <i>Croton bonplandianus</i>. Bail fractions in correlation with polyphenol content. | Diabetes mellitus, a carbohydrate metabolic disorder, occurs due to absolute or relative deficiency of insulin. Current treatment strategies involve either preventing or delaying the intestinal absorption of glucose to lower the levels of postprandial hyperglycemia (PPHG). Herbal remedies have been since ancient times for treating diabetes mellitus. Therefore, identifying novel phytocompounds with α-amylase and α-glucosidase inhibitory activity that would reduce the glucose absorption as well as the rise in postprandial blood glucose level is vital. Consequently, the present study was aimed to investigate the anti-hyperglycemic activity of <i>Croton bonplandianus</i> against these pancreatic enzymes. The methanol extract of <i>C. bonplandianus</i> leaf was prepared and further fractionation was performed with n-hexane, ethyl acetate and chloroform. The antioxidant activity and anti-hyperglycemic activity of the extracts and its fractions were determined. Further, GC-MS analysis was performed for the leaf extract. The chloroform fraction (ChF) was found to contain highest quantity of polyphenols (114.28 µg/ml of GAE), flavonoids (95.68 µg/ml of quercetin) and tannins (63.80 µg/ml of GAE) and also possessed effective inhibitory activity against α amylase (IC<sub>50</sub>95.78 µg/ml) and α glucosidase (IC<sub>50</sub> 126.81µg/ml). The antioxidant activity of ChFwas also higher when compared to other fractions. Further, GC-MS analysis of ChF showed the presence of various components that may be responsible for the above mentioned activities. The study findings suggest that the components present in the leaves of <i>C. bonplandianus</i>, may provide a potential therapeutic source in developing treatment forhyperglycemia. Further bioassay guided fractionation procedure is required to identify the active constituents. | Antihyperglycemia;Polyphenols;Postprandial hyperglycemia;α-Amylase;α-Glucosidase | pubmed |
Therapeutic options for carbapenem-resistant Enterobacteriaceae infections. | In recent years, carbapenem resistance among Enterobacteriaceae has dramatically increased and represents an important threat to global health. The optimal therapeutic management of carbapenem-resistant Enterobacteriaceae (CRE) infections has not been established, because to date, no clinical trials have been performed with this objective. We aimed to summarize in the present review data provided by previous observational clinical studies that have investigated the impact of different treatment strategies on the outcome of CRE infections. Most of these studies reported that combination therapy with 2 or more drugs is superior to monotherapy in providing a survival benefit. The use of carbapenems in association with other active drugs is likely ineffective for CRE isolates with carbapenem Minimum Inhibitory Concentrations (MICs) >8 mg/l. The effectiveness of further therapeutic options for the treatment of extensively or pan-drug-resistant Enterobacteriaceae infections has been reported in vivo and in vitro, although few cases/case series have been reported. Novel antimicrobials that are effective against CRE are urgently needed. | carbapenem-resistant Enterobacteriaceae;combination therapy;double-carbapenem combination;monotherapy;mortality | pubmed |
Implications of Entropy and Surgical Pleth Index-guided general anaesthesia on clinical outcomes in critically ill polytrauma patients. A prospective observational non-randomized single centre study. | Being highly unstable, the critically ill polytrauma patient represents a challenge for the anaesthesia team. The aim of this study was to compare the Entropy and Surgical Pleth Index (SPI)-guided general anaesthesia with standard haemodynamic monitoring methods used in the critically ill polytrauma patients and to evaluate the incidence of hemodynamic events, as well as the opioid and vasopressor demand. 72 patients were included in this prospective observational study, divided in two groups, the ESPI Group (N = 37, patients that benefited from Entropy and SPI monitoring) and the STDR Group (N = 35 patients that benefited from standard hemodynamic monitoring). In the ESPI Group general anaesthesia was modulated in order to maintain the Entropy levels between 40 and 60. Analgesia control was achieved by maintaining the SPI levels between 20 and 50. In the STDR Group hypnosis and analgesia were maintained using the standard criteria based on hemodynamic changes. ClinicalTrials.gov identifier NCT03095430. The incidence of hypotension episodes was significantly lower in the ESPI Group (N = 3), compared to the STDR Group (N = 71) (p < 0.05). Moreover, the Fentanyl demand was significantly lower in the ESPI Group (p < 0.0001, difference between means 5.000 ± 0.038, 95% confidence interval 4.9250-5.0750), as well as vasopressor medication demand (p < 0.0001, difference between means 0.960 ± 0.063, 95% confidence interval 0.8.334-1.0866). The implementation of multimodal monitoring in the critically ill polytrauma patient brings substantial benefits both to the intraoperative clinical status and to the clinical outcome of these patients by reducing the incidence of anesthesia-related complications. | Entropy;General anesthesia;Multimodal monitoring;Surgical pleth index (SPI) | pubmed |
On Plant Modularity Traits: Functions and Challenges. | On-spot persistence, space occupancy, and recovery after damage are key plant functions largely understudied. Traits relevant to these functions are difficult to assess because of their relationships to plant modularity. We suggest that developing collection protocols for these traits is feasible and could facilitate their inclusion in global syntheses. | clonality;longevity;resprouting;standardized protocols | pubmed |
Empirically derived patterns of psychiatric symptoms in youth: A latent profile analysis. | By conceptualizing domains of behavior transdiagnostically, the National Institute of Mental Health Research Domain Criteria (NIMH RDoC) initiative facilitates new ways of studying psychiatric symptoms. In this study, latent profile analysis (LPA) was used to empirically derive classes or patterns of psychiatric symptoms in youth that transect traditional nosologic boundaries. Data were drawn from 509 children and adolescents (ages 7-18 years; mean age =12.9 years; 54% male) who were evaluated in the NIMH Emotion and Development Branch and were heterogeneous with respect to presenting diagnoses and symptoms. Youth and/or their parents completed measures of several core symptom dimensions: irritability, anxiety, depression, and attention deficit hyperactivity disorder (ADHD). LPA was used to parse response patterns into distinct classes, based on the levels of, and interrelations among, scores on the different measures. Five classes emerged: low levels of symptomatology (52% of sample); anxiety and mild depressive symptoms (17%); parent-reported irritability and ADHD (16%); irritability and mixed comorbid symptoms (10%); and high levels of irritability, anxiety, depression, and ADHD (5%). Importantly, these latent classes cut across informants and the clinical conditions for which youth were initially evaluated. Further, the classes characterized by irritability exhibited the poorest overall functioning. These data were cross-sectional. Examination of external validators, including neurobiological correlates and symptom course, is warranted. Results inform our understanding of the structure of psychiatric symptoms in youth and suggest new ways to operationalize psychopathology and examine it in relation to neurobiology. | Children;Comorbidity;Latent profile analysis;Symptoms;Transdiagnostic | pubmed |
The Relevance of Osteoclastic and Osteoblastic Activity Markers Follow-Up in Patients on Antiresorptive Osteoporosis Treatment. | In general, markers of bone formation and markers of bone resorption are changing synergistically, so the monitoring of any osteoclastic and any osteoblastic marker should reflect the rate of bone transformation. The aim of the study is to monitor the bone metabolism markers in postmenopausal women with osteoporosis and osteopenia along with the variations caused by the effects of bisphosphonate therapy. The study involved 55 women of average age of 57.95 years, with osteopenia or osteoporosis. The patients with osteoporosis were treated with bisphosphonates (75 mg once a week); the laboratory tests were performed before the treatment and 6 months later. Patients with osteopenia were evaluated at the first assessment and 6 months later. The tests included bone densitometry, dual-energy X-ray absorptiometry, osteocalcin, alkaline phosphatase, collagen 1 N-terminal pro-peptide (P1NP), and beta C telopeptide of type I collagen (CTX). The mean T-score was -2.80 ± 0.63 before therapy and -2.64 ± 0.45 6 months later (p < 0.001). Women with osteoporosis had elevated levels of osteocalcin and P1NP at the first assessment, whereas the alkaline phosphatase level did not change with the treatment. After the introduction of antiresorptive therapy, the levels of osteocalcin and P1NP significantly decreased (p < 0.001). In the group with osteopenia, the biochemical markers activity were increased in both assessments. In patients with osteoporosis, Beta-CTX was increased in the first evaluation, and decreased after treatment (p = 0.001). The results indicate that the assessment of biochemical markers of bone metabolism show excellent results in the assessment of prognosis, monitoring the course and the response to various treatment regimens of osteoporosis and evince strong correlation with standard densitometry and dual-energy X-ray absorptiometry procedures. P1NP and CTX show better diagnostic applicability compared with osteocalcin and alkaline phosphatase. The analysis of the activity of biochemical markers may obtain early information on the therapeutic response, before definitive assessment by bone density measurements. | CTX;P1NP;T-score;Z-score;osteopenia;osteoporosis | pubmed |
Involvement of central nesfatin-1 neurons on oxytocin-induced feeding suppression in rats. | Peripheral anorectic hormones, such as peptide YY (PYY) and oxytocin (OXT), suppress food intake. A newly identified anorectic neuropeptide, nesfatin-1, is synthesized in both peripheral tissue and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. Here, we examined the effects of intraperitoneal (ip) administration of PYY<sub>3-36</sub>, OXT, and OXT analog, on nesfatin-1-immunoreactive (ir) neurons in the rat hypothalamus and brainstem, using Fos double fluorescence-immunohistochemistry. The ip administration of OXT and OXT analog significantly increased the number of nesfatin-1-ir neurons expressing Fos-ir in the paraventricular nucleus, the arcuate nucleus, and the nucleus tractus solitarius, but not in the supraoptic nucleus, the lateral hypothalamic area, and the area postrema. No differences in the percentage of nesfatin-1-ir neurons expressing Fos in the nuclei of the hypothalamus and brainstem were observed, between rats treated with vehicle or those treated with PYY<sub>3-36</sub>. The decreased food intake, induced by OXT and OXT analog, was attenuated significantly by pretreatment with intracerebroventricular administration of antisense nesfatin-1. These results suggested that nesfatin-1-expressing neurons in the hypothalamus and brainstem may play a role in sensing the peripheral level of OXT and its suppression of feeding in rats. | Food intake;Fos;Nesfatin-1;Oxytocin;Oxytocin analog;PYY | pubmed |
Differences in testosterone and its precursors by sex of the offspring in meconium. | Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroid levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p=0.0333), and DHEA was higher in meconium from females (p=0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis. | Androgens;Mass spectrometry;Meconium;Prenatal development;Sexual differentiation;Steroids | pubmed |
Linking Incidents in Long-Term Care Facilities to Worker Activities. | This article reports on a study examining staff activities being performed when incidents were reported to have occurred. The risk for injury among health care providers who engage in patient handling activities is widely acknowledged. For those working in long-term care, the risk of occupational injury is particularly high. Although injuries and injury prevention have been widely studied, the work has generally focused on incident rates and the impact of specific assistive devices on worker safety. The purpose of this study was to examine reported staff incidents in relation to staff activities. A multicenter cross-sectional exploratory study used retrospective data from reported staff incidents (2010, 2011, and 2012) and prospective data from 360 hours of staff observations in five long-term care facilities during 2013. Descriptive statistics were used to analyze data. A total of 898 staff incidents were reviewed from the facilities. Incidents were most likely to occur in resident rooms. Resident aides were more likely to be engaged in high-risk activities than other care providers. Times when staff incidents were reported to have occurred were not associated with periods of high staff-to-resident contact. Safe handling during low and moderate risk activities should be promoted. Education on what constitutes a reportable incident and strategies to ensure compliance with reporting policies and procedures may be needed to ensure accuracy and completeness of incident data. | occupational hazards;occupational injuries;research;safety;workforce | pubmed |
Brain activity during a lower limb functional task in a real and virtual environment: A comparative study. | Virtual Reality (VR) has been contributing to Neurological Rehabilitation because of its interactive and multisensory nature, providing the potential of brain reorganization. Given the use of mobile EEG devices, there is the possibility of investigating how the virtual therapeutic environment can influence brain activity. To compare theta, alpha, beta and gamma power in healthy young adults during a lower limb motor task in a virtual and real environment. Ten healthy adults were submitted to an EEG assessment while performing a one-minute task consisted of going up and down a step in a virtual environment - Nintendo Wii virtual game "Basic step" - and in a real environment. Real environment caused an increase in theta and alpha power, with small to large size effects mainly in the frontal region. VR caused a greater increase in beta and gamma power, however, with small or negligible effects on a variety of regions regarding beta frequency, and medium to very large effects on the frontal and the occipital regions considering gamma frequency. Theta, alpha, beta and gamma activity during the execution of a motor task differs according to the environment that the individual is exposed - real or virtual - and may have varying size effects if brain area activation and frequency spectrum in each environment are taken into consideration. | EEG;Virtual Reality exposure therapy;physiotherapy | pubmed |
Inter-rater reliability of cutaneous sarcoidosis assessment tools via remote photographic assessment. | <i>Background:</i> Recently two outcome instruments have been developed and validated for assessing cutaneous sarcoidosis in a live, in-person setting. Teledermatology is a rapidly growing field; yet, to date, no instrument has been validated for use in a remote setting, which could ultimately impact clinical trial design. <i>Objective:</i> To assess the interrater reliability of these outcome instruments for store-and-forward teledermatology. <i>Methods:</i> Seven sarcoidosis experts, including both pulmonologists and dermatologists, scored photographs of cutaneous sarcoidosis lesions in 13 patients utilizing the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI), the Sarcoidosis Activity and Severity Index (SASI) and the Physician Global Assessment (PGA). Interrater reliability was assessed for each instrument and was compared to results obtained from a prior study involving sarcoidosis experts evaluating the same patient population in an in-person setting. <i>Results:</i> Interrater reliability (presented as ICC [95%CI]) was poor for the CSAMI Activity scale (0.36 [0.16 - 0.65]) and the CSAMI Damage scale (0.17 [0.04 - 0.43]) and was fair for the Modified Facial SASI (0.59 [0.36 - 0.82]) and the PGA (0.47 [0.23 - 0.74]). All results were inferior to those obtained from the prior studies validating these instruments for in-person use. <i>Conclusions:</i> Given the superiority of these instruments when utilized in person, it is recommended to have an on-site sarcoidosis expert evaluate cutaneous sarcoidosis lesions whenever possible. <i>(Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 165-169)</i>. | cutaneous sarcoidosis;outcome instruments;reliability;teledermatology | pubmed |
Determination of nitrite in water samples using atmospheric pressure glow discharge microplasma emission and chemical vapor generation of NO species. | In this work, a low-power (<25 W), portable direct current (dc) atmospheric pressure glow discharge microplasma (4 mm × 10 mm) molecular emission spectrometer (APGD-MES) is developed for the determination of nitrite by using chemical vapor generation. Nitrite is on-line reduced to volatile nitric oxide (NO) by 1.5% (m/v) ascorbic acid and 1.0 mol L<sup>-1</sup> hydrochloric acid. Then, the generated NO was separated and transferred into the APGD microplasma by an argon stream (100 mL min<sup>-1</sup>) for its excitation, and NO emission was measured by a microspectrometer. The effects of operational parameters of the APGD microplasma source and vapor generation of nitrite were investigated and the analytical figures of merit for nitrite detection was evaluated. The limit of detection of the proposed method was calculated to be 0.26 μg mL<sup>-1</sup> of nitrite by measuring NO emission at 237.0 nm. The calibration curve is linear for the nitrite concentration in the range of 2.0-100.0 μg mL<sup>-1</sup> and good precision (2.3%, RSD) is readily achieved for 5.0 μg mL<sup>-1</sup> nitrite. The accuracy of this procedure was demonstrated by nitrite detection in a certified reference material. Analyte recoveries test were also performed to verify the accuracy of the method for nitrite determination in a series of environmental water samples. It was found that the concentration of nitrite of these samples were all below the LOD, and the obtained recoveries were in the range of 95-117%. The proposed APGD-MES method provides an alternative useful technique for screening potential nitrite pollution of potable waters. | Atmospheric pressure glow discharge;Microplasma;Molecular emission spectroscopy;Nitrite determination;Potable waters | pubmed |
Prevalence of malnutrition and validation of bioelectrical impedance analysis for the assessment of body composition in patients with systemic sclerosis. | The aims were to assess the prevalence of malnutrition and to validate bioelectrical impedance analysis (BIA) against whole-body DXA for the assessment of body composition in patients with SSc. Malnutrition was defined as BMI <18.5 kg/m 2 or unintentional weight loss >10% in combination with a fat-free mass index (FFMI) <15 kg/m 2 for women or <17 kg/m 2 for men or BMI <20.0 kg/m 2 (age <70 years) or <22 kg/m 2 (age >70 years). Body composition was assessed in 72 patients with whole-body DXA (Hologic, Discovery A) and BIA (Bodystat Quadscan 400). The manufacturer's equation and the Geneva equation were used to estimate FFM and fat mass. The agreement between BIA and whole-body DXA was assessed with Bland-Altman analysis and intraclass correlation coefficient. Malnutrition was found in 8.3% (n = 6) and low FFMI in 20.8% (n = 15) of patients. The mean difference in FFM between BIA and DXA applying the Geneva equation was 0.02 ( s . d . 2.4) kg, intraclass correlation coefficient 0.97 (95% CI: 0.95, 0.98). Limits of agreement were ±4.6 kg. The manufacturer's equation was less adequate to predict FFM. This study shows a relatively low prevalence of malnutrition in comparison with other studies, but a high prevalence of low FFMI, underlining the necessity of measuring body composition in SSc patients with a standardized and validated method. A good validity of BIA in determining FFM was found at a group level, while at an individual level the FFM may vary by 4.6 kg. | bioelectrical impedance analysis;body composition;dual-energy X-ray absorptiometry;malnutrition;systemic sclerosis | pubmed |
A Journey Through Wonderland: A Novice, Her Mentor, Tea Parties, and Tenure. | When novice nurse educators cross over into the academic threshold, they enter into a state of culture shock. The tenets of teaching, research, and service combined with the expectations of mastering clinical and academic competencies can overwhelm new nurse educators. A successful synergistic mentor-mentee relationship is essential for a positive transition to the educator role. This lighthearted adventure of Alice entering Wonderland University is intended to provide a humorous simile for both new nurse educators and tenured faculty. It is also the intent of the authors to let new nurse educators know that they are not alone in their frustration during the acclimation process to the multitude of role changes they are expected to master. | Mentor;novice nurse educator | pubmed |
Squamous cell carcinoma antigen as a novel candidate marker for amniotic fluid embolism. | We aimed to evaluate the clinical usefulness of serum squamous cell carcinoma (SCC) antigen for the diagnosis of amniotic fluid embolism (AFE). Sera and information of 20 patients with AFE (autopsy-proven AFE, four cases; clinical AFE, 16 cases) were obtained from the Japan Amniotic Fluid Embolism Registration Center at Hamamatsu University School of Medicine. As controls, we included 74 gestational-age-matched healthy women who gave birth to healthy newborns during the period from December 2012 to January 2014. Receiver-operator curves (ROC) were used to evaluate the diagnostic performance of SCC levels for prediction of AFE. Serum SCC antigen levels in women with autopsy-proven AFE (112.0 ± 169.4 ng/mL, P = 0.001) and clinical AFE (9.5 ± 10.3 ng/mL, P = 0.004) were significantly higher than those in healthy controls with normal delivery (4.4 ± 2.2 ng/mL). On ROC analysis, the optimal cut-off value for SCC antigen levels was 7.15 ng/mL, for which the sensitivity and specificity for AFE prediction was 60.0% and 89.2%, respectively (area under the ROC, 0.785; 95% confidence interval, 0.663-0.908; P < 0.001). Serum SCC antigen may be a promising predictor of the entry of amniotic fluid into the maternal circulation, potentially serving as a candidate marker for noninvasive diagnosis of AFE. | amniotic fluid embolism;amniotic fluid-specific protein;diagnosis;squamous cell carcinoma antigen | pubmed |
On True Score Evaluation Using Item Response Theory Modeling. | Building on prior research on the relationships between key concepts in item response theory and classical test theory, this note contributes to highlighting their important and useful links. A readily and widely applicable latent variable modeling procedure is discussed that can be used for point and interval estimation of the individual person true score on any item in a unidimensional multicomponent measuring instrument or item set under consideration. The method adds to the body of research on the connections between classical test theory and item response theory. The outlined estimation approach is illustrated on empirical data. | classical test theory;delta method;interval estimation;item response theory;standard error;true score | pubmed |
Intact Protein Analysis at 21 Tesla and X-Ray Crystallography Define Structural Differences in Single Amino Acid Variants of Human Mitochondrial Branched-Chain Amino Acid Aminotransferase 2 (BCAT2). | Structural technologies are an essential component in the design of precision therapeutics. Precision medicine entails the development of therapeutics directed toward a designated target protein, with the goal to deliver the right drug to the right patient at the right time. In the field of oncology, protein structural variants are often associated with oncogenic potential. In a previous proteogenomic screen of patient-derived glioblastoma (GBM) tumor materials, we identified a sequence variant of human mitochondrial branched-chain amino acid aminotransferase 2 as a putative factor of resistance of GBM to standard-of-care-treatments. The enzyme generates glutamate, which is neurotoxic. To elucidate structural coordinates that may confer altered substrate binding or activity of the variant BCAT2 T186R, a ~45 kDa protein, we applied combined ETD and CID top-down mass spectrometry in a LC-FT-ICR MS at 21 T, and X-Ray crystallography in the study of both the variant and non-variant intact proteins. The combined ETD/CID fragmentation pattern allowed for not only extensive sequence coverage but also confident localization of the amino acid variant to its position in the sequence. The crystallographic experiments confirmed the hypothesis generated by in silico structural homology modeling, that the Lys59 side-chain of BCAT2 may repulse the Arg186 in the variant protein (PDB code: 5MPR), leading to destabilization of the protein dimer and altered enzyme kinetics. Taken together, the MS and novel 3D structural data give us reason to further pursue BCAT2 T186R as a precision drug target in GBM. Graphical Abstract ᅟ. | Collisionally induced dissociation;Electron-transfer dissociation;High field Fourier transform mass spectrometry;High resolution;Precision medicine;Protein sequence variant;Protein structure;X Ray crystallography | pubmed |
Targeted strategies directed at the molecular defect: Toward precision medicine for select primary immunodeficiency disorders. | Primary immunodeficiency disorders (PIDs) represent a range of genetically determined diseases that typically have increased susceptibility to infections and in many cases also have evidence of immune dysregulation that often presents as autoimmunity. Most recently, the concept of gain-of-function mutations associated with PIDs has become well recognized and adds a new dimension to the understanding of this group of disorders, moving beyond the more commonly seen loss-of-function mutations. The rapidly expanding genetic defects that have been identified in patients with previously uncharacterized PIDs has opened up the potential for targeted therapy directed at the specific disease-causing abnormality. This has been driven by linking PID-specific genetic defects to the associated unique abnormalities in cellular signaling pathways amenable to directed therapies. These include agents that either block overactive or enhance underresponsive cellular pathways. Selected primary immunodeficiencies were chosen, the genetic defects of which have been recently characterized and are amenable to targeted therapy, as a reflection of the power of precision medicine. | Personalized medicine;autoimmunity;immune dysregulation;mutation;primary immunodeficiency disorders;therapy | pubmed |
Effects of Type 1 Diabetes Risk Alleles on Immune Cell Gene Expression. | Genetic studies have identified 61 variants associated with the risk of developing Type 1 Diabetes (T1D). The functions of most of the non-HLA (Human Leukocyte Antigen) genetic variants remain unknown. We found that only 16 of these risk variants could potentially be linked to a protein-coding change. Therefore, we investigated whether these variants affected susceptibility by regulating changes in gene expression. To do so, we examined whole transcriptome profiles of 600 samples from the Type 1 Diabetes Genetics Consortium (T1DGC). These comprised four different immune cell types (Epstein-Barr virus (EBV)-transformed B cells, either basal or after stimulation; and cluster of differentiation (CD)4+ and CD8+ T cells). Many of the T1D-associated risk variants regulated expression of either neighboring (<i>cis</i>-) or distant (<i>trans</i>-) genes. In brief, 24 of the non-HLA T1D variants affected the expression of 31 nearby genes (<i>cis</i>) while 25 affected 38 distant genes (<i>trans</i>). The effects were highly significant (False Discovery Rate <i>p</i> < 0.001). In addition, we searched in public databases for expression effects of T1D single nucleotide polymorphisms (SNPs) in other immune cell types such as CD14+ monocytes, lipopolysaccharide (LPS) stimulated monocytes, and CD19+ B cells. In this paper, we review the (expression quantitative trait loci (eQTLs) associated with each of the 60 T1D variants and provide a summary of the genes impacted by T1D risk alleles in various immune cells. We then review the methodological steps involved in analyzing the function of genome wide association studies (GWAS)-identified variants, with emphasis on those affecting gene expression. We also discuss recent advancements in the methodologies and their advantages. We conclude by suggesting future study designs that will aid in the study of T1D risk variants. | B-cells;T-cells;dendritic cells;eQTLs;type 1 diabetes | pubmed |
Is the Glasgow Prognostic Score Applicable to Both Early- and Advanced-Stage Gastric Cancers? | The Glasgow prognostic score (GPS) has been reported as a sensitive prognostic marker for gastric cancer. This study aimed to investigate whether the GPS is equally applicable to patients with early-stage and advanced-stage gastric cancers. Patients (n = 544) who underwent elective gastrectomy for gastric cancer between 2007 and 2015 were retrospectively studied. GPSs of 2, 1, and 0 were allocated to patients with both an elevated C-reactive protein level (> 1.0 mg/dL) and hypoalbuminemia (< 3.5 mg/dL), patients with only one of these abnormalities, and patients with neither abnormality, respectively. The prognostic factors relevant to patients with early-stage (pStage I, n = 304) and advanced-stage (pStage II, III, and IV, n = 240) gastric cancer were analyzed through univariate and multivariate analyses. In the early-stage group, only the serum carbohydrate antigen (CA) 19-9 level (P = 0.037) was a significant prognostic factor in the multivariate analysis; the GPS was not significant (P = 0.095). In the advanced-stage group, an American Society of Anesthesiologists physical status of 3 or 4 (P = 0.032), elevated carcinoembryonic antigen (CEA) (P = 0.043) and CA19-9 (P = 0.045) levels, a GPS 1 - 2 (P = 0.017), and type 4 tumor (P = 0.020) correlated significantly with worse overall survival. GPS is a simple and useful prognostic score for patients with advanced-stage, but is not applicable to early-stage patients. | Gastric cancer;Prognostic score;Survival | pubmed |
Genetic analysis of adults heterozygous for ALPL mutations. | Hypophosphatasia (HPP) is a rare inherited metabolic bone disease due to a deficiency of the tissue nonspecific alkaline phosphatase isoenzyme (TNSALP) encoded by the ALPL gene. Patients have consistently low serum alkaline phosphatase (AP), so that this parameter is a good hallmark of the disease. Adult HPP is heterogeneous, and some patients present only mild nonpathognomonic symptoms which are also common in the general population such as joint pain, osteomalacia and osteopenia, chondrocalcinosis, arthropathy and musculoskeletal pain. Adult HPP may be recessively or dominantly inherited; the latter case is assumed to be due to the dominant negative effect (DNE) of missense mutations derived from the functional homodimeric structure of TNSALP. However, there is no biological argument excluding the possibility of other causes of dominant HPP. Rheumatologists and endocrinologists are increasingly solicited for patients with low AP and nonpathognomonic symptoms of HPP. Many of these patients are heterozygous for an ALPL mutation and a challenging question is to determine if these symptoms, which are also common in the general population, are attributable to their heterozygous ALPL mutation or not. In an attempt to address this question, we reviewed a cohort of 61 adult patients heterozygous for an ALPL mutation. Mutations were distinguished according to their statistical likelihood to show a DNE. One-half of the patients carried mutations predicted with no DNE and were slightly less severely affected by the age of onset, serum AP activity and history of fractures. We hypothesized that these mutations result in another mechanism of dominance or are recessive alleles. To identify other genetic factors that could trigger the disease phenotype in heterozygotes for potential recessive mutations, we examined the next-generation sequencing results of 32 of these patients for a panel of 12 genes involved in the differential diagnosis of HPP or candidate modifier genes of HPP. The heterozygous genotype G/C of the COL1A2 coding SNP rs42524 c.1645C > G (p.Pro549Ala) was associated with the severity of the phenotype in patients carrying mutations with a DNE whereas the homozygous genotype G/G was over-represented in patients carrying mutations without a DNE, suggesting a possible role of this variant in the disease phenotype. These preliminary results support COL1A2 as a modifier gene of HPP and suggest that a significant proportion of adult heterozygotes for ALPL mutations may have unspecific symptoms not attributable to their heterozygosity. | Adult hypophosphatasia;Dominant inheritance;Dominant negative effect;Modifier gene | pubmed |
Spatial and temporal genetic dynamics of the grasshopper <i>Oedaleus decorus</i> revealed by museum genomics. | Analyzing genetic variation through time and space is important to identify key evolutionary and ecological processes in populations. However, using contemporary genetic data to infer the dynamics of genetic diversity may be at risk of a bias, as inferences are performed from a set of extant populations, setting aside unavailable, rare, or now extinct lineages. Here, we took advantage of new developments in next-generation sequencing to analyze the spatial and temporal genetic dynamics of the grasshopper <i>Oedaleus decorus</i>, a steppic Southwestern-Palearctic species. We applied a recently developed hybridization capture (hyRAD) protocol that allows retrieving orthologous sequences even from degraded DNA characteristic of museum specimens. We identified single nucleotide polymorphisms in 68 historical and 51 modern samples in order to (i) unravel the spatial genetic structure across part of the species distribution and (ii) assess the loss of genetic diversity over the past century in Swiss populations. Our results revealed (i) the presence of three potential glacial refugia spread across the European continent and converging spatially in the Alpine area. In addition, and despite a limited population sample size, our results indicate (ii) a loss of allelic richness in contemporary Swiss populations compared to historical populations, whereas levels of expected heterozygosities were not significantly different. This observation is compatible with an increase in the bottleneck magnitude experienced by central European populations of <i>O. decorus</i> following human-mediated land-use change impacting steppic habitats. Our results confirm that application of hyRAD to museum samples produces valuable information to study genetic processes across time and space. | conservation genetics;hybridization capture RAD;phylogeography;population genetics | pubmed |
A valid method to determine the site of drowning. | The diatom test is considered a useful aid in determining the site of death from drowning. Nevertheless, there is disagreement within the scientific community concerning its reliability, and its findings have been challenged and sometimes overturned in courts of law. Using a model based on animal experimentation, we have developed a diatom test to discriminate between the locations of drowning sites from different aquatic systems. We carried out a complementary combination of quantitative and qualitative analyses together with a statistical analysis based on the Kullback-Leibler distance of the samples. A restrictive selection of exclusive diatom species from each reservoir was also made. This approach allowed us to validate the usefulness of the diatom test in determining the location of the site of drowning. | Diatom test;Drowning;Forensic pathology;Site of drowning | pubmed |
Chloroformate derivatization for tracing the fate of Amino acids in cells and tissues by multiple stable isotope resolved metabolomics (mSIRM). | Amino acids have crucial roles in central metabolism, both anabolic and catabolic. To elucidate these roles, steady-state concentrations of amino acids alone are insufficient, as each amino acid participates in multiple pathways and functions in a complex network, which can also be compartmentalized. Stable Isotope-Resolved Metabolomics (SIRM) is an approach that uses atom-resolved tracking of metabolites through biochemical transformations in cells, tissues, or whole organisms. Using different elemental stable isotopes to label multiple metabolite precursors makes it possible to resolve simultaneously the utilization of these precursors in a single experiment. Conversely, a single precursor labeled with two (or more) different elemental isotopes can trace the allocation of e.g. C and N atoms through the network. Such dual-label experiments however challenge the resolution of conventional mass spectrometers, which must distinguish the neutron mass differences among different elemental isotopes. This requires ultrahigh resolution Fourier transform mass spectrometry (UHR-FTMS). When combined with direct infusion nano-electrospray ion source (nano-ESI), UHR-FTMS can provide rapid, global, and quantitative analysis of all possible mass isotopologues of metabolites. Unfortunately, very low mass polar metabolites such as amino acids can be difficult to analyze by current models of UHR-FTMS, plus the high salt content present in typical cell or tissue polar extracts may cause unacceptable ion suppression for sources such as nano-ESI. Here we describe a modified method of ethyl chloroformate (ECF) derivatization of amino acids to enable rapid quantitative analysis of stable isotope labeled amino acids using nano-ESI UHR-FTMS. This method showed excellent linearity with quantifiable limits in the low nanomolar range represented in microgram quantities of biological specimens, which results in extracts with total analyte abundances in the low to sub-femtomole range. We have applied this method to profile amino acids and their labeling patterns in <sup>13</sup>C and <sup>2</sup>H doubly labeled PC9 cell extracts, cancerous and non-cancerous tissue extracts from a lung cancer patient and their protein hydrolysates as well as plasma extracts from mice fed with a liquid diet containing <sup>13</sup>C<sub>6</sub>-glucose (Glc). The multi-element isotopologue distributions provided key insights into amino acid metabolism and intracellular pools in human lung cancer tissues in high detail. The <sup>13</sup>C labeling of Asp and Glu revealed de novo synthesis of these amino acids from <sup>13</sup>C<sub>6</sub>-Glc via the Krebs cycle, specifically the elevated level of <sup>13</sup>C<sub>3</sub>-labeled Asp and Glu in cancerous versus non-cancerous lung tissues was consistent with enhanced pyruvate carboxylation. In addition, tracking the fate of double tracers, (<sup>13</sup>C<sub>6</sub>-Glc + <sup>2</sup>H<sub>2</sub>-Gly or <sup>13</sup>C<sub>6</sub>-Glc + <sup>2</sup>H<sub>3</sub>-Ser) in PC9 cells clearly resolved pools of Ser and Gly synthesized de novo from <sup>13</sup>C<sub>6</sub>-Glc (<sup>13</sup>C<sub>3</sub>-Ser and <sup>13</sup>C<sub>2</sub>-Gly) versus Ser and Gly derived from external sources (<sup>2</sup>H<sub>3</sub>-Ser, <sup>2</sup>H<sub>2</sub>-Gly). Moreover the complex <sup>2</sup>H labeling patterns of the latter were results of Ser and Gly exchange through active Ser-Gly one-carbon metabolic pathway in PC9 cells. | Amino acids;Direct infusion nano-electrospray;Stable isotope resolved metabolomics;Ultrahigh resolution fourier transform mass spectrometry | pubmed |
Morphological characteristics of Street Workout practitioners. | The determination of the morphological characteristics of the most popular sports has allowed the evaluation and comparison between athletes, which has helped to improve their performance. The Street Workout is an emerging sport based on calisthenics, which recently has become popular. Despite its popularization, neither the morphologic profile nor the morphologic characteristics of Street Workout athletes has been determined. Determine the profile and morphological characteristics of Street-Workout athletes, through anthropometry. Fourteen athletes (22.7 ± 3.26 years) were recruited from the National Calisthenics Tournament 2015 in Chile. The athletes were evaluated following the protocol of the International Society for the Advancement of Kinanthropometry to determine the somatotype, body composition, as well as indices of body composition such as body mass index, waist to hip ratio, waist to height ratio, fat/muscle mass and muscle/bone mass indexes. Street Workout practitioners presented a balanced-mesomorphic somatotype, a low fat mass and a high muscular development, with upper arms and trunk predominance. Regarding body composition indices, the values obtained allow us to classify them as a low-risk population of chronic non-communicable diseases. The present study sets a first antecedent of the morphological characteristics of Street Workout, determining that the Street Workout athletes presented balanced-mesomorphic somatotype and were classified as a healthy and athletic sample by their body composition indexes. | Calisthenics. Anthropometry. Somatotype. Body composition. Sport. | pubmed |
Antibacterial efficacy of silver nanoparticles synthesized employing Terminalia arjuna bark extract. | In the present investigation, we have explored simple, robust, inexpensive, and eco-friendly method for the synthesis of silver nanoparticles (AgNPs) using Terminalia arjuna bark extract (TA-AgNPs). Various parameters dictating the biosynthesis of TA-AgNPs such as time and temperature of reaction, concentration of AgNO<sub>3</sub>, and T. arjuna extract amount were investigated. Characterization of TA-AgNPs was done via UV-vis spectroscopy along with FT-IR, XRD, SEM and dynamic light scattering. The antimicrobial activity of TA-AgNPs was investigated against Escherichia coli. Comparable zone of inhibition was exhibited by TA-AgNPs. This study suggests that TA-AgNPs possesses significant antibacterial properties. | Silver nanoparticles;T. arjuna;UV-vis spectroscopy;antibacterial;biosynthesis | pubmed |
Pericardial Masses, Cysts and Diverticula: A Comprehensive Review Using Multimodality Imaging. | Pericardial masses/tumors, cysts, and diverticula are quite rare. Presentation is variable and often patients may be asymptomatic with pericardial involvement initially only detected at time of autopsy. When patients do present with symptoms they are often non-specific and often mimic other conditions of the pericardium such as pericarditis, pericardial effusion, constriction or tamponade. Therefore, echocardiography and cross-sectional imaging are essential in identifying and characterizing pericardial disease. Imaging findings vary in specificity depending on the type of tumor. The purpose of this review is to describe the role of multi-modality imaging and characteristic findings in patients with pericardial masses/tumors, cysts, and diverticula. | Cardiac CT;Cardiac MRI;Echocardiography;Pericardial mass;Pericardial tumor | pubmed |
Maternal HIV and Paediatric Lung Health. | With improved prevention of mother to child transmission of HIV, paediatric HIV disease is less common. However, the number of HIV exposed but uninfected infants is growing. Exposure to maternal HIV impacts infant respiratory health through an increase in known risk factors such as increased preterm birth and low birth weight, suboptimal breastfeeding, increased psychosocial stressors and increased exposure to infective pathogens. Exposure to the HIV virus and altered maternal immune environment result in immunologic changes in the infant that may contribute to respiratory disease risk. HIV exposed infants are at increased risk for severe pneumonia with poorer outcomes compared to unexposed infants. Maternal ART and optimal nutrition, including breastfeeding in high infective disease burden settings, reduce morbidity and mortality in HIV exposed infants and should be prioritized. The impact of exposure to maternal HIV on normal lung growth and risk for chronic respiratory disease is unknown and warrants further investigation. | HIV;infant;maternal exposure;respiratory disease | pubmed |
Comparison of Candida Albicans Adherence to Conventional Acrylic Denture Base Materials and Injection Molding Acrylic Materials. | Candida species are believed to play an important role in initiation and progression of denture stomatitis. The type of the denture material also influences the adhesion of candida and development of stomatitis. The aim of this study was comparing the adherence of <i>candida albicans</i> to the conventional and injection molding acrylic denture base materials. Twenty injection molding and 20 conventional pressure pack acrylic discs (10×10×2 mm) were prepared according to their manufacturer's instructions. Immediately before the study, samples were placed in sterile water for 3 days to remove residual monomers. The samples were then sterilized using an ultraviolet light unit for 10 minutes. 1×10<sup>8</sup> Cfu/ml suspension of <i>candida albicans</i> ATCC-10231 was prepared from 48 h cultured organism on sabouraud dextrose agar plates incubated at 37oC. 100 μL of this suspension was placed on the surface of each disk. After being incubated at 37oC for 1 hour, the samples were washed with normal saline to remove non-adherent cells. Attached cells were counted using the colony count method after shaking at 3000 rmp for 20 seconds. Finally, each group was tested for 108 times and the data were statistically analyzed by t-test. Quantitative analysis revealed that differences in colony count average of <i>candida albicans</i> adherence to conventional acrylic materials (8.3×10<sup>3</sup>) comparing to injection molding acrylic resins (6×10<sup>3</sup>) were statistically significant (<i>p</i><0.001). Significant reduction of <i>candida albicans</i> adherence to the injection acrylic resin materials makes them valuable for patients with high risk of denture stomatitis. | Acrylic Resins ; Denture;Candida albicans | pubmed |
ENRI: A tool for selecting structure-based virtual screening target conformations. | Finding pharmaceutically relevant target conformations from an arbitrary set of protein conformations remains a challenge in structure-based virtual screening (SBVS). The growth in the number of available conformations, either experimentally determined or computationally derived, obscures the situation further. While the inflated conformation space potentially contains viable druggable targets, the increase of conformational complexity, as a consequence, poses a selection problem. To address this challenge, we took advantage of machine learning methods, namely an over-sampling and a binary classification procedure, and present a novel method to select druggable receptor conformations. Specifically, we trained a binary classifier on a set of nuclear receptor conformations, wherein each conformation was labeled with an enrichment measure for a corresponding SBVS. The classifier enabled us to formulate suggestions and identify enriching SBVS targets for six of seven nuclear receptors. Further, the classifier can be extended to other proteins of interest simply by feeding new training data sets to the classifier. Our work, thus, provides a methodology to identify pharmaceutically interesting receptor conformations for nuclear receptors and other drug targets. | binding pocket;classification;conformational dynamics;molecular docking;molecular dynamics simulation;virtual screening | pubmed |
Frequencies of the precision ID ancestry panel markers in Basques using the Ion Torrent PGM<sup>TM</sup> platform. | The Precision ID Ancestry Panel for the Ion Torrent PGM™ platform is able to genotype 165 autosomal SNPs by massively parallel sequencing (MPS). In the present study, we evaluated the depth of coverage, the locus strand balance and the heterozygote balance of the above panel. The SNPs rs1569175, rs2306040, rs9845457, rs1407434, and rs10007810 showed a low performance, due either to a low coverage, locus strand imbalance or heterozygote imbalance. To further to assess this panel, we analyzed 108 Basques. All loci proved to be in Hardy-Weinberg equilibrium and we did not detect any association between them with the exception of the pair rs3916235-rs4891825 in chromosome 18. The forensic parameters combined match probability and combined power of exclusion were estimated to be 3.13×10<sup>-35</sup> and 99.9972%, respectively. In conclusion, the Precision ID Ancestry panel along with this new MPS technology constitute a very promising tool for human identification and biogeographical ancestry inference in routine casework in the forensic field. | Basques;Ion Torrent PGM(TM);Massively parallel sequencing (MPS);Population genetics;Precision ID Ancestry Panel | pubmed |
The non-Darwinian evolution of behavers and behaviors. | Many readers of this journal have been schooled in both Darwinian evolution and Skinnerian psychology, which have in common the vision of powerful control of their subjects by their sequalae. Individuals of species that generate more successful offspring come to dominate their habitat; responses of those individuals that generate more reinforcers come to dominate the repertoire of the individual in that context. This is unarguable. What is questionable is how large a role these forces of selection play in the larger landscape of existing organisms and the repertoires of their individuals. Here it is argued that non-Darwinian and non-Skinnerian selection play much larger roles in both than the reader may appreciate. The argument is based on the history of, and recent advances in, microbiology. Lessons from that history re-illuminate the three putative domains of selection by consequences: The evolution of species, response repertoires, and cultures. It is argued that before, beneath, and after the cosmically brief but crucial epoch of Darwinian evolution that shaped creatures such as ourselves, non-Darwinian forces pervade all three domains. | Lateral gene transfer;Meme;Microbes;Non-Darwinian evolution;Selection by consequences;Tree of life | pubmed |
Feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus™ for frail elderly: study protocol for a feasibility trial. | Frailty can be defined as a medical syndrome with multiple causes and contributors, characterized by diminished strength and endurance and reduced physiological function that increases the vulnerability to develop functional dependency and/or death. Studies have shown that the most commonly studied exercise protocol for frail older adults is the multimodal training. Interactive video games (IVGs) involve tasks in virtual environments that combine physical and cognitive demands in an attractive and challenging way. The aim of this study will be to evaluate the feasibility, safety, acceptability, and functional outcomes of playing Nintendo Wii Fit Plus<sup>TM</sup> (NWFP) for frail older adults. The study is a randomized controlled, parallel group, feasibility trial. Participants will be randomly assigned to the experimental group (EG) and control group (CG). The EG will participate in 14 training sessions, each lasting 50 min, twice a week. In each training session, the participants will play five games, with three attempts at each game. The first attempt will be performed with the assistance of a physical therapist to correct the movements and posture of the patients and subsequent attempts will be performed independently. Scores achieved in the games will be recorded. The participants will be evaluated by a blinded physical therapist at three moments: before and after intervention and 30 days after the end of the intervention (follow-up). We will assess the feasibility, acceptability, safety, and clinical outcomes (postural control, gait, cognition, quality of life, mood, and fear of falling). Due to the deficiencies in multiple systems, studies have shown that multimodal interventions including motor-cognitive stimulation can improve the mobility of frail elderly adults. IVGs, among them the NWFP, are considered as a multimodal motor-cognitive intervention that can potentially improve motor and cognitive functions in the frail elderly. However, there is still no evidence in the literature that proves the feasibility, safety, acceptability, and functional outcomes of this intervention in frail elderly individuals. Brazilian Registry of Clinical Trials (RBR-823rst). World Health Organization Trial Registration Data Set (Additional file 1). | Aged;Frail elderly;Rehabilitation;Virtual reality therapy | pubmed |
Development of practical decontamination process for the removal of uranium from gravel. | In this study, a practical decontamination process was developed to remove uranium from gravel using a soil washing method. The effects of critical parameters including particle size, H<sub>2</sub>SO<sub>4</sub> concentration, temperature, and reaction time on uranium removal were evaluated. The optimal condition for two-stage washing of gravel was found to be particle size of 1-2 mm, 1.0 M H<sub>2</sub>SO<sub>4</sub>, temperature of 60°C, and reaction time of 3 h, which satisfied the required uranium concentration for self-disposal. Furthermore, most of the extracted uranium was removed from the waste solution by precipitation, implying that the treated solution can be reused as washing solution. These results clearly demonstrated that our proposed process can be indeed a practical technique to decontaminate uranium-polluted gravel. | Uranium;decontamination;gravel;precipitation;soil washing | pubmed |
Why do pregnant women participate in research? A patient participation investigation using Q-Methodology. | Patient participation in study design is paramount to design studies that are acceptable to patients. Despite an increase in research involving pregnant women, relatively little is known about the motivational factors that govern their decision to be involved in a clinical trial, compared to other patient groups. To better understand the viewpoints of pregnant women who take part in clinical trials. We chose to use Q-Methodology, a method of exploring the structure of opinions surrounding a topic. We developed a set of 40 statements that encompassed the reasons why pregnant women might want to take part in research and 30 research participants from the PRiDE study (an observational trial investigating the role of micronutrients in gestational diabetes) were asked to rank them in order of agreement. The finished matrices from each participant were compared and analysed to produce capturing viewpoints. About 30 women aged 19-40 involved in the PRiDE study completed the questionnaire. There were two overarching motivators that emerged: a willingness to help medical research and improve our knowledge of medical science, and having a personal connection to the disease, therefore a potential fear of being affected by it. A third, less significant viewpoint, was that of a lack of inconvenience being a motivating factor. Understanding what motivates pregnant women to decide to take part in a research study is valuable and helps researchers maximize their uptake and retention rates when designing a trial involving pregnant women. | Q-Methodology;consent;participation;patient choice;pregnancy research | pubmed |
The Relationship between Social Networking Site Use and the Internalization of a Thin Ideal in Females: A Meta-Analytic Review. | Previous research has indicated that exposure to traditional media (i.e., television, film, and print) predicts the likelihood of internalization of a thin ideal; however, the relationship between exposure to internet-based social media on internalization of this ideal remains less understood. Social media differ from traditional forms of media by allowing users to create and upload their own content that is then subject to feedback from other users. This meta-analysis examined the association linking the use of social networking sites (SNSs) and the internalization of a thin ideal in females. Systematic searches were performed in the databases: PsychINFO, PubMed, Web of Science, Communication and Mass Media Complete, and ProQuest Dissertations and Theses Global. Six studies were included in the meta-analysis that yielded 10 independent effect sizes and a total of 1,829 female participants ranging in age from 10 to 46 years. We found a positive association between extent of use of SNSs and extent of internalization of a thin ideal with a small to moderate effect size (<i>r</i> = 0.18). The positive effect indicated that more use of SNSs was associated with significantly higher internalization of a thin ideal. A comparison was also made between study outcomes measuring broad use of SNSs and outcomes measuring SNS use solely as a function of specific appearance-related features (e.g., posting or viewing photographs). The use of appearance-related features had a stronger relationship with the internalization of a thin ideal than broad use of SNSs. The finding suggests that the ability to interact with appearance-related features online and be an active participant in media creation is associated with body image disturbance. Future research should aim to explore the way SNS users interact with the media posted online and the relationship linking the use of specific appearance features and body image disturbance. | Facebook;body image;eating disorders;internalization;social networking | pubmed |
Impact of cold on the immune system of burying beetle, Nicrophorus vespilloides (Coleoptera: Silphidae). | Insect overwintering is one of the most astonishing phases of the insect life cycle. Despite vast amounts of knowledge available about the physiological mechanisms of this phenomenon, the impact of stress factors on insect immune system functioning during the winter is still unknown. The aim of this study is to analyze how low temperatures influence the immune system of the beetle Nicrophorus vespilloides. The results show that the beetle's immune system is differently modulated by cold induced in laboratory settings than that which occurs in natural conditions. Among beetles cultured in conditions similar to summer, low temperatures, did not influence the number of circulating haemocytes, phenoloxidase activity, haemocytes morphology, and percentage ratio of haemocyte types. In these beetles, differences were noted only in the ability of haemocytes to perform phagocytosis. Individuals acclimated in natural conditions in autumn had a higher level of humoral response and a different percentage ratio of haemocyte types. During the winter period, the number of haemocytes in the beetles decreased, but the percentage ratio of phagocytic haemocytes increased. Furthermore, we noted an increase of phenoloxidase activity. Our study also showed mitotic divisions of haemocytes in haemolymph collected from burying beetles after cold exposure and from burying beetles collected from natural conditions during autumn and winter. Differences in response to low temperatures in laboratory conditions and the natural environment suggest that the simultaneous presence of other stress factors during winter such as desiccation and starvation have a significant influence on the activity of burying beetle's immune system. | burying beetles;cold;immune system;overwintering;phagocytosis;phenoloxidase | pubmed |
The Use of Pit and Fissure Sealants-A Literature Review. | This paper reviews the literature and discusses the latest updates on the use of pit and fissure sealants. It demonstrates the effectiveness of pit and fissure sealants in preventing caries and the management of early carious lesions. It compares the use of different sealant materials and their indications. It describes the application technique for sealants. It also reviews the cost-effectiveness of sealants as a preventive strategy. From this review and after the discussion of recently published studies on pit and fissure sealants, it is evident that sealants are effective in caries prevention and in preventing the progression of incipient lesions. It is therefore recommended that pit and fissure sealant be applied to high-caries-risk children for optimum cost-effectiveness. It is a highly sensitive technique that needs optimum isolation, cleaning of the tooth surface, etching, and the application of a thin bonding layer for maximum benefit. Recall and repair, when needed, are important to maximize the effectiveness of such sealant use. | caries prevention;pit and fissure sealants;resin-based sealants | pubmed |
The Forebrain Thirst Circuit Drives Drinking through Negative Reinforcement. | The brain transforms the need for water into the desire to drink, but how this transformation is performed remains unknown. Here we describe the motivational mechanism by which the forebrain thirst circuit drives drinking. We show that thirst-promoting subfornical organ neurons are negatively reinforcing and that this negative-valence signal is transmitted along projections to the organum vasculosum of the lamina terminalis (OVLT) and median preoptic nucleus (MnPO). We then identify molecularly defined cell types within the OVLT and MnPO that are activated by fluid imbalance and show that stimulation of these neurons is sufficient to drive drinking, cardiovascular responses, and negative reinforcement. Finally, we demonstrate that the thirst signal exits these regions through at least three parallel pathways and show that these projections dissociate the cardiovascular and behavioral responses to fluid imbalance. These findings reveal a distributed thirst circuit that motivates drinking by the common mechanism of drive reduction. | OVLT;angiotensin;circuit;drinking behavior;drive reduction;homeostasis;hypothalamus;lamina terminalis;lateral hypothalamus;median preoptic nucleus;motivation;negative reinforcement;optogenetics;paraventricular hypothalamus;paraventricular thalamus;subfornical organ;thirst;valence | pubmed |
In vitro and in vivo activity of EDTA and antibacterial agents against the biofilm of mucoid Pseudomonas aeruginosa. | Refractory infection caused by bacterial biofilm is an important clinical problem. Pseudomonas aeruginosa is a common pathogen responsible for persistent and chronic biofilm infections. We aimed to explore the in vitro and in vivo activity of ethylenediamine tetraacetic acid (EDTA) in combination with antibacterial agents against mucoid P. aeruginosa biofilm. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration of ciprofloxacin, gentamicin, and ampicillin alone or with EDTA against P. aeruginosa were determined in vitro. Extracellular polysaccharides (EPS) and structural parameters of the biofilm were monitored. P. aeruginosa was aerosolized and delivered into the lungs of guinea pigs, which were treated with ciprofloxacin with or without EDTA. The colony-forming units (CFUs) of P. aeruginosa were determined from the lungs. EDTA reduced the MIC of ciprofloxacin and ampicillin by about 30-fold and that of gentamicin by twofold. EDTA reduced the biofilm EPS and the proportion of viable bacteria. The thickness, average diffusion distance, and textural entropy of EDTA-treated biofilm were significantly decreased. EDTA plus antibiotics reduced the colony counting from 10<sup>7</sup> to 10<sup>3</sup> CFU/mL. In vivo, EDTA plus ciprofloxacin had a significantly lower mean CFU/g of lung tissue (EDTA + ciprofloxacin 1.3 ± 0.19; EDTA 4.4 ± 0.57; ciprofloxacin 4.2 ± 0.47), and lung lesions were less severe compared with the single treatment groups. EDTA can destroy the biofilm structures of mucoid P. aeruginosa in vitro. Moreover, EDTA and ciprofloxacin had a significant bactericidal effect against biofilm in vivo. | Antibacterial agents;Biofilm;Ethylenediamine tetraacetic acid;Pseudomonas aeruginosa | pubmed |
Best friends' interactions and substance use: The role of friend pressure and unsupervised co-deviancy. | Best friends exert a substantial influence on rising alcohol and marijuana use during adolescence. Two mechanisms occurring within friendship - friend pressure and unsupervised co-deviancy - may partially capture the way friends influence one another. The current study aims to: (1) examine the psychometric properties of a new instrument designed to assess pressure from a youth's best friend and unsupervised co-deviancy; (2) investigate the relative contribution of these processes to alcohol and marijuana use; and (3) determine whether gender moderates these associations. Data were collected through self-report questionnaires completed by 294 Canadian youths (62% female) across two time points (ages 15-16). Principal component analysis yielded a two-factor solution corresponding to friend pressure and unsupervised co-deviancy. Logistic regressions subsequently showed that unsupervised co-deviancy was predictive of an increase in marijuana use one year later. Neither process predicted an increase in alcohol use. Results did not differ as a function of gender. | Adolescence;Alcohol use;Friend pressure;Friendship;Marijuana use;Unsupervised co-deviancy | pubmed |
The potential of health literacy to address the health related UN sustainable development goal 3 (SDG3) in Nepal: a rapid review. | Health literacy has been linked to health outcomes across population groups around the world. Nepal, a low income country, experiences the double burden of highly prevalent communicable as well as non-communicable diseases. The World Health Organization (WHO) has positioned health literacy as a key mechanism to meet the health-related Sustainable Development Goal (SDG3). However, there is little known about the status of health literacy in developing countries such as Nepal. This paper aims to review the potential of health literacy to address SDG3 in Nepal. A rapid review was conducted using the knowledge to action evidence summary approach. Articles included in the review were those reporting on barriers to health care engagements in Nepal published in English language between January 2000 and December 2015. Barriers for healthcare engagement included knowledge and education as strong factors, followed by culture, gender roles, quality of service and cost of services. These barriers influence the Nepalese community to access and engage with services, and make and enact healthcare decisions, not only at the individual level but at the family level. These factors are directly linked to health literacy. Health literacy is a pivotal determinant of understanding, accessing and using health information and health services, it is important that the health literacy needs of the people be addressed. Locally identified and developed health literacy interventions may provide opportunities for systematic improvements in health to address impediments to healthcare in Nepal. Further research on health literacy and implementation of health literacy interventions may help reduce inequalities and increase the responsiveness of health systems which could potentially facilitate Nepal to meet the sustainable development goals. While there is currently little in place for health literacy to impact on the SDG3, this paper generates insights into health literacy's potential role. | Development;Equity;Health literacy;Health system responsiveness;Impediments to public health in Nepal;Nepal;SDG;Sustainable development goals | pubmed |
Purified citritin in combination with vancomycin inhibits VRE in vitro and in vivo. | Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) have been frequently associated with bacterial resistance mechanisms. These mechanisms, in turn, restrict a range of therapeutic opportunities for the treatment of infections caused by these micro-organisms. Faced with this problem, the present study aims to isolate and characterize molecules with antimicrobial activity derived from the fungus Penicillium citrinum isolated from Cerrado soil. Furthermore, we also tested possible antibacterial potential alone and in combination with commercial antimicrobial agents. In this context, citrinin was isolated and characterized by nuclear magnetic resonance and electrospray ionization. Functional analyses showed MIC of 128 µg ml<sup>-1</sup> against S. aureus ATCC 25923, E. faecalis ATCC 29212 and a clinical isolate of vancomycin-resistant E. faecium (VRE01). However, for a clinical strain of methicillin-resistant S. aureus (MRSA01), the MIC was 256 µg ml<sup>-1</sup>. In order to avoid such high concentrations and reduce the collateral effects, additive effects were evidenced by combining citrinin with cefoxitin against MRSA01 (FIC index=0.5) and also citrinin with vancomycin toward VRE01 (FIC index=0.5). In vivo studies with BALB/c-tipe mice (MRSA assay) demonstrated a clinical ineffectiveness of cefoxitin associated with citrinin (9.8 mg kg<sup>-1</sup> of cefoxitin +0.2 mg kg<sup>-1</sup> of citrinin), with this combination being inefficient to increase animal survival. However, the combination used in the treatment of VRE (23.5 mg kg<sup>-1</sup> of citrinin +1.5 mg kg<sup>-1</sup> of vancomycin) sepsis model was extremely promising, leading to an animal survival rate of 80 percent. In summary, our data show, for the first time, the possible successful use of citrinin associated with vancomycin for pathogenic bacteria control. | MRSA infection;VRE infection;citrinin;sepsis model;synergism | pubmed |
Deep Phenotyping of Systemic Arterial Hemodynamics in HFpEF (Part 2): Clinical and Therapeutic Considerations. | Multiple phase III trials over the last few decades have failed to demonstrate a clear benefit of various pharmacologic interventions in heart failure with a preserved left ventricular (LV) ejection fraction (HFpEF). Therefore, a better understanding of its pathophysiology is important. An accompanying review describes key technical and physiologic aspects regarding the deep phenotyping of arterial hemodynamics in HFpEF. This review deals with the potential of this approach to enhance our clinical, translational, and therapeutic approach to HFpEF. Specifically, the role of arterial hemodynamics is discussed in relation to (1) the pathophysiology of left ventricular diastolic dysfunction, remodeling, and fibrosis, (2) impaired oxygen delivery to peripheral skeletal muscle, which affects peripheral oxygen extraction, (3) the frequent presence of comorbidities, such as renal failure and dementia in this population, and (4) the potential to enhance precision medicine approaches. A therapeutic approach to target arterial hemodynamic abnormalities that are prevalent in this population (particularly, with inorganic nitrate/nitrite) is also discussed. | Afterload;Arterial hemodynamics;Comorbidities;Dementia;Exercise intolerance;Heart failure with preserved ejection fraction;Pulsatile load;Renal disease;Wave reflections | pubmed |
Air quality modelling in Catalonia from a combination of solar radiation, surface reflectance and elevation. | Air quality;Elevation;Geoprocessing tools;Multivariate statistics;Solar radiation;Surface reflectance | pubmed |
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Intravenous oxygen: a novel method of oxygen delivery in hypoxemic respiratory failure? | Hypoxemic respiratory failure is a common problem in critical care. Current management strategies, including mechanical ventilation and extracorporeal membranous oxygenation, can be efficacious but these therapies put patients at risk for toxicities associated with invasive forms of support. Areas covered: In this manuscript, we discuss intravenous oxygen (IVO<sub>2</sub>), a novel method to improve oxygen delivery that involves intravenous administration of a physiologic solution containing dissolved oxygen at hyperbaric concentrations. After a brief review of the physiology behind supersaturated fluids, we summarize the current evidence surrounding IVO<sub>2</sub>. Expert commentary: Although not yet at the stage of clinical testing in the United States and Europe, IVO<sub>2</sub> has been used safely in Asia. Furthermore, preliminary laboratory data have been encouraging, suggesting that IVO<sub>2</sub> may play a role in the management of patients with hypoxemic respiratory failure in years to come. However, significantly more work needs to be done, including definitive evidence that such a therapy is safe, before it can be included in an intensivist's arsenal for hypoxemic respiratory failure. | Hypoxia;critical care;intravenous oxygen;lung injury;mechanical ventilation;oxygen delivery;respiratory failure | pubmed |
Protocol for the prospective validation study: 'Screening programme for pre-eclampsia' (SPREE). | Pre-eclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. Early detection of PE can improve pregnancy outcome by providing timely intervention and closer monitoring. The current guideline from the UK National Institute for Health and Care Excellence (NICE) recommends that, at the booking visit, women identified with one major risk factor or more than one moderate risk factor for PE should be advised to take low-dose aspirin daily from 12 weeks until delivery. However, performance of the current method of screening is poor and identifies only about 35% of PE. Extensive studies in the last decade have established that the best performance for early prediction of PE can be achieved by using a novel Bayes' theorem-based method that combines maternal characteristics and medical history together with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation. This forms the 'combined test', which could be simplified to the 'mini combined test' when only maternal factors, MAP and PAPP-A are taken into consideration. We present the protocol (version 3.1, 14 November 2016) for the 'Screening programme for pre-eclampsia' (SPREE) study, a prospective multicenter cohort study that will be carried out in seven National Health Service maternity hospitals in England. Eligible pregnant women attending their routine scan at 11-13 weeks' gestation will be invited to participate in this study. Maternal characteristics and history and measurements of MAP, UtA-PI, serum PAPP-A and PlGF will be recorded according to standardized protocols. The patient-specific risk for PE will be calculated and data on pregnancy outcomes collected. We hypothesize that the first-trimester mini combined test and combined test for PE screening, using the Bayes' theorem-based method, are likely to be superior to the current method recommended by NICE that is based on maternal demographics and history alone. Enrollment for the study commenced in April 2016. The study is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. | Bayes' theorem;National Institute for Health and Care Excellence;first-trimester screening;mean arterial pressure;placental growth factor;pre-eclampsia;pregnancy-associated plasma protein-A;uterine artery Doppler | pubmed |
Mercury levels in human population from a mining district in Western Colombia. | A biomonitoring study was carried out to examine the adverse impacts of total mercury in the blood (HgB), urine (HgU) and human scalp hair (HgH) on the residents of a mining district in Colombia. Representative biological samples (scalp hair, urine and blood) were collected from volunteered participants (n=63) to estimate the exposure levels of THg using a Direct mercury analyzer. The geometric mean of THg concentrations in the hair, urine and blood of males were 15.98μg/g, 23.89μg/L and 11.29μg/L respectively, whereas the females presented values of 8.55μg/g, 5.37μg/L and 8.80μg/L. Chronic urinary Hg (HgU) levels observed in male workers (32.53μg/L) are attributed to their long termed exposures to inorganic and metallic mercury from gold panning activities. On an average, the levels of THg are increasing from blood (10.05μg/L) to hair (12.27μg/g) to urine (14.63μg/L). Significant positive correlation was found between hair and blood urinary levels in both male and female individuals. Thus the present biomonitoring investigation to evaluate the Hg levels and associated health issues would positively form a framework for further developmental plans and policies in building an ecofriendly ecosystem. | Biomarkers;Colombia;Gold panning;Humans;Mercury;Toxicity | pubmed |
The Potential Application of Multiscale Entropy Analysis of Electroencephalography in Children with Neurological and Neuropsychiatric Disorders. | Electroencephalography (EEG) is frequently used in functional neurological assessment of children with neurological and neuropsychiatric disorders. Multiscale entropy (MSE) can reveal complexity in both short and long time scales and is more feasible in the analysis of EEG. Entropy-based estimation of EEG complexity is a powerful tool in investigating the underlying disturbances of neural networks of the brain. Most neurological and neuropsychiatric disorders in childhood affect the early stage of brain development. The analysis of EEG complexity may show the influences of different neurological and neuropsychiatric disorders on different regions of the brain during development. This article aims to give a brief summary of current concepts of MSE analysis in pediatric neurological and neuropsychiatric disorders. Studies utilizing MSE or its modifications for investigating neurological and neuropsychiatric disorders in children were reviewed. Abnormal EEG complexity was shown in a variety of childhood neurological and neuropsychiatric diseases, including autism, attention deficit/hyperactivity disorder, Tourette syndrome, and epilepsy in infancy and childhood. MSE has been shown to be a powerful method for analyzing the non-linear anomaly of EEG in childhood neurological diseases. Further studies are needed to show its clinical implications on diagnosis, treatment, and outcome prediction. | EEG;Tourette syndrome;attention deficit/hyperactivity disorder;autism;epilepsy;multiscale entropy;neonatal seizure | pubmed |
Assessment of antigenic supplementation of bovine purified protein derivative for diagnosis of subclinical infection with Mycobacterium bovis in cattle. | Bovine tuberculosis (bTB) is usually diagnosed in vivo and ex vivo on the basis of delayed hypersensitivity reactions with a complex pool of antigens named bovine tuberculin (PPDB). The IFN-γ release assay (IGRA) for bTB is a blood-based assay that improves detection of infected cattle at early stages that escape skin testing. Improvements to IFN-γ testing with specific proteins have been performed to increase sensitivity. DosR regulon-related antigens are well known mycobacterial proteins expressed during the non-replicative phases of infection, this has been useful to improve the diagnosis of subclinical forms of TB in suspected individuals. Transcripts of DosR genes mb2054c, mb2057c, and mb2660c have been identified by our group in lymph nodes of IFN-γ test negative cattle. This led us to hypothesize that DosR-related proteins may potentiate the IFN-γ response to PPDB in animals with a false negative IFN-γ test, making evident subclinical infection. Three hundred animals were evaluated by means of IGRA and post-mortem microbiological analysis of tissue samples to validate M. bovis infection. We found that 176 out of 300 animals showed an overall increased OD in complemented IGRA with two purified protein cocktails in comparison to PPDB alone, and were scrutinized for a subclinical infection; thirty percent when PPDB was supplemented with a cocktail of four DosR antigens, and 70% when PPDB was supplemented with a cocktail of six antigens (four DosR and two RD1 antigens). Forty five animals showed a substantial IFN-γ overproduction but remained negative, and 40 animals changed the result to a positive test. Only 18 out of 176 IFN-γ high producing animals were also positive to M. bovis isolation. Fifty seven animals with no visible lesions at slaughter and with a negative IGRA test result contained M. bovis DNA in tissue samples. In conclusion, Mb1762c, Mb2054c, Mb2057c, and Mb2660c have the potential to increase sensitivity of the IFN-γ in vitro test for bTB diagnosis when supplemented to PPDB. | Antigenicity;Bovine tuberculosis;DosR proteins;IGRA;Interferon-γ;Mycobacterium bovis;Non-replicative persistence;Protein cocktails | pubmed |
Mass spectrometry based in vitro assay investigations on the transformation of pharmaceutical compounds by oxidative enzymes. | The ubiquitous presence of trace organic chemicals in wastewater and surface water leads to a growing demand for novel removal technologies. The use of isolated enzymes has been shown to possess the capability for a targeted application but requires a clearer mechanistic understanding. In this study, the potential of peroxidase from horseradish (HRP) and laccase from Pleurotus ostreatus (LccPO) to transform selected trace organic chemicals was studied using mass spectrometry (MS)-based in vitro enzyme assays. Conversion by HRP appeared to be more efficient compared to LccPO. Diclofenac (DCF) and sotalol (STL) were completely transformed by HRP after 4 h and immediate conversion was observed for acetaminophen (APAP). During treatment with LccPO, 60% of DCF was still detectable after 24 h and no conversion was found for STL. APAP was completely transformed after 20 min. Sulfamethoxazole (SMX), carbamazepine (CBZ), ibuprofen (IBP) and naproxen (NAP) were insusceptible to enzymatic conversion. In pharmaceutical mixtures, HRP exhibited a preference for DCF and APAP and the generally less efficient conversion of STL was enhanced in presence of APAP. Transformation product pattern after treatment with HRP revealed polymerization products for DCF while STL showed cleavage reactions. DCF product formation shifted towards a proposed dimeric iminoquinone product in presence of APAP whereas a generally less pronounced product formation in mixtures was observed for STL. In conclusion, the enzymatic treatment approach worked selectively and efficiently for a few pharmaceuticals. However, for application the investigation and possibly immobilization of multiplex enzymes being able to transform diverse chemical structures is recommended. | Enzymatic transformation;Laccase;Mass spectrometry;Peroxidase;Pharmaceuticals;Transformation products | pubmed |
Validation of a Score Developed to Estimate the 6-month Survival of Patients Treated with Palliative Local Radiotherapy for Advanced Lung Cancer. | To validate a score estimating the 6-month survival of lung cancer patients irradiated for locally advanced disease. The validation cohort of this study included 125 patients. The score for each patient was calculated by adding the points (6-month survival divided by 10) from the factors lymph node stage, distant metastasis and performance score. Patients were divided into three groups, 10-11 (N=36), 12-14 (N=69) and 15-17 points (N=20). Six-month survival of each group from the original study was compared to its corresponding group from this validation study. Six-month survival rates were 19% (10-11 points), 51% (12-14 points) and 75% (16-17 points) in the validation cohort (p<0.001) and 13%, 47% and 82% in the previous study (p<0.001). The group-by-group comparisons between both cohorts did not reveal any significant differences. The score was reproducible and valid for estimating the 6-month survival of lung cancer patients assigned to palliative thoracic radiotherapy. | Locally advanced lung cancer;palliative radiotherapy;prognostic score;survival prognosis;thoracic radiotherapy;validation | pubmed |
Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Levels and Its Association with Renal Allograft Rejection. | CCL2 is a chemoattractant for monocytes/macrophages, T cells, and natural killer cells. It is shown to be involved in the immunological responses against renal allograft. This study was conducted to access the role of urinary CCL2 expression in predicting the rejection episodes in renal transplant patients. A total of 409 urine samples included in this study. The samples were consisted of (a) biopsy-proven graft rejection (n = 165); (b) non-rejection (n = 93); (c) non-biopsy stable-graft (n = 42), and (d) healthy renal donors (n = 109). The samples were quantified for the CCL2 using the MCP-1/CCL2 ELISA kit. The data were analyzed using the Statistical Package for Social Sciences (SPSS<sup>®</sup>) and MedCalc<sup>®</sup> statistical software. Results showed that the CCL2 levels were significantly increased in rejection group when compared with the non-rejection, stable-graft, and control, P < 0.05. The receiver operating curve's characteristics illustrated that the urinary CCL2 level is a good predictor for graft rejection, with an area under the curve of 0.81 ± 0.03 with optimum sensitivity and specificity of 87% and 62%, respectively, at a cut-off value of 198 pg/mL. Kaplan-Meier curve also showed better cumulative rejection-free graft survival time in group with less than 198 pg/mL of CCL2 as compared to those with expression levels of more than 198 pg/mL (30 weeks vs. 3 weeks; log-rank test, P < 0.001). In our study, noninvasive investigation of CCL2 levels in urine has showed potential to predict rejection episodes. It is suggested that the CCL2, with others markers, may help in early detection and monitoring of graft rejection episodes. | Allograft rejection;CCL2;biomarkers;chemokines;kidney transplantation | pubmed |
Nitric oxide inhibits aluminum-induced programmed cell death in peanut (Arachis hypoganea L.) root tips. | It had been reported that Aluminum (Al) stress altered nitric oxide (NO) concentration and induced programmed cell death (PCD) in plants. However, the relationship between NO and PCD occurrence under Al stress is unclear. The results showed that cell death induced by Al was significant negative correlation with the inhibition of Al on root elongation growth in peanut. AlCl<sub>3</sub> at 100μmolL<sup>-1</sup> induced DNA ladder, chromatin condensation, typical apoptotic chromatin condensation staining with DAPI, apoptosis related gene Hrs203j expression and caspase3-like protease activation in peanut root tip cells, and showed that Al-induced cell death in peanut root tip cells was a typical PCD. Exogenous NO donor sodium nitroprusside (SNP) at 200μmolL<sup>-1</sup> inhibited Al-induced PCD occurrence, but NO specific scavenger cPTIO aggravated PCD production. It suggests that NO is a negative regulator of Al-induced PCD in peanut root tips. | Al toxicity;Nitric oxide;Peanut;Programmed cell death;Root tips | pubmed |
Green Biosynthesis, Characterization, <i>In vitro</i> Antidiabetic Activity, and Investigational Acute Toxicity Studies of Some Herbal-mediated Silver Nanoparticles on Animal Models. | Diabetes is a metabolic disorder characterized by hyperglycemia, altered carbohydrate, lipid and protein metabolism. In recent studies, Nanoscience and nanotechnology are blazing fields for researchers; for researchers; of late there has been a prodigious excitement in the field of nanopharmacology to study silver nanoparticle (SNP) synthesis using natural products. Biological methods have been used to synthesize SNPs using medicinally active plants having an antidiabetic role, and this made us to assess the biologically synthesized SNPs from the seed extract of <i>Psoralea corylifolia</i> using 1 mM silver nitrate solution. The synthesized herbal-mediated SNPs (HMSNPs) were subjected to various characterization techniques such as X-ray diffraction analysis (XRD), energy dispersive X-ray (EDX) analysis, transmission electron microscope (TEM), and differential light scattering (DLS), respectively. In the current study the HMSNPs were tested to observe the <i>in vitro</i> antidiabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Huge data from biochemical, cellular, mouse, and chemical inhibitor studies have recognized protein tyrosine phosphatase 1B (PTP1B) as a major negative regulator of insulin signaling. In addition, corroboration suggests that insulin action can be enhanced by the inhibition of PTP1B. Keeping in view of the above fact, the PTP1B assay was done to determine the PTP1 B inhibitory effect of HMSNPs. It can be concluded that medicinal plants can be a good source for the synthe sis of HMSNPs. This study can be used for the development of valuable nanomedicines to treat various ailments, and it also highlights the safety and biocompatibility of SNPs within a biological cell; <i>in vivo</i> parameters need to be considered for further discoveries. In present research, acute oral toxicity studies and <i>in vitro</i> anti diabetic activity of Herbal mediated silver nanoparticles (HMSNPs) has been investigated. Characterization techniques employed to determine the Crystallanity, size, shape and elemental composition of HMSNPs. The results obtained from acute oral toxicity studies and histopathological studies showed that the synthesized HMSNPs were non-toxic and safe. and also had good <i>in vitro</i> anti diabetic activity. The results would provide certain references to screen out more pharmacological activities of silver nanoparticles using green biosynthesis methods. <b>Abbreviations used:</b> HMSNPs: Herbal mediated silver nanoparticles, XRD: X-ray diffraction, EDX: Energy dispersive X-ray analysis, TEM: Transmission electron microscope, PTP1B: Protein tyrosine phosphotase 1B, OECD: Organization for economic cooperation and development. | 425 OECD guidelines;Female albino mice;Psoralea corylifolia;herbal-mediated silver nanoparticles (HMSNPs);protein tyrosine phosphatase 1B (PTP1B) in vitro antidiabetic assay;toxicity of silver nanoparticles | pubmed |
Melatonin protects against behavioral deficits, dopamine loss and oxidative stress in homocysteine model of Parkinson's disease. | Hyperhomocysteinemia and homocysteine (Hcy) mediated dopaminergic neurotoxicity is a matter of concern in the pathophysiology of Parkinson's disease (PD). Our previous study established the involvement of oxidative stress in the substantia nigra (SN) of Hcy rat model of PD; however, the role of antioxidants, such as melatonin, was not tested in this model. Melatonin (10, 20 and 30mg/kg, i.p.) was administered to rats injected with Hcy in right SN (1.0μmol in 2μl saline) to investigate its potency in attenuating the behavioral abnormalities, dopamine depletion and oxidative stress prompted by Hcy. Treatment of melatonin protected against nigral dopamine loss and replenished the striatal dopamine loss that resulted in amelioration of rotational behavioral bias in Hcy denervated animals. Melatonin administration significantly improved mitochondrial complex-I activity and protected the SN neurons from the toxic insults of oxidative stress induced by Hcy. Amelioration of oxidative stress by melatonin in Hcy-infused SN was bought by dose-dependently scavenging of hydroxyl radicals, restoration of glutathione level and elevation in the activity of antioxidant enzymes. The observations bring into light the significant neuroprotective potentials of melatonin in Hcy model of PD which is attributed to the attenuation of oxidative stress in SN. | Antioxidant;Complex-I;Dopamine;Hydroxyl radical;Neuroprotection;Rotational bias | pubmed |
Overexpression of the immediate-early genes Egr1, Egr2, and Egr3 in two strains of rodents susceptible to audiogenic seizures. | Genetic animal models of epilepsy are an important tool for further understanding the basic cellular mechanisms underlying epileptogenesis and for developing novel antiepileptic drugs. We conducted a comparative study of gene expression in the inferior colliculus, a nucleus that triggers audiogenic seizures, using two animal models, the Wistar audiogenic rat (WAR) and the genetic audiogenic seizure hamster (GASH:Sal). For this purpose, both models were exposed to high intensity auditory stimulation, and 60min later, the inferior colliculi were collected. As controls, intact Wistar rats and Syrian hamsters were subjected to stimulation and tissue preparation protocols identical to those performed on the experimental animals. Ribonucleic acid was isolated, and microarray analysis comparing the stimulated Wistar and WAR rats showed that the genomic profile of these animals displayed significant (fold change, |FC|≥2.0 and p<0.05) upregulation of 38 genes and downregulation of 47 genes. Comparison of gene expression profiles between stimulated control hamsters and stimulated GASH:Sal revealed the upregulation of 10 genes and the downregulation of 5 genes. Among the common genes that were altered in both models, we identified the zinc finger immediate-early growth response gene Egr3. The Egr3 protein is a transcription factor that is induced by distinct stress-elicited factors. Based on immunohistochemistry, this protein was expressed in the cochlear nucleus complex, the inferior colliculus, and the hippocampus of both animal models as well as in lymphoma tumors of the GASH:Sal. Our results support that the overexpression of the Egr3 gene in both models might contribute to neuronal viability and development of lymphoma in response to stress associated with audiogenic seizures. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". | Audiogenic epilepsy;Early growth response;GASH:Sal;Microarray;Seizure-induced transcriptome;WAR | pubmed |
Novel tumor markers provide improved prediction of survival after diagnosis of human immunodeficiency virus (HIV)-related diffuse large B-cell lymphoma. | Existing prognostic tools for HIV + diffuse large B-cell lymphoma (DLBCL) fail to accurately predict patient outcomes. To develop a novel prognostic algorithm incorporating molecular tumor characteristics and HIV disease factors, we included 80 patients with HIV-related DLBCL diagnosed between 1996 and 2007. Immunohistochemistry staining was used to analyze the expression of 26 tumor markers. Clinical data were collected from medical records. Logistic regression and bootstrapping were used to select and assess stability of the prognostic model, respectively. Of the tumor markers examined, expression of cMYC, Ki 67, CD44, EBV, SKP2, BCL6, p53, CD20 and IgM were associated with two-year mortality. The final prognostic model, confirmed in bootstrapped samples, included IPI, circulating CD4 cell count, history of clinical AIDS, and expression of CD44, p53, IgM and EBV. This model incorporating HIV disease history and tumor markers, achieved better prediction for two-year mortality [AUC = 0.87, 95% CI: 0.78-0.96] compared with IPI alone [AUC = 0.63 (0.51-0.75)]. | AIDS;CD4;HIV;Lymphoma;diffuse large B-cell lymphoma;prognosis | pubmed |
Distribution and chemical composition of estrogen receptor β neurons in the paraventricular nucleus of the female and male mouse hypothalamus. | Activation of estrogen receptor beta (ERβ)-expressing neurons regulates the mammalian stress response via the hypothalamic-pituitary-adrenal (HPA) axis. These neurons densely populate the paraventricular nucleus of the hypothalamus (PVN). Recent research has revealed striking differences between rat and mouse PVN cytochemistry, but careful exploration of PVN ERβ neurons in mice has been hindered by a lack of specific ERβ antisera. Therefore, we used male and female transgenic mice expressing EGFP under the control of the mouse ERβ promoter (ERβ-EGFP) to examine the chemical architecture of PVN ERβ cells. Using immunohistochemistry, we found that 90% of ERβ-immunoreactivity (-ir) colocalized with EGFP. Cellular colocalization of EGFP with neuropeptides, transcription modulators, and neuronal tracers was examined throughout the PVN. ERβ-EGFP cells expressed oxytocin more abundantly in the rostral (71 ± 3%) than caudal (33 ± 8%) PVN. Arginine vasopressin colocalized with EGFP more often in females (18 ± 3%) than males (4 ± 1%). Moreover, estrogen receptor α-ir colocalized with ERβ-EGFP at low levels (15 ± 3%). Using a corticotropin releasing hormone-cre driver X tdTomato reporter mouse, we found a moderate colocalization with ERβ-ir (48 ± 16%) in the middle PVN. Peripheral injection of fluorogold revealed that the rostral PVN ERβ-EGFP cells are neuroendocrine neurons whereas non-neuroendocrine (presumably pre-autonomic) ERβ-EGFP neurons predominated in the posterior PVN. These data demonstrate chemoarchitectural differences in ERβ neurons of the mouse PVN that are different from that previously described for the rat, thus, elucidating potential neuronal pathways involved in the regulation of the HPA axis in mice. | ESR2;RRID:IMSR_JAX:007908;RRID:MMRRC_036904-UC;cytochemistry;estrogen receptor beta;paraventricular nucleus of the hypothalamus | pubmed |
A frog's view of EphrinB signaling. | Cell-cell and cell-substrate adhesion are essential to the proper formation and maintenance of tissue patterns during development, and deregulation of these processes can lead to invasion and metastasis of cancer cells. Cell surface adhesion and signaling molecules are key players in both normal development and cancer progression. One set of cell surface proteins, the Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, are significant regulators of these processes. During embryonic development, the Eph/ephrin signaling system is involved in cell-cell contact events that result in cell sorting and boundary formation between receptor and ligand bearing cells. When migrating cells that display the membrane bound ligands or receptors come in contact with cells bearing the cognate partner, the response may be adhesion or repulsion, ultimately leading to the proper positioning of these cells. During cancer progression, the signaling between these receptor/ligand pairs is often deregulated, leading to increased invasion and metastasis. To gain mechanistic insight into the pathways that mediate Eph receptor and ephrin signaling we have relied upon a very tractable system, the frog Xenopus. This model system has proven to be extremely versatile, and represents a relatively quick and manipulable system to explore signaling events and the in vivo processes affected by these signals. | Eph;Xenopus;development | pubmed |
Investigating vaginal bleeding in postmenopausal women found to have an endometrial thickness of equal to or greater than 10 mm on ultrasonography. | This aim of this study is to determine the risk of endometrial cancer in symptomatic postmenopausal women, when endometrial thickness on transvaginal ultrasonography is equal to or greater than 10 mm, and subsequent office-based endometrial sampling histology is negative. This is a prospective cross-sectional study, performed in a gynaecological oncology centre in the United Kingdom between February 2008 and July 2012. All postmenopausal women presenting with vaginal bleeding were investigated using transvaginal ultrasonography. Women with endometrial thickness measurements equal to or greater than 10 mm and negative office-based endometrial biopsy underwent hysteroscopy and endometrial biopsies. Over a 52-month period, 4148 women were investigated for postmenopausal vaginal bleeding. 588 (14.2%) women were found to have endometrial thickness measurements of equal to or greater than 10 mm on transvaginal ultrasonography. 170 (28.9%) cases of endometrial cancer were diagnosed in this group: 149 (87.6%) of the cancer cases were diagnosed in the outpatient setting with a Pipelle<sup>®</sup> endometrial sampler, whilst 21 (12.4%) had a negative Pipelle<sup>®</sup> sample and were diagnosed with hysteroscopy. The group diagnosed with hysteroscopy had lower BMI (32.7 kg/m<sup>2</sup> versus 39.7 kg/m<sup>2</sup>, p < 0.001) whilst the group diagnosed with Pipelle was more likely to have a history of hypertension and diabetes mellitus (p = 0.019 for both). The sensitivity of Pipelle was 87.65%. For women presenting with postmenopausal bleeding and where the endometrial thickness is equal to or greater than 10 mm and Pipelle sampling is negative, hysteroscopic evaluation with directed biopsy is strongly recommended. | Endometrial Cancer;Endometrial thickness;Hysteroscopy;Postmenopausal vaginal bleeding | pubmed |
Time for the two-spirits: Shaping the inclusive policy environment for hispanics and transgenders through global health diplomacy. | Minority populations in the world are permanently challenged with unequal living and working conditions in their daily lives that compromise their access to needed clinical and preventive services. When we discuss the health-care conditions for minorities, we must address the social determinants of access that are ultimately determined by the policies and politics of the governments. Renowned experts of quality in healthcare have been critical of the current design and implementation of randomized clinical trials, the gold standard of clinical research because they believe that they often, but not always, presume a linear, mechanistic system when in fact improvement in health care takes place within complex adaptive systems that evolve. The combined action of ignorance and prejudice can impair the efficient recruitment and retaining of "different people" like hispanics and transgender that have long suffered discrimination in their access to health-care services in spite that they are more prone to have chronic conditions. Even though the incidence of AIDS has decreased in the general population during the past two decades, it is continuing in the gay population due to educational issues, discrimination in health-care access and lack of proper public and private funding for the life-saving retroviral medication. The declaration of the "International Conference on Health Promotion" sponsored by PAHO in Colombia in 1992 have emphasized the aim of reducing differences in health status as well as ensuring equal opportunities and resources to enable all people to achieve their full health potential. Through the entreaties of the Global Health Diplomacy, the resiliently hardcore issues of discrimination and marginalization must be addressed by encouraging public policies that guarantee equity and ensure access for the most socially castigated groups. | Equality;equity;global health diplomacy;hispanics;social determinants;transgender | pubmed |
Existing forms and changes of nitrogen inside of horizontal subsurface constructed wetlands. | Horizontal zeolite subsurface constructed wetland system (HZCWs) and horizontal limestone subsurface constructed wetland system (HLCWs) were applied to the removal of nitrogen in lightly polluted wastewater, and the existing forms, changes, and removal mechanism of nitrogen in the constructed wetlands were analyzed. The results indicated that compared with HLCWs, HZCWs exhibited better nitrogen removal effect, and the maximum removal rates of ammonia nitrogen and total nitrogen could reach 96.97 ± 5.29 and 93.12 ± 3.35%, respectively. Besides, analysis of the removal effect on nitrogen in different existing forms on different substrate heights in the constructed wetlands showed that variation of nitrogen removal efficiency had certain regularities, which were related to the interior construction features of the wetland systems, and agreed with the regularities in the changes of the influential factors such as DO inside of the wetlands. In addition, degradation mechanism of pollutions was also analyzed, and the results indicated that the quantity of microorganisms and enzymes, including FDA, catalase, and urease, on the surface of the substrates had significant influence on the removal regularities and effects of the major pollutions in constructed wetlands. | Limestone;Microorganism characteristics;Nitrogen removal;Substrate height;Subsurface constructed wetland system;Zeolite | pubmed |
Microcephalic Osteodysplastic Primordial Dwarfism, Type II: a Clinical Review. | This review will provide an overview of the microcephalic primordial dwarfism (MPD) class of disorders and provide the reader comprehensive clinical review with suggested care guidelines for patients with microcephalic osteodysplastic primordial dwarfism, type II (MOPDII). Over the last 15 years, significant strides have been made in the diagnosis, natural history, and management of MOPDII. MOPDII is the most common and well described form of MPD. The classic features of the MPD group are severe pre- and postnatal growth retardation, with marked microcephaly. In addition to these features, individuals with MOPDII have characteristic facies, skeletal dysplasia, abnormal dentition, and an increased risk for cerebrovascular disease and insulin resistance. Biallelic loss-of-function mutations in the pericentrin gene cause MOPDII, which is inherited in an autosomal recessive manner. | MOPDII;Pericentrin;Primordial dwarfism | pubmed |
Effects of Tungsten Addition on the Microstructure and Corrosion Resistance of Fe-3.5B Alloy in Liquid Zinc. | The effects of tungsten addition on the microstructure and corrosion resistance of Fe-3.5B alloys in a liquid zinc bath at 520 °C were investigated by means of scanning electron microscopy, X-ray diffraction and electron probe micro-analysis. The microstructure evolution in different alloys is analyzed and discussed using an extrapolated Fe-B-W ternary phase diagram. Experimental results show that there are three kinds of borides, the reticular (Fe, W)₂B, the rod-like (Fe, W)₃B and flower-like FeWB. The addition of tungsten can refine the microstructure and improve the stability of the reticular borides. Besides, it is beneficial to the formation of the metastable (Fe, W)₃B phase. The resultant Fe-3.5B-11W (wt %) alloy possesses excellent corrosion resistance to liquid zinc. When tungsten content exceeds 11 wt %, the formed flower-like FeWB phase destroys the integrity of the reticular borides and results in the deterioration of the corrosion resistance. Also, the corrosion failure resulting from the spalling of borides due to the initiation of micro-cracks in the grain boundary of borides is discussed in this paper. | Fe-B alloy;corrosion resistance;molten zinc;reticular boride;tungsten | pubmed |
Direct oral anticoagulants in patients with cervical artery dissection and cerebral venous thrombosis. A case series and review of the literature. | To date, very little is known about the effects of direct oral anticoagulants (DOA) use in patients with cervical artery dissection (CAD) and cerebral venous thrombosis (CVT). We present our initial experience with the use of DOA for CAD and CVT and an overview of the published literature. From our database, we identified 4 patients who received DOA after CAD and 4 patients after CVT. Also, we analyzed the data reported for 45 patients who received DOA after CAD and 23 after CVT from review of the literature. Among patients with CAD, resolved or improved arterial stenosis was noted in 27 (55%), and symptomatic recurrent ischemic stroke in 2 (4%). Among patients with CVT, complete or partial recanalization was noted in 25 (90%), and no significant functional disability in 26 (93%). No patient developed intracranial hemorrhage. Although no statistical conclusions can be drawn from these data, DOA could be an alternative in patients with CAD-related embolic infarct and CVT-related hemorrhagic venous infarct. A large-scale clinical trial will be needed to validate these results. | Cerebral venous thrombosis;Cervical artery dissection;Direct oral anticoagulants;New oral anticoagulants;Non-vitamin K anticoagulants | pubmed |
Nutrigenomic studies on hilsa to evaluate flesh quality attributes and genes associated with fatty acid metabolism from the rivers Hooghly and Padma. | The Indian shad hilsa (Tenualosa ilisha), a commercially important food fish rich in oils, enjoys high consumer preference in the South Asian countries owing to its unique flavour and culinary properties. The present study was undertaken with the primary objective of determining the flesh quality attributes of hilsa in terms of nutritive value (gross chemical composition, amino acid, fatty acid and mineral composition), pH, water holding capacity (WHC) and expression of genes associated with fatty acid metabolism and flesh quality. Additionally, comparative studies on the flesh quality attributes in hilsa from two distributaries of river Ganga i.e. Hooghly and Padma were also carried out. A high WHC (>80%) suggested juicy and tender nature of hilsa meat. The protein content was 18-21% in hilsa from both the rivers and essential amino acid lysine, valine and functional amino acids leucine and arginine were significantly higher in Hooghly hilsa (P<0.05). The predominance of umami taste amino acids, glutamic acid and aspartic acid and sweet taste amino acids, serine, glycine and alanine in hilsa from both the rivers could be the contributing factors to its unique flavour. The fat content in hilsa from river Hooghly and Padma were found to be 9.94 and 7.84%, respectively. The concentration of flavouring fatty acids like saturated fatty acids (SFA) (myristic acid) and omega (ω)-3 polyunsaturated fatty acids (PUFAs) (linoleic acid, α-linolenic acid, arachidonic acid, eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) were significantly higher in Hooghly hilsa (P<0.05). Among the genes associated with fatty acid metabolism studied, expression of cluster of differentiation (CD36), acetyl CoA oxidase (ACO), fatty acid synthase (FAS), peroxisome proliferator activated receptor beta (PPARβ), peroxisome proliferator activated receptor gamma (PPARγ) and desaturase were significantly higher in Padma hilsa (P<0.05), and the change was <2 fold. Comparative gene expression profiling of flesh quality genes (actin, GAPDH, LDH, TPI) showed similar levels of expression in hilsa from both the rivers (P<0.05). The nutrigenomic information generated on various flesh quality attributes of hilsa has enriched the knowledgebase. Further, from comparative nutrient analysis on hilsa from river Hooghly and Padma, it was observed that Hooghly hilsa is superior in terms of oil content, ω-3 PUFAs EPA and DHA and essential amino acids; however, the expression profile of genes associated with flesh quality were found to be similar. Thus, within the scope of the present study, Hooghly hilsa (medium size category, 500-700g size) was found to be nutritionally superior. | Flesh quality;Ganga;Hilsa;Hooghly;Muscle;Padma | pubmed |
Relapse and Mortality Risk of Stage I Testicular Cancer. | - To assess the medical insurance risk for patients with stage I testicular cancer (TC), by calculating the overall mortality risk with and without relapse, and compare it to men from the Danish population. - Testicular cancer is the most common malignancy in young males. Outcomes of a Danish cohort of 3366 patients with stage I TC (1366 non-seminomas (NSTC) and 2000 Seminomas (STC)), were analyzed. - The data were analyzed by the "illness-death" model. For the analysis of the transitions between diagnosis, relapse and death we adopted a parametric approach, where the relationship between the intensities and the effect of covariates were specified by Poisson regression models for NSTC and STC individually. - In the NSTC group, 422 patients relapsed. Six relapses (1.4%) occurred after 5 years of follow-up. In the STC group, 389 relapsed. The relapse rate after 5 years was 4.1%. The overall mortality analyses showed that the standardized mortality ratio (SMR) for men with NSTC without relapse, was slightly lower than in the matched general population of Danish men (SMR = 0.9). In STC patients without relapse, SMR was 0.80. Relapse raised the overall mortality by a factor 2.0 for NSTC and 1.5 for STC. - The fact that few relapses occur 5 years after diagnosis is an important finding for risk assessment in life insurance. It makes it possible to insure men diagnosed with stage I TC, who have not experienced relapse 5 years after diagnosis, on normal terms. | Testicular cancer;life insurance;non-seminoma;seminoma;stage I disease | pubmed |
Semiconductor diode laser device adjuvanting intradermal vaccine. | A brief exposure of skin to a low-power, non-tissue damaging laser light has been demonstrated to augment immune responses to intradermal vaccination. Both preclinical and clinical studies show that this approach is simple, effective, safe and well tolerated compared to standard chemical or biological adjuvants. Until now, these laser exposures have been performed using a diode-pumped solid-state laser (DPSSL) devices, which are expensive and require labor-intensive maintenance and special training. Development of an inexpensive, easy-to-use and small device would form an important step in translating this technology toward clinical application. Here we report that we have established a handheld, near-infrared (NIR) laser device using semiconductor diodes emitting either 1061, 1258, or 1301nm light that costs less than $4000, and that this device replicates the adjuvant effect of a DPSSL system in a mouse model of influenza vaccination. Our results also indicate that a broader range of NIR laser wavelengths possess the ability to enhance vaccine immune responses, allowing engineering options for the device design. This small, low-cost device establishes the feasibility of using a laser adjuvant approach for mass-vaccination programs in a clinical setting, opens the door for broader testing of this technology with a variety of vaccines and forms the foundation for development of devices ready for use in the clinic. | Adjuvant;Handheld;Laser;Near-infrared;Semiconductor laser diode;Vaccine | pubmed |
Cuspal flexure of composite-restored typodont teeth and correlation with polymerization shrinkage values. | The relationship between post-gel shrinkage, total shrinkage, and cuspal flexure was examined. Cuspal flexure was measured on restored typodont teeth, which offered a standardized tooth shape for comparison of shrinkage stress effects among restorative composites. Six restorative composites were compared (Filtek LS, Venus Flowable, Tetric EvoCeram, Filtek Flowable, Esthet-X, and Filtek Supreme). Total shrinkage was determined from changes in projected surface area before and after polymerization (n=10). Post-gel shrinkage was determined with a biaxial strain gauge that measured strain development during polymerization (n=10). Cuspal flexure was determined using typodont maxillary second premolars with standard MOD slot preparation (n=10). Flexure was determined by comparing the three-dimensionally scanned cuspal surfaces before and after restoration. Restoration bonding to the typodont cavity was achieved by sandblasting and adhesive application. Bond integrity was verified by measuring dye penetration. Results were analyzed using ANOVA and Student-Newman-Keuls post hoc test (significance level 0.05). Pearson was used for correlations. Total and post-gel shrinkage were significant different for all composites (t-test; P<0.001). Depending on the composite, only 9-41% of the total shrinkage was recorded as post-gel shrinkage. Bond integrity of restored typodont teeth was 96-99%. Cuspal flexure correlated strongly with post-gel shrinkage, but there was no correlation with total shrinkage. Cuspal flexure of restored typodont teeth showed the effect of shrinkage stress caused by polymerizing composite restorations, ensuring standardization while maintaining the effects of tooth/cavity geometry. Post-gel shrinkage gave a good indication to screen composites for the stress they may generate; total shrinkage had no direct correlation with stress. | Composites;Cuspal flexure;Restorations;Shrinkage;Typodont tooth | pubmed |
Remote Ischemic Preconditioning in High-risk Cardiovascular Surgery Patients: A Randomized-controlled Trial. | Remote ischemic preconditioning (RIPC) may reduce biomarkers of ischemic injury after cardiovascular surgery. However, it is unclear whether RIPC has a positive impact on clinical outcomes. We performed a blinded, randomized controlled trial to determine if RIPC resulted in fewer adverse clinical outcomes after cardiac or vascular surgery. The intervention consisted of 3 cycles of RIPC on the upper limb for 5 minutes alternated with 5 minutes of rest. A sham intervention was performed on the control group. Patients were recruited who were undergoing (1) high-risk cardiac or vascular surgery or (2) cardiac or vascular surgery and were at high risk of ischemic complications. The primary end point was a composite outcome of mortality, myocardial infarction, stroke, renal failure, respiratory failure, and low cardiac output syndrome, and the secondary end points included the individual outcome parameters that made up this score, as well as troponin-I values. A total of 436 patients were randomized and analysis was performed on 215 patients in the control group and on 213 patients in the RIPC group. There were no differences in the composite outcome between the 2 groups (RIPC: 67 [32%] and control: 72 [34%], relative risk [0.94 {0.72-1.24}]) or in any of the individual components that made up the composite outcome. Additionally, we did not observe any differences between the groups in troponin-I values, the length of intensive care unit stay, or the total hospital stay. RIPC did not have a beneficial effect on clinical outcomes in patients who had cardiovascular surgery. | cardiovascular surgery;ischemia-reperfusion;remote ischemic preconditioning | pubmed |
Development of DNA tetrahedron-based drug delivery system. | Nanocarriers of drugs have attracted significant attention to tackle the problems of drug resistance or nucleic acid drug delivery, which can optimize pharmaceutical parameters and enhance the cellular uptake efficiency. Nowadays, DNA nanostructure presents an opportunity in the field of nanomaterial due to its precise control in shape and size, excellent biocompatibility, as well as multiple sites for targeting decoration. DNA tetrahedron, which is stable and easily synthesized, is used for various applications, including nuclear magnetic resonance imaging, molecular diagnosis, targeting drug delivery, and so on. In this review, we will discuss the applications of DNA tetrahedron about drug delivery, intracellular routes and its fates. Also challenges and possible solutions for developing DNA tetrahedron-based drug delivery system are detailed. | DNA tetrahedron;Nanotechnology;drug delivery system;modifications;programmable structures | pubmed |
Evaluation of in vitro toxicity of polymeric micelles to human endothelial cells under different conditions. | Polymeric micelles have been extensively studied in the area of antitumor therapy, and more recently explored as nanocarriers for atherosclerosis. These applications of polymeric micelles in biomedicine will increase their contact with human blood vessels. However, few studies have considered the interactions between polymeric micelles and endothelial cells, especially in a complex system. This study used human umbilical vein endothelial cells (HUVECs) as an in vitro model for endothelial cells to investigate the toxic effects of methoxy-poly(ethylene glycol)-poly(d,l-lactide) (MPEG-PLA) based micelles. In addition, an endoplasmic reticulum stress inducer thapsigargin (TG), and a pro-atherogenic stimulus palmitate (PA), were used to co-expose HUVECs to further mimic the responses of diseased endothelial cells to micelle exposure. Overall, up to 200 μg/mL micelles did not significantly induce cytotoxicity, reactive oxygen species (ROS), release of inflammatory mediators in terms of interleukin 6 (IL-6), IL-8 and soluble vascular cell adhesion molecule 1 (sVCAM-1), or adhesion of THP-1 monocytes to HUVECs. TG and PA significantly induced cytotoxicity and THP-1 adhesion as well as modestly promoted the release of IL-6, but did not affect ROS or release of sVCAM-1 and IL-8. Co-exposure of micelles did not significantly enhance the effects of TG and PA to HUVECs, and ANOVA analysis indicated no interaction between concentrations of micelles and the presence of TG/PA. Taken together, these data indicated that micelles are not toxic to HUVECs under different conditions in vitro. | Human umbilical vein endothelial cells (HUVECs);Methoxy-poly(ethylene glycol)-poly(D,L-lactide) (MPEG-PLA);Micelles;Palmitate (PA);Thapsigargin (TG) | pubmed |
What is the duration of life expectancy in the state of frailty? Estimates in the SIPAF study. | The screening of frailty can trigger interventions aiming to delay disability in older people. Whereas the prevalence, the consequences, and the factors associated with frailty are well described, little is known about the duration of the state of frailty. This study aimed to estimate the time spent in the state of frailty in men and women using the Sullivan method. Data used were the age- and sex-specific prevalence of frailty found in SIPAF study ("Système d'Information sur la Perte d'Autonomie Fonctionnelle de la personne âgée") and statistics of mortality from the Human Mortality Database. The SIPAF study included 2350 individuals aged 70 and over and living in France. Participants were interviewed at home by trained nurses. Frailty was defined as impairment in three domains or more among nutrition, energy, physical activity, strength, and mobility. People requiring assistance in basic activities of daily living were considered in a separate category. Mean age of the study sample was 83.3 ± 7.5 years, with 59.4% of women. Overall, the prevalence of pre-frailty, frailty, and dependency was 39.1, 17.0, and 15.4%, respectively. Life expectancy at age 70 was 18.3 years for women, of which 7.4 years (95% CI 6.9-7.9) were pre-frail, 3.4 years (95% CI 3.0-3.8) frail, and 2.4 (95% CI 2.1-2.7) with disability. In contrast, LE for men at 70 was 14.8 years, of which pre-frail, frail, and disabled years were 6.0 years (95% CI 5.5-6.5), 1.2 years (95% CI 1.0-1.5), and 1.2 (95% CI 1.0-1.5), respectively. In conclusion, frailty is a transition state that is relatively limited in time compared to pre-frailty that may represent a larger time window for prevention. | Disability;Frailty;Health expectancy;Pre-frailty;Sullivan method | pubmed |
Molecular landscape of arthrofibrosis: Microarray and bioinformatic analysis of the temporal expression of 380 genes during contracture genesis. | Inflammatory changes are suspected in the pathophysiology of arthrofibrosis formation and require early molecular examination. Here, we assessed the hypothesis that early inflammatory genes are related to arthrofibrosis by ascertaining gene expression during the early stages of contracture genesis in an animal model. Joint trauma was incited surgically in a cohort of rabbits (n=36) knees followed by immobilization in a model of contracture. Six groups of 6 rabbits were sacrificed at multiple time points (0, 6, 12, 24, 72h and 2weeks). Microarray expression and RT-qPCR profiling were performed to determine genes that are significantly up or downregulated. Bioinformatic analysis was carried out to understand which biological programs and functional groups of genes are modulated in arthrofibrosis. Gene expression profiling revealed a large number biologically relevant genes (>100) that are either upregulated or downregulated by at least a 1.5 fold (log2) during the first two weeks after joint injury during contracture development. Gene ontology analysis identified molecular pathways and programs that act during the course of fibrosis and joint contracture. Our main finding is that the development of contractures occur concomitant with modulation of genes mediating inflammatory responses, ECM remodeling and the epithelial-to-mesenchymal transition. The genesis of joint contracture reflects an imbalance between pro- and anti-fibrotic expression. Our study indicates that inflammatory genes may be involved in the process of contracture genesis and initiated at relatively early stages. Our findings also may inform clinical practice in the future by suggesting potential therapeutic targets in preventing the long-term development of arthrofibrosis. | Animal model;Arthrofibrosis;Contracture;Genes;Microarray | pubmed |
Influence of environmental factors on biodegradation of quinalphos by <i>Bacillus thuringiensis</i>. | The extensive and intensive uses of organophosphorus insecticide-quinalphos in agriculture, pose a health hazard to animals, humans, and environment because of its persistence in the soil and crops. However, there is no much information available on the biodegradation of quinalphos by the soil micro-organisms, which play a significant role in detoxifying pesticides in the environment; so research is initiated in biodegradation of quinalphos. A soil bacterium strain, capable of utilizing quinalphos as its sole source of carbon and energy, was isolated from soil via the enrichment method on minimal salts medium (MSM). On the basis of morphological, biochemical and 16S rRNA gene sequence analysis, the bacterium was identified as to be <i>Bacillus thuringiensis</i>. <i>Bacillus thuringiensis</i> grew on quinalphos with a generation time of 28.38 min or 0.473 h in logarithmic phase. Maximum degradation of quinalphos was observed with an inoculum of 1.0 OD, an optimum pH (6.5-7.5), and an optimum temperature of 35-37 °C. Among the additional carbon and nitrogen sources, the carbon source-sodium acetate and nitrogen source-a yeast extract marginally improved the rate of degradation of quinalphos. Display of degradation of quinalphos by <i>B</i>. <i>thuringiensis</i> in liquid culture in the present study indicates the potential of the culture for decontamination of quinalphos in polluted environment sites. | 16S rRNA gene;B. thuringiensis;Generation time;Quinalphos | pubmed |
What the SIF Is Happening-The Role of Intracellular <i>Salmonella</i>-Induced Filaments. | A common strategy among intracellular bacterial pathogens is to enter into a vacuolar environment upon host cell invasion. One such pathogen, <i>Salmonella enterica</i>, resides within the <i>Salmonella</i>-containing vacuole (SCV) inside epithelial cells and macrophages. <i>Salmonella</i> hijacks the host endosomal system to establish this unique intracellular replicative niche, forming a highly complex and dynamic network of <i>Salmonella</i>-induced filaments (SIFs). SIFs radiate outwards from the SCV upon onset of bacterial replication. SIF biogenesis is dependent on the activity of bacterial effector proteins secreted by the <i>Salmonella</i>-pathogenicity island-2 (SPI-2) encoded type III secretion system. While the presence of SIFs has been known for almost 25 years, their precise role during infection remains elusive. This review summarizes our current knowledge of SCV maturation and SIF biogenesis, and recent advances in our understanding of the role of SIFs inside cells. | Salmonella typhimurium;Salmonella-containing vacuole;Salmonella-induced filaments;endosomal system;multiple contact sites | pubmed |
Upregulation of vascular endothelial growth factor (VEGF), its role in progression and prognosis of non-small cell lung carcinoma. | Elevated VEGF mRNA (-ΔC<sub>T</sub>) was significantly associated with adenocarcinoma histology (vs squamous) and advanced NSCLC clinical stages in a univariable analysis; however, this association did not remain significant in the multivariable analysis. Of interest, a Kaplan-Meier analysis showed that NSCLC patients with higher VEGF mRNA (-ΔC<sub>T</sub> ≥10) had a significantly poorer overall survival and shorter postoperative relapse time in adenocarcinoma and in stage III/IV than those with VEGF mRNA of -ΔC<sub>T</sub> <10 (P < 0.001). The multivariable analysis confirmed that patients with higher VEGF mRNA levels, as well as with adenocarcinoma and advanced stages, were independent predictors of a poorer survival. However, only the histology of adenocarcinoma remained a significant prognostic factor of a shorter postoperative relapse in the multivariable model. Quantity of VEGF mRNA can be used as a prognosis factor to predict shorter overall survival in patients with NSCLC. | NSCLC;VEGF;prognosis;progression | pubmed |
Alterations in the Salivary Proteome and N-Glycome of Sjögren's Syndrome Patients. | We used isobaric mass tagging (iTRAQ) and lectin affinity capture mass spectrometry (MS)-based workflows for global analyses of parotid saliva (PS) and whole saliva (WS) samples obtained from patients diagnosed with primary Sjögren's Syndrome (pSS) who were enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) as compared with two control groups. The iTRAQ analyses revealed up- and down-regulation of numerous proteins that could be involved in the disease process (e.g., histones) or attempts to mitigate the ensuing damage (e.g., bactericidal/permeability increasing fold containing family (BPIF) members). An immunoblot approach applied to independent sample sets confirmed the pSS associated up-regulation of β2-microglobulin (in PS) and down-regulation of carbonic anhydrase VI (in WS) and BPIFB2 (in PS). Beyond the proteome, we profiled the N-glycosites of pSS and control samples. They were enriched for glycopeptides using lectins Aleuria aurantia and wheat germ agglutinin, which recognize fucose and sialic acid/N-acetyl glucosamine, respectively. MS analyses showed that pSS is associated with increased N-glycosylation of numerous salivary glycoproteins in PS and WS. The observed alterations of the salivary proteome and N-glycome could be used as pSS biomarkers enabling easier and earlier detection of this syndrome while lending potential new insights into the disease process. | N-glycosylation;Sjögren’s Syndrome;glycosite;iTRAQ;isobaric mass tagging;lectin affinity capture;parotid saliva;whole saliva | pubmed |
Accuracy of infraspinatus isometric testing in predicting tear size and tendon reparability: comparison with imaging and arthroscopy. | The purpose of this study was to examine the accuracy of external rotation in neutral (0° external position) and in shortened position (45° external position) in relation to rotator cuff tear size, tendon reparability, and other clinical, surgical, and imaging findings. This was a prospective blinded diagnostic study of consecutive surgical candidates for rotator cuff repair using magnetic resonance imaging and arthroscopic surgery as the "gold standards." The area under a receiver operating characteristic (AUROC) curve was calculated for each position. Eighty-five patients (35 female [41%] and 50 male [59%]; age, 65 years [standard deviation = 10]) were included. Sixty patients (71%) had a minor tear (4 small, 56 moderate), and 25 patients (29%) had a major tear (17 large and 8 massive). Seventy patients (82%) had a full repair, and 15 (18%) patients underwent a partial repair. There were 26 (31%) associated full-thickness tears of the infraspinatus. The isometric strength testing in both positions had good to excellent accuracy (range, 0.80-0.90) for detecting reparability, tear retraction, infraspinatus atrophic changes observed by the clinician, and infraspinatus fatty infiltration on magnetic resonance images. The shortened position had an overall higher accuracy than the neutral position and was more clinically useful for detecting an infraspinatus full-thickness tear (AUROC = 0.84 vs 0.78) and rotator cuff tear size (AUROC = 0.80 vs. 0.75). The isometric external rotation is an accurate test in diagnosing different aspects of rotator cuff disease and specifically of the infraspinatus muscle. The isometric strength at the shortened position was a better predictor of clinical, surgical, and imaging findings. | Rotator cuff;accuracy;arthroscopy;infraspinatus;isometric;validity | pubmed |
The added mass forces in insect flapping wings. | The added mass forces of three-dimensional (3D) flapping wings of some representative insects, and the accuracy of the often used simple two-dimensional (2D) method, are studied. The added mass force of a flapping wing is calculated by both 3D and 2D methods, and the total aerodynamic force of the wing is calculated by the CFD method. Our findings are as following. The added mass force has a significant contribution to the total aerodynamic force of the flapping wings during and near the stroke reversals, and the shorter the stroke amplitude is, the larger the added mass force becomes. Thus the added mass force could not be neglected when using the simple models to estimate the aerodynamics force, especially for insects with relatively small stroke amplitudes. The accuracy of the often used simple 2D method is reasonably good: when the aspect ratio of the wing is greater than about 3.3, error in the added mass force calculation due to the 2D assumption is less than 9%; even when the aspect ratio is 2.8 (approximately the smallest for an insect), the error is no more than 13%. | Insect aerodynamics;Three-dimensional added mass method;Two-dimensional added mass method | pubmed |
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