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Characterization of Functional, Safety, and Probiotic Properties of Enterococcus faecalis AG5 Isolated From Wistar Rat, Demonstrating Adherence to HCT 116 Cells and Gastrointestinal Survivability. | Gut microbiota remains a prominent source for a diverse range of potential probiotics. In this context, the current study explored the rectal region of experimental Wistar rat for the isolation of potent probiotic. Sixteen lactic acid bacteria (LAB), from rectal swab of Wistar rats, were subjected to evaluation of probiotic properties. Among all, AG5 was found unique with consistent probiotic properties and was further identified as Enterococcus faecalis AG5 (NCBI accession number KT248537) using 16S rDNA sequencing, followed by BLAST analysis. Since the Enterococci strains inhibit various food-borne pathogens efficiently while proving itself as a safe probiotic candidate, the study further evaluated the safety of the strain AG5 using primer specific PCR amplification which revealed the existence of gene encoding gelE, asa1, efaA, ace, vanA, and vanB and negative for cylA, hyl, and esp respectively. SEM analysis confirmed the adherence ability of AG5 to HCT 116 cells. Adherence was found to be non-colonial and scattered manner. Furthermore, the strain demonstrated a significant survivability during simulated gastrointestinal transit. Taken together, the E. faecalis AG5 was found potential probiotic candidate with future implication in both food and health industry. | Adhesion;Antimicrobial;Enterococcus faecalis;Probiotics;Virulence | pubmed |
Transconjunctival suturing of the scleral flap in late hypotony maculopathy after non-penetrating deep sclerectomy. | A 63-year-old man presents with late hypotony maculopathy after non-penetrating deep sclerectomy. Hypotonia and visual acuity are improved after transconjunctival suturing of the scleral flap. Hypotony maculopathy may occur as a late complication after glaucoma surgery. Transconjunctival suturing of the scleral flap can be useful when conservative measures have failed. | Esclerectomía profunda no perforante;Hipotonía;Hypotonia;Hypotony maculopathy;Maculopatía hipotónica;Non-penetrating deep sclerectomy;Suturas transconjuntivales;Transconjunctival suturing | pubmed |
The roles of TNFAIP2 in cancers and infectious diseases. | TNFα-induced protein 2 (TNFAIP2) is a primary response gene of TNFα. TNFAIP2 is highly expressed in immune cells and the urinary bladder. The expression of TNFAIP2 is regulated by multiple transcription factors and signalling pathways, including NF-κB, KLF5 and retinoic acid. Physiologically, TNFAIP2 appears to be a multiple functional mediator not only for inflammation, angiogenesis and tunneling nanotube (TNT) formation but also as a regulator of cell proliferation and migration. The expression of TNFAIP2 is frequently abnormal in human cancers and in infectious diseases. Due to its significant functions in cell proliferation, angiogenesis, migration and invasion, TNFAIP2 could be a potential diagnostic biomarker and therapeutic target for cancer. | TNFAIP2;angiogenesis;inflammation;migration;nanotube formation;proliferation | pubmed |
A quantitative study of attitudes toward the research participation of adults with intellectual disability: Do stakeholders agree? | Attitudes toward the research participation of adults with intellectual disability inform research policy and practice, impact interest in and support for research participation, and promote or discourage the generation of new knowledge to promote health among adults with intellectual disability. Yet we know little about these beliefs among the public and the scientific community. We quantitatively studied attitudes among adults with intellectual disability, family and friends, disability service providers, researchers, and Institutional Review Board (IRB) members. We predicted that adults with intellectual disability, and researchers would espouse views most consistent with disability rights, whereas IRB members, and to a lesser degree family, friends, and service providers, would espouse more protective views. We surveyed five hundred and twelve members of the five participant stakeholder groups on their attitudes toward the research participation of adults with intellectual disability. We found broad support for research about people with intellectual disability, though slightly more tempered support for their direct participation therein. In general, IRB members and to some extent adults with intellectual disability endorsed direct participation less than others. We also found that adults with intellectual disability strongly believed in their consent capacity. Resources should be directed toward health-related research with adults with intellectual disability, and interventions should be pursued to address ethical challenges and promote beliefs consistent with human rights. | Attitudes;Intellectual disability;Research ethics;Research participation | pubmed |
Are they high on steroids? Tailored interventions help improve screening for steroid-induced hyperglycaemia in hospitalised patients. | Steroid-induced hyperglycaemia (SIH) is a common adverse effect in patients both with and without diabetes. This project aimed to improve the screening and diagnosis of SIH by improving the knowledge of healthcare professionals who contribute to the management of SIH in hospitalised patients. Monitoring and diagnosis of SIH were measured in areas of high steroid use in our hospital from May 2016 to January 2017. Several interventions were implemented to improve knowledge and screening for SIH including a staff education programme for nurses, healthcare assistants and doctors. The Trust guidelines for SIH management were updated based on feedback from staff. The changes to the guideline included shortening the document from 14 to 4 pages, incorporating a flowchart summarising the management of SIH and publishing the guideline on the Trust intranet. A questionnaire based on the recommendations of the Joint British Diabetes Societies for SIH was used to assess the change in knowledge pre-intervention and post-intervention. Results showed an increase in junior doctors' knowledge of this topic. Although there was an initial improvement in screening for SIH, this returned to near baseline by the end of the study. This study highlights that screening for SIH can be improved by increasing the knowledge of healthcare staff. However, there is a need for ongoing interventions to sustain this change. | health professions education;healthcare quality improvement;patient-centred care;quality improvement;team training | pubmed |
Preimplantation genetic diagnosis in early pregnancy loss<sup>✰</sup>. | Miscarriage is a frequent outcome seen in obstetrics with 1 in 5 pregnancies ending in an early pregnancy loss. Aneuploidy is the most significant single factor affecting early pregnancy failure and miscarriage. The risk of aneuploidy increases significantly with increasing maternal age. There has been tremendous advancement in technology that has made preimplantation genetic testing for aneuploidy reliable and accessible. For women in their mid-to-late 30s there is great utility in the use of PGT-A to facilitate single embryo transfer, reduce the risk of clinical miscarriage and ongoing aneuploidy gestations. The current data supports use of preimplantation genetic testing for aneuploidy and single embryo transfer for this population of women. At this time, more prospective data is needed to determine the effect of preimplantation genetic testing for aneuploidy on rates of miscarriage in the recurrent pregnancy loss population. | early pregnancy loss;miscarriage;preimplantation genetic testing for aneuploidy | pubmed |
Gastrointestinal stromal tumours: advances in surgical and pharmacological management options. | Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. The stomach is most commonly affected. Advances in immunopathology have identified a mutation in the c-KIT proto-oncogene, leading to the development of the tyrosine-kinase inhibitor Imatinib as targeted therapy for advanced disease. Surgery, however, remains the only curative treatment of resectable primary GIST. This review article aims at reviewing the management of primary GISTs, investigating recurrences, exploring the role of surgery in metastatic disease and looking into combined surgery and molecular therapy for GISTs. | Gastrointestinal stromal tumour (GIST);imatinib | pubmed |
The 2018 Revision to the Process of Care Model for Management of Erectile Dysfunction. | Erectile dysfunction (ED) is a common condition the treatment of which over the years has expanded from specialty care settings to various other clinical settings. A Process of Care Model was developed in 1999 to provide primary care physicians with guidance in the diagnosis and management of ED. This update to the Process of Care Model aims to reflect current ED management practices, because the study of ED has changed since 1999. Updates to the Process of Care Model were developed during a meeting of international experts from diverse disciplines. The updated model is data-driven, evidence-based, and relevant to a wide range of healthcare providers. This article summarizes the results of the expert meeting and focuses on ED management. The evaluation of ED is discussed in a separate article. The updated model presents modification of risk factors and correction of comorbidities frequently associated with ED as critical parts of patient management. Patients should be encouraged to make positive lifestyle changes such as improving diet and increasing physical exercise. Lifestyle changes may be accompanied by the first-line medical therapies of sexual counseling and therapy, which takes into consideration patient sexual dynamics and pharmacotherapy with phosphodiesterase 5 inhibitors (PDE5Is). The updated model provides guidance regarding risk factors associated with ED, their modification, sexual counseling, and PDE5I selection, dosing, and patient education. This update leverages the extensive clinical expertise and experience of the authors to provide updated, comprehensive guidance for ED management. The model reflects the views and experiences of a limited number of contributors; however, these authors draw upon a diverse array of clinical specialties and are regarded as experts in their fields. Additionally, no meta-analyses were performed to further support the ED evaluation guidelines presented. Effective management of ED may be achieved through a combination of patient risk factor modification and first-line therapy, taking into consideration any patient comorbidities known to be associated with ED. Treatment goals should be individualized to restore sexual satisfaction to the patient and/or couple and improve quality of life based on the patient's expressed needs and desires. Mulhall JP, Giraldi A, Hackett G, et al. The 2018 Revision to the Process of Care Model for Management of Erectile Dysfunction. J Sex Med 2018;15:1434-1445. | Cardiovascular Disease;Depression;Diabetes;Erectile Dysfunction;Hypertension | pubmed |
Protective roles of fenofibrate against cisplatin-induced ototoxicity by the rescue of peroxisomal and mitochondrial dysfunction. | Cisplatin is an alkylating agent that interferes with DNA replication and kills proliferating carcinogenic cells. Several studies have been conducted to attenuate the side effects of cisplatin; one such side effect in cancer patients undergoing cisplatin chemotherapy is ototoxicity. However, owing to a lack of understanding of the precise mechanism underlying cisplatin-induced side effects, management of cisplatin-induced ototoxicity remains unsolved. We investigated the protective effects of fenofibrate, a PPAR-α activator, on cisplatin-induced ototoxicity. Fenofibrate prevented cisplatin-induced loss of hair cells and improved cell viability; moreover, fenofibrate significantly attenuated the threshold of auditory brainstem responses (ABR) in cisplatin-injected mice. Fenofibrate significantly increased PPAR-α, PPAR-γ, and PGC-1α expression, which consequently resulted in increased number and functional enzyme levels of peroxisomes and mitochondria, and markedly decreased phospho-p53 (S15), activated caspase-3, cleaved-PARP, and NF-κB p65 nuclear translocation, which reduced NADPH oxidase isoform (NOX3 and NOX4) expression, thereby decreasing reactive oxygen species (ROS) production in cisplatin-treated tissues ex vivo. Taken together, these results indicate that fenofibrate rescues cisplatin-induced ototoxicity by maintaining peroxisome and mitochondria number and function, reducing inflammation, and decreasing ROS levels. Our findings suggest that fenofibrate administration might serve as an effective therapeutic agent against cisplatin-induced ototoxicity. | Cisplatin;Fenofibrate;NADPH Oxidase Isoforms;Ototoxicity;PPAR-α | pubmed |
Piperlongumine derivative, CG-06, inhibits STAT3 activity by direct binding to STAT3 and regulating the reactive oxygen species in DU145 prostate carcinoma cells. | Piperlongumine (PL), isolated from Piper longum L., is receiving intense interest due to its selectively ability to kill cancer cells but not normal cells. We synthesized a number of analogues by replacing the cyclic amide of PL with aliphatic amides to explore structural diversity. Compound CG-06 had the strongest cytotoxic profile of this series, showing potent effects in human prostate cancer DU-145 cells, in which signal transducer and activator of transcription 3 (STAT3) is constitutively active. CG-06 inhibited STAT3 phosphorylation at tyrosine 705 in a dose- and time dependent manner in DU-145 cells and suppressed IL-6-induced STAT3 phosphorylation at Tyr-705 in DU-145 and LNCaP cell lines. CG-06 decreased the expression levels of STAT3 target genes, such as cyclin A, Bcl-2, and survivin. Notably, we used drug affinity responsive target stability (DARTS) to show that CG-06 binds directly to STAT3, and the reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) rescued the CG-06-induced suppression p-STAT3. Our results suggest that CG-06 is a novel inhibitor of STAT3 and may be a useful lead molecule for the development of a therapeutic STAT3 inhibitor. | Apoptosis;Piperlongumine;Prostate cancer;ROS;STAT3 | pubmed |
Prediabetes is associated with glomerular hyperfiltration in a European Mediterranean cohort study. | Glomerular hyperfiltration is well recognized as an early renal alteration in subjects with diabetes mellitus. However, what is not well-known is whether hyperfiltration also occurs in the early stages of hyperglycaemia, for instance in prediabetes. Identifying subjects with glomerular hyperfiltration from among those with prediabetes might be helpful to implement preventive and therapeutic strategies. This study aimed to investigate the association of prediabetes with glomerular hyperfiltration and its associated variables. A representative sample of 9238 people aged ≥ 30 years and whose entire clinical and laboratory data were available, were included in this study. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. After adjustment for age, gender, body mass index, systolic blood pressure and diastolic blood pressure, cholesterol, log (triglycerides), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum uric acid, smoking status, hypertension, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, fasting plasma glucose (FPG) was found to be independently positively associated with eGFR. The hazard ratios (95% confidence interval) for hyperfiltration were 1.61 (1.28-2.03) and 2.30 (1.89-2.79) for prediabetes and diabetes, respectively, when compared with participants with normoglycemia. Prediabetes was associated with glomerular hyperfiltration. Longitudinal studies are needed to investigate whether hyperfiltration in prediabetes is associated with a later decline in eGFR. | Chronic kidney disease;Glomerular hyperfiltration;Impaired fasting glucose;Prediabetes;Retrospective poblational cohort | pubmed |
Laparoscopic treatment of cornual heterotopic pregnancy: A retrospective cohort study. | To report on our experience of laparoscopic cornuostomy or cornual repair for cornual heterotopic pregnancy. A single center, retrospective review of patients who were diagnosed as cornual heterotopic pregnancy, which developed after in vitro fertilization and embryo transfer (IVF/ET) between January 2009 and June 2014. All patients were managed by laparoscopic cornuostomy or cornual repair. 14 patients were enrolled and 4 patients were finally confirmed to have a ruptured cornu. 4/4 presented as acute abdominal pain and 3/4 as metrorrhagia. The blood pressure of all the patients were stable. The earliest ruptured patient of this series happened at 23 days after IVF/ET. The hemoglobin levels of the 4 ruptured patients were significantly lower than the other patients (8.6 ± 1.8 g/dl versus 12.2 ± 1.1 g/dl, p < 0.001). Internal bleeding before operation was significantly higher in the ruptured patients than in the intact patients (1050.0 ± 369.8 ml versus 0.0 ± 0.0 ml, p < 0.001). All 14 patients were managed by laparoscopic cornuostomy or cornual repair. No one was converted to laparotomy. Post-operation pregnancy was uneventful. All neonates were delivered by cesarean section with no evident complications. Laparoscopic cornuostomy or cornual repair appears to be an effective treatment for cornual heterotopic pregnancy, even in ruptured ones. These operations can be safely performed in an institution with well-trained gynecological laparoscopists with experienced support teams. | Cornual;Cornuostomy;Heterotopic;Laparoscopy;Pregnancy | pubmed |
Predator odor stress blunts alcohol conditioned aversion. | Alcohol use disorder is highly co-morbid with traumatic stress disorders in humans, and dually diagnosed individuals cite negative affective symptoms as a primary reason for drinking alcohol. Therefore, it is reasonable to hypothesize that traumatic stress history increases the rewarding properties and/or blunts the aversive properties of alcohol. We used a place conditioning procedure to test the rewarding/aversive properties of alcohol in adult male Wistar rats with or without a traumatic stress (i.e., predator odor exposure) history, and with or without an alcohol drinking history. Because extended amygdala regions have documented roles in stress, reward, and stress-induced changes in reward, we also tested the effect of acute alcohol on CREB phosphorylation (pCREB) and striatal-enriched protein tyrosine phosphatase (STEP) expression in central amygdala (CeA) and bed nucleus of stria terminalis (BNST). Our results show that a moderate alcohol dose (1.0 g/kg) produces conditioned place aversion (CPA) that is blunted by stress history but is not affected by alcohol drinking history, and this effect differed in pair-housed versus single-housed rats. Stress history reduced pCREB expression in BNST of rats with and without an alcohol drinking history. Finally, acute alcohol effects on pCREB and STEP expression in CeA were positively associated with preference for the alcohol-paired chamber. These data suggest that stress history reduces the aversive properties of moderate alcohol doses, and that alcohol aversion is associated with acute alcohol effects on pCREB and STEP expression in the extended amygdala. | Alcohol reward;Place conditioning;Post-traumatic stress disorder (PTSD) | pubmed |
Autism in India: a case-control study to understand the association between socio-economic and environmental risk factors. | Autism spectrum disorder is a neurodevelopmental disorder and the cause of autism is still unclear. The aim of this study was to investigate the association of socioeconomic, environmental, pregnancy and newborn-related risk factors among children with autism spectrum disorders. This was a population-based case-control study. The study included 55 children with autism spectrum disorder and 55 age and sex matched typically developing normal children (TD) between 3 and 12 years. Several socio-economic factors, environmental factors, pregnancy related, natal, post-natal factors and the first noticed signs by the parents were analyzed. Chi-square test was used to compare nominal variables. For multivariate analysis, forward stepwise logistic regression model was employed to examine the association between autism and the chances that the child develops ASD to assess the odds ratios. Male predominance was observed in the study. Logistic regression model showed statistical significance of the following factors: paternal age greater than 40 years, family history of autism, nutrition during pregnancy, mode of labor, fetal hypoxia, NICU stay and history of breast feeding. In this epidemiological study of autism in Coimbatore city, we found correlation between several environmental factors during fetal development and can be transmitted to succeeding generations, causing atypical behavior phenotypes. The exact exposure magnitude, exposure time in relation to vital developmental periods need to be studied to understand the influence of socioeconomic and environmental factors, which can be improved to prevent ASD-related challenges. | Autism;Environment;Parental age;Risk factors;Socio-economic | pubmed |
Do Programs for Runaway and Homeless Youth Work? A Qualitative Exploration From the Perspectives of Youth Clients in Diverse Settings. | Runaway and homeless youth (RHY) comprise a large population of young people who reside outside the control and protection of parents and guardians and who experience numerous traumas and risk factors, but few buffering resources. Specialized settings have developed to serve RHY, but little is known about their effects. The present cross-sectional qualitative descriptive study, grounded in the positive youth development approach and the Youth Program Quality Assessment model, addressed this gap in the literature. From a larger sample of 29 RHY-specific settings across New York State, RHY ages 16-21 from 11 settings were purposively sampled for semi-structured in-depth interviews on their transitions into homelessness, experiences with settings, and unmet needs (<i>N</i> = 37 RHY). Data were analyzed with a theory-driven and inductive systematic content analysis approach. Half of participants (54%) were female; almost half (49%) identified as non-heterosexual; and 42% were African American/Black, 31% were Latino/Hispanic, and 28% were White/other. Results indicated that because RHY are a uniquely challenged population, distrustful of service settings and professional adults and skilled at surviving independently, the population-tailored approaches found in RHY-specific settings are vital to settings' abilities to effectively engage and serve RHY. We found the following four major themes regarding the positive effects of settings: (1) engaging with an RHY setting was emotionally challenging and frightening, and thus the experiences of safety and services tailored to RHY needs were critical; (2) instrumental support from staff was vital and most effective when received in a context of emotional support; (3) RHY were skilled at survival on the streets, but benefited from socialization into more traditional systems to foster future independent living; and (4) follow-through and aftercare were needed as RHY transitioned out of services. With respect to gaps in settings, RHY highlighted the following: (1) a desire for better management of tension between youths' needs for structure and wishes for autonomy and (2) lack of RHY input into program governance. This study advances our understanding of RHY, their service needs, and the ways settings meet these needs, as well as remaining gaps. It underscores the vital, life-changing, and even life-saving role these settings play for RHY. | Youth Program Quality Assessment;effectiveness;homeless youth;organizations;positive youth development;programs;qualitative research;runaway behavior | pubmed |
Biotransformation of α-Acetylbutyrolactone in <i>Rhodotorula</i> Strains. | Due to its structural similarity, the α'-1'-hydroxyethyl-γ-butyrolactone obtained by reduction of (±)-α-acetyl-γ-butyrolactone may have a similar function in the body to γ-butyrolactone (GBL). In the work presented, biotransformation of α-acetyl-γ-butyrolactone by three <i>Rhodotorula</i> strains was performed obtaining enantiomerically enriched alcohol. The process was carried out in growing and resting cultures. We studied how both media composition and organic solvent volume affected stereoselectivity and effectiveness of biotransformation. After 2 h, the enantiomerically pure (3<i>R</i>, 1'<i>S</i>)-α'-1'-hydroxyethyl-γ-butyrolactone was obtained using the <i>R. marina</i> AM77 strain in YPG (Yeast extract-Peptone-Glucose) medium enriched with 5% glycerol. To our best knowledge there is no previous information in the literature about the (±)-α-acetyl-γ-butyrolactone biotransformation performed in medium with addition of organic and deep eutectic solvents. | DES;biotransformation;glycerol;lactone;yeast | pubmed |
New approaches to ranking countries for the allocation of development assistance for health: choices, indicators and implications. | The distributions of income and health within and across countries are changing. This challenges the way donors allocate development assistance for health (DAH) and particularly the role of gross national income per capita (GNIpc) in classifying countries to determine whether countries are eligible to receive assistance and how much they receive. Informed by a literature review and stakeholder consultations and interviews, we developed a stepwise approach to the design and assessment of country classification frameworks for the allocation of DAH, with emphasis on critical value choices. We devised 25 frameworks, all which combined GNIpc and at least one other indicator into an index. Indicators were selected and assessed based on relevance, salience, validity, consistency, and availability and timeliness, where relevance concerned the extent to which the indicator represented country's health needs, domestic capacity, the expected impact of DAH, or equity. We assessed how the use of the different frameworks changed the rankings of low- and middle-income countries relative to a country's ranking based on GNIpc alone. We found that stakeholders generally considered needs to be the most important concern to be captured by classification frameworks, followed by inequality, expected impact and domestic capacity. We further found that integrating a health-needs indicator with GNIpc makes a significant difference for many countries and country categories-and especially middle-income countries with high burden of unmet health needs-while the choice of specific indicator makes less difference. This together with assessments of relevance, salience, validity, consistency, and availability and timeliness suggest that donors have reasons to include a health-needs indicator in the initial classification of countries. It specifically suggests that life expectancy and disability-adjusted life year rate are indicators worth considering. Indicators related to other concerns may be mainly relevant at different stages of the decision-making process, require better data, or both. | Aid;development assistance for health;equity;health financing | pubmed |
High plasma adiponectin levels are associated with frailty in a general old-old population: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. | The objective of the present study was to investigate the association between frailty and plasma adiponectin levels in a general population of Japanese older adults. The volunteer older adults, aged approximately 83 years, were recruited randomly from a general population in the Japanese Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. We used the modified Cardiovascular Health Study criteria to assess the frailty status of the study participants. The study participants were classified as non-frail, pre-frail and frail according to their physical activities. We compared plasma adiponectin levels among these three groups and applied a multivariate logistic regression analysis including plasma adiponectin levels to clarify the factors associated with frailty status in the cross-sectional design. The mean age of the participants was 83.1 ± 0.9 years, and 51.8% were men. The frailty index was available to assess 353 participants, of whom 24.6% were classified as non-frail, 62.3% as prefrail and 13.0% as frail. The log-transformed plasma adiponectin levels increased stepwise in the following order: non-frail, pre-frail and frail. A multivariate logistic regression analysis showed that higher plasma adiponectin levels, a higher estimated glomerular filtration rate and lower hemoglobin levels were independent determinants for pre-frail/frail status compared with non-frail status. The present study showed that higher plasma adiponectin levels were associated with frailty status in older Japanese adults in the general population. Further longitudinal study is essential to clarify the role of plasma adiponectin in the progression of frailty. Geriatr Gerontol Int 2018; 18: 839-846. | Japanese;adiponectin;cross-sectional study;elderly;frailty | pubmed |
American Sign Language Interpreters Perceptions of Barriers to Healthcare Communication in Deaf and Hard of Hearing Patients. | Communication barriers between healthcare providers and patients contribute to health disparities and the effectiveness of health promotion messages. This is especially true regarding communication between providers and deaf and hard of hearing (HOH) patients due to lack of understanding of cultural and linguistic differences, ineffectiveness of various means of communication and level of health literacy within that population. This research aimed to identify American Sign Language (ASL) interpreters' perceptions of barriers to effective communication between deaf and HOH patients and healthcare providers. We conducted a survey of ASL interpreters attending the 2015 National Symposium on Healthcare Interpreting with an overall response rate of 25%. Results indicated a significant difference (p < 0.05) in all areas of preferred communication between providers and deaf/HOH patients as perceived by interpreters. ASL interpreters observed that patients did not understand provider instructions in nearly half of appointments. Eighty-one percent of interpreters said that providers "hardly ever" use "teach-back" methods with patients to ensure understanding. A focus on improving health care and health promotion efforts in the deaf/HOH community depends on improving communication, health literacy, and patient empowerment and involves holding health care organizations accountable for assuring adequate staffing of ASL interpreters and communication resources in order to reduce health disparities in this population. | American Sign Language (ASL) interpreters;Deaf and hard of hearing;Health communication;Health disparities | pubmed |
Hybrid Au@alendronate nanoparticles as dual chemo-photothermal agent for combined cancer treatment. | A gold therapeutic nanoplatform with the same molecule used as reductant, coating and therapeutic agent has been developed in a one-pot, one-phase process using alendronate, a drug from the bisphosphonate family known for its antitumor effects. In addition, the core made of gold nanoparticles (NPs) brings thermal functionalities under irradiation within the first biological window (650-900 nm). The Au@alendronate nanoplatform thus provided a combined antitumor activity through drug delivery and photothermal therapy. Au@alendronate NPs inhibited in vitro the proliferation of prostate cancer cells (PC3) in a dose-dependent manner, with an IC<sub>50</sub> value of 100 µM. Under NIR irradiation a temperature increase was observed leading to a reduction of the IC<sub>50</sub> value to 1 µM, with total tumor cell death at 100 µM. | alendronate;bisphosphonate;cancer treatment;gold nanoparticles;photothermia | pubmed |
Sex-chromosome dosage effects on gene expression in humans. | A fundamental question in the biology of sex differences has eluded direct study in humans: How does sex-chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex-chromosome aneuploidies (XO, XXX, XXY, XYY, and XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity among evolutionarily preserved X-Y homologs and update prevailing theoretical models for SCD compensation by detecting X-linked genes that increase expression with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex-chromosome genes regulate specific coexpression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. These gene coexpression results converge with analysis of transcription factor binding site enrichment and measures of gene expression in murine knockout models to spotlight the dosage-sensitive X-linked transcription factor ZFX as a key mediator of SCD effects on wider genome expression. Our findings characterize the effects of SCD broadly across the genome, with potential implications for human phenotypic variation. | Klinefelter syndrome;Turner syndrome;X-inactivation;sex chromosomes;sex differences | pubmed |
Contouring of prostate tumors on multiparametric MRI: Evaluation of clinical delineations in a multicenter radiotherapy trial. | To date no guidelines are available for contouring prostate cancer inside the gland, as visible on multiparametric (mp-) MRI. We assessed inter-institutional differences in interpretation of mp-MRI in the multicenter phase III FLAME trial. We analyzed clinical delineations on mp-MRI and clinical characteristics from 260 patients across three institutes. We performed a logistic regression analysis to examine each institute's weighting of T2w, ADC and K<sup>trans</sup> intensity maps in the delineation of the cancer. As reviewing of all delineations by an expert panel is not feasible, we made a selection based on discrepancies between a published tumor probability (TP) model and each institute's clinical delineations using Areas Under the ROC Curve (AUC) analysis. Regression coefficients for the three institutes were -0.07, -0.27 and -0.11 for T2w, -1.96, -0.53 and -0.65 for ADC and 0.15, 0.20 and 0.62 for K<sup>trans</sup>, with significant differences between institutes for ADC and K<sup>trans</sup>. AUC analysis showed median AUC values of 0.92, 0.80 and 0.79. Five patients with lowest AUC values were reviewed by a uroradiologist. Regression coefficients revealed considerably different interpretations of mp-MRI in tumor contouring between institutes and demonstrated the need for contouring guidelines. Based on AUC values outlying delineations could efficiently be identified for review. | FLAME;Multicenter trial;Multiparametric MRI;Prostate cancer;Tumor delineation | pubmed |
Proteins of TNF-α and IL6 Pathways Are Elevated in Serum of Type-1 Diabetes Patients with Microalbuminuria. | Soluble cytokine receptors may play an important role in development of microalbuminuria (MA) in type-1 diabetes (T1D). In this study, we measured 12 soluble receptors and ligands from TNF-α/IL6/IL2 pathways in T1D patients with MA (<i>n</i> = 89) and T1D patients without MA (<i>n</i> = 483) participating in the PAGODA study. Twelve proteins in the sera from T1D patients with and without MA were measured using multiplex Luminex assays. Ten serum proteins (sTNFR1, sTNFR2, sIL2Rα, MMP2, sgp130, sVCAM1, sIL6R, SAA, CRP, and sICAM1) were significantly elevated in T1D patients with MA. After adjusting for age, duration of diabetes, and sex in logistic regression, association remained significant for seven proteins. MA is associated with increasing concentrations of all 10 proteins, with the strongest associations observed for sTNFR1 (OR = 108.3, <i>P</i> < 10<sup>-32</sup>) and sTNFR2 (OR = 65.5, <i>P</i> < 10<sup>-37</sup>), followed by sIL2Rα (OR = 12.9, <i>P</i> < 10<sup>-13</sup>), MMP2 (OR = 5.5, <i>P</i> < 10<sup>-6</sup>), sgp130 (OR = 5.2, <i>P</i> < 10<sup>-3</sup>), sIL6R (OR = 4.6, <i>P</i> < 10<sup>-4</sup>), and sVCAM1 (OR = 3.3, <i>P</i> < 10<sup>-4</sup>). We developed a risk score system based on the combined odds ratios associated with each quintile for each protein. The risk scores cluster MA patients into three subsets, each associated with distinct risk for MA attributable to proteins in the TNF-α/IL6 pathway (mean OR = 1, 13.5, and 126.3 for the three subsets, respectively). Our results suggest that the TNF-α/IL6 pathway is overactive in approximately 40% of the MA patients and moderately elevated in the middle 40% of the MA patients. Our results suggest the existence of distinct subsets of MA patients identifiable by their serum protein profiles. | cytokine receptors;cytokines;diabetes;inflammation;microalbuminuria | pubmed |
Isolated limb infusion as a treatment option for malignant granular cell tumour. | A 54-year-old man presented with a painful lesion on the right posterior calf with MRI identifying a 5 cm lesion in the medial head of the gastrocnemius. He underwent wide local excision of the tumour, and the final pathology was consistent with atypical granular cell tumour. Three years later, he developed a recurrent right popliteal mass. Complete staging workup also identified multiple lung nodules and a caecal polyp that were consistent with metastatic granular cell tumour. He was started on pazopanib and deemed a poor candidate for palliative resection due to encasement of the popliteal vessels. The patient refused above-the-knee amputation (AKA) at that point and was evaluated for isolated limb infusion as an alternative. He received three cycles of isolated limb infusion within a 2-year period and achieved good response from the first two cycles. He underwent AKA 4 years after his diagnosis of malignant granular cell tumours and is currently doing well. | chemotherapy;surgical oncology | pubmed |
Stereolithography for Personalized Left Atrial Appendage Occluders. | Advancements in 3D additive manufacturing have spurred the development of effective patient-specific medical devices. Prior applications are limited to hard materials, however, with few implementations of soft devices that better match the properties of natural tissue. This paper introduces a rapid, low cost, and scalable process for fabricating soft, personalized medical implants via stereolithography of elastomeric polyurethane resin. The effectiveness of this approach is demonstrated by designing and manufacturing patient-specific endocardial implants. These devices occlude the left atrial appendage, a complex structure within the heart prone to blood clot formation in patients with atrial fibrillation. Existing occluders permit residual blood flow and can damage neighboring tissues. Here, the robust mechanical properties of the hollow, printed geometries are characterized and stable device anchoring through in vitro benchtop testing is confirmed. The soft, patient-specific devices outperform non-patient-specific devices in embolism and occlusion experiments, as well as in computational fluid dynamics simulations. | 3D printing;elastomers;medical devices;patient-specific;stereolithography | pubmed |
Association between aortic valvular calcification and characteristics of the aortic valve in patients with bicuspid aortic valve stenosis. | Aortic valve calcification quantification using cardiac computed tomography (CCT) is a reliable marker for aortic stenosis (AS) in patients with bicuspid aortic valve (BAV) disease. To determine the association of Agatston aortic valve calcium score (AVCS) with morphological and hemodynamic characteristics of BAV and define cut-off AVCS for optimizing the grade of AS in patients with bicuspid AS. This study included 161 BAV patients with AS regardless of aortic regurgitation who underwent transthoracic echocardiography and CCT. BAVs were classified according to orientation of cusps and presence of raphe. Associations of AVCS with characteristics of BAV morphology and functional variables were determined by linear regression analysis. Area under the receiver operating characteristic curve (AUC) was used to determine the cut-off AVCS greater than which the diagnosis of severe AS was optimized. AVCS was significantly different according to sex ( P < 0.001), AS severity ( P < 0.001), type of valvular dysfunction ( P = 0.011), and orientation of cusps ( P = 0.028). Multiple linear regression showed that AVCS was significantly associated with sex (estimate = -0.583, P < 0.001) and AS severity (estimate = 0.817, P < 0.001). AVCS was a predictor for severe AS with AUC of 0.80 in both women ( P = 0.002) and men ( P < 0.001). Its cut-off value was 1423 Agatston unit (AU) in women and 2573 AU in men. In patients with bicuspid AS, AVCS was significantly higher in men and those with severe AS. However, AVCS was not significantly associated with morphological characteristics of BAV or the type of valvular dysfunction. | Aortic valve;aortic valve stenosis;calcium;echocardiography;multidetector computed tomography | pubmed |
Cocoa ingestion protects plasma lipids in healthy males against ex vivo oxidative conditions: A randomized clinical trial. | The effects of in vivo cocoa-based supplementation were studied as a preconditioning treatment for ex vivo acute oxidative conditions in a controlled randomized clinical trial. Subjects were 100 healthy young men at Universidad Industrial de Santander blinded to the intervention and divided into two groups: The intervention group (n = 50) receiving 30 g of cocoa powder and 50 g of dark chocolate/d for 1 week with the remaining subjects receiving placebo. Cocoa products preconditioning for 1 week resulted in modifications in the susceptibility of plasma lipids over ex vivo oxidative conditions with effects of i) a significant increase in the oxidative resistance of plasma lipids measured by dienes formation (4.2, CI: 0.18, 8.2; P = 0.04), and ii) a significant reduction in the production of toxic aldehydes as established by a decrease in the content of hexanal, quantified by gas chromatography (-0.22, CI: -0.38, -0.05; P = 0.009). The in vivo cocoa-based preconditioning demonstrated protective properties against ex vivo oxidative modifications, improving total plasma lipids resistance to oxidation and protecting plasma lipids against great acute oxidative insult in comparison with placebo. This trial was registered at clinical clinicaltrials.gov as NCT01347450. | Acute oxidative stress condition;Chocolate;Cocoa;Humans;Lipid peroxidation;Preconditioning | pubmed |
Can contrast-enhanced ultrasound and acoustic radiation force impulse imaging characterize CT-indeterminate renal masses? A prospective evaluation with histological confirmation. | To prospectively characterize computed tomography (CT)-indeterminate renal masses (CTIRM) using acoustic radiation force impulse (ARFI) elastography and contrast-enhanced ultrasound (CEUS) and to correlate quantitative imaging findings with histopathology or interim follow-up (FU). 123 patients with CTIRM (longest diameter < 4 cm) underwent ARFI and CEUS with CT image fusion (IF). Exclusion criteria included all contraindications for CEUS and IF. Shear wave velocity (SWV), shear wave ratio (SWR), peak intensity (PE), time to peak (TTP) and wash-in rate (Wi) were quantified. In case of a cystic lesion classified as ≤ Bosniak 2F, follow-up imaging was performed. 77 out of 123 patients underwent surgical resection of a lesion due to suspect imaging findings, whereas 46 patients underwent FU, which did not show upgrading in Bosniak category. Histopathology revealed 58 renal cell carcinomas [five chromophobe (chRCC), 18 papillary (pRCC) and 35 clear cell (ccRCC)], ten oncocytomas and nine non-malignant renal lesions (one minimal fat AML, three focal nephritis and five infected cysts). SWV and SWR differed significantly between ccRCC, pRCC, chRCC (p = 0.0024, F = 13.94) and in SWR also for oncocytoma (p < 0.0001, F = 14.35). In CEUS, oncocytoma and ccRCC showed significant higher PE values (p < 0.0001, F = 77.31) as well as higher Wi and lower TTP compared to all other solid lesions. Quantitative CEUS and ARFI imaging can provide relevant information to further characterize CT-indeterminate renal masses to guide urological decision making and offer the possibility of differentiation between ccRCC from less malignant RCC subtypes and from oncocytoma. | ARFI;CEUS;Indeterminate renal masses;Ultrasound | pubmed |
2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide Radical (PTIO•) Trapping Activity and Mechanisms of 16 Phenolic Xanthones. | This study used the 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) trapping model to study the antioxidant activities of 16 natural xanthones in aqueous solution, including garcinone C, γ-mangostin, subelliptenone G, mangiferin, 1,6,7-trihydroxy-xanthone, 1,2,5-trihydroxyxanthone, 1,5,6-trihydroxyxanthone, norathyriol, 1,3,5,6-tetrahydroxy-xanthone, isojacareubin, 1,3,5,8-tetrahydroxyxanthone, isomangiferin, 2-hydroxyxanthone, 7-<i>O</i>-methylmangiferin, neomangiferin, and lancerin. It was observed that most of the 16 xanthones could scavenge the PTIO• radical in a dose-dependent manner at pH 4.5 and 7.4. Among them, 12 xanthones of the <i>para</i>-di-OHs (or <i>ortho</i>-di-OHs) type always exhibited lower half maximal inhibitory concentration (IC<sub>50</sub>) values than those not of the <i>para</i>-di-OHs (or <i>ortho</i>-di-OHs) type. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis revealed that most of these xanthones gave xanthone-xanthone dimers after incubation with PTIO•, except for neomangiferin. Based on these data, we concluded that the antioxidant activity of phenolic xanthone may be mediated by electron-transfer (ET) <i>plus</i> H⁺-transfer mechanisms. Through these mechanisms, some xanthones can further dimerize unless they bear huge substituents with steric hindrance. Four substituent types (i.e., <i>para</i>-di-OHs, 5,6-di-OHs, 6,7-di-OHs, and 7,8-di-OHs) dominate the antioxidant activity of phenolic xanthones, while other substituents (including isoprenyl and 3-hydroxy-3-methylbutyl substituents) play a minor role as long as they do not break the above four types. | antioxidant;ortho-di-OHs;para-di-OHs;structure-activity relationship;xanthone | pubmed |
Factors associated with imaging overuse in the emergency department: A systematic review. | Emergency departments (ED) are sites of prevalent imaging overuse; however, determinants that drive imaging in this setting are not well-characterized. We systematically reviewed the literature to summarize the determinants of imaging overuse in the ED. We searched MEDLINE® and Embase® from January 1998 to March 2017. Studies were included if they were written in English, contained original data, pertained to a U.S. population, and identified a determinant associated with overuse of imaging in the ED. Twenty relevant studies were included. Fourteen evaluated computerized tomography (CT) scanning in patents presenting to a regional ED who were then transferred to a level 1 trauma center; incomplete transfer of data and poor image quality were the most frequently described reasons for repeat scanning. Unnecessary pre-transfer scanning or repeated scanning after transfer, in multiple studies, was highest among older patients, those with higher Injury Severity Scores (ISS) and those being transferred further. Six studies explored determinants of overused imaging in the ED in varied conditions, with overuse greater in older patients and those having more comorbid diseases. Defensive imaging reportedly influenced physician behavior. Less integration of services across the health system also predisposed to overuse of imaging. The literature is heterogeneous with surprisingly few studies of determinants of imaging in minor head injury or of spine imaging. Older patient age and higher ISS were the most consistently associated with ED imaging overuse. This review highlights the need for precise definitions of overuse of imaging in the ED. | Emergency department;Health care costs;Imaging;Overuse;Quality measurement | pubmed |
Effect of LigaSure™, Monopolar Cautery, and Bipolar Cautery on Surgical Margins in Breast-Conserving Surgery. | We compared the differences in thermal damage at the surgical margin between monopolar cautery, bipolar cautery, and LigaSure™ in breast cancer lumpectomy specimens and assessed the effect of these techniques on the evaluation of the surgical margins. 30 patients scheduled for breast-conserving surgery for breast cancer were included in this study. During lumpectomy, each of the superior, inferior, lateral, and medial borders of the tumour was excised using one of the following: a scalpel, monopolar cautery, bipolar cautery, and LigaSure technology. The surgical margins of frozen and paraffin-embedded tissue sections of the lumpectomy specimen were evaluated. Thermal damage was defined as the maximum depth of thermal damage (in mm) from the surgical margin, and the level was categorized as none, low (≤1 mm), or high (>1 mm). There was no statistically significant difference between monopolar cautery, bipolar cautery, and LigaSure in terms of thermal damage. There was no thermal damage at the surgical margin in tissues dissected by scalpel. Thermal damage due to the excision method may cause false-negative and false-positive results in the surgical margin evaluation of lumpectomy specimens. More research is needed on the effects of different energy modalities on surgical margin evaluation in breast-conserving surgery. | Breast cancer;Breast-conserving surgery;Electrosurgery;Lumpectomy;Thermal destruction | pubmed |
Eliminating Glutamatergic Input onto Horizontal Cells Changes the Dynamic Range and Receptive Field Organization of Mouse Retinal Ganglion Cells. | In the mammalian retina, horizontal cells receive glutamatergic inputs from many rod and cone photoreceptors and return feedback signals to them, thereby changing photoreceptor glutamate release in a light-dependent manner. Horizontal cells also provide feedforward signals to bipolar cells. It is unclear, however, how horizontal cell signals also affect the temporal, spatial, and contrast tuning in retinal output neurons, the ganglion cells. To study this, we generated a genetically modified mouse line in which we eliminated the light dependency of feedback by deleting glutamate receptors from mouse horizontal cells. This genetic modification allowed us to investigate the impact of horizontal cells on ganglion cell signaling independent of the actual mode of feedback in the outer retina and without pharmacological manipulation of signal transmission. In control and genetically modified mice (both sexes), we recorded the light responses of transient OFF-α retinal ganglion cells in the intact retina. Excitatory postsynaptic currents (EPSCs) were reduced and the cells were tuned to lower temporal frequencies and higher contrasts, presumably because photoreceptor output was attenuated. Moreover, receptive fields of recorded cells showed a significantly altered surround structure. Our data thus suggest that horizontal cells are responsible for adjusting the dynamic range of retinal ganglion cells and, together with amacrine cells, contribute to the center/surround organization of ganglion cell receptive fields in the mouse.<b>SIGNIFICANCE STATEMENT</b> Horizontal cells represent a major neuronal class in the mammalian retina and provide lateral feedback and feedforward signals to photoreceptors and bipolar cells, respectively. The mode of signal transmission remains controversial and, moreover, the contribution of horizontal cells to visual processing is still elusive. To address the question of how horizontal cells affect retinal output signals, we recorded the light responses of transient OFF-α retinal ganglion cells in a newly generated mouse line. In this mouse line, horizontal cell signals were no longer modulated by light. With light response recordings, we show that horizontal cells increase the dynamic range of retinal ganglion cells for contrast and temporal changes and contribute to the center/surround organization of their receptive fields. | gain control;ganglion cells;glutamate receptor;horizontal cells;receptive field;retina | pubmed |
Lung injury and expression of p53 and p16 in Wistar rats induced by respirable chrysotile fiber dust from four primary areas of China. | Chrysotile products were widely used in daily life, and a large amount of respirable dust was produced in the process of production and application. At present, there was seldom research on the safety of chrysotile fiber dust, and whether its long-term inhalation can lead to lung cancer was unknown. In order to determine whether respirable chrysotile fiber dust of China caused lung cancer, four major chrysotile-producing mine areas in China were selected for this study. Chrysotile fibers were prepared into respirable dust. Particle size was measured by laser particle analysis, morphology was observed by scanning electron microscope, chrysotile fiber phase was analyzed by X-ray diffraction, trace chemical elements were identified by X-ray fluorescence, and the structure and the active groups of the dust were determined after grinding by Fourier transform infrared spectroscopy. Male Wistar rats were exposed to non-exposed intratracheal instillation with different concentrations of chrysotile fiber dust. The rats were weighed after 1, 3, and 6 months, then the lung tissues were separated, the lung morphology was observed, and the pulmonary index was calculated. Pathological changes in lung tissues were observed by optical microscope after the HE staining of tissues, and the gene expression of p53 and p16 was determined by reverse transcription polymerase chain reaction. First, the results showed that the particle sizes of the four fibers were less than 10 μm. Four primary areas of chrysotile had similar fibrous structure, arranged in fascicles, or mixed with thin chunks of material. Second, the elementary composition of the four fibers was mainly chrysotile, and the structure and the active groups of the grinding dust were not damaged. Third, the weights of the treated rats were obviously lower, and the lung weights and the pulmonary index increased significantly (P < 0.05). Fourth, the treated Wistar rat lung tissues revealed different degrees of congestion, edema, inflammatory cell infiltration, and mild fibrosis. Fifth, the p53 and p16 genes decreased in the Mangnai group after 1 month of exposure, and the other groups increased. The expression of p53 and p16 in each group decreased significantly after 6 months (P < 0.05). In conclusion, the respirable chrysotile fiber dust from the four primary areas of China had the risk of causing lung injury, and these changes may be related to the physical and chemical characteristics of chrysotile from different production areas. | Antioncogene;Chrysotile;Pulmonary index;Respirable dust;p16;p53 | pubmed |
Infections and Risk of Peripartum Stroke During Delivery Admissions. | Peripartum strokes during delivery admissions are rare but have high maternal morbidity. Infections have been proposed as a possible stroke trigger. We hypothesized that women who had infections diagnosed at the time of delivery admission would have higher risk of stroke during their delivery hospitalization. We conducted a case-control study using state inpatient administrative databases for California (2007-2011), Florida (2009-2011), and New York (2009-2011). Women whose admission included a vaginal or cesarean delivery, with a new diagnosis of stroke during the admission, were considered cases and were randomly matched to 3 in-state controls by age/admission year and presence and severity of hypertensive disorders of pregnancy. The primary exposure of interest was infection of any type present on admission. Secondary exposures included race/ethnicity, payer status, delivery method, and known vascular risk factors such as chronic hypertension, diabetes mellitus, smoking, alcohol abuse, hypercoagulable states, coagulopathies, and renal disease. We used multivariable conditional logistic regression to estimate the odds ratios and 95% confidence intervals for the association of infections and known vascular risk factors with stroke risk. A total of 455 cases (mean age, 29.8), of whom 195 (42.9%) had hypertensive disorders of pregnancy, were matched with 1365 controls. Infection of any type present on admission increased the odds of stroke diagnosis during the admission (adjusted odds ratio, 1.74; 95% confidence interval, 1.29-2.35). Risk was higher for genitourinary infections (adjusted odds ratio, 2.56; 95% confidence interval, 1.25-5.24) and sepsis (adjusted odds ratio, 10.4; 95% confidence interval, 2.15-20.0). The association between infection and stroke during delivery admission did not differ by the presence of hypertensive disorders of pregnancy. Infections present on admission increased stroke risk during delivery admissions in women with and without hypertensive disorders of pregnancy. The results were driven by genitourinary infections and sepsis. Infections may be an underrecognized precipitant of peripartum stroke. | hypertension;preeclampsia;pregnancy;risk factors;sepsis;stroke | pubmed |
Gamma radiation induces dose-dependent oxidative stress and transcriptional alterations in the freshwater crustacean Daphnia magna. | Among aquatic organisms, invertebrate species such as the freshwater crustacean Daphnia magna are believed to be sensitive to gamma radiation, although information on responses at the individual, biochemical and molecular level is scarce. Following gamma radiation exposure, biological effects are attributed to the formation of free radicals, formation of reactive oxygen species (ROS) and subsequently oxidative damage to lipids, proteins and DNA in exposed organisms. Thus, in the present study, effects and modes of action (MoA) have been investigated in D. magna exposed to gamma radiation (dose rates: 0.41, 1.1, 4.3, 10.7, 42.9 and 106 mGy/h) after short-term exposure (24 and 48 h). Several individual, cellular and molecular endpoints were addressed, such as ROS formation, lipid peroxidation, DNA damage and global transcriptional changes. The results showed that oxidative stress is one of the main toxic effects in gamma radiation exposed D. magna, mediated by the dose-dependent increase in ROS formation and consequently oxidative damage to lipids and DNA over time. Global transcriptional analysis verified oxidative stress as one of the main MoA of gamma radiation at high dose rates, and identified a number of additional MoAs that may be of toxicological relevance. The present study confirmed that acute exposure to gamma radiation caused a range of cellular and molecular effects in D. magna exposed to intermediate dose rates, and highlights the need for assessing effects at longer and more environmentally relevant exposure durations in future studies. | Daphnia magna;Gamma radiation;Gene expression;Mode of action;Oxidative stress | pubmed |
Membranes: A Variety of Energy Landscapes for Many Transfer Opportunities. | A membrane can be represented by an energy landscape that solutes or colloids must cross. A model accounting for the momentum and the mass balances in the membrane energy landscape establishes a new way of writing for the Darcy law. The counter-pressure in the Darcy law is no longer written as the result of an osmotic pressure difference but rather as a function of colloid-membrane interactions. The ability of the model to describe the physics of the filtration is discussed in detail. This model is solved in a simplified energy landscape to derive analytical relationships that describe the selectivity and the counter-pressure from ab initio operating conditions. The model shows that the stiffness of the energy landscape has an impact on the process efficiency: a gradual increase in interactions (such as with hourglass pore shape) can reduce the separation energetic cost. It allows the introduction of a new paradigm to increase membrane efficiency: the accumulation that is inherent to the separation must be distributed across the membrane. Asymmetric interactions thus lead to direction-dependent transfer properties and the membrane exhibits diode behavior. These new transfer opportunities are discussed. | interaction;membrane transport;osmosis | pubmed |
A snapshot of drug background levels on surfaces in a forensic laboratory. | While background studies have been commonplace in many occupational fields for a long time, attempts to understand the chemical background in forensics labs has been largely understudied. Such studies can help define the efficiency of cleaning procedures and the integrity of collected data, which is becoming increasingly important due to improving sensitivity of instrumentation and the prevalence with which potent drugs of abuse, such as the opioids, are being seen. The results from this study provide a snapshot of the drug background levels on surfaces in a laboratory system comprised of a central laboratory and two satellite laboratories. Samples were collected from work surfaces by swiping with meta-aramid wipes, and extracted for analysis by LC/MS/MS, for quantitation, and TD-DART-MS, for non-targeted screening. Surfaces were sampled from within the drug unit (where drug evidence is processed) and the evidence receiving unit (where drug cases are handled) in all laboratories as well as the report writing area, the toxicology unit and the crime scene unit in the central laboratory. Results showed that the background was restricted primarily to the benches, balances, and instrumentation within the drug unit - with approximately an order of magnitude higher concentrations observed on the balances, compared to the benches. Higher levels were also observed in analyst specific surfaces when compared to general use surfaces within the drug unit - which corresponded to where bulk evidence handling was completed. Background in the evidence receiving and report writing sections was minimal. Comparison of the main laboratory to the satellite laboratories showed similarities amongst frequently encountered drugs like cocaine, but noticeable differences in opioids which could be attributed to differences in the make-up of exhibits each laboratory receives. Understanding the background levels of drugs in a forensic laboratory environment is crucial to improving cleaning protocols, helping define detection limits for highly sensitive analyses, and providing additional results to the broader community that has been establishing background levels in other environments. | Background;LC/MS/MS;Narcotics;Quantitation;TD-DART-MS | pubmed |
Comparison of Widefield and Circumpapillary Circle Scans for Detecting Glaucomatous Neuroretinal Thinning on Optical Coherence Tomography. | Our purpose was to compare the effectiveness of detecting progressive retinal nerve fiber layer (RNFL) thickness changes using widefield scans compared to circumpapillary circle scans derived from optic disc volume scans when using a manual region-of-interest (ROI) approach<b>.</b> In a prospective observational study, a total of 125 eyes diagnosed clinically with glaucoma or suspected glaucoma that had both widefield (12 × 9 mm) and optic disc (6 × 6 mm) scans obtained at least one year apart were included. Changes in the RNFL thickness between the two visits were evaluated within region(s) of observed or suspected glaucomatous damage, which were manually outlined after reviewing key features from each scan on the second visit (described as a manual ROI approach). Within ROI(s), changes in the widefield and circumpapillary RNFL thickness (wfRNFL<sub>ROI</sub> and cpRNFL<sub>ROI</sub>), as well as in the global circumpapillary RNFL thickness (cpRNFL<sub>G</sub>), were determined. The performance of these three methods for detecting progressive changes was compared using longitudinal signal-to-noise ratios (SNRs), whereby the rate of change determined by each method was normalized by individualized estimates of measurement variability and age-related change. On average, the longitudinal SNRs for the wfRNFL<sub>ROI</sub>, cpRNFL<sub>ROI</sub>, and cpRNFL<sub>G</sub> methods were -0.57, -0.38, and -0.23 y<sup>-1</sup>, respectively, being significantly more negative for the wfRNFL<sub>ROI</sub> than the latter two methods (<i>P</i> ≤ 0.009). Progressive RNFL thickness changes were more effectively detected on widefield optical coherence tomography (OCT) scans using a manual ROI approach compared to conventional derived circumpapillary circle scans. Widefield OCT scans show promise for improving the detection of glaucomatous progression<b>.</b> | glaucoma;optical coherence tomography;progression;widefield | pubmed |
Multiparametric Magnetic Resonance Imaging Is an Independent Predictor of Salvage Radiotherapy Outcomes After Radical Prostatectomy. | The Stephenson nomogram is widely used to estimate the success of salvage radiotherapy (sXRT) for prostate cancer (PCa) recurrence after radical prostatectomy (RP). To determine whether multiparametric pelvic magnetic resonance imaging (mpMRI) performed for biochemical recurrence after RP improves prognostication of sXRT relative to the Stephenson nomogram. Men undergoing RP at our institution from 2003 to 2012 who had biochemical recurrence evaluated by mpMRI within 12 mo of sXRT were retrospectively reviewed. Exclusion criteria included PCa treatment prior to RP, adjuvant XRT after RP, salvage cryotherapy before sXRT, and hormone refractory disease prior to sXRT. Multivariable Cox regression analyses (adjusting for Stephenson nomogram covariates) associated mpMRI findings with prostate-specific antigen (PSA) recurrence and metastasis after sXRT. The mpMR images were compared in a binary fashion: no lesion versus vesicourethral/seminal vesical bed/prostate fossa lesions. Among 473 sXRT patients, 57%(204) had lesions on mpMRI: 26%(124) vesicourethral, 28%(135) seminal vesical bed/prostatic fossa, 7%(34) nodal, and 1%(3) bone. Median PSA at mpMRI with lesions was 0.46 versus 0.40ng/ml without lesions. After excluding nodal/bone lesions, 29% of men developed PSA recurrence and 14% metastasis (median follow-up 45 mo after sXRT). For patients with a pre-sXRT PSA of ≤0.5ng/ml, negative mpMRI was associated with increased PSA recurrence (39% vs 12%, p<0.01) and metastasis (16% vs 2%, p<0.01) at 4 yr after sXRT. For patients with a PSA of ≤0.5ng/ml, the addition of mpMRI to the propensity score (created using variables from the original Stephenson nomogram) improved the c-statistic from 0.71 to 0.77 for PSA recurrence (hazard ratio [HR] 3.60, p<0.01) and from 0.66 to 0.77 for metastasis (HR 6.68, p<0.01). Limitations include evolutions in MRI technique and lack of a cohort of men undergoing mpMRI electing against sXRT. Pre-sXRT mpMRI improves clinicopathologic variables to estimate sXRT success, particularly in the early sXRT setting. Men who have biochemically recurrent prostate cancer after radical prostatectomy often receive salvage radiotherapy. In our study, multiparametric pelvic magnetic resonance imaging prior to salvage radiotherapy was a significant predictor of prostate-specific antigen failure and metastasis after radiotherapy. | Biochemical recurrence;Magnetic resonance imaging;Outcomes;Prostate cancer;Salvage radiotherapy | pubmed |
The impact of PTSD clusters on cannabis use in a racially diverse trauma-exposed sample: An analysis from ecological momentary assessment. | Accumulating evidence indicates a link between post-traumatic stress disorder (PTSD) and cannabis use and suggests that this link may vary as a function of the PTSD symptom cluster type. Consistent with negative reinforcement models of substance use, individuals with elevated Cluster D (Hyperarousal) symptoms may be more likely to use cannabis in response to elevated state anxiety and experience decreases in state anxiety after using cannabis. We aimed to test hypotheses that the interaction of Cluster D and state anxiety would be related to subsequent cannabis use and that those with elevated Cluster D symptoms who used cannabis would report the greatest decreases in state anxiety. To test the specificity, we tested whether Clusters B (re-experiencing) and C (avoidance) showed similar relationships. The present study used ecological momentary assessment to examine cannabis use among 87 cannabis-using individuals with PTSD symptoms (64.4% male, 56.3% non-Hispanic Caucasian). State anxiety and cannabis use were assessed over the two-week period via signal contingent (six random prompts per day), interval contingent (each bedtime), and event contingent (cannabis use episodes) assessments. Consistent with negative reinforcement models, participants with clinically significant Cluster D symptoms with elevated state anxiety had a greater likelihood of subsequent cannabis use and cannabis use resulted in less subsequent anxiety. The negative reinforcement hypothesis was only partially supported for those with Cluster B and C symptoms. The results suggest that negative reinforcement models may be especially relevant to understanding cannabis use among those with clinically elevated Cluster D symptoms. | Cannabis;ecological momentary assessment;marijuana;negative reinforcement;post-traumatic stress | pubmed |
Environmental proteomic studies: closer step to understand bacterial biofilms. | Advancement in proteome analytical techniques and the development of protein databases have been helping to understand the physiology and subtle molecular mechanisms behind biofilm formation in bacteria. This review is to highlight how the evolving proteomic approaches have revealed fundamental molecular processes underlying the formation and regulation of bacterial biofilms. Based on the survey of research reports available on differential expression of proteins in biofilms of bacterial from wide range of environments, four important cellular processes viz. metabolism, motility, transport and stress response that contribute to formation of bacterial biofilms are discussed. This review might answer how proteins related to these cellular processes contribute significantly in stabilizing biofilms of different bacteria in diverse environmental conditions. | Bacteria;Biofilm;Proteomics;Techniques;Tools | pubmed |
Genetic Optimization Algorithm for Metabolic Engineering Revisited. | To date, several independent methods and algorithms exist for exploiting constraint-based stoichiometric models to find metabolic engineering strategies that optimize microbial production performance. Optimization procedures based on metaheuristics facilitate a straightforward adaption and expansion of engineering objectives, as well as fitness functions, while being particularly suited for solving problems of high complexity. With the increasing interest in multi-scale models and a need for solving advanced engineering problems, we strive to advance genetic algorithms, which stand out due to their intuitive optimization principles and the proven usefulness in this field of research. A drawback of genetic algorithms is that premature convergence to sub-optimal solutions easily occurs if the optimization parameters are not adapted to the specific problem. Here, we conducted comprehensive parameter sensitivity analyses to study their impact on finding optimal strain designs. We further demonstrate the capability of genetic algorithms to simultaneously handle (i) multiple, non-linear engineering objectives; (ii) the identification of gene target-sets according to logical gene-protein-reaction associations; (iii) minimization of the number of network perturbations; and (iv) the insertion of non-native reactions, while employing genome-scale metabolic models. This framework adds a level of sophistication in terms of strain design robustness, which is exemplarily tested on succinate overproduction in <i>Escherichia coli</i>. | constraint-based modeling;heuristic optimization;metabolic strain design | pubmed |
Effects of phosphodiestrase type 5 inhibitors in epinephrine-induced arrhythmia in rats: Involvement of lactate dehydrogenase and creatine kinase downregulation and adiponectin expression. | Cardiac arrhythmia is a common cause of mortality, and its progression may be due to abnormal sympathetic nerve activity and catecholamine release. Besides, lactate dehydrogenase (LDH) and creatine kinase (CK) downregulation and adiponectin expression play important roles in promoting coronary artery disease. The study aimed to examine the possible cardioprotective effect of members of phosphodiesterase type 5 (PDE-5) inhibitors in epinephrine-induced arrhythmia in rats. Arrhythmia was induced by cumulative boluses of epinephrine (4, 8, 16, 32, 64, and 128 mg/kg) given at 10-min intervals. Rats were randomly allocated into five groups. Group I: Normal control group received only saline. Group II: Rats injected with epinephrine and served as arrhythmia group. Groups III, IV, and V: Rats received daily oral sildenafil (0.5 mg/kg), vardenafil (3 mg/kg), and tadalafil (10 mg/kg), respectively, for 30 days prior to epinephrine injections. Injection of epinephrine to rats decreased heart rate and QTc interval but increased RR interval and duration of arrhythmia. Epinephrine group had lower serum reduced glutathione (GSH) and adiponectin levels and higher serum malondialdehyde (MDA), nitric oxide (NO), heart LDH, and CK contents. Histopathological investigations of epinephrine group provoked necrotic changes with strong positive immunoreactivity for caspases-3. While pretreatment of rats with PDE-5 inhibitors improved GSH and adiponectin contents, ameliorated serum MDA and NO levels and heart LDH and CK contents and corrected epinephrine-induced histopathological changes. PDE-5 inhibitors may delay epinephrine-induced arrhythmia through expression of adiponectin and downregulation of heart LDH and CK. | Arrhythmia;adiponectin;creatine kinase;lactate dehydrogenase;phosphodiesterase type 5 inhibitors | pubmed |
A retrospective study of shrinking field radiation therapy during chemoradiotherapy in stage III non-small cell lung cancer. | and purpose: This retrospective study aimed to investigate the feasibility of shrinking field radiotherapy during chemoradiotherapy in non-small cell lung cancer (NSCLC). Ninety-seven patients with stage III NSCLC who achieved a good response to chemoradiation were analyzed. Computed tomography was performed after 40-50 Gy dose radiation to evaluate curative effect. Patients in the shrinking field group underwent resimulation CT scans and shrinking field radiotherapy. Acute symptomatic irradiation-induced pneumonia (ASIP), progression patterns and survival were assessed. Of the 97 patients who achieved response after a median total dose of 60 Gy, fifty patients received shrinking field radiotherapy. The incidence of acute symptomatic irradiation-induced pneumonia tended to be lower for the shrinking field group (18.0% vs. 23.4%, <i>P =</i> 0.51). The rate of disease progression was significantly higher in the non-shrinking than shrinking field group (95.7% vs. 66.0%, <i>P</i> < 0.001). Compared to the non-shrinking field group, the shrinking field group had similar overall survival (30.0 vs. 30.0 months, <i>P =</i> 0.58) but significantly better median progression-free survival (14.0 vs. 11.0 months, <i>P =</i> 0.006). Shrinking field radiotherapy during chemoradiotherapy in stage III non-small cell lung cancer seems safe with acceptable toxicities and relapse, and potentially spares normal tissues and enables dose escalation. Prospective trials are warranted. | adaptive radiotherapy;chemoradiation therapy;dose escalation;lung cancer | pubmed |
Revamping downdraft gasifier to minimize clinker formation for high-ash garden waste as feedstock. | The conventional downdraft gasifier, when used with garden waste pellets (ash ∼10%) as feedstock, exhibits formation of clinker due to hardening of softened ash, which results in discontinuous flame and intermittent operation. The design and operation protocol of the gasifier was appropriately modified to circumvent this problem. The effects of parameters such as grate movement, equivalence ratio (ER), and ratio of air entering at combustion and drying zones (split ratio) were systematically studied to maximize the lower heating value (LHV) of gas and minimize the amount of clinker. The grate movement of once in 20 min, ER of 0.32, and air split ratio of 0:100 together proved to be the best for garden waste pellets. The producer gas LHV and cold gas efficiency were 3.59 MJ/Nm<sup>3</sup> and 62.61%, respectively, and comparable to the producer gas obtained from other biomass resources such as rice husk, wheat straw, and cotton stalks. | Air split ratio;Clinker;Downdraft gasifier;Garden waste pellets;Grate movement interval | pubmed |
General practitioners' views on managing knee osteoarthritis: a thematic analysis of factors influencing clinical practice guideline implementation in primary care. | Osteoarthritis (OA) is diagnosed and managed primarily by general practitioners (GPs). OA guidelines recommend using clinical criteria, without x-ray, for diagnosis, and advising strengthening exercise, aerobic activity and, if appropriate, weight loss as first-line treatments. These recommendations are often not implemented by GPs. To facilitate GP uptake of guidelines, greater understanding of GP practice behaviour is required. This qualitative study identified key factors influencing implementation of these recommendations in the primary-care setting. Semi-structured interviews with eleven GPs were conducted, transcribed verbatim, coded by two independent researchers and analysed with an interpretive thematic approach using the COM-B model (Capability/Opportunity/Motivation-Behaviour) as a framework. Eleven themes were identified. Psychological capability themes: knowledge gaps, confidence to effectively manage OA, and skills to facilitate lifestyle change. Physical opportunity themes: system-related factors including time limitations, and patient resources. Social opportunity theme: influences from patients. Reflective motivation themes: GP's perceived role, and assumptions about people with knee OA. Automatic motivation themes: optimism, habit, and unease discussing weight. The findings demonstrated diverse and interacting influences on GPs' practice. The identified themes provide insight into potential interventions to improve OA management in primary-care settings. Key suggestions include: improvements to OA clinical guidelines; targeting GP education to focus on identified knowledge gaps, confidence, and communication skills; development and implementation of new models of service delivery; and utilising positive social influences to facilitate best-practice behaviours. Complex, multimodal interventions that address multiple factors (both barriers and facilitators) are likely to be necessary. | Clinical guidelines;General practitioner;Knee osteoarthritis;Primary care;Qualitative | pubmed |
Correlation between endocapillary proliferative and nephrotic-range proteinuria in children with Henoch-Schönlein purpura nephritis. | The endocapillary proliferative (EP) lesion is not included in the International Study of Kidney Disease in Children (ISKDC) pathological classification of Henoch-Schönlein purpura nephritis (HSPN). The main objective of the study was to determine the pathological importance of EP in the development of proteinuria in children with Henoch-Schönlein purpura nephritis (HSPN). The pathological features of 148 HSPN children with nephrotic-range proteinuria were investigated retrospectively. Urinary IgG, transferrin, and albumin levels were measured by immunonephelometry. The correlations between EP lesion and 24-h proteinuria, urinary IgG, urinary transferrin, and urinary albumin were analyzed. Renal biopsy specimens were immunohistochemically stained for nephrin and podocalyxin. Of the total 581 cases of children with HSPN who underwent renal biopsy, 148 cases (25.5%) presented with nephrotic-range proteinuria. The pathological types of HSPN with nephrotic-range proteinuria were categorized as IIb, IIIa, IIIb, IIIb with diffuse EP, IVb, pure focal EP type, and pure diffuse EP type. Among these types, pure diffuse EP type accounted for 7.4%. The levels of 24-h proteinuria and urinary albumin were the highest in pure diffuse EP type among all pathological types, and the percentage of EP correlated with 24-h proteinuria and urinary albumin levels. 24-h proteinuria was significantly higher in pure diffuse EP type relative to HSPN IIb type, and significantly higher in IIIb with EP, compared with HSPN IIIb. Nephrin, but not podocalyxin, was downregulated in EP segment. EP is an independent pathogenic factor in HSPN with nephrotic-range proteinuria. Downregulation of nephrin in EP segment is a potential molecular mechanism of nephrotic-range proteinuria. Albumin is the major urinary protein component in HSPN with EP. | Endocapillary proliferative;HSPN;Nephrotic-range proteinuria | pubmed |
International dog travelling and risk for zoonotic Onchocerca lupi. | Onchocerca lupi is a recently recognized threat for the health of animals and humans in European, American, African and Middle Eastern countries. We describe a case of imported O. lupi infection in Italy and report the lifespan of this parasite in a non-endemic area, to advocate increased awareness of the veterinary community for this zoonotic parasitosis. |
Onchocerca lupi
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PETS
;animal travelling;travel medicine;zoonoses | pubmed |
Surgical Management and Outcomes of Cavernous Sinus Hemangiomas: A Single-Institution Series of 47 Patients. | The purpose of this study was to analyze the outcomes of cavernous sinus hemangiomas (CSHs) treated surgically, and to investigate factors that affect the gross total resection (GTR), newly developed or deteriorated cranial nerve injury (NDDCNI), and follow-up neurologic performance, and to further discuss the optimal treatment for CSHs. Clinical data of 47 patients with CSHs treated surgically at our institution between 2012-2018 were retrospectively reviewed. GTR was achieved in 26 (55.3%) patients. Significant relations were identified between the invasion of the sella turcica (odds ratio [OR] = 0.012; 95% confidence interval [CI], 0.001-0.213; P = 0.002), skull base ward (OR = 27.838; 95% CI, 2.995-258.748; P = 0.003), and GTR. The preoperative Karnofsky Performance Scale (KPS) score (OR = 2.966, per 10 score increase; 95% CI, 1.136-7.743; P = 0.026) and the invasion of the sella turcica (OR = 7.137; 95% CI, 1.282-39.726; P = 0.025) were factors that significantly affected the incidence of NDDCNI. The average follow-up KPS score, which increased significantly compared with the pre (P < 0.001) and postoperative KPS scores (P < 0.001), was 89.1. Increased tumor size (OR = 0.044, per 1cm increase; 95% CI, 0.004-0.477; P = 0.010) was a risk factor for unfavorable follow-up KPS score. Being treated by an experienced skull base surgeon favors the total removal of CSHs, whereas the invasion of the sella turcica does just the opposite. Increased tumor size is a risk factor for unfavorable follow-up KPS score. The invasion of the sella turcica was related to NDDCNI and unfavorable follow-up KPS score. | Cavernous sinus hemangioma;Extent of resection;Morbidity;Risk factor;Surgical management | pubmed |
Reduced spinal cord parenchymal cerebrospinal fluid circulation in experimental autoimmune encephalomyelitis. | An alteration of parenchymal cerebrospinal fluid circulation (CSF) has been proposed to take part in the pathophysiology of multiple sclerosis. By using an intragate T1-weighted high-resolution MRI of the spinal cord of freely breathing mice injected with a gadolinium chelate in the <i>cisterna magna</i>, we show that a parenchymal CSF circulation exists in the spinal cord, in addition to that originally described in the brain. In experimental autoimmune encephalomyelitis, a model of multiple sclerosis, we show a reduction of parenchymal CSF circulation specifically in the spinal cord but not in the brain. | Glymphatic;drainage;neuroinflammation;paravascular;perivascular | pubmed |
Hypocalcemic disorders. | Calcium is vital for life, and extracellular calcium concentrations must constantly be maintained within a precise concentration range. Low serum calcium (hypocalcemia) occurs in conjunction with multiple disorders and can be life-threatening if severe. Symptoms of acute hypocalcemia include neuromuscular irritability, tetany, and seizures, which are rapidly resolved with intravenous administration of calcium gluconate. However, disorders that lead to chronic hypocalcemia often have more subtle manifestations. Hypoparathyroidism, characterized by impaired secretion of parathyroid hormone (PTH), a key regulatory hormone for maintaining calcium homeostasis, is a classic cause of chronic hypocalcemia. Disorders that disrupt the metabolism of vitamin D can also lead to chronic hypocalcemia, as vitamin D is responsible for increasing the gut absorption of dietary calcium. Treatment and management options for chronic hypocalcemia vary depending on the underlying disorder. For example, in patients with hypoparathyroidism, calcium and vitamin D supplementation must be carefully titrated to avoid symptoms of hypocalcemia while keeping serum calcium in the low-normal range to minimize hypercalciuria, which can lead to renal dysfunction. Management of chronic hypocalcemia requires knowledge of the factors that influence the complex regulatory axes of calcium homeostasis in a given disorder. This chapter discusses common and rare disorders of hypocalcemia, symptoms and workup, and management options including replacement of PTH in hypoparathyroidism. | hypocalcemia;hypoparathyroidism;parathyroid hormone;pseudohypoparathyroidism;vitamin D | pubmed |
Synthesis and effect of a new Terbium gibberellic complex on the histopathological alteration induced by Gibberellic acid on liver and kidney of mice Mus musculus. | The objective of this study was to synthesize Gibberellic lanthanide complex and evaluate its biological activity to reduce the Gibberellic acid toxicity on liver and kidney. The new bis(Gibberellic)-nitro-terbium(III) complex was characterized by different analytical methods: elemental analyses, UV-Vis, molar ratio, fluorescence, FT-IR, and TGA-DTA measurements. Thirty newborns were classified into three groups control, Gibberellic acid, and Terbium gibberellic acid complex. Livers and kidneys of studied groups proceed for general histology and immunohistochemical staining of Cyr61, cytochrome C, and TNFR2. From the absorption titration measurements, the binding constants of DNA with Tb(III)-(GA)<sub>2</sub> complex and free ligand were found to be 3.9 × 10<sup>4</sup> and 2.1 × 10<sup>3</sup> m<sup>-1</sup> , respectively, with the stoichiometry of 1:1. Hypochromism was observed from the absorption titration experiment which indicates the intercalation of Tb(III)-(GA)<sub>2</sub> complex between the base pairs of DNA. Gibberellic acid-treated group showed alteration in the histological picture of livers and kidneys that accompanied with the reduction in the expression of Cyr61, cyt C, and TNFR2. The amelioration was observed in Gibberellic acid complex with Terbium group. The study concluded that Terbium gibberellic complex is less dangerous effects than Gibberellic acid alone. | Gibberellic acid;Terbium complex;hepatotoxicity;nephrotoxicity | pubmed |
Admitting Service Affects Cost and Length of Stay of Hip Fracture Patients. | The purpose of this study was to analyze the effect of the admitting service on cost of care for hip fracture patients by comparing the cost difference between patients admitted to the medicine service versus those admitted to a surgical service. A 2-year cohort of patients 55 years or older who were admitted to a single level 1 trauma center with an operative hip fracture were included. Patient demographics, comorbidities, admitting service, complications, and hospital length of stay were recorded for each patient. Cost of hospitalization, discharge disposition, and 30-day readmissions were collected. Patients who were admitted to the medicine service (medicine cohort) were compared to those admitted to a surgery service (surgery cohort). Multivariate regression models controlling for age, Charlson comorbidity index (CCI), and American Society of Anesthesiology (ASA) scores were used to evaluate hospitalization costs with a <i>P</i> value of <.05 as significant. Two hundred twenty-five hip fracture patients were included; 143 (63.6%) patients were admitted to a surgical service, while 82 (36.4%) were admitted to the medicine service. Patients admitted to medicine service had greater CCI and ASA scores, longer lengths of stay, and more complications than those patients admitted to surgery service. Linear regression model controlling for age, CCI, ASA score, and time to surgery demonstrates that patients admitted to a surgical service will have 2.0-day (95% confidence interval [CI]: 0.561-3.503; <i>P</i> = .007) shorter admissions with a US$4215 reduction in cost (95% CI: US$314-US$8116; <i>P</i> = .034) compared to patients admitted to the medicine service. In our urban safety net hospital, hip fracture patients admitted to medicine service had longer lengths of stay and higher total hospitalization costs than patients who were admitted to surgery service. This study highlights that the admitting service should be an area of focus for hospitals when developing programs to provide effective and cost-conscious care to hip fracture patients. | admitting service;complications;cost of care;hip fracture;length of stay | pubmed |
Superstorm Sandy's impact on the provision of WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) services in New York State. | Services provided by the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) were interrupted in 2012 when Superstorm Sandy struck New York State (NYS). The present study evaluates the impact on WIC providers. A focus group, telephone interviews and anonymous online survey were conducted. Qualitative data were analysed by coding transcribed text into key words and identifying major and minor themes for strengths, challenges and recommendations using national public health preparedness capabilities. Survey responses were analysed quantitatively; reported challenges were classified by preparedness capability. The focus group was held at a 2014 regional WIC meeting. Interviews and a survey were conducted via telephone in 2014 and online in 2015, respectively. WIC staff representing New York City and three NYS counties. In the focus group (n 12) and interviews (n 6), 'emergency operations coordination' was the most cited capability as a strength, 'environmental health protection' (against environmental hazards) as a challenge and 'flexibility' (on rules and procedures) as a recommendation. In the survey (n 24), the capability 'information sharing' was most often cited as a challenge. Most staff (66·6 %) reported their programmes were at least somewhat prepared for future weather-related disasters. Only 16·7 % indicated having practiced a work-related emergency response plan since Sandy. Staff who practiced an emergency response plan were more likely to indicate they were prepared (P < 0·05). The study identified WIC programme areas requiring preparedness improvements. The research methodology can be utilized to assess the continuity of other public health services during disasters. | Disaster planning;Emergency preparedness;Hurricane;Public health;WIC | pubmed |
Detection of IgM-rheumatoid factor and anti-citrullinated protein antibodies in healthy horses and their comparison. | Rheumatoid factor (RF) is used in human and veterinary medicine in the form of IgM RF traditionally to support the diagnosis of rheumatoid arthritis (RA). In the latest diagnostic criteria, presence of anti - citrullinated protein antibodies (ACPA) was added to the grading system for the diagnosis of RA in humans. A change which is not integrated or routinely used in veterinary medicine. The criteria changed partly because of RF's diagnostic shortcomings, which include its increased titer detection in humans with non-rheumatoid diseases, inability to predict the disease and increased titers over the limit in the older population. Clinical signs similar to human RA were reported in horses in a condition known as idiopathic polysynovitis. Similarities in the clinical presentation to RA raised a question to the usability of RF and ACPA in horses. In our study, sixty clinically healthy horses, ranging from 3 days to 30 years of age, were evaluated for their serum levels of IgM RF. 55 of these horses were tested for ACPA, using methods of ELISA measuring Anti - CFG (Anti citrullinated fibrinogen antibody). The results of the study demonstrated the existence of an age-dependent increase in the level of IgM RF up to the age of about 9 years and ACPA's independence of the horse's age as well as both markers independence of the horse sex. | ACPA;Age-dependency;ELISA;Horse;IgM RF;Polysynovitis | pubmed |
Calcium-dependent protein kinase CPK9 negatively functions in stomatal abscisic acid signaling by regulating ion channel activity in Arabidopsis. | In this manuscript, we demonstrated the negative role of CPK9 in stomatal ABA signaling, and both CPK9 and CPK33 for accurate guard cell function was explored via cpk9/cpk33 double mutants' phenotype. Abscisic acid (ABA) can inhibit stomatal opening and promote stomatal closure by regulating ion channel activity in guard cell membranes. As an important second messenger, calcium (Ca<sup>2+</sup>) is essentially needed in ABA regulation of stomatal movement. Calcium-dependent protein kinases (CDPKs) have been proposed to contribute to central Ca<sup>2+</sup> signal transduction in plants. Here, we report the functional characterization of CPK9 in Arabidopsis stomatal ABA signaling. CPK9 had high expression in guard cells and the protein was subcellularly located in the cell membrane. A loss-of-function mutant cpk9 showed a much more sensitive phenotype to ABA regulation of stomatal movement and ion channel activity, while CPK9 overexpression lines had opposite phonotypes. These findings demonstrated the negative role of CPK9 in stomatal ABA signaling. As the closest homolog of CPK33, we also proved that stomatal movement of the cpk9/cpk33 double mutants was more sensitive to ABA than either single mutants. These results revealed the role of CPK9 in guard cells, and the need of both CPK9 and CPK33 for accurate guard cell function. | Abscisic acid;CPK9;Guard cell;Ion channel;Stomatal movement | pubmed |
Hollow Mesoporous Silica@Metal-Organic Framework and Applications for pH-Responsive Drug Delivery. | Metal--organic frameworks (MOFs), a new type of porous crystalline material, hold great potential in biomedical applications, such as drug delivery. However, the efficacy of drug delivery is limited by low drug loading. In this work, we synthesized hollow mesoporous silica (HMS)@MOF capsules that can be used as a pH-responsive drug delivery system for the anticancer drug doxorubicin (DOX). DOX is loaded into the inner cavity of HMS. Zeolitic imidazolate framework-8 (ZIF-8) nanoparticles are then coated on the outer surface of the DOX-loaded HMS. The obtained material is a capsule (denoted as DOX/HMS@ZIF), in which DOX is encapsulated. The DOX/HMS@ZIF can be used as an efficient pH-responsive drug delivery system. DOX is not released under physiological conditions (pH 7.4), but is released at low pH (4-6) from DOX/HMS@ZIF. The DOX/HMS@ZIF capsule shows much higher cytotoxicity than free DOX and alters the delivery pathway for DOX in cancer cells, while the drug-free HMS@ZIF shows excellent biocompatibility. This opens new opportunities to construct a safe and efficient delivery system for targeted molecules using pH-responsive release for a wide range of applications. | drug delivery;hollow mesoporous silica;metal-organic frameworks;pH-responsive systems | pubmed |
A comparison of methods for estimating substitution rates from ancient DNA sequence data. | Phylogenetic analysis of DNA from modern and ancient samples allows the reconstruction of important demographic and evolutionary processes. A critical component of these analyses is the estimation of evolutionary rates, which can be calibrated using information about the ages of the samples. However, the reliability of these rate estimates can be negatively affected by among-lineage rate variation and non-random sampling. Using a simulation study, we compared the performance of three phylogenetic methods for inferring evolutionary rates from time-structured data sets: regression of root-to-tip distances, least-squares dating, and Bayesian inference. We also applied these three methods to time-structured mitogenomic data sets from six vertebrate species. Our results from 12 simulation scenarios show that the three methods produce reliable estimates when the substitution rate is high, rate variation is low, and samples of similar ages are not all grouped together in the tree (i.e., low phylo-temporal clustering). The interaction of these factors is particularly important for least-squares dating and Bayesian estimation of evolutionary rates. The three estimation methods produced consistent estimates of rates across most of the six mitogenomic data sets, with sequence data from horses being an exception. We recommend that phylogenetic studies of ancient DNA sequences should use multiple methods of inference and test for the presence of temporal signal, among-lineage rate variation, and phylo-temporal clustering in the data. | Ancient DNA;Bayesian phylogenetics;Least-squares dating;Mitogenomes;Substitution rate;Tip dating | pubmed |
New Species of Falcaustra (Nematoda: Kathlaniidae) in Batagur trivittata (Testudines: Geoemydidae) from Myanmar. | Falcaustra tintlwini sp. nov. (Ascaridida, Kathlaniidae) from the large intestine of Batagur trivittata (Testudines, Geoemydidae) is described and illustrated. Falcaustra tintlwini represents the 20th Oriental species assigned to the genus and is distinguished from other Oriental species by the distribution pattern of the caudal papillae (6 precloacal, 12 postcloacal, and 1 median), length of spicules (0.43-0.50 mm) and absence of a pseudosucker. | Batagur trivittata;Falcaustra tintlwini sp;Myanmar;Nematoda;Testudines;nov | pubmed |
Mesophyll conductance does not contribute to greater photosynthetic rate per unit nitrogen in temperate compared with tropical evergreen wet-forest tree leaves. | Globally, trees originating from high-rainfall tropical regions typically exhibit lower rates of light-saturated net CO<sub>2</sub> assimilation (A) compared with those from high-rainfall temperate environments, when measured at a common temperature. One factor that has been suggested to contribute towards lower rates of A is lower mesophyll conductance. Using a combination of leaf gas exchange and carbon isotope discrimination measurements, we estimated mesophyll conductance (g<sub>m</sub> ) of several Australian tropical and temperate wet-forest trees, grown in a common environment. Maximum Rubisco carboxylation capacity, V<sub>cmax</sub> , was obtained from CO<sub>2</sub> response curves. g<sub>m</sub> and the drawdown of CO<sub>2</sub> across the mesophyll were both relatively constant. V<sub>cmax</sub> estimated on the basis of intercellular CO<sub>2</sub> partial pressure, C<sub>i</sub> , was equivalent to that estimated using chloroplastic CO<sub>2</sub> partial pressure, C<sub>c</sub> , using 'apparent' and 'true' Rubisco Michaelis-Menten constants, respectively Having ruled out g<sub>m</sub> as a possible factor in distorting variations in A between these tropical and temperate trees, attention now needs to be focused on obtaining more detailed information about Rubisco in these species. | CO2 drawdown;carboxylation capacity;mesophyll conductance;photosynthetic limitation;temperate;tropical | pubmed |
Stability of barotropic vortex strip on a rotating sphere. | We study the stability of a barotropic vortex strip on a rotating sphere, as a simple model of jet streams. The flow is approximated by a piecewise-continuous vorticity distribution by zonal bands of uniform vorticity. The linear stability analysis shows that the vortex strip becomes stable as the strip widens or the rotation speed increases. When the vorticity constants in the upper and the lower regions of the vortex strip have the same positive value, the inner flow region of the vortex strip becomes the most unstable. However, when the upper and the lower vorticity constants in the polar regions have different signs, a complex pattern of instability is found, depending on the wavenumber of perturbations, and interestingly, a boundary far away from the vortex strip can be unstable. We also compute the nonlinear evolution of the vortex strip on the rotating sphere and compare with the linear stability analysis. When the width of the vortex strip is small, we observe a good agreement in the growth rate of perturbation at an early time, and the eigenvector corresponding to the unstable eigenvalue coincides with the most unstable part of the flow. We demonstrate that a large structure of rolling-up vortex cores appears in the vortex strip after a long-time evolution. Furthermore, the geophysical relevance of the model to jet streams of Jupiter, Saturn and Earth is examined. | barotropic flow;contour dynamics;linear stability;rotating sphere;vortex dynamics | pubmed |
A double-edged sword? Sub-types of psychological flexibility are associated with distinct psychiatric disorders. | Psychological flexibility is associated with both better and worse health outcomes. The objective of this study was to differentiate two types of psychological flexibility - affective instability and interpersonal flexibility - and to estimate associations with psychiatric disorders. Study participants were drawn from a large outpatient psychiatric sample that completed standard assessment batteries at an academic hospital (<i>N</i> = 1,358, 55.5% males, mean age=43.87, <i>SD</i>=16.57). Less interpersonal flexibility was associated with depressive diagnoses. Greater affective instability was associated with bipolar disorder and was negatively associated with psychotic disorders, but showed no association with depressive disorders. Differing degrees of flexibility and instability in emotional and interpersonal domains may be uniquely associated with specific classes of psychological disorders. | affective lability;interpersonal flexibility;psychiatric disorders;psychological flexibility | pubmed |
A Review on Bacteriorhodopsin-Based Bioelectronic Devices. | Bacteriorhodopsin protein extracted from <i>Halobacterium salinarum</i> is widely used in many biohybrid electronic devices and forms a research subject known as bioelectronics, which merges biology with electronic technique. The specific molecule structure and components of bR lead to its unique photocycle characteristic, which consists of several intermediates (bR, K, L, M, N, and O) and results in proton pump function. In this review, working principles and properties of bacteriorhodopsin are briefly introduced, as well as bR layer preparation method. After that, different bR-based devices divided into photochemical and photoelectric applications are shown. Finally, outlook and conclusions are drawn to inspire new design of high-performance bR-based biohybrid electronic devices. | bacteriorhodopsin;biohybrid electronic devices;photochemical;photocycle intermediates;photoelectric;proton pump function | pubmed |
Two macamide extracts relieve physical fatigue by attenuating muscle damage in mice. | Macamides, the main active components contained in maca, have attracted increasing attention due to their various bioactivities. In this study, crude macamide extract (CME) and purified macamide extract (PME) were prepared by enzyme-assisted extraction and macroporous resin separation, and the anti-fatigue effects of CME and PME were evaluated in a forced swimming model. The composition analysis results revealed that both CME and PME mainly contain eight kinds of macamide. Based on the results of a weight-loaded forced swimming test, compared with a control group, CME and and PME groups could prolong exhaustive swimming time, increase levels of liver glycogen (LG) and muscle glycogen (MG), accelerate fatty acid oxidation in serum to provide energy, eliminate the accumulation of blood lactic acid (BLA) and blood urea nitrogen (BUN), and decrease the serum biomarkers for muscle damage, such as lactate dehydrogenase (LDH) and creatine kinase (CK). Histological analysis also indicated that CME and PME attenuated damage to skeletal muscle and the myocardium in mice during exercise. Two macamide extracts have a beneficial effect on relieving physical fatigue by attenuating the damage of skeletal muscle and myocardium during exercise, and a better effect was observed in the PME group. © 2018 Society of Chemical Industry. | anti-fatigue;histological analysis;macamide extract;muscle damage | pubmed |
Respiratory-digestive tract fistula: two-center retrospective observational study. | Background Aerodigestive fistulae can be defined as abnormal communications between the gastrointestinal tract and the respiratory tract. Choking after meals, coughing, feeding difficulties, tachycardia, and persistent pneumonia are the main presentations. The aim of our study was to review our experience in the management of 27 cases of acquired aerodigestive fistulae of different types, levels, and management. Methods We conducted a retrospective observational study on 27 cases of fistulae between the respiratory and digestive tracts, which were managed in 2 hospitals in Saudi Arabia in the last 5 years. The patients comprised 16 females and 11 males, with a mean age of 29 years (range 17-67 years). Results The most common aerodigestive tract fistula was tracheoesophageal in 8 patients, followed by esophagobronchial in 6, and esophagopleural in 5. Four postendoscopic fistulae were included. The least common were gastropleural and esophagopulmonary fistulae. The most common etiologies were iatrogenic and esophageal cancer, and the least common was blunt chest trauma. The main presentations were fever, chocking after or during meals, and tachycardia. We used various modalities of treatment: conservative, cervical repair, thoracoabdominal repair, hybrid insertion of a T-tube, endoscopic esophageal stenting, and endoscopic clipping of the fistulous tract. During follow-up, 6 patients died due to advanced esophageal cancer in 5 and upper airway obstruction after iatrogenic tracheobronchial fistula in one. Conclusion Acquired aerodigestive fistula is a devastating condition that should be managed early and aggressively by a multidisciplinary team. | Bronchial fistula;Esophageal fistula;Intubation;Postoperative complications;Tracheoesophageal fistula;Treatment outcome;intratracheal | pubmed |
CJEM Debate Series: #ChoosingWisely - The Choosing Wisely campaign will not impact physician behaviour and choices. | change management;emergency medicine;quality improvement | pubmed |
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Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to EGFR-TKIs in non-small cell lung cancer. | Compensatory activation of the signal transduction pathways is one of the major obstacles for the targeted therapy of non-small cell lung cancer (NSCLC). Herein, we present the therapeutic strategy of combined targeted therapy against the MEK and phosphoinositide-3 kinase (PI3K) pathways for acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC. We investigated the efficacy of combined trametinib plus taselisib therapy using experimentally established EGFR-TKI-resistant NSCLC cell lines. The results showed that the feedback loop between MEK/ERK and PI3K/AKT pathways had developed in several resistant cell lines, which caused the resistance to single-agent treatment with either inhibitor alone. Meanwhile, the combined therapy successfully regulated the compensatory activation of the key intracellular signals and synergistically inhibited the cell growth of those cells in vitro and in vivo. The resistance mechanisms for which the dual kinase inhibitor therapy proved effective included (MET) mesenchymal-epithelial transition factor amplification, induction of epithelial-to-mesenchymal transition (EMT) and EGFR T790M mutation. In further analysis, the combination therapy induced the phosphorylation of p38 MAPK signaling, leading to the activation of apoptosis cascade. Additionally, long-term treatment with the combination therapy induced the conversion from EMT to mesenchymal-to-epithelial transition in the resistant cell line harboring EMT features, restoring the sensitivity to EGFR-TKI. In conclusion, our results indicate that the combined therapy using MEK and PI3K inhibitors is a potent therapeutic strategy for NSCLC with the acquired resistance to EGFR-TKIs. | MEK inhibitor;PI3K inhibitor;acquired resistance;compensatory activation;non-small cell lung cancer | pubmed |
Oral administration of l-carnitine improves the clinical outcome of fertility in patients with IVF treatment. | Age-dependent decline of mitochondrial function has been proposed to be a main cause of decline of embryo quality. Then, l-carnitine plays important roles in reducing the membranous toxicity of free-fatty acids by forming acyl-carnitine and promoting β-oxidation, preventing cell damage. Recent research revealed that l-carnitine played important roles in vitro in oocyte growth, oocyte maturation and embryo development. However, such beneficial effects of l-carnitine in vivo have yet to be verified. The effect of oral l-carnitine supplementation on embryo quality and implantation potential was examined. A total of 214 patients were included in this study. They all previously received in vitro fertilization-embryo transfer (IVF-ET) and failed to conceive. Then they were administered l-carnitine for 82 days on average and underwent IVF-ET again. There were no significant differences in the total number of retrieved oocytes, and their maturation and fertilization rates between before and after l-carnitine administration. The quality of embryos on Days 3 and 5 after insemination was improved following l-carnitine administration (p < .05) in cycles after l-carnitine administration compared with previous cycles. Healthy neonates were born after IVF-ET following l-carnitine administration. Our data suggested that oral administration of l-carnitine to fertility patients improved the developmental competence of their oocytes after insemination. | Fertility treatment;free-fatty acids;mitochondria | pubmed |
GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial: rationale and study protocol for a randomised controlled trial. | Optimising the use of antibiotic agents is a pressing challenge to overcoming the rapid emergence and spread of multidrug-resistant pathogens in intensive care units (ICUs). Although Gram staining may possibly provide immediate information for predicting pathogenic bacteria, Gram stain-guided initial antibiotic treatment is not well established in the ICU setting. We planned the GRam stain-guided Antibiotics ChoicE for Ventilator-Associated Pneumonia (GRACE-VAP) trial to investigate whether Gram staining can safely restrict the use of broad-spectrum antibiotics in patients with ventilator-associated pneumonia (VAP), which is one of the most common hospital-acquired infections in ICUs. The GRACE-VAP trial is a multicentre, randomised, open-label parallel-group trial to assess the non-inferiority of Gram stain-guided initial antibiotic treatment to guidelines-based initial antibiotic treatment for the primary endpoint of clinical response rate in patients with VAP. Secondary endpoints include the coverage rates of initial antibiotic therapies, the selected rates of anti-pseudomonal agents and anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) agents as initial antibiotic therapies, 28-day all-cause mortality, ICU-free days, ventilator-free days and adverse events. Patients are randomly assigned to receive Gram stain-guided treatment or guidelines-based treatment at a ratio of 1:1. In the Gram stain group, results of Gram staining of endotracheal aspirate are used to guide the selection of antibiotics. In the guidelines group, the combination of an anti-pseudomonal agent and an anti-MRSA agent is administered. A total sample size of 200 was estimated to provide a power of 80% with a one-sided alpha level of 2.5% and a non-inferiority margin of 20%, considering 10% non-evaluable patients. The GRACE-VAP trial is expected to reveal whether Gram staining can reduce the use of broad-spectrum antibiotics without impairing patient outcomes and thereby provide evidence for an antibiotic selection strategy in patients with VAP. Clinicaltrials.gov, NCT03506113 . Registered on 29 March 2018. University Hospital Medical Information Network, UMIN000031933. Registered on 26 March 2018. | Antimicrobial therapy;Empirical therapy;Gram staining;ICU;MDR;Mechanical ventilation;Nosocomial infection;RCT;VAP | pubmed |
Health insurance status and risk factors of mortality in patients with septic acute kidney injury in Ningbo, China. | To investigate the relationship between health insurance status and outcomes of septic acute kidney injury (AKI) related hospitalizations in an intensive care unit (ICU) in Ningbo, China. For this retrospective study, information was extracted from patients notes and billing records for patients >18 years of age with a diagnosis of AKI admitted to the ICU department, Ningbo First Hospital from April 2013 to March 2018. Of the 368 patients with sepsis admitted to ICU, 167 (45%) developed AKI; 95 patients were insured and 72 were uninsured. Compared with insured patients, uninsured patients were younger, had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, but had less catheter interventions and received less renal replacement therapy (RRT). Results from a multivariate analysis showed that independent predictors of ICU mortality were age, APACHE II scores, MODS scores, use of RRT and lack of insurance. Uninsured patients with septic AKI were younger, stayed a shorter time in ICU, had higher illness severity scores and a higher ICU mortality than insured patients. Importantly a major risk factor for ICU mortality in this group was lack of insurance. | Health insurance;acute kidney injury;renal replacement therapy;sepsis | pubmed |
Protective Effects of Ginsenoside Rb1 against Blood-Brain Barrier Damage Induced by Human Immunodeficiency Virus-1 Tat Protein and Methamphetamine in Sprague-Dawley Rats. | Although antiretroviral therapy has helped to improve the lives of individuals infected with human immunodeficiency virus 1 (HIV-1), these patients are often still afflicted with HIV-1-associated neurocognitive disorders, which can lead to neurocognitive impairment and even dementia, and continue to hamper their quality of life. Methamphetamine abuse in HIV-1 patients poses a potential risk for HIV-associated neurocognitive disorders, because methamphetamine and HIV-1 proteins such as transactivator of transcription can synergistically damage the blood-brain barrier (BBB). In this study, we aimed to examine the effects of methamphetamine and HIV-1 Tat protein on the blood-brain barrier function and to determine whether ginsenoside Rb1 (GsRb1) plays a role in protecting the BBB. Sprague-Dawley rats were divided into four groups. The experimental groups received methamphetamine and HIV-1 Tat protein or both and the control group received saline or GsRb1 pretreatment. Oxidative stress-related factors, tight junction (TJ) proteins, blood-brain barrier permeability, and morphological changes were recorded in each group. The results showed that the group treated with Methamphetamine[Formula: see text]Tat showed a significant change at the ultrastructural level and in the levels of oxidative stress-related factors, TJ proteins, and BBB permeability, suggesting that the BBB function was severely damaged by HIV-1 Tat and methamphetamine synergistically. However, malondialdehyde levels and BBB permeability were lower and the oxidative stress-related factors superoxide dismutase and glutathione were higher in the GsRb1-treated group than in the Methamphetamine[Formula: see text]Tat-treated group, indicating that GsRb1 can protect the BBB against the toxic effects of HIV-1 Tat and methamphetamine. These results show that GsRb1 may offer a potential therapeutic option for patients with HIV-associated neurocognitive disorders or other neurodegenerative diseases. | Blood–Brain Barrier;Ginsenoside Rb1;HIV-Tat Protein;Methamphetamine;Tight Junction Proteins | pubmed |
Pseudohypoparathyroidism. | Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of uncommon, yet related metabolic disorders that are characterized by impaired activation of the Gsα/cAMP/PKA signaling pathway by parathyroid hormone (PTH) and other hormones that interact with Gsa-coupled receptors. Proximal renal tubular resistance to PTH and thus hypocalcemia and hyperphosphatemia, frequently in presence of brachydactyly, ectopic ossification, early-onset obesity, or short stature are common features of PHP. Registries and large cohorts of patients are needed to conduct clinical and genetic research, to improve the still limited knowledge regarding the underlying disease mechanisms, and allow the development of novel therapies. | Acrodysostosis;Brachydactyly;Early-onset obesity;GNAS;PTH resistance;Pseudohypoparathyroidism;Subcutaneous ossifications | pubmed |
The Svedberg Lecture 2017. From nano to micro: the huge dynamic range of the analytical ultracentrifuge for characterising the sizes, shapes and interactions of molecules and assemblies in Biochemistry and Polymer Science. | The analytical ultracentrifuge (AUC) invented by T. Svedberg has now become an extremely versatile and diverse tool in Biochemistry and Polymer Science for the characterisation of the sizes, shapes and interactions of particles ranging in size from a few nanometres to tens of microns, or in molecular weight, M (molar mass) terms from a few hundred daltons to hundreds of megadaltons. We illustrate this diversity by reviewing recent work on (1) small lignin-like isoeugenols of M ~ 0.4-0.9 kDa for archaeological wood conservation, (2) protein-like association of a functional amino-cellulose M = 3.25 kDa, (3) a small glycopeptide antibiotic (M ~ 1.5 kDa) and its association with a protein involved in antibiotic resistance (M ~ 47 kDa), (4) tetanus toxoid protein TTP (M ~ 150 kDa) and (5) the incorporation of TTP into two huge glycoconjugates considered in glycovaccine development with molecular weight species in a broad distribution appearing to reach 100 MDa. In illustrating the diversity, we will highlight developments in hydrodynamic analysis which have made the AUC such an exciting and important instrument, and point to a potential future development for extending its capability to highly concentrated systems. | Amino-cellulose;Glycovaccines;Lignin;Tetanus toxoid;Vancomycin | pubmed |
A Novel Risk prediction Model for Patients with Combined Hepatocellular-Cholangiocarcinoma. | <b>Backgrounds:</b> Regarding the difficulty of CHC diagnosis and potential adverse outcomes or misuse of clinical therapies, an increasing number of patients have undergone liver transplantation, transcatheter arterial chemoembolization (TACE) or other treatments. <b>Objective:</b> To construct a convenient and reliable risk prediction model for identifying high-risk individuals with combined hepatocellular-cholangiocarcinoma (CHC). <b>Methods:</b> 3369 patients who underwent surgical resection for liver cancer at Zhongshan Hospital were enrolled in this study. The epidemiological and clinical characteristics of the patients were collected at the time of tumor diagnosis. Variables (<i>P</i> <0.25 in the univariate analyses) were evaluated using backward stepwise method. A receiver operating characteristic (ROC) curve was used to assess model discrimination. Calibration was performed using the Hosmer-Lemeshow test and a calibration curve. Internal validation was performed using a bootstrapping approach. <b>Results:</b> Among the entire study population, 250 patients (7.42%) were pathologically defined with CHC. Age, HBcAb, red blood cells (RBC), blood urea nitrogen (BUN), AFP, CEA and portal vein tumor thrombus (PVTT) were included in the final risk prediction model (area under the curve, 0.69; 95% confidence interval, 0.51-0.77). Bootstrapping validation presented negligible optimism. When the risk threshold of the prediction model was set at 20%, 2.73% of the patients diagnosed with liver cancer would be diagnosed definitely, which could identify CHC patients with 12.40% sensitivity, 98.04% specificity, and a positive predictive value of 33.70%. <b>Conclusions:</b> Herein, the study established a risk prediction model which incorporates the clinical risk predictors and CT/MRI-presented PVTT status that could be adopted to facilitate the diagnosis of CHC patients preoperatively. | combined hepatocellular-cholangiocarcinoma;liver cancer;preoperation.;risk prediction model | pubmed |
Synovial Fluid Alpha-Defensin Is an Adjunctive Tool in the Equivocal Diagnosis of Periprosthetic Joint Infection. | Synovial fluid alpha-defensin has shown to be a reliable diagnostic test for the diagnosis of periprosthetic joint infection (PJI), but its use in equivocal cases has yet to be established. The purpose of this study was to determine the reliability of alpha-defensin testing in patients, where the diagnosis of PJI was unclear. A consecutive series of 41 synovial aspirations by a single surgeon that were sent for alpha-defensin testing in equivocal cases of PJI were retrospectively reviewed. Indications for alpha-defensin testing included recent antibiotic use, borderline synovial fluid cell count, and differential, suspected culture-negative infection, and suspected false-positive culture. PJI was diagnosed using the Musculoskeletal Infection Society (MSIS) criteria. Of the 39 aspirations in 32 patients included in the study, there were 33 (85%) knee and 6 (15%) hip samples. Eleven (28%) samples met MSIS criteria for PJI. Of the 23 samples that had recent antibiotic use (6 MSIS positive, 17 negative), alpha-defensin results confirmed the correct MSIS diagnosis in 19 (83%) samples. Of the 11 samples in which alpha-defensin testing was performed for a borderline cell count (3 MSIS positive, 8 negative), alpha-defensin confirmed the MSIS diagnosis in 10 of 11 (91%) samples. Finally, among the 5 samples with suspected false-positive or false-negative cultures (2 MSIS positive, 3 negative), alpha-defensin confirmed the correct diagnosis in 3 (60%) samples. The overall sensitivity, specificity, negative predictive value, and positive predictive value of synovial alpha-defensin were 82%, 82%, 92%, and 64%, respectively. In patients for whom the diagnosis of PJI is unclear because of recent antibiotic use, equivocal laboratory findings, or suspected false-negative or false-positive cultures, synovial fluid alpha-defensin can provide an additional data point to assist the clinician in determining whether PJI is present but is prone to false-positive results in this challenging population. | biomarkers;complications;periprosthetic joint infection;total hip arthroplasty;total knee arthroplasty | pubmed |
Topically applied hypericin exhibits skin penetrability on nude mice. | Hypericin, a powerful natural photosensitizer in photodynamic therapy (PDT), is suitable for treating skin diseases involving excess capillary proliferation. In the present study, we aimed to evaluate the skin penetrability of topically applied hypericin, expecting a reduced risk of prolonged skin photosensitivity, which often occurs after systemic administration. Firstly, the Franz diffusion cell assays were performed to evaluate the penetration effects of different enhancers, including menthol, propylene glycol, camphanone, azone, and carbamide. In view of above evaluation results, we selected menthol as the enhancer in the subsequent in vivo studies. The setting groups were as follows: the blank control group, the light-exposure control group, the gel-base control group, the hypericin gel group, and a hypericin gel-containing menthol group. Except for the blank control, all other animals were irradiated by a LED light. Then, fluorescence microscopy was performed to examine the distribution of hypericin in the skin of nude mouse. Macroscopic and microscopic analyses were also carried out to detect pathological changes in the skin after topical hypericin-PDT treatment. Immunohistochemistry was used to determine the expression change of PECAM-1. As shown in the results, menthol facilitated hypericin penetrate the skin of nude mice most. The results of in vivo assays revealed that hypericin penetrated nude mouse skin, spread to the dermis, and resulted in obvious photosensitivity reaction on the dermal capillaries. Moreover, skin injured by the photosensitive reaction induced by hypericin-PDT treatment was replaced by normal skin within 7 days. We concluded that topical applied hypericin could penetrate nude mouse skin well and has a great potential in PDT treatment of skin diseases. | Hypericin;Photodynamic therapy;Photosensitizer;Skin penetrability | pubmed |
Iron overload impact on P-ATPases. | Iron is a chemical element that is active in the fundamental physiological processes for human life, but its burden can be toxic to the body, mainly because of the stimulation of membrane lipid peroxidation. For this reason, the action of iron on many ATPases has been studied, especially on P-ATPases, such as the Na<sup>+</sup>,K<sup>+</sup>-ATPase and the Ca<sup>2+</sup>-ATPase. On the Fe<sup>2+</sup>-ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe<sup>2+</sup> and playing a protection role for the cell. On the Ca<sup>2+</sup>-ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca<sup>2+</sup> and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca<sup>2+</sup> concentrations, which could promote an enzyme oxidation, nitration, and fragmentation. However, the iron overload effect on the Na<sup>+</sup>,K<sup>+</sup>-ATPase may change according to the tissue expressions. On the renal cells, as well as on the brain and the heart, iron promotes an enzyme inactivation, whereas its effect on the erythrocytes seems to be the opposite, directly stimulating the ATPase activity, or stimulating it by signaling pathways involving ROS and PKC. Modulations in the ATPase activity may impair the ionic transportation, which is essential for cell viability maintenance, inducing irreversible damage to the cell homeostasis. Here, we will discuss about the iron overload effect on the P-ATPases, such as the Na<sup>+</sup>,K<sup>+</sup>-ATPase, the Ca<sup>2+</sup>-ATPase, and the Fe<sup>2+</sup>-ATPase. | Ca2+-ATPase;Fe2+-ATPase;Iron overload;Na+,K+-ATPase;Oxidative stress;P-type ATPase | pubmed |
Nocturnal Aphanistes (Hymenoptera: Ichneumonidae: Anomaloninae) in the Neotropical region, with the description of five new species. | The crepuscularis species group of the ichneumonid genus Aphanistes Förster currently comprises three species-Aphanistes crepuscularis Dasch, A. guatemalenus (Cameron), and A. arcei Gauld Bradshaw. Five new species are described: A. augustoi sp. n., A. cachil sp. n., A. paolae sp. n., A. ruthae sp. n., and A. silviae sp. n. A key for the species group is also presented. | Hymenoptera, Ichneumonoidea, taxonomy, wasps, parasitoids | pubmed |
Perspectives on Factors Related to HIV Risk and Preventative Interventions at Multiple Levels: A Study of African Immigrant Women Survivors of Cumulative Trauma. | African immigrant women survivors of cumulative trauma are at high risk for HIV infection. This study aims to identify survivors' perceptions of (a) contextual (i.e., community, and relationship) and individual-level risk and protective factors for HIV among African immigrant women in the United States and (b) areas and strategies of HIV prevention intervention at contextual and individual levels. Qualitative data for this study were collected from African-born women (n = 39) in Maryland, Virginia, and Washington, DC, from February 2017 to March 2018. Seventeen in-depth interviews and five focus groups were conducted with African immigrant survivors of cumulative trauma. Results revealed HIV prevention intervention needs and risk and protective factors for HIV at the community (e.g., community education), relationship (e.g., intimate partner violence, family), and individual (e.g., women's empowerment) levels. These findings can inform the development of culturally tailored multilevel HIV prevention interventions for African immigrant women. | African immigrant;HIV;cumulative trauma;women | pubmed |
Effect of microwave treatment on structure of binders based on sodium carboxymethyl starch: FT-IR, FT-Raman and XRD investigations. | The paper deals with the influence of the microwave treatment on sodium carboxymethyl starch (CMS-Na) applied as a binder for moulding sands. The Fourier transformation infrared spectrometry (FT-IR), Raman spectroscopy (FT-Raman) and XRD analysis data of native potato starch and three different carboxymethyl starches (CMS-Na) with various degree of substitution (DS) before and after exposition to microwave radiation have been compared. FT-IR studies showed that polar groups present in CMS-Na structure take part in the formation of new hydrogen bonds network after water evaporation. However, these changes depend on DS value of the modified starch. The FT-Raman study confirmed that due to the impact on the samples by microwave, the changes of intensity in the characteristic bands associated with the crystalline regions in the sample were noticed. The X-ray diffraction data for microwave treated CMS-Na samples have been compared with the diffractograms of initial materials and analysis of XRD patterns confirmed that microwave-treated samples exhibit completely amorphous structure. Analysis of structural changes allows to state that the binding of sand grains in moulding sand with CMS-Na polymeric binder consists in the formation of hydrogen bonds networks (physical cross-linking). | Amorphization;FT-IR;Hydrogen bonds;Microwave radiation;Polymer binders;Sodium carboxymethyl starch;XRD | pubmed |
A new Miocene skate from the Central Paratethys (Upper Austria): the first unambiguous skeletal record for the Rajiformes (Chondrichthyes: Batomorphii). | A new fossil skate, <i>Ostarriraja parva</i> gen. et sp. nov., represented by a single partial articulated skeleton collected from the early Miocene fish-bearing strata of Upper Austria, is described here in detail. This taxon exhibits a unique combination of skeletal and dental features (e.g. nasal capsules broad and oval; presence of pectoral arch; compound radial articulated with single radial segments in serial fashion; separated pelvic girdle condyles; reduced catenated calcification of radials; about 86 pectoral radials; 20-21 pelvic-fin radials; 65-70 predorsal vertebrae) that clearly support its assignment to a new genus of the order Rajiformes, and the phylogenetic analyses reveal its basal position within the group. The comparison between <i>Ostarriraja</i> and the holomorphic batoids from Late Cretaceous of Lebanon traditionally aligned with skates concurs to suggest that this Neogene occurrence represents unquestionably the first known skeletal record for the group. The morphological and phylogenetic affinities of <i>Ostarriraja</i> with the living skates suggest a close association of this taxon with the temperate-cold water environments hypothesized for the Central Paratethys during the early Miocene. http://zoobank.org/urn:lsid:zoobank.org:pub:8BB8F0F3-35C5-47FA-AE3C-2CBF445C4BCA. | Austria;Burdigalian;Central Paratethys;Ostarriraja parva gen. et sp. nov.;Rajiformes;phylogeny | pubmed |
Perioperative chemotherapy for urothelial carcinoma of the upper urinary tract: A systematic review and meta-analysis. | Upper tract urothelial carcinomas are rare malignancies with differences in anatomy and biology requiring therapeutic strategies that differ from bladder cancer. The role of perioperative systemic therapy in this disease remains uncertain with limited data to support its use. A systematic review of the literature and meta-analysis was therefore undertaken to provide more information and guide clinical practice. A literature search was performed using Embase and Medline databases with additional searches performed manually using terms associated with upper tract urothelial malignancies. Data was extracted from studies of patients that underwent nephrouretectomy for the management of upper tract urothelial carcinoma and received either neoadjuvant or adjuvant systemic therapy. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were summated and analyzed using Cochrane Revman software Version 5.3. There were 13 comparative studies and no randomized studies identified for data extraction; 11 adjuvant and 2 neoadjuvant with 1170 patients receiving perioperative systemic therapy and 3472 controls that did not. Perioperative chemotherapy was associated with improved OS (HR 0.75, 95%CI 0.57-0.99), DFS (HR 0.54, 95%CI 0.32-0.92), and CSS (HR 0.69, 95%CI 0.42-1.15). The available data suggests that perioperative systemic therapy is associated with improved survival in patients with upper tract urothelial cancer. | Adjuvant;Chemotherapy;Upper tract;Urothelial | pubmed |
N<sub>2</sub>-fixation and N contribution by grain legumes under different soil fertility status and cropping systems in the Guinea savanna of northern Ghana. | Continuous cereal-based cropping has led to a rapid decline in soil fertility in the Guinea savanna agro-ecological zone of northern Ghana with corresponding low crop yields. We evaluated the effects of cropping system and soil fertility status on grain yields and N<sub>2</sub>-fixation by grain legumes and net N contribution to soil fertility improvement in contrasting sites in this agro-ecological zone. Maize was intercropped with cowpea, soybean and groundnut within a row, with a maize stand alternated with two equally spaced cowpea or groundnut stands and in the maize-soybean system, four equally spaced soybean stands. These intercrops were compared with sole crops of maize, cowpea, soybean and groundnut in fertile and poorly fertile fields at sites in the southern (SGS) and the northern (NGS) Guinea savanna. The proportion of N derived from N<sub>2</sub>-fixation (%Ndfa) was comparable between intercrops and sole crops. However, the amount of N<sub>2</sub>-fixed was significantly larger in sole crops due to a greater biomass accumulation. Legumes in poorly fertile fields had significantly smaller shoot <i>δ</i><sup>15</sup>N enrichment (-2.8 to +0.7‰) and a larger %Ndfa (55-94%) than those in fertile fields (-0.8 to +2.2‰; 23-85%). The N<sub>2</sub>-fixed however was larger in fertile fields (16-145 kg N ha<sup>-1</sup>) than in poorly fertile fields (15-123 kg N ha<sup>-1</sup>) due to greater shoot dry matter and N yields. The legumes grown in the NGS obtained more of their N requirements from atmospheric N<sub>2</sub>-fixation (73-88%) than legumes grown in the SGS (41-69%). The partial soil N balance (in kg ha<sup>-1</sup>) was comparable between intercrops (-14 to 21) and sole legumes (-8 to 23) but smaller than that of sole maize receiving N fertiliser (+7 to +34). With other N inputs (aerial deposition) and outputs (leaching and gaseous losses) unaccounted for, there is uncertainty surrounding the actual amount of soil N balances of the cropping systems, indicating that partial N balances are not reliable indicators of the sustainability of cropping systems. Nevertheless, the systems with legumes seem more attractive due to several non-N benefits. Our results suggest that soybean could be targeted in the SGS and cowpea in the NGS for greater productivity while groundnut is suited to both environments. Grain legumes grown in poorly fertile fields contributed more net N to the soil but growing legumes in fertile fields seems more lucrative due to greater grain and stover yields and non-N benefits. | Cowpea;Groundnut;Maize;Partial N balance;Soybean | pubmed |
Would the control of invasive alien plants reduce malaria transmission? A review. | Vector control has been the most effective preventive measure against malaria and other vector-borne diseases. However, due to concerns such as insecticide resistance and budget shortfalls, an integrated control approach will be required to ensure sustainable, long-term effectiveness. An integrated management strategy should entail some aspects of environmental management, relying on coordination between various scientific disciplines. Here, we review one such environmental control tactic: invasive alien plant management. This covers salient plant-mosquito interactions for both terrestrial and aquatic invasive plants and how these affect a vector's ability to transmit malaria. Invasive plants tend to have longer flowering durations, more vigorous growth, and their spread can result in an increase in biomass, particularly in areas where previously little vegetation existed. Some invasive alien plants provide shelter or resting sites for adult mosquitoes and are also attractive nectar-producing hosts, enhancing their vectorial capacity. We conclude that these plants may increase malaria transmission rates in certain environments, though many questions still need to be answered, to determine how often this conclusion holds. However, in the case of aquatic invasive plants, available evidence suggests that the management of these plants would contribute to malaria control. We also examine and review the opportunities for large-scale invasive alien plant management, including options for biological control. Finally, we highlight the research priorities that must be addressed in order to ensure that integrated vector and invasive alien plant management operate in a synergistic fashion. | Biological control;Environmental management;Invasive alien plants;Larval habitat;Nectar feeding;Plant-vector interactions;Resting;Vector-borne disease | pubmed |
Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization. | Ameloblasts are sensitive cells whose metabolism and function may be affected by inflammatory stimuli. The aim of this study was to evaluate the possible association between polymorphisms in immune response-related genes and molar-incisor hypomineralization (MIH), and their interaction with polymorphisms in amelogenesis-related genes. DNA samples were obtained from 101 nuclear families that had at least 1 MIH-affected child. Eleven single-nucleotide polymorphisms (SNPs) were investigated in immune response genes using TaqMan® technology allele-specific probes. A transmission disequilibrium test was performed to verify overtransmission of alleles in all MIH families, as well as in families only with mild or severe MIH-affected children. Gene-gene interactions between the immune-related and amelogenesis-related polymorphisms were analyzed by determining whether alleles of those genes were transmitted from heterozygous parents more often in association than individually with MIH-affected children. In severe cases of MIH, significant results were observed for rs10733708 (TGFBR1, OR = 3.5, 95% CI = 1.1-10.6). Statistical evidence for gene-gene interactions between rs6654939 (AMELX) and the SNPs rs2070874 (IL4), rs2275913 (IL17A), rs1800872 (IL10), rs1800587 (IL1A), and rs3771300 (STAT1) was observed. The rs2070874 SNP (IL4) was also significantly overtransmitted from heterozygous parents with the rs7526319 (TUFT1) and the rs2355767 (BMP2) SNPs, suggesting a synergistic effect of the transmission of these alleles with susceptibility to MIH. This family-based study demonstrated an association between variation in TGFBR1 and MIH. Moreover, the polymorphisms in immune response and amelogenesis genes may have an additive effect on the risk of developing MIH. | Amelogenesis;Dental enamel;Dental enamel hypoplasia;Genetic association study;Genetic polymorphisms;Pediatric dentistry | pubmed |
Variation of polypharmacy in older primary care attenders occurs at prescriber level. | Polypharmacy is particularly important in older persons as they are more likely to experience adverse events compared to the rest of the population. Despite the relevance, there is a lack of studies on the possible association of patient, prescriber and practice characteristics with polypharmacy. Thus, the aim of this study was to determine the rate of polypharmacy among older persons attending public and private primary care clinics, and its association with patient, prescriber and practice characteristics. We used data from The National Medical Care Survey (NMCS), a national cross-sectional survey of patients' visits to primary care clinics in Malaysia. A weighted total of 22,832 encounters of patients aged ≥65 years were analysed. Polypharmacy was defined as concomitant use of five medications and above. Multilevel logistic regression was performed to examine the association of polypharmacy with patient, prescriber and practice characteristics. A total of 20.3% of the older primary care attenders experienced polypharmacy (26.7%% in public and 11.0% in private practice). The adjusted odds ratio (OR) of polypharmacy were 6.37 times greater in public practices. Polypharmacy was associated with patients of female gender (OR 1.49), primary education level (OR 1.61) and multimorbidity (OR 14.21). The variation in rate of polypharmacy was mainly found at prescriber level. Polypharmacy is common among older persons visiting primary care practices. Given the possible adverse outcomes, interventions to reduce the burden of polypharmacy are best to be directed at individual prescribers. | Epidemiology;Medication;Multilevel modelling;Multimorbidity | pubmed |
A direct demonstration of functional TRPV1 in Cajal-Retzius cells. | Cajal Retzius cell;TRPV1;hippocampus | pubmed |
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Poisson Model To Generate Isotope Distribution for Biomolecules. | We introduce a simplified computational algorithm for computing isotope distributions (relative abundances and masses) of biomolecules. The algorithm is based on Poisson approximation to binomial and multinomial distributions. It leads to a small number of arithmetic operations to compute isotope distributions of molecules. The approach uses three embedded loops to compute the isotope distributions, as compared with the eight embedded loops in exact calculations. The speed improvement is about 3-fold compared to the fast Fourier transformation-based isotope calculations, often termed as ultrafast isotope calculation. The approach naturally incorporates the determination of the masses of each molecular isotopomer. It is applicable to high mass accuracy and resolution mass spectrometry data. The application to tryptic peptides in a UniProt protein database revealed that the mass accuracy of the computed isotopomers is better than 1 ppm. Even better mass accuracy (below 1 ppm) is achievable when the method is paired with the exact calculations, which we term a hybrid approach. The algorithms have been implemented in a freely available C/C++ code. | Poisson distribution;isotope envelope;mass spectrometry;stable isotope labeling | pubmed |
A Case of Anaphylaxis to Intramuscular but Not to Oral Application of Thiamine (Vitamin B1). | We report a 78 year-old non-atopic female with polyneuropathy who started to receive monthly intramuscular injections of thiamine hydrochloride. She had an anaphylaxis after the fourth injection. Skin prick test (SPT) with pure commercially available aqueous preparations was positive for thiamine hydrochloride. A titrated, single blinded, placebo-controlled oral provocation test with thiamine hydrochloride was well tolerated. The patient was then diagnosed as compartment allergy with hypersensitivity to parenteral but not to oral thiamine. Because in our patient, oral intake of thiamine has never been reported to lead to any adverse reaction. Oral tolerability might be due to the uptake mechanism of thiamine in the gastrointestinal system. | Anaphylaxis;Hypersensitivity;Thiamine;Thiamine deficiency;Vitamin B1 | pubmed |
Oxidative pathways in the sickle cell and beyond. | Polymerization of deoxy sickle cell hemoglobin (HbS) is well recognized as the primary event that triggers the classic cycles of sickling/unsickling of patients red blood cells (RBCs). RBCs are also subjected to continuous endogenous and exogenous oxidative onslaughts resulting in hemolytic rate increases which contribute to the evolution of vasculopathies associated with this disease. Compared to steady-state conditions, the occurrences of vaso-occlusive crises increase the levels of both RBC-derived microparticles as well as extracellular Hb in circulation. Common byproduct resulting from free Hb oxidation and from Hb-laden microparticles is heme (now recognized as damage associated molecular pattern (DAMP) molecule) which has been shown to initiate inflammatory responses. This review provides new insights into the interplay between microparticles, free Hb and heme focusing on Hb's pseudoperoxidative activity that drives RBC's cytosolic, membrane changes as well as oxidative toxicity towards the vascular system. Emerging antioxidative strategies that include the use of protein and heme scavengers in controlling Hb oxidative pathways are discussed. | Ferryl hemoglobin;Heme oxidation;Microparticles;Pseudoperoxidase;Sickle cell hemoglobin | pubmed |
Surprising Conformers of the Biologically Important A·T DNA Base Pairs: QM/QTAIM Proofs. | For the first time novel high-energy conformers-A·T(w<sub>WC</sub>) (5.36), A·T(w<sub>rWC</sub>) (5.97), A·T(w<sub>H</sub>) (5.78), and A·T(w<sub>rH</sub>) (ΔG = 5.82 kcal·mol<sup>-1</sup>) (See <b>Graphical Abstract</b>) were revealed for each of the four biologically important A·T DNA base pairs - Watson-Crick A·T(WC), reverse Watson-Crick A·T(rWC), Hoogsteen A·T(H) and reverse Hoogsteen A·T(rH) at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of quantum-mechanical theory in the continuum with ε = 4 under normal conditions. Each of these conformers possesses substantially non-planar wobble (w) structure and is stabilized by the participation of the two anti-parallel N6H/N6H'…O4/O2 and N3H…N6 H-bonds, involving the pyramidalized amino group of the A DNA base as an acceptor and a donor of the H-bonding. The transition states - TS<sub>A·T(WC)↔A·T(wWC)</sub>, TS<sub>A·T(rWC)↔A·T(wrWC)</sub>, TS<sub>A·T(H)↔A·T(wH)</sub>, and TS<sub>A·T(rH)↔A·T(wrH)</sub>, controlling the dipole-active transformations of the conformers from the main plane-symmetric state into the high-energy, significantly non-planar state and <i>vice versa</i>, were localized. They also possess wobble structures similarly to the high-energy conformers and are stabilized by the participation of the N6H/N6H'…O4/O2 and N3H…N6 H-bonds. Discovered conformers of the A·T DNA base pairs are dynamically stable short-lived structures [lifetime τ = (1.4-3.9) ps]. Their possible biological significance and future perspectives have been briefly discussed. | A·T DNA base pairs;DNA breathing;DNA pre-melting;Hoogsteen;Watson-Crick;reverse Hoogsteen;reverse Watson-Crick;wobble structure | pubmed |
Metformin inhibits the migration and invasion of esophageal squamous cell carcinoma cells by downregulating the protein kinase B signaling pathway. | Previous studies have suggested that metformin, a biguanide family member widely used as an oral antidiabetic drug, may inhibit proliferation and induce apoptosis in certain types of cancer cell. However, the molecular mechanisms underlying metformin-associated anticancer effects, and in particular antimetastatic effects, remain to be fully understood. The present study assessed the efficacy of metformin in inhibiting the migration and invasion of the esophageal carcinoma cell line EC109, and evaluated the effect of metformin on the protein kinase B (AKT) signaling pathway. EC109 cells were treated with 0, 5, 10 or 20 mM metformin during the logarithmic growth phase. A Transwell assay and western blot analysis revealed that metformin inhibited the migration and invasion of EC109 cells, nuclear factor-κB activation, matrix metallopeptidase 9 and N-cadherin expression in a phosphorylated-AKT dependent manner. These results suggested that metformin inhibits the migration and invasion of human esophageal carcinoma cells by suppressing AKT phosphorylation and regulating the expression of migration- and invasion-associated genes. | esophageal carcinoma;invasion;metformin;migration;protein kinase B | pubmed |
Clinical and Environmental Predictors of Health-Related Quality of Life in Lithuanian Children and Adolescents with Spina Bifida: A Cross-Sectional Analysis of a Nationally Represented Sample. | <i>Background and objectives</i>: In pediatric chronic health conditions, health-related quality of life (HRQOL) is a useful indicator of health, development, and well-being. The purpose of the study was to assess the effect of clinical and environmental factors on the HRQOL of children and adolescents with spina bifida (SB). <i>Materials and methods</i>: A cross-sectional study of the sample of 99 children and adolescents with SB aged 5 to 17 years. The questionnaires used in the study were the Spina Bifida Health-Related Quality of Life instrument (HRQOL-SB), and the Participation and Environment Measure for Children and Youth. Medical data were obtained from the medical records and the clinical examination. <i>Results</i>: A multivariate linear regression revealed that the most potent predictors of the HRQOL in children with SB were the community overall environmental supports (β = 0.504; <i>p</i> = 0.0001), a number of health conditions (β = -0.395; <i>p</i> = 0.0001), access to personal transportation (β = 0.236; <i>p</i> = 0.023), and supplies (β = 0.181; <i>p</i> = 0.031), explaining 80.3% of the variance in the SB-HRQOL scores. The most significant predictors of the HRQOL in adolescents were a number of health conditions (β = -0.387; <i>p</i> = 0.0001), cognitive demands of activities at home (β = 0.345; <i>p</i> = 0.0001), supplies (β = 0.267; <i>p</i> = 0.0001), money (β = 0.303; <i>p</i> = 0.0001), physical layout at school (β = 0.188; <i>p</i> = 0.008), and access to public transportation (β = 0.206; <i>p</i> = 0.019), explaining 89.5% of the variance in the SB-HRQOL scores. <i>Conclusions</i>: Both clinical and environmental factors determined the HRQOL of children and adolescents with SB. Environmental supports and resources contributed to HRQOL more than medical problems, especially in adolescents. The number of associated medical problems, reflecting disease severity, was the more potent clinical predictor compared to an individual health problem. | children;environment;quality of life;spina bifida | pubmed |
Aβ pathology downregulates brain mGluR5 density in a mouse model of Alzheimer. | The aim of the present study was to evaluate functional changes of mGluR5 expression in advanced Alzheimer's disease (AD) using positron emission tomography (PET) with an mGluR5 specific radiotracer ([<sup>18</sup>F]FPEB) in 5xFAD AD model. Subsequently, in the same animal, mGluR5 expression was quantified by immunoassay techniques. The non-displaceable binding potential values for mGluR5 was estimated by the Logan's graphical analysis. Brain PET imaging revealed that radioactivities in the hippocampus and the striatum were significantly lower in 5xFAD mice compared to control animals. Binding values were also significantly lowered in 5xFAD mice. This decline was validated by immunoblotting of protein isolates from brain tissues, as the mean band density for 5xFAD mice had a lower mGluR5 intensity than for wild type mice. These results indicated that mGluR5 levels in 5xFAD mice were down regulated in the limbic system. | 5xFAD mice;Alzheimer's disease;PET;[(18)F]FPEB;mGluR5;β-Amyloid | pubmed |
Structure-affinity relationship of the interaction between phenolic acids and their derivatives and β-lactoglobulin and effect on antioxidant activity. | In this study, 71 phenolic acids and their derivatives were used to investigate the structure-affinity relationship of β-lactoglobulin binding, and the effect of this interaction on antioxidant activity. Based on a fluorescence quenching method, an improved mathematical model was adopted to calculate the binding constants, with a correction for the inner-filter effect. Hydroxylation at the 3-position increased the affinity of the phenolic acids for β-lactoglobulin, while hydroxylation at the 2- or 4-positions had a negative effect. Complete methylation of all hydroxy groups, except at the 3-position, enhanced the binding affinity. Replacing the hydroxy groups with methyl groups at the 2-position also had a positive effect. Hydrogen bonding was one of the binding forces for the interaction. The antioxidant activity of phenolic acid-β-lactoglobulin complexes was higher than that of phenolic acids alone. These findings provide an understanding of the structure-activity relationship of the interaction between β-lactoglobulin and phenolic acids. | Antioxidant activity;Gallic acid (PubChem CID: 370);Gentisic acid (PubChem CID: 3469);Inner-filter effect;Isovanillic acid (PubChem CID: 12575);Phenolic acid;Protocatechuic acid (PubChem CID: 72);Salicylic acid (PubChem CID: 338);Structure–affinity relationship;Syringic acid (PubChem CID: 10742);Vanillic acid (PubChem CID: 8468);β-Lactoglobulin | pubmed |
Objective Analysis of Vaginal Ultrasound Video Clips for Exploring Uterine Peristalsis Post Vaginal and Cesarean Section Deliveries. | The nonpregnant uterus is characterized by cyclic contractions that assist in sperm transport to the fallopian tube, embryo transport to implantation site, and expulsion of menstrual debris. The effect of post-Cesarean section (CS) scar on uterine peristalsis is unclear, while worldwide the prevalence of CS deliveries is increasing. In this study, we developed a new objective method for analysis of dynamic characteristics of the nonpregnant uterus from transvaginal ultrasound (TVUS) recordings when the uterine cavity is not clearly observed, as may be the case in post-CS uteri. The method of active contours was utilized to detect the contours of the endometrium-myometrium interface (EMI) from sagittal cross-section TVUS images of nonpregnant uteri. The contours were straightened along the uterus centerline and registered with respect to the fundal end in order to reduce the noise due to movements of the physician and the participant. A dynamic analysis was conducted on these time-dependent contours in order to explore the frequency and amplitude of the EMI motility. The analysis was conducted on TVUS video clips from 12 nonpregnant participants, 7 post-CS and 5 controls. The frequencies of the EMI motility was 0.010 to 0.064 Hz at days 8 to 17 in the control participants and 0.014 to 0.073 Hz at days 9 to 15 in post-CS participants. The maximal amplitude of motility was 0.67 to 2.00 mm and 0.48 to 2.58 mm for the control and post-CS participants, respectively. In this preliminary study, we have not observed significant difference between the EMI motility of healthy and post-CS uteri. | Cesarean section;active contours;embryo transport;sperm transport;uterine contraction | pubmed |
Soft tissue sarcoma in Asia. | Sarcoma is an uncommon and heterogeneous group of malignancies linked by their mesenchymal origin. They are rare and account for 1% of adult cancers, and 10-20% of adolescent and young adult (AYA) cancers. While there is good published literature on the incidence and distribution of sarcoma subtypes in the western populations, there is a paucity of data from Asia, particularly on the epidemiology, treatment and outcomes of STS in Asia. Formalized prospective national registries in soft tissue sarcoma (STS) are lacking and little is known about how sarcomas are treated and managed throughout the Asia-Pacific region. Due to geographical and varying affluence levels across over 50 countries, no single uniform guideline exists across Asia to inform of chemotherapeutic options. Any existent guidelines tend to be country-specific, reflecting resource availability and geographical limitation. To understand and improve STS care in Asia, one must appreciate the macroeconomics and healthcare structures in place and to work within the limitations imposed by them. Concurrently, there exists an urgency to develop strong sarcoma centres of excellence (SCE) across Asia to deliver state-of-art care to our patients. Equally important is the need to facilitate sarcoma education to patients and healthcare workers. Development of such centres is vital in improving clinical care as they provide high-quality sub-specialized care to patients within that geographical location, serve as reference centres for knowledge and education as well as nerve centres for care-coordination in a hub-and-spoke model. Key to these centres of excellence is the sarcoma multi-disciplinary team (MDT). Studies have consistently shown that patients managed in high-volume sarcoma centres, by an expert sarcoma MDT, achieve better clinical outcomes. This report serves to highlight the challenges and opportunities of sarcoma care in Asia, map out a vision for the development of SCE across Asia and highlight the areas of potential collaboration between centres to advance the science of sarcoma. | Asia sarcoma;adolescent and young adult cancer (AYA cancer);rare cancer in Asia | pubmed |
Genetic characterisation of class 1 integrons among multidrug-resistant Salmonella serotypes in broiler chicken farms. | Antimicrobial resistance in Salmonella serotypes has been reported. Integrons play an important role in the dissemination of antimicrobial resistance genes in bacteria. Scarce literature is available on the identification of integrons in Salmonella isolated from broiler chickens. In this study, antimicrobial susceptibility testing and characterisation of class 1 integrons among multidrug-resistant (MDR) Salmonella enterica serotypes in broiler chicken farms in Egypt were performed. Antimicrobial susceptibility was determined by the disk diffusion method. PCR was performed to detect antimicrobial resistance genes and class 1 integrons in the tested Salmonella serotypes. Gene sequencing of the variable region of a class 1 integron was performed. Salmonella spp. were detected in 26 (13.5%) of 192 broiler samples, with Salmonella Enteritidis being the most frequently detected serotype, followed by Salmonella Kentucky and Salmonella Typhimurium and other serotypes. A very high resistance rate was observed to trimethoprim/sulfamethoxazole (100%), whilst a low resistance rate was observed to cefuroxime (57.7%). MDR S. enterica isolates displayed resistance to ciprofloxacin and azithromycin. Class 1 integrons were detected in 20 (76.9%) of the 26 Salmonella isolates. A high prevalence of class 1 integrons, as the first recorded percentage in the literature, associated with MDR Salmonella isolates was observed. Antimicrobial resistance rates in Salmonella serotypes from broiler chicken farms were alarming, especially for ciprofloxacin and azithromycin. Thus, another therapeutic strategy other than antimicrobials is recommended to prevent outbreaks of MDR Salmonella. | Antimicrobial resistance;Broilers;Integrons;Salmonella | pubmed |
Inability of positive phase II clinical trials of investigational treatments to subsequently predict positive phase III clinical trials in glioblastoma. | Glioblastoma is the most common primary malignant brain tumor in adults, but effective therapies are lacking. With the scarcity of positive phase III trials, which are increasing in cost, we examined the ability of positive phase II trials to predict statistically significant improvement in clinical outcomes of phase III trials. A PubMed search was conducted to identify phase III clinical trials performed in the past 25 years for patients with newly diagnosed or recurrent glioblastoma. Trials were excluded if they did not examine an investigational chemotherapy or agent, if they were stopped early owing to toxicity, if they lacked prior phase II studies, or if a prior phase II study was negative. Seven phase III clinical trials in newly diagnosed glioblastoma and 4 phase III clinical trials in recurrent glioblastoma met the inclusion criteria. Only 1 (9%) phase III study documented an improvement in overall survival and changed the standard of care. The high failure rate of phase III trials demonstrates the urgent need to increase the reliability of phase II trials of treatments for glioblastoma. Strategies such as the use of adaptive trial designs, Bayesian statistics, biomarkers, volumetric imaging, and mathematical modeling warrant testing. Additionally, it is critical to increase our expectations of phase II trials so that positive findings increase the probability that a phase III trial will be successful. | clinical trials;glioblastoma;phase II;phase III | pubmed |
Endogenous dopamine and endocannabinoid signaling mediate cocaine-induced reversal of AMPAR synaptic potentiation in the nucleus accumbens shell. | Repeated exposure to drugs of abuse alters the structure and function of neural circuits mediating reward, generating maladaptive plasticity in circuits critical for motivated behavior. Within meso-corticolimbic dopamine circuitry, repeated exposure to cocaine induces progressive alterations in AMPAR-mediated glutamatergic synaptic transmission. During a 10-14 day period of abstinence from cocaine, AMPAR signaling is potentiated at synapses on nucleus accumbens (NAc) medium spiny neurons (MSNs), promoting a state of heightened synaptic excitability. Re-exposure to cocaine during abstinence, however, rapidly reverses and depotentiates enhanced AMPAR signaling. To understand how re-exposure to cocaine alters AMPAR synaptic transmission, we investigated the roles of dopamine and endocannabinoid (eCB) signaling in modifying synaptic strength in the NAc shell. Using patch-clamp recordings from NAc slices prepared after 10-14 days of abstinence from repeated cocaine, we found that AMPAR-mediated depotentiation is rapidly induced in the NAc shell within 20 min of cocaine re-exposure ex vivo, and persists for up to five days before synapses return to levels of potentiation observed during abstinence. In cocaine-treated animals, global dopamine receptor activation was both necessary and sufficient for the cocaine-evoked depotentiation of AMPAR synaptic function. Additionally, we identified that CB1 receptors are engaged by endogenous endocannabinoids (eCBs) during re-exposure to cocaine ex vivo. Overall, these results indicate the central role that dopamine and eCB signaling mechanisms play in modulating cocaine-induced AMPAR plasticity in the NAc shell. | AMPA receptor;Cocaine;Dopamine;Endocannabinoid;Nucleus accumbens;Synaptic plasticity | pubmed |
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