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Assessment of Knowledge, Attitudes, and Practices Regarding Chronic Hepatitis C Treatment and Its Challenges: A Survey of Internal Medicine Residents in a Community Hospital. | Despite recent advances in chronic hepatitis C (CHC) treatment, only a small proportion of patients are connected with care and receive treatment. Internal medicine (IM) residents spend nearly one-third of their training in primary care settings and play a crucial role in diagnosing and counseling patients as well as linking patients with care and following up. IM residents in a community hospital completed an anonymous questionnaire regarding their knowledge, attitude, and practice associated with CHC treatment and its challenges. Descriptive analysis of the survey showed that there is a substantial gap in knowledge regarding the newer treatment of CHC between IM residents' perceptions of patient awareness and IM residents. Updated education regarding CHC that is geared towards medical residents and focused on new modalities of treatment can narrow the gap and lead to considerable increases in the rates of diagnosis and treatment and decreases in morbidity and mortality. | Attitude;Barrier;Chronic hepatitis C;Internal medical;Knowledge;Patient;Practice;Resident | pubmed |
Stigma and functional disability in relation to marriage and employment in young people with epilepsy in rural Tanzania. | To assess the impact of childhood epilepsy on social transitioning outcomes for young people with epilepsy (YPWE) living in Tanzania, and to explore influences on these outcomes. At six years from baseline, we followed up 84 YPWE and 79 age- sex- and village- matched controls recruited into a case-control study of childhood epilepsy in rural northern Tanzania. Data were collected from interviews with young people and their carers using a structured questionnaire. Perceived stigma was evaluated using the Kilifi Stigma Score and functional disability using the Barthel Index (BI). The effects of age, gender, functional disability and stigma on selected markers of social transitioning (education, employment and relationships) were estimated using multivariable modelling. Fewer YPWE than controls were in an intimate relationship (42.3% vs. 76.9%) or in education or paid employment (33.3% vs. 91.1%) and they reported elevated perceived stigma scores (27.4% vs. 3.8%). Among YPWE, a positive education or employment outcome was predicted by a lower seizure frequency (adjusted OR 3.79) and a higher BI score (adj. OR 12.12); a positive relationship outcome was predicted by a higher BI score (adj. OR 45.86) and being male (adj. OR 8.55). YPWE were more likely to experience adverse employment, educational and relationship outcomes in the transition to adult life than controls, with the greatest disadvantage experienced by females, those with greater functional disability and those with poorer seizure control. Markers of social transitioning should be included in any prospective evaluation of interventions designed to support these groups. | Adolescents;Economic outcomes;Seizure;Social outcomes;Sub-Saharan Africa | pubmed |
Inhibitors of the proteasome stimulate the epithelial sodium channel (ENaC) through SGK1 and mimic the effect of aldosterone. | The epithelial sodium channel (ENaC) marks the tightly regulated, rate-limiting step of sodium re-absorption in the aldosterone-sensitive distal nephron (ASDN). Stimulation of ENaC activity by aldosterone involves the serum and glucocorticoid-induced kinase 1 (SGK1) and is mediated via complex mechanisms including inhibition of channel retrieval. Retrieved channels may be recycled or degraded, e.g. by the proteasomal pathway. The aim of the present study was to investigate whether inhibitors of the proteasome affect ENaC activity and surface expression, and to explore a possible involvement of SGK1. Short circuit current (I <sub>SC</sub>) measurements were performed on confluent mCCD<sub>cl1</sub> murine cortical collecting duct cells to investigate the effect of two distinct proteasomal inhibitors, MG132 and bortezomib, on amiloride-sensitive ENaC-mediated I <sub>SC</sub>. Both inhibitors robustly stimulated amiloride-sensitive I <sub>SC</sub>. The time course and magnitude of the stimulatory effect of the proteasomal inhibitors on I <sub>SC</sub> were similar to those of aldosterone. Both, MG132 and aldosterone, significantly increased the abundance of β-ENaC at the cell surface. SGK1 activity was assessed by monitoring the phosphorylation of a downstream target, NDRG1, and was found to be increased by MG132. Importantly, inhibiting SGK1 activity prevented not only the stimulatory effect of aldosterone but also that of proteasomal inhibition. In conclusion, these data suggest that ENaC stimulation following proteasomal inhibition is due to an accumulation of active SGK1 resulting in increased expression of ENaC at the cell surface. Thus, inhibition of the proteasome mimics SGK1-dependent stimulation of ENaC by aldosterone. | Aldosterone;ENaC;MG132;Proteasome;Renal collecting duct cells;SGK1 | pubmed |
Changes in duodenal CD163-positive cells in dogs with chronic enteropathy after successful treatment. | Chronic enteropathy (CE) in dogs is characterized retrospectively per treatment response as food-responsive enteropathy (FRE), antibiotic-responsive enteropathy (ARE), and immunosuppressant-responsive enteropathy (IRE) - the latter most resembling inflammatory bowel disease in people. The aim of this study was to characterize duodenal macrophages (Mϕ) in CE using immunohistochemistry; with calprotectin (CAL) as a marker of early differentiated Mϕ and CD163 expression as a marker for resident Mϕ in the duodenum before and after treatment. Prior to treatment, dogs with FRE and IRE had a lower CD163<sup>+</sup>/CAL<sup>+</sup> ratio than control dogs (CTRL) in crypts; this increased significantly and normalized compared with CTRL after treatment. Conversely, the CD163<sup>+</sup>/CAL<sup>+</sup> ratio in dogs with ARE was comparable to that in healthy dogs before and after treatment. In summary, these results suggest that Mϕ play a role in the pathogenesis of CE in FRE and IRE, with a decrease in resident Mϕ and an increase in early differentiated Mϕ, but not in ARE dogs. Mϕ normalize after successful treatment. | CD163;Canine;chronic enteropathy;inflammatory bowel disease;macrophage | pubmed |
Accounting for Missing Correlation Coefficients in Fixed-Effects MASEM. | Meta-analytic structural equation modeling (MASEM) is increasingly applied to advance theories by synthesizing existing findings. MASEM essentially consists of two stages. In Stage 1, a pooled correlation matrix is estimated based on the reported correlation coefficients in the individual studies. In Stage 2, a structural model (such as a path model) is fitted to explain the pooled correlations. Frequently, the individual studies do not provide all the correlation coefficients between the research variables. In this study, we modify the currently optimal MASEM-method to deal with missing correlation coefficients, and compare its performance with existing methods. This study is the first to evaluate the performance of fixed-effects MASEM methods under different levels of missing correlation coefficients. We found that the often used univariate methods performed very poorly, while the multivariate methods performed well overall. | Meta-analytic structural equation modeling;TSSEM;meta-analysis;missing data | pubmed |
Dendrimeric Antigens for Drug Allergy Diagnosis: A New Approach for Basophil Activation Tests. | Dendrimeric Antigens (DeAns) consist of dendrimers decorated with multiple units of drug antigenic determinants. These conjugates have been shown to be a powerful tool for diagnosing penicillin allergy using in vitro immunoassays, in which they are recognized by specific IgE from allergic patients. Here we propose a new diagnostic approach using DeAns in cellular tests, in which recognition occurs through IgE bound to the basophil surface. Both IgE molecular recognition and subsequent cell activation may be influenced by the tridimensional architecture and size of the immunogens. Structural features of benzylpenicilloyl-DeAn and amoxicilloyl-DeAn (G2 and G4 PAMAM) were studied by diffusion Nuclear Magnetic Resonance (NMR) experiments and are discussed in relation to molecular dynamics simulation (MDS) observations. IgE recognition was clinically evaluated using the basophil activation test (BAT) for allergic patients and tolerant subjects. Diffusion NMR experiments, MDS and cellular studies provide evidence that the size of the DeAn, its antigen composition and tridimensional distribution play key roles in IgE-antigen recognition at the effector cell surface. These results indicate that the fourth generation DeAns induce a higher level of basophil activation in allergic patients. This approach can be considered as a potential complementary diagnostic method for evaluating penicillin allergy. | PAMAM;basophil activation tests;dendrimeric antigens;drug allergy;penicillin | pubmed |
Timely Visualization of the Collaterals Formed during Acute Ischemic Stroke with Fe<sub>3</sub> O<sub>4</sub> Nanoparticle-based MR Imaging Probe. | Ischemic stroke is one of the major leading causes for long-term disability and mortality. Collateral vessels provide an alternative pathway to protect the brain against ischemic injury after arterial occlusion. Aiming at visualizing the collaterals occurring during acute ischemic stroke, an integrin α<sub>v</sub> β<sub>3</sub> -specific Fe<sub>3</sub> O<sub>4</sub> -Arg-Gly-Asp (RGD) nanoprobe is prepared for magnetic resonance imaging (MRI) of the collaterals. Rat models are constructed by occluding the middle cerebral artery for imaging studies of cerebral ischemia and ischemia-reperfusion on 7.0 Tesla MRI using susceptibility-weighted imaging sequence. To show the binding specificity to the collaterals, the imaging results acquired with the Fe<sub>3</sub> O<sub>4</sub> -RGD nanoprobe and the Fe<sub>3</sub> O<sub>4</sub> mother nanoparticles, respectively, are carefully compared. In addition, an RGD blocking experiment is also carried out to support the excellent binding specificity of the Fe<sub>3</sub> O<sub>4</sub> -RGD nanoprobe. Following the above experiments, cerebral ischemia-reperfusion studies show the collateral dynamics upon reperfusion, which is very important for the prognosis of various revascularization therapies in the clinic. The current study has, for the first time, enabled the direct observation of collaterals in a quasi-real time fashion and further disclosed that the antegrade flow upon reperfusion dominates the blood supply of primary ischemic tissue during the early stage of infarction, which is significantly meaningful for clinical treatment of stroke. | Fe3O4 nanoparticles;MRI;antegrade flow;collaterals;αvβ3 | pubmed |
Lactation ketoacidosis: case presentation and literature review. | A 35-year-old woman presented to the emergency department with a 2 days history of malaise and headache. She was breastfeeding her 5-month old infant and had recently started an altered diet based on reducing carbohydrate amount. Moreover, she had also started exercising 2 weeks prior to her illness. Initial blood tests revealed high anion gap metabolic acidosis and hypoglycaemia (pH 7.13 (normal 7.30-7.40), bicarbonate 9.4 mmol/L (normal 21.0-28.0), anion gap 22.6 mmol/L (normal 8-12), glucose 2.9 mmol/L (normal fasting 3.9-5.8) and ketones 6.4 mmol/L (normal <0.6)). The patient was treated with intravenous dextrose and showed complete resolution of ketoacidosis and hypoglycaemia within 48 hours. She was discharged home and remained well with a balanced diet. After excluding all other the causes of hypoglycaemia and ketoacidosis, the diagnosis of lactation ketoacidosis was made and it was considered triggered by altered diet, exercise and skipping meals. All 11 cases of lactation ketoacidosis which has previously been published are reviewed as well. | endocrinology;metabolic disorders | pubmed |
Exogenous hydrogen sulfide promotes hepatocellular carcinoma cell growth by activating the STAT3-COX-2 signaling pathway. | The effects of hydrogen sulfide (H<sub>2</sub>S) on cancer are controversial. Our group previously demonstrated that exogenous H<sub>2</sub>S promotes the development of cancer via amplifying the activation of the nuclear factor-κB signaling pathway in hepatocellular carcinoma (HCC) cells (PLC/PRF/5). The present study aimed to further investigate the hypothesis that exogenous H<sub>2</sub>S promotes PLC/PRF/5 cell proliferation and migration, and inhibits apoptosis by activating the signal transducer and activator of transcription 3 (STAT3)-cyclooxygenase-2 (COX-2) signaling pathway. PLC/PRF/5 cells were treated with 500 µmol/l NaHS (a donor of H<sub>2</sub>S) for 24 h. The expression levels of phosphorylated (p)-STAT3, STAT3, cleaved caspase-3 and COX-2 were measured by western blot assay. Cell viability was detected by Cell Counting kit-8 assay. Apoptotic cells were observed by Hoechst 33258 staining. The expression of STAT3 and COX-2 messenger RNA (mRNA) was detected by semiquantitative reverse transcription-polymerase chain reaction. The production of vascular endothelial growth factor (VEGF) was evaluated by ELISA. The results indicated that treatment of PLC/PRF/5 cells with 500 µmol/l NaHS for 24 h markedly increased the expression levels of p-STAT3 and STAT3 mRNA, leading to COX-2 and COX-2 mRNA overexpression, VEGF induction, decreased cleaved caspase-3 production, increased cell viability and migration, and decreased number of apoptotic cells. However, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 30 µmol/l AG490 (an inhibitor of STAT3) or 20 µmol/l NS-398 (an inhibitor of COX-2) for 24 h significantly reverted the effects induced by NaHS. Furthermore, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 30 µmol/l AG490 markedly decreased the NaHS-induced increase in the expression level of COX-2. By contrast, co-treatment of PLC/PRF/5 cells with 500 µmol/l NaHS and 20 µmol/l NS-398 inhibited the NaHS-induced increase in the expression level of p-STAT3. In conclusion, the findings of the present study provide evidence that the STAT3-COX-2 signaling pathway is involved in NaHS-induced cell proliferation, migration, angiogenesis and anti-apoptosis in PLC/PRF/5 cells, and suggest that the positive feedback between STAT3 and COX-2 may serve a crucial role in hepatocellular carcinoma carcinogenesis. | COX-2;PLC/PRF/5 cells;STAT3;growth;hydrogen sulfide | pubmed |
Review of Primary Cutaneous Mucinoses in Nonlupus Connective Tissue Diseases. | Lichen myxedematosus is an idiopathic, cutaneous mucinosis with 2 clinicopathologic subsets. There is the generalised papular and sclerodermoid form, more properly termed scleromyxedema, and the localised papular form. We report the first case, to our knowledge, of lichen myxedematosus in association with rheumatoid arthritis as well as a case in association with dermatomyositis. An up-to-date literature review on cutaneous mucinoses and connective tissue diseases, excluding the common association of primary and secondary mucinoses with systemic lupus erythematosus, was also performed. | connective tissue disease;cutaneous mucinosis;lichen myxedematosus | pubmed |
Comparison of diagnostic efficacy between CLE, tissue sampling, and CLE combined with tissue sampling for undetermined pancreaticobiliary strictures: a meta-analysis. | The accurate diagnosis of undetermined pancreaticobiliary strictures remains challenging. Current ERCP-guided tissue sampling methods are of low sensitivity. Confocal laser endomicroscopy (CLE) is a new procedure and allows real optical biopsies that may improve the diagnosis of undetermined pancreaticobiliary strictures. The aim of this meta-analysis was to determine the diagnostic yield of CLE, tissue sampling, and CLE combined with tissue sampling for undetermined pancreaticobiliary strictures. Pubmed, Embase, and the Cochrane Library database were reviewed for relevant studies. Pooled estimates of sensitivity and specificity with 95% confidence intervals (CIs) were calculated using the random-effects meta-analysis model. The summary receiver-operating characteristic (SROC) curve was constructed, and the area under the receiver operating characteristic curve (AUC) was calculated. Twelve studies involving 591 patients were enrolled in our analysis. The overall sensitivity and the specificity estimate of CLE for discriminating benign and malignant pancreaticobiliary strictures were 87% (95%CI, 83-91%) and 76% (95%CI, 70-81%), respectively. The AUC to assess the diagnostic efficacy was 0.8705. For tissue sampling, the overall sensitivity and the specificity estimate were 64% (95%CI, 57-70%) and 94% (95%CI, 90-97%), respectively. The AUC to assess the diagnostic efficacy was 0.8040. A combination of both methods increased the sensitivity (93%; 95%CI, 88-96%) with a specificity of 82% (95%CI, 74-89%). The AUC to assess the diagnostic efficacy was 0.9377. There was no publication bias by Deeks' Funnel Plot with p = .936. Compared with tissue sampling, CLE may increase the sensitivity for the diagnosis of malignant pancreaticobiliary strictures. A combination of both can effectively diagnose malignant pancreaticobiliary strictures. | Confocal laser endomicroscopy;meta-analysis;pancreaticobiliary strictures;sensitivity;tissue sampling | pubmed |
Effect and mechanism of lentivirus-mediated silencing of TPX2 gene on proliferation and apoptosis of human hepatoma cells. | This study aimed to investigate the role and mechanism of action of targeting protein for Xklp2 (TPX2) in liver cancer, we compared TPX messenger RNA (mRNA) expression in liver cancer tissue samples and adjacent normal liver tissue samples as well as in human liver cancer cell lines and nonmalignant cell line by quantitative reverse transcription polymerase chain reaction (qRT-PCR). TPX2 gene was silenced in HepG2 cells by transfection with the lentiviral vector expressing TPX2-targeting short hairpin RNA (shRNA), and the knockdown efficiency was evaluated by RT-qPCR. Cell proliferation, apoptosis as well as protein level of c-Myc, cyclin D1, caspase-3, phosphorylated glycogen synthase kinase-3β (p-GSK-3β), and β-catenin in HepG2 cells were evaluated before and after the TPX2 knockdown. Wnt/β-catenin signaling pathway was inhibited by treatment with 20 μM of XAV-939 or activated by treatment with 20 mM of LiCl. We found that TPX2 mRNA level was significantly increased in liver cancer tissue samples and cell lines comparing to noncancerous counterparts (P < 0.05). TPX2 knockdown significantly reduces TPX2 expression (P < 0.01), cell proliferation (P < 0.05), protein level of c-Myc and cyclin D1 (P < 0.01), activation of Wnt/β-catenin signaling in HepG2 cells (P < 0.01) while increasing cell apoptosis (P < 0.01). Treatment with XAV-939 significantly reduced HepG2 cell proliferation (P < 0.05) while increasing cell apoptosis (P < 0.01). Treatment with LiCl significantly attenuated the antiproliferative and apoptosis-promoting effect of TPX2 knockdown on HepG2 cells (P < 0.05). Lentivirus-mediated silencing of TPX2 gene could inhibit proliferation and induce apoptosis in hepatoma cells by inhibiting Wnt signaling pathway and regulating cyclin and apoptosis-related proteins. | apoptosis;lentivirus;liver cancer;proliferation;targeting protein for Xklp2 | pubmed |
Overweight/obesity among school aged children in Bahir Dar City: cross sectional study. | Developing countries, including Ethiopia are experiencing a double burden of malnutrition. There is limited information about prevalence of overweight/obesity among school aged children in Ethiopia particularly in Bahir Dar city. Hence this study aimed to assess the prevalence of overweight/obesity and associated factors among school children aged 6-12 years at Bahir Dar City, Northwest Ethiopia. A school based cross-sectional study was carried out. A total of 634 children were included in the study. Multi stage systematic random sampling technique was used. A multivariable logistic regression analysis was used to identify factors associated with overweight/obesity. The association between dependent and independent variables were assessed using odds ratio with 95% confidence interval and p-value ≤0.05 was considered statistically significant. The overall prevalence of overweight and/or obesity was 11.9% (95% CI, 9.3, 14.4) (out of which 8.8% were overweight and 3.1% were obese). Higher wealth status[adjusted OR = 3.14, 95% CI:1.17, 8.46], being a private school student [AOR = 2.21, 95% CI:1.09, 4.49], use of transportation to and from school [AOR = 2.53, 95% CI: 1.26,5.06], fast food intake [AOR = 3.88, 95% CI: 1.42,10.55], lack of moderate physical activity [AOR = 2.87, 95% CI: 1.21,6.82], low intake of fruit and vegetable [AOR = 6.45, 95% CI:3.19,13.06] were significant factors associated with overweight and obesity. This study revealed that prevalence of overweight/obesity among school aged children in Bahir Dar city is high. Thus, promoting healthy dietary habit, particularly improving fruit and vegetable intake is essential to reduce the burden of overweight and obesity. Furthermore, it is important to strengthen nutrition education about avoiding junk food consumption and encouraging regular physical activity. | Body mass index for age;Ethiopia;Obesity;Overweight;School aged children | pubmed |
Pyrosequencing analysis of methylation levels of clock genes in leukocytes from Parkinson's disease patients. | DNA methylation of neuronal PAS domain protein 2 (NPAS2) and cryptochrome circadian clock 1 (CRY1) promoters may be associated with Parkinson's disease (PD). However, there is no simple and cost-effective method to quantify DNA methylation in these regions. Additionally, it is not clear whether DNA methylation of NPAS2 and CRY1 promoters is altered in peripheral blood of PD patients, especially newly diagnosed drug-naïve PD patients, and thus can be used as a PD biomarker. In the present study, we utilized bisulfite pyrosequencing assays to examine DNA methylation levels of six CpG sites in the NPAS2 promoter and five CpG sites in the CRY1 promoter. We compared DNA methylation levels at these sites in leukocytes from 80 medicated PD patients, 30 drug-naïve PD patients, and 80 healthy controls. Our results indicate that NPAS2 hypomethylation occurs at the early stage of PD and is a moderate biomarker for distinguishing PD patients from healthy subjects. | CRY1;DNA methylation;Leukocytes;NPAS2;Pyrosequencing | pubmed |
Stress alters social behavior and sensitivity to pharmacological activation of kappa opioid receptors in an age-specific manner in Sprague Dawley rats. | The dynorphin/kappa opioid receptor (DYN/KOR) system has been identified as a primary target of stress due to behavioral effects, such as dysphoria, aversion, and anxiety-like alterations that result from activation of this system. Numerous adaptations in the DYN/KOR system have also been identified in response to stress. However, whereas most studies examining the function of the DYN/KOR system have been conducted in adult rodents, there is growing evidence suggesting that this system is ontogenetically regulated. Likewise, the outcome of exposure to stress also differs across ontogeny. Based on these developmental similarities, the objective of this study was to systematically test effects of a selective KOR agonist, U-62066, on various aspects of social behavior across ontogeny in non-stressed male and female rats as well as in males and females with a prior history of repeated exposure to restraint (90 min/day, 5 exposures). We found that the social consequences of repeated restraint differed as a function of age: juvenile stress produced substantial increases in play fighting, whereas adolescent and adult stress resulted in decreases in social investigation and social preference. The KOR agonist U-62066 dose-dependently reduced social behaviors in non-stressed adults, producing social avoidance at the highest dose tested, while younger animals displayed reduced sensitivity to this socially suppressing effect of U-62066. Interestingly, in stressed animals, the socially suppressing effects of the KOR agonist were blunted at all ages, with juveniles and adolescents exhibiting increased social preference in response to certain doses of U-62066. Taken together, these findings support the hypothesis that the DYN/KOR system changes with age and differentially responds and adapts to stress across development. | Adolescent;Adult;Development;Juvenile;Kappa opioid receptor;Restraint stress;Social behavior | pubmed |
CD11b-activated Src signal attenuates neuroinflammatory pain by orchestrating inflammatory and anti-inflammatory cytokines in microglia. | CD11b;Neuropathic pain;Src;TLR4;neuroinflammation | pubmed |
|
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</math> -lacunary statistical convergence of double sequences. | In this paper, we introduce and study the notion of rough <math xmlns="http://www.w3.org/1998/Math/MathML">
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</math>-convergence;Double sequences;Lacunary sequences;Rough convergence;Statistical convergence | pubmed |
Military and industrial performance: the critical role of noise controls. | Noise control is a well understood and important engineering skill. The science has been developed to address operational needs of being quiet on the one hand, and avoiding hearing loss on the other, both in industry and military operations. Noise control is also the first priority step in systems safety risk mitigation for noise hazards, as evidenced in U.S. industry by the requirement stated in Federal OSHA regulation 1910.95: "(b)(1) When employees are subjected to sound exceeding those listed in Table G-16, feasible administrative or engineering controls shall be utilized." In actual practice, engineering controls are of first preference, while the second step is administrative noise controls, reducing noise exposures by removing personnel from high-noise environments. The third is the use of personal protective equipment (PPE), commonly known as earmuffs and earplugs. Each of these topics is discussed herein. The U.S. Navy has developed and/or implemented many groundbreaking noise control efforts on ships, and that provides the basis of discussion in this article. This article, as an overview of noise control, also addresses issues associated with high-noise environments and consideration of noise control techniques. | Noise control;acoustic performance;noise modelling;systems engineering | pubmed |
Antithrombotic Agents and Cancer. | Platelet activation is the first response to tissue damage and, if unrestrained, may promote chronic inflammation-related cancer, mainly through the release of soluble factors and vesicles that are rich in genetic materials and proteins. Platelets also sustain cancer cell invasion and metastasis formation by fostering the development of the epithelial-mesenchymal transition phenotype, cancer cell survival in the bloodstream and arrest/extravasation at the endothelium. Furthermore, platelets contribute to tumor escape from immune elimination. These findings provide the rationale for the use of antithrombotic agents in the prevention of cancer development and the reduction of metastatic spread and mortality. Among them, low-dose aspirin has been extensively evaluated in both preclinical and clinical studies. The lines of evidence have been considered appropriate to recommend the use of low-dose aspirin for primary prevention of cardiovascular disease and colorectal cancer by the USA. Preventive Services Task Force. However, two questions are still open: (i) the efficacy of aspirin as an anticancer agent shared by other antiplatelet agents, such as clopidogrel; (ii) the beneficial effect of aspirin improved at higher doses or by the co-administration of clopidogrel. This review discusses the latest updates regarding the mechanisms by which platelets promote cancer and the efficacy of antiplatelet agents. | antiplatelet drugs;cancer;epithelial-mesenchymal transition;immune surveillance;metastasis;platelets | pubmed |
From Prodromal to Overt Parkinson's Disease: Towards a New Definition in the Year 2040. | The field of prodromal PD is still in its infancy, and at the cusp of major advances. This article summarizes where we are, and most importantly where we need to go in order for the promise of prodromal PD to be realized. In the immediate future, the criteria need to be updated with additional markers and disseminated broadly. In the near future, they need to better incorporate changes in likelihood ratio with age and sex, combine markers in novel ways using big data approaches, identify subtypes, and incorporate better higher-specificity markers as they are discovered. Integration of smartphone/wearable markers and biomarkers of progression from the prodromal phase will allow development of neuroprotective trials in early stages. By 2040, it is hoped that prodromal criteria will be incorporated into active neuroprotective treatment programs, allowing a program of population-based screening followed by early treatment and ultimately the prevention of clinical PD from ever becoming manifest. | Prodromal Parkinson’s disease;big data approaches;gene-specific therapy;higher-specificity markers;individual mechanism-specific therapy;neuroprotective trials;population-based screening;progression markers;subtypes | pubmed |
Ambulatory Inotrope Infusions in Advanced Heart Failure: A Systematic Review and Meta-Analysis. | This study sought to systematically review the available evidence of risks and benefits of ambulatory intravenous inotrope therapy in advanced heart failure (HF). Ambulatory inotrope infusions are sometimes offered to patients with advanced Stage D HF; however, an understanding of the relative risks and benefits is lacking. On August 7, 2016, we searched SCOPUS, Web of Science, Ovid EMBASE, and Ovid MEDLINE for studies of long-term use of intravenous inotropes in outpatients with advanced HF. Meta-analysis was performed using random effects models. A total of 66 studies (13 randomized controlled trials and 53 observational studies) met inclusion criteria. Most studies were small and at high risk for bias. Pooled rates of death (41 studies), all-cause hospitalization (15 studies), central line infection (13 studies), and implantable cardioverter-defibrillator shocks (3 studies) of inotropes were 4.2, 22.2, 3.6, and 2.4 per 100 person-months follow-up, respectively. Improvement in New York Heart Association (NYHA) functional class was greater in patients taking inotropes than in controls (mean difference of 0.60 NYHA functional classes; 95% confidence interval [CI]: 0.22 to 0.98; p = 0.001; 5 trials). There was no significant difference in mortality risk in those taking inotropes compared with controls (pooled risk ratio: 0.68; 95% CI: 0.40 to 1.17; p = 0.16; 9 trials). Data were too limited to pool for other outcomes or to stratify by indication (i.e., bridge-to-transplant or palliative). High-quality evidence for the risks and benefits of ambulatory inotrope infusions in advanced HF is limited, particularly when used for palliation. Available data suggest that inotrope therapy improves NYHA functional class and does not impact survival. | death;hospitalization;palliative care;risk;transplant | pubmed |
Hoffa's Fat Pad Abnormality in the Development of Knee Osteoarthritis. | Over the past two decades, many hypotheses have been put forward to explain the cause of knee osteoarthritis. Scientific reports bring up the role of adipose tissue in the activation of the inflammatory mechanisms, which is a characteristic feature of osteoarthritis natural history. Adipose tissue produces and releases cytokines, interleukins, and growth factors by means of paracrine, endocrine, and autocrine mechanisms. Hoffa's fat pad (infrapatellar adipose tissue) plays a viable role in the initiation and progression of osteoarthritis due to its role in the activation and release of pro-inflammatory mediators. The degenerative joint disease is considered an inflammatory process. Therefore, in this article we overview the importance of Hoffa's fat pad in the development and progression of osteoarthritis. | Adipokine;Adipose tissue;Cytokines;Inflammation;Leptin;Osteoarthritis | pubmed |
Reduction-sensitive mixed micelles for selective intracellular drug delivery to tumor cells and reversal of multidrug resistance. | Stimuli-responsive nanocarriers have demonstrated their potentials in optimizing chemotherapeutics and anticancer efficacy. In this study, a mixed micelle system (THSP) was prepared by combining reduction-sensitive hyaluronic acid-poly(lactide) (HA-ss-PLA) conjugates and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), with objective to achieve multiple functionalities of selective intracellular rapid release, active targeting capability and multidrug resistance reversal. The mixed micelle possessed desirable particle diameter of 124.32 nm and high entrapment efficiency at 87.97%. Importantly, the THSP mixed micelles demonstrated good stability in systemic circulation and rapidly released PTX in intracellular reductive environment. In vitro cellular uptake study and cytotoxicity assay indicated that the mixed micelles effectively increased drug accumulation in A549 cells and Taxol resistant A549/Taxol cells, and inhibited growth of tumor cells. In addition, the redox-responsive THSP micelles preferentially accumulated to the tumor site and improved anticancer drug activity in vivo, with a TIR of 69.08%. It was concluded that redox-sensitive mixed micelles THSP provided a potential vehicle for efficient anticancer drug delivery and enhancement in treating MDR tumor in the future. | Hyaluronic acid;Mixed micelles;Multidrug resistance;Reduction-response delivery;TPGS;Tumor targeting capability | pubmed |
Extracellular Galectin-3 Induces Accelerated Oligodendroglial Differentiation Through Changes in Signaling Pathways and Cytoskeleton Dynamics. | Galectin-3 (Gal-3) is a chimeric protein structurally composed of unusual tandem repeats of proline and short glycine-rich segments fused onto a carbohydrate recognition domain. Our studies have previously demonstrated that Gal-3 drives oligodendrocyte (OLG) differentiation to control myelin integrity and function. The cytoskeleton plays a key role in OLG maturation: the initial stage of OLG process extension requires dynamic actin filament assembly, while subsequent myelin wrapping coincides with the upregulation of actin disassembly proteins which are dependent on myelin basic protein (MPB) expression. In this context, the aim of the present work was to elucidate the mechanism by which recombinant Gal-3 (rGal-3) induces OLG maturation, giving special attention to the actin cytoskeleton. Our results show that rGal-3 induced early actin filament assembly accompanied by Erk signaling deactivation, which led to a decrease in the number of platelet-derived growth factor receptor α (PDGFRα)+ cells concomitantly with an increase in the number of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase)+ cells at 1 day of treatment (TD1), and Akt signaling activation at TD1 and TD3. Strikingly, rGal-3 induced an accelerated shift from polymerized to depolymerized actin between TD3 and TD5, accompanied by a significant increase in MBP, gelsolin, Rac1, Rac1-GTP, and β-catenin expression at TD5. These results were strongly supported by assays using Erk 1/2 and Akt inhibitors, indicating that both pathways are key to rGal-3-mediated effects. Erk 1/2 inhibition in control-treated cells resembled an rGal-3 like state characterized by an increase in MBP, β-catenin, and gelsolin expression. In contrast, Akt inhibition in rGal-3-treated cells reduced MBP, β-catenin, and gelsolin expression, indicating a blockade of rGal-3 effects. Taken together, these results indicate that rGal-3 accelerates OLG maturation by modulating signaling pathways and protein expression which lead to changes in actin cytoskeleton dynamics. | Akt;Galectin-3;Oligodendrocytes;actin;gelsolin | pubmed |
A Satellite-Based Lagrangian View on Phytoplankton Dynamics. | The well-lit upper layer of the open ocean is a dynamical environment that hosts approximately half of global primary production. In the remote parts of this environment, distant from the coast and from the seabed, there is no obvious spatially fixed reference frame for describing the dynamics of the microscopic drifting organisms responsible for this immense production of organic matter-the phytoplankton. Thus, a natural perspective for studying phytoplankton dynamics is to follow the trajectories of water parcels in which the organisms are embedded. With the advent of satellite oceanography, this Lagrangian perspective has provided valuable information on different aspects of phytoplankton dynamics, including bloom initiation and termination, spatial distribution patterns, biodiversity, export of carbon to the deep ocean, and, more recently, bottom-up mechanisms that affect the distribution and behavior of higher-trophic-level organisms. Upcoming submesoscale-resolving satellite observations and swarms of autonomous platforms open the way to the integration of vertical dynamics into the Lagrangian view of phytoplankton dynamics. | Lagrangian analysis;horizontal stirring;marine ecosystem;mesoscale;phytoplankton;remote sensing | pubmed |
MPS dose reconstruction for internal emitters: some site-specific issues and approaches. | As part of the Million Person Study (MPS), dose reconstructions for internal emitters have been performed for several U.S. facilities where large quantities of radionuclides were handled. The main challenges and dominant sources of potential error in retrospective dose estimates for internally exposed workers have been found to vary from site to site. This article discusses some important issues encountered in dose reconstructions performed for selected MPS sites and the approaches used to address those issues. The focus is on some foundational components of retrospective dose assessments that have received little attention in the literature. The discussion is built around illustrative exposure data and dose reconstructions for workers at selected facilities addressed in the MPS. Related findings at some non-MPS sites are also discussed. Each of the following items has been found to be a major source of potential error in reconstructed tissue doses for some MPS sites: identification of all dosimetrically important internal emitters; the time pattern of intake; the mode(s) of intake; reliability of bioassay measurements; application of surrogate (coworker) information in lieu of, or in conjunction with, worker-specific monitoring data; the chemical and physical forms of inhaled radionuclides; and the relation of air monitoring data to actual intake. (1) Much of the dose reconstruction effort for internal emitters should be devoted to development of best feasible exposure scenarios. (2) Coworker data should be used to assign exposure scenarios or dose estimates to workers with missing exposure data only if there is compelling evidence of similar coworker exposure. (3) Bioassay data for some radionuclides and periods of operation at MPS sites are of questionable reliability due to sizable uncertainties associated with contamination, recovery, or background issues. (4) Dose estimates derived solely from air monitoring data should be treated as highly uncertain values in the absence of site-specific information demonstrating that the data are reasonably predictive of intake. (5) For intakes known or assumed to be via inhalation, the uncertainty in lung dose typically is much greater than the uncertainty in dose to systemic tissues, when dose estimates are based on urinary excretion data. (6) The lung dose estimate often can be improved through development of site-specific respiratory absorption parameter values. (7) There is generally insufficient site-specific information to justify development of site-specific systemic models. | Dose reconstruction;plutonium;polonium ;uranium | pubmed |
Genetic variations in the PI3K/PTEN/AKT/mTOR pathway predict tumor response and disease-free survival in locally advanced rectal cancer patients receiving preoperative chemoradiotherapy and radical surgery. | <b>Objective:</b> Although preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is the standard treatment for locally advanced rectal cancer (LARC), the clinical efficacy differs among patients. This study was conducted to determine the association between genetic variations in the PI3K/PTEN/AKT/mTOR pathway and clinical outcomes in LARC patients. <b>Methods:</b> Sixteen tagging single-nucleotide polymorphisms (SNPs) in five core genes (PIK3CA, PTEN, AKT1, AKT2, and FRAP1) were genotyped. The associations of these SNPs with tumor response to preoperative CRT, postoperative disease-free survival (DFS) and overall survival (OS) were identified. Crude odds ratios (ORs) and hazard ratios (HRs) were adjusted by age, sex, clinical stage, tumor differentiation, tumor location, cycles of preoperative chemotherapy and time interval from CRT completion to surgery. <b>Results:</b> In an analysis of 97 LARC patients, the G/T+G/G genotype of AKT1:rs2498804 was associated with an increased tumor response rate (adjusted OR = 2.909, 95% confidence interval (CI), 1.127-7.505, P = 0.027). At a median of 65.7 months of follow-up, the G/C+C/C genotype of AKT2:rs8100018 was associated with a reduced risk of postoperative recurrence (adjusted HR = 0.414; 95% CI, 0.187-0.914, P = 0.029). Patients carrying the G/C+C/C genotype in AKT2:rs8100018 presented a higher 5-year DFS rate than those with the wild-type genotype (79.2% vs. 62.3%, P = 0.038). None of the SNPs were significantly associated with pathological complete response (pCR) or 5-year OS. <b>Conclusions:</b> The current study indicates that genetic variations within the PI3K/ PTEN/AKT/mTOR signaling pathway are associated with the clinical outcomes of LARC patients undergoing preoperative CRT followed by radical surgery. | PI3K;clinical outcomes;preoperative chemoradiotherapy;rectal cancer | pubmed |
Delayed initiation of breastfeeding in Bukavu, South Kivu, eastern Democratic Republic of the Congo: a cross-sectional study. | Timely initiation of breastfeeding can decrease neonatal mortality. However, about 50% of newborns are not breastfeed within 1 h of birth in the Democratic Republic of Congo. The aim of this study was to identify factors associated with delayed initiation of breastfeeding in an urban and rural area of Bukavu, South Kivu province, Democratic Republic of Congo. We interviewed 396 mother-newborn pairs (185 in the urban area and 211 in the rural area) between 20 July and 10 October 2016. We used descriptive statistics to demonstrate the prevalence of early initiation of breastfeeding. Variables that showed association with delayed initiation of breastfeeding in the bivariate models were entered in a multivariable logistic model. Overall, the rate of early initiation of breastfeeding was 65.9% (69.7% in the rural area, 61.6% in the rural area). Two hundred and seventy-four (62.9%) mothers (159 in rural area and 115 in urban area) were counselled on early initiation of breastfeeding during prenatal care. Most mothers, 65.2% received counselling by a health professional. On multivariable regression analyses after adjusting for other variables in the model, unmarried mothers [Odds Ratio (OR): 1.5 (95% Confidence Interval (CI): 1.13, 1.95)], cesarean delivery [OR: 2.24 (95% CI: 1.74, 2.88)], no counselling on timely initiation of breastfeeding [OR: 1.71 (95% CI: 1.29, 2.20)] and counselling by a non-health professional [OR: 1.84 (95% CI: 1.08, 3.12)] were associated with delayed initiation of breastfeeding. Systemic changes are needed for women having caesarean births to experience skin-to-skin and early initiation. In addition, information, education and communication on the importance of timely initiation of breastfeeding must be supported to improve maternal and infant wellbeing. | Breastfeeding;Delayed;Early;Initiation;Newborn;Timely | pubmed |
Local convergence of the boundary element method on polyhedral domains. | The local behavior of the lowest order boundary element method on quasi-uniform meshes for Symm's integral equation and the stabilized hyper-singular integral equation on polygonal/polyhedral Lipschitz domains is analyzed. We prove local <i>a priori</i> estimates in <math xmlns="http://www.w3.org/1998/Math/MathML">
<msup>
<mi>L</mi>
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</math> for Symm's integral equation and in <math xmlns="http://www.w3.org/1998/Math/MathML">
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<mi>H</mi>
<mn>1</mn>
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</math> for the hyper-singular equation. The local rate of convergence is limited by the local regularity of the sought solution and the sum of the rates given by the global regularity and additional regularity provided by the shift theorem for a dual problem. | 65N38 | pubmed |
Natural deep eutectic solvents as eco-friendly and sustainable dilution medium for the determination of residual organic solvents in pharmaceuticals with static headspace-gas chromatography. | Reported here is a simple and rapid static headspace gas chromatography (SHS-GC) method for the determination of trace solvents including ethanol, isopropanol, n-butanol, 1,4-dioxane, tetrahydrofuran, acetonitrile, methanol and acetone which commonly used in drug production process. Natural deep eutectic solvents (NADESs) are firstly used as the matrix medium for this method, which provided high sensitivity for residual solvents detection. With the optimized method, validation experiments were performed and the data showed excellent linearity for all the solvents (R<sup>2</sup> ≥ 0.999, n = 7). The limits of detection (LOD) for ethanol, isopropanol, n-butanol, 1,4-dioxane, tetrahydrofuran, acetonitrile, methanol and acetone are 0.09, 0.08, 0.07, 0.11, 0.06, 0.10, 0.12 and 0.08 μg g<sup>-1</sup>, respectively. Accuracy was checked by a recovery experiment at three different levels, and the recoveries of the tested solvents were ranged from 94.3% to 105.4%. The relative standard deviation (RSD) of each solvent for intra- and inter-day precision is in the range of 0.85 to 3.65 and 1.51 to 4.53, respectively. The developed approach can be readily used for determination of the residual solvents in six active pharmaceutical ingredients including pramipexole dihydrochloride, rivaroxaban, lisinopril, ramipril, imatinib mesylate and sitagliptin. | Matrix media;Natural deep eutectic solvents;Residual solvents;Static headspace gas chromatography | pubmed |
Remote Sensing of Wildland Fire-Induced Risk Assessment at the Community Level. | Wildland fires are some of the critical natural hazards that pose a significant threat to the communities located in the vicinity of forested/vegetated areas. In this paper, our overall objective was to study the structural damages due to the 2016 Horse River Fire (HRF) that happened in Fort McMurray (Alberta, Canada) by employing primarily very high spatial resolution optical satellite data, i.e., WorldView-2. Thus, our activities included the: (i) estimation of the structural damages; and (ii) delineation of the wildland-urban interface (WUI) and its associated buffers at certain intervals, and their utilization in assessing potential risks. Our proposed method of remote sensing-based estimates of the number of structural damages was compared with the ground-based information available from the Planning and Development Recovery Committee Task Force of Regional Municipality of Wood Buffalo (RMWB); and found a strong linear relationship (i.e., r² value of 0.97 with a slope of 0.97). Upon delineating the WUI and its associated buffer zones at 10 m, 30 m, 50 m, 70 m and 100 m distances; we found existence of vegetation within the 30 m buffers from the WUI for all of the damaged structures. In addition, we noticed that the relevant authorities had removed vegetation in some areas between 30 m and 70 m buffers from the WUI, which was proven to be effective in order to protect the structures in the adjacent communities. Furthermore, we mapped the wildland fire-induced vulnerable areas upon considering the WUI and its associated buffers. Our analysis revealed that approximately 30% of the areas within the buffer zones of 10 m and 30 m were vulnerable due to the presence of vegetation; in which, approximately 7% were burned during the 2016 HRF event that led the structural damages. Consequently, we suggest to remove the existing vegetation within these critical zones and also monitor the region at a regular interval in order to reduce the wildland fire-induced risk. | 2016 Horse River Fire;WorldView-2;structural damages;very high spatial resolution;wildland-urban interface (WUI) | pubmed |
Reevaluation of intrapartum fetal monitoring using fetal oximetry: A review. | Although several studies reported the measurement of fetal oxygen saturation using fetal pulse oximetry (FPO) for evaluation of the fetal intrapartum condition, a systematic review of the seven randomized controlled trials (RCTs) provided no evidence to support FPO for intrapartum fetal monitoring. In the present review, we re-evaluate an overview for the use of FPO and seven RCTs of FPO. We reviewed numerous previous reports on FPO and seven RCTs of intrapartum FPO. RCTs were conducted with the main outcome measure being a reduction in the cesarean section rate. The largest trial with 5341 entries failed to show any reduction. The negative result from this RCT may be explained by the use of a different cutoff value for fetal oxygen saturation compared to the other RCT; in addition, there were differences in the indications for cesarean section due to dystocia and in the definition of non-reassuring fetal status (NRFS). An abnormal FPO value, defined as the fetal oxygen saturation value <30% for at least 10 min, is useful for making a diagnosis of fetal acidosis. A newly developed device, an examiner's finger-mounted tissue oximetry, accurately measures tissue oxygen saturation while overcoming the drawbacks of FPO, such as infection risk and slipping off of the sensor during descent of the fetal head. FPO (including the new device) with fetal heart rate monitoring in selected cases of NRFS may reduce the cesarean section rate. | examiner's mounting probe;fetal monitoring;fetal pulse oximetry;near-infrared spectroscopy;tissue oximetry | pubmed |
Brewer's yeast is a potent inducer of fever, sickness behavior and inflammation within the brain. | Brewer's yeast, derived from the yeast species Saccharomyces cerevisiae (S. cerevisiae), is commonly used for inducing pyrexia in pharmacological studies screening antipyretics in rats. Despite its widespread use, the peripheral and central inflammatory response associated with Brewer's yeast-induced fever and sickness behavior in rats has not been investigated. Thus, we injected male Sprague-Dawley rats (150-200 g) subcutaneously with a high (4 g/kg, n = 9), medium (2 g/kg, n = 5) or low (0.4 g/kg, n = 6) dose of Brewer's yeast solution or saline (0.9%, n = 6) and measured core body temperature, cage activity, food intake and body mass for six days after injection. Blood and brain samples were collected at 2, 8, 18 and 72 h after injection; n = 5-7 per time point. Brewer's yeast administration dose-dependently induced fever, lethargy, anorexia and body mass stunting that was accompanied by increased blood plasma levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and activation of inflammatory transcription factors (nuclear factor (NF) for interleukin-6, signal transducer and activator of transcription (STAT)-3, and NF-κB)) in the hypothalamus and circumventricular organs. The increased activation of transcription factors following Brewer's yeast administration was accompanied by increased hypothalamic mRNA expression of TNF-α, IL-1β and IL-6 and rate-limiting enzymes for prostaglandin synthesis. Our results show that subcutaneous administration of S. cerevisae induces prolonged fever, anorexia and lethargy that is accompanied by a pronounced increase in the synthesis of pro-inflammatory cytokines, key prostaglandin synthesizing enzymes and transcription factors, in the periphery and brain. | Anorexia;Circumventricular organs;Cytokines;Lethargy;Saccharomyces cerevisiae;Systemic inflammation;Transcription factors | pubmed |
Cobalt not detected in contemporary US consumer paint colorants by cobalt indicator solution or X-ray fluorescence spectroscopy. | allergic contact dermatitis;cobalt;consumer exposure;metal allergy;paint | pubmed |
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Applicability Evaluation of Simplified Cognitive Behavioral Therapy. | We have developed a structured cognitive behavioral therapy manual for anxiety disorder in China, and the present study evaluated the applicability of simplified cognitive behavioral therapy based on our previous research. To evaluate the applicability of simplified cognitive behavioral therapy (SCBT) on generalized anxiety disorder (GAD) by conducting a multi-center controlled clinical trial. A multi-center controlled clinical trial of SCBT was conducted on patients with GAD, including institutions specializing in mental health and psychiatry units in general hospitals. The participants were divided into 3 groups: SCBT group, SCBT with medication group and medication group. The drop-out rates of these three groups, the therapy satisfaction of patients who received SCBT and the evaluation of SCBT from therapists were compared. (1) There was no significant difference among the drop-out rates in the three groups. (2) Only the duration and times of therapy were significantly different between the two groups of patients who received the SCBT, and the therapy satisfaction of the SCBT group was higher than that of the SCBT with medication group. (3) Eighteen therapists who conducted the SCBT indicated that the manual was easy to comprehend and operate, and this therapy could achieve the therapy goals. The applicability of SCBT for patients with GAD is relatively high, and it is hopeful that SCBT can become a psychological treatment which can be applied in medical institutions of various levels. | evaluation;generalized anxiety disorder;manual;simplified cognitive behavioral therapy | pubmed |
Management of Posterior Cruciate Ligament Tibial Avulsion Injuries: A Systematic Review. | Tibial-sided avulsion injuries of the posterior cruciate ligament (PCL) generally require surgical intervention. No consensus exists concerning the optimal surgical treatment approach for these injuries. To perform a systematic review investigating the open and arthroscopic surgical treatment modalities, outcomes, and complications of PCL tibial-sided bony avulsions. Systematic review; Level of evidence, 4. The authors performed a systematic review of the literature utilizing PubMed and EMBASE from 1975 to present outlining open versus arthroscopic surgical repair of PCL bony avulsion injuries and comparing subjective and objective postoperative patient-reported outcomes, including Tegner, IKDC (International Knee Documentation Committee), and Lysholm scoring systems, as well as rates of patient complications. The quest was performed in June 2016, and searched terms included posterior cruciate ligament, PCL, bony, avulsion(s), tibial-sided, open, and arthroscopic. Inclusion criteria included English-language studies involving surgical fixation strategies for PCL tibial-sided bony avulsions. Exclusion criteria included non-English language, case studies/case series, and subject matter not pertaining to PCL bony avulsions. Twenty-eight articles comprising 637 patients met the criteria and were included in the final review. PCL injuries with a tibial-sided avulsion were the result of motor vehicle accidents in 68.4% of patients, with 59.0% of these injuries resulting from motorcycle accidents. The arthroscopic group had better IKDC grade A scores (78.9%), indicating a normal knee postoperatively, as compared with the open group (65.9%). The postoperative Lysholm scores were similar between the groups, with a mean of 95.0 in the arthroscopic group and 92.8 in the open group. The arthroscopic group also reported 100% return to preinjury level of activity, compared with 86.2% in the open group. The most common complication in both groups was arthrofibrosis, which was reported more often in the arthroscopic group (0%-35%) versus the open treatment group (0%-25%). In patients with displaced tibial-sided PCL avulsion fractures treated operatively, surgical approaches render similar outcomes and risks. While the arthroscopic group had somewhat higher subjective and objective knee outcome scores, it demonstrated a slightly higher rate of arthrofibrosis. The clear advantage of the arthroscopic approach is that concomitant intra-articular injuries seen on preoperative magnetic resonance imaging, such as meniscal tears or osteochondral loose fragments, can be addressed at the time of the index operation. | PCL;arthroscopic;avulsion;bony;knee;open;posterior cruciate ligament | pubmed |
MicroRNA-200a Affects the Proliferation of Airway Smooth Muscle Cells and Airway Remodeling by Targeting FOXC1 via the PI3K/AKT Signaling Pathway in Ovalbumin-Induced Asthmatic Mice. | The etiology of asthma, which is a complicated disorder with various symptoms, including wheezing, coughing, and airflow obstruction, remains poorly understood. In addition, the effects of microRNAs (miRs) have not been explored. This study explored the effect of microRNA-200a (miR-200a) on airway smooth muscle cells (ASMCs) and airway remodeling in asthmatic mice. Furthermore, we speculated that miR-200a achieves its effect by targeting FOXC1 via the PI3K/AKT signaling pathway based on differentially expressed gene screening, target miR predictions and a bioinformatics analysis. Eighty mice were assigned to a saline group or an ovalbumin (OVA) group, and the OVA group was transfected with a series of inhibitors, activators, and siRNAs to test the established mouse model. Airway reactivity and the ratio of eosinophils (EOSs) to leukocytes were detected. An ELISA was adopted to measure the levels of interleukin (IL)-4, IL-6, IL-8, tumor necrosis factor (TNF)-α, and immunoglobulin E (IgE). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to determine the expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1, TGF-β1 and p-AKT in ASMCs. Finally, CCK-8 assays were performed to detect cell proliferation and flow cytometry to detect apoptosis and cell cycle entry. The bioinformatics analysis indicated that miR-200a mediated the PI3K/AKT signaling pathway by targeting FOXC1. In addition, mouse models of asthma were established. An elevated expression of miR-200a, a decreased mRNA and protein expression of FOXC1, PI3K, AKT, NF-κB, cyclin D1 and TGF-β1, a decreased expression of p-AKT, suppressed cell proliferation, accelerated apoptosis, and an increased number of cells at the G0/G1 phase were observed following the upregulation of miR-200a and downregulation of FOXC1. The overexpression of miR-200a may downregulate FOXC1, thereby inhibiting the activation of the PI3K/AKT signaling pathway and ultimately suppressing ASMC proliferation and airway remodeling in asthmatic mice. This evidence supports the potential that miR-200a represents a new approach to treating asthma. | Airway remodeling;Airway smooth muscle cell;Asthma;FOXC1;MicroRNA-200a;PI3K/AKT signaling pathway | pubmed |
Antibiotics for urethral catheterization in children undergoing cystography: retrospective evaluation of a single-center cohort of pediatric non-toilet-trained patients. | Antibiotics are often used to prevent post-catheterization urinary tract infections (UTIs) in patients undergoing cystography. However, there is no universally accepted protocol and the literature data are conflicting. We aimed to determine prevalence and risk factors of post-cystography UTIs in non-toilet-trained children. We retrospectively evaluated 216 non-toilet-trained children not assuming antibiotics when undergoing cystography. Only the patients with dilated vesico-ureteral reflux (VUR) assumed antibiotics just after the exam (within 15 min). One hundred eleven patients without vesico-ureteral reflux (VUR) and 29 patients with non-dilated VUR did not receive post-procedure antibiotics and did not develop UTIs. Out of the 76 patients who showed a dilated VUR and received post-procedure antibiotics, only 5 (6.6%) developed a UTI. The most significant factor associated with post-cystography UTIs was the presence of dilated VUR (p = 0.005) with the presence of bilateral VUR also being significant (p = 0.02).Conclusion: Patients without dilated VUR or bilateral VUR could not benefit from antibiotic prophylaxis for cystography. What is Known: • There is no universally accepted protocol about antibiotic administration in children undergoing cystography. • Literature data are conflicting. What is New: • Among 216 non-toilet-trained children undergoing cystography, 111 patients without vesico-ureteral reflux (VUR) and 29 patients with non-dilated VUR did not receive post-procedure antibiotics and did not develop UTIs. Out of the 76 patients who showed a dilated VUR and received post-procedure antibiotics, only 5 (6.6%) developed a UTI. • The most significant factor associated to post-cystography UTIs was the presence of dilated VUR (p = 0.005) with presence of bilateral VUR also being significant (p = 0.02). | Children;Cystography;Urinary catheterization;Urinary tract infections;Vesico-ureteral reflux | pubmed |
Alternative Routes to the Click Method for the Synthesis of 1,2,3-Triazoles, an Important Heterocycle in Medicinal Chemistry. | Heterocyclic rings having nitrogen atoms are the molecular fragments most used in drug design by using the tools of medicinal chemistry. The 1,2,4-triazole rings are part of an extensive family of drugs that are in use in the pharmaceutical market. More recently, 1,2,3-triazole rings have begun to arouse the great interest of scientists and therefore, many researches have been developed seeking the synthesis of new substances and their possible biological activities. A number of articles have been published by us and others highlighting the synthetic and biological aspects of 1,2,3-triazoles. The growth of new substances of this class was largely due to the simple and selective synthetic method of 1,2,3- triazole ring developed by Sharpless et al. However, some 1,2,3-triazole cannot be synthesized by this method. This review focuses on other synthetic methods that give access to other variations around the 1,2,3-triazole core. The systematic arrangement in this review explores the possibility of providing practical guidance to alternatives of this heterocycle. It has been divided into sections according to the types of starting materials and reactions. | 1,2,3-Triazoles;Azocompounds;Biological activity;Drug design;Drugs;Heterocycles. | pubmed |
Where there is smoke: Introduction to the virtual special issue of health impacts of wildland fire smoke exposure - Selected papers from the 2nd International Smoke Symposium. | Air pollution;Health impacts;Prescribed fire;Public health;Smoke;Wildland fire | pubmed |
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US regional variations in rates, outcomes, and costs of spinal arthrodesis for lumbar spinal stenosis in working adults aged 40-65 years. | OBJECTIVEIt is important to identify differences in the treatment of common diseases over time and across geographic regions. Several studies have reported increased use of arthrodesis to treat lumbar spinal stenosis (LSS). The purpose of this study was to investigate geographic variations in the treatment of LSS by US region.METHODSThe authors reviewed inpatient and outpatient medical claims from 2010 to 2014 using the MarketScan Commercial Claims and Encounters database (Truven Health Analytics), which includes data on commercially insured members younger than 65 years. ICD-9 code 724.02 was used to identify patients aged ≥ 40 and < 65 years who underwent surgery for "spinal stenosis of the lumbar region" and for whom LSS was the only principal diagnosis. The primary outcome was the performance of spinal arthrodesis as part of the procedure. Geographic regions were based on patient residence and defined according to the US Census Bureau as the Northeast, Midwest, South, and West.RESULTSRates of arthrodesis, as opposed to decompression alone, varied significantly by region, from 48% in the South, to 42% in the Midwest, 36% in the Northeast, and 31% in the West. After controlling for patient age, sex, and Charlson Comorbidity Index values, the differences remained significant. Compared with patients in the Northeast, those in the South (OR 1.6, 95% CI 1.50-1.75) and Midwest (OR 1.3, 95% CI 1.18-1.41) were significantly more likely to undergo spinal arthrodesis. On multivariate analysis, patients in the West were significantly less likely to have a prolonged hospital stay (> 3 days) than those in the Northeast (OR 0.84, 95% CI 0.75-0.94). Compared with the rate in the Northeast, the rates of discharge to a skilled nursing facility were lower in the South (OR 0.41, 95% CI 0.31-0.55) and West (OR 0.72, 95% CI 0.53-0.98). The 30-day readmission rate was significantly lower in the West (OR 0.81, 95% CI 0.65-0.98) than in the Northeast and similar between the other regions. Mean payments were significantly higher in the Midwest (mean difference $5503, 95% CI $4279-$6762), South (mean difference $6187, 95% CI $5041-$7332), and West (mean difference $7732, 95% CI $6384-$9080) than in the Northeast.CONCLUSIONSThe use of spinal arthrodesis, as well as surgical outcomes and payments for the treatment of LSS, varies significantly by US region. This highlights the importance of developing national recommendations for the treatment of LSS. | CCI = Charlson Comorbidity Index;CI = confidence interval;ICD-9 = International Classification of Diseases, Ninth Revision;LOS = length of stay;LSS = lumbar spinal stenosis;OR = odds ratio;SD = standard deviation;SNF = skilled nursing facility;USD = US dollars;geographic region;lumbar spinal stenosis;spinal arthrodesis;surgical trends | pubmed |
Maspin Enhances the Anticancer Activity of Curcumin in Hormone-refractory Prostate Cancer Cells. | Androgen deprivation therapy remains the principal treatment for patients with advanced prostate cancer, though, most patients will eventually develop hormone-refractory prostate cancer (HRPC). Androgen ablation mediated maspin-induction has been identified in cancer patients. However, the role of maspin on the anticancer activity of curcumin derived from turmeric (Curcuma longa) in HRPC cells has not been elucidated. The anticancer action of curcumin in hormone-independent prostate cancer cells (DU145, and PC-3) was determined by measures of cell survival rate. The cause of maspin silencing on the anti-tumor abilities of curcumin in PC-3 cells was evaluated by measures of cell survival rate, cell-cycle distribution, and apoptosis signaling analysis. Our present study showed that PC-3 cells (with higher maspin expression) were more sensitive than DU145 cells to curcumin treatment (with lower maspin expression). RNA interference-mediated maspin silencing reduced curcumin sensitivity of PC-3 cells, as evidenced by reduced apoptotic cell death. After exposure to curcumin, maspin-knockdown cells showed lower expression levels of pro-apoptotic proteins, Bad and Bax, as compared with control cells. Maspin can enhance the sensitivity of HRPC cells to curcumin treatment. | Maspin;curcumin;hormone-refractory prostate cancer | pubmed |
Attenuating Effects of Nortrachelogenin on IL-4 and IL-13 Induced Alternative Macrophage Activation and on Bleomycin-Induced Dermal Fibrosis. | Excessive alternative macrophage activation contributes to fibrosis. We studied the effects of nortrachelogenin, the major lignan component of Pinus sylvestris knot extract, on alternative (M2) macrophage activation. J774 murine and THP-1 human macrophages were cultured with IL-4+IL-13 to induce alternative activation, together with the extract and its components. Effects of nortrachelogenin were also studied in bleomycin-induced murine dermal fibrosis model. Knot extract significantly decreased the expression of alternative activation markers-arginase 1 in murine macrophages (97.4 ± 1.3% inhibition at 30 μg/mL) and CCL13 and PDGF in human macrophages-as did nortrachelogenin (94.9 ± 2.4% inhibition of arginase 1 at 10 μM). Nortrachelogenin also decreased PPARγ expression but had no effect on STAT6 phosphorylation. In vivo, nortrachelogenin reduced bleomycin-induced increase in skin thickness as well as the expression of collagens COL1A1, COL1A2, and COL3A1 (all by >50%). In conclusion, nortrachelogenin suppressed IL-4+IL-13-induced alternative macrophage activation and ameliorated bleomycin-induced fibrosis, indicating therapeutic potential in fibrosing conditions. | Pinus sylvestris;alternative macrophage activation;bleomycin;fibrosis;nortrachelogenin | pubmed |
SIRT6 drives epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer via snail-dependent transrepression of KLF4. | Epithelial-to-mesenchymal transition (EMT) contributes to the invasion and metastasis of epithelial tumors. Sirtuin 6 (SIRT6), an NAD-dependent deacetylase, is known to promote metastasis of non-small cell lung cancer (NSCLC). In this work, we determined the role of SIRT6 in the EMT of NSCLC cells and identified the key EMT-related genes involved in the oncogenic activity of SIRT6. We report that depletion of SIRT6 inhibits transforming growth factor-β1 (TGF-β1)-induced EMT in A549 and H1299 NSCLC cells, which is rescued by ectopic expression of SIRT6. Knockdown of SIRT6 leads to a reduction in Snail protein without affecting the mRNA level. Immunoprecipitation experiments demonstrate a physical association between SIRT6 and Snail. SIRT6 deacetylates Snail and prevents its proteasomal degradation. Silencing of Snail blunts SIRT6-induced NSCLC cell migration and invasion, while overexpression of Snail restores the invasion and EMT in SIRT6-depleted NSCLC cells. SIRT6 depletion leads to an upregulation of kruppel-like factor 4 (KLF4) and reduced Snail binding to the promoter of Klf4 in NSCLC cells. Knockdown of KLF4 rescues the invasive capacity in SIRT6-depleted NSCLC cells. Conversely, co-expression of KLF4 impairs SIRT6-induced aggressive behavior. In vivo data further demonstrate that SIRT6-induced NSCLC metastasis is antagonized by overexpression of KLF4. These findings provide mechanistic insights into the pro-metastatic activity of SIRT6 and highlight the role of the SIRT6/Snail/KLF4 axis in regulating EMT and invasion of NSCLC cells. | Lung cancer;Metastasis;SIRT6;Snail;Transrepress | pubmed |
How Can Prosocial Behavior Be Motivated? The Different Roles of Moral Judgment, Moral Elevation, and Moral Identity Among the Young Chinese. | Prior research has shown that moral judgment, moral elevation, and moral identity contribute to prosocial behavior. However, how these three motivating factors interact in predicting prosocial behaviors is not yet clear. The current study proposed and examined a moderated mediation model to illustrate the specific process of how prosocial behavior is motivated by these factors. A total of 264 Chinese undergraduate and graduate students participated in the present study (140 females; age range 17-26, <i>M</i> = 20.25, <i>SD</i> = 1.57). Moral judgment competence, intensity of moral elevation, and moral identity were measured by self-reported scales, and the tendency to engage in prosocial behavior was assessed in a simulated "Ask for help" situation. The multiple regressive results showed that moral elevation mediated the effect of moral judgment on prosocial behavior, and moral identity moderated this mediation through interacting with moral elevation. However, within the proposed model, the mediating effect of moral elevation was stronger in women than in men, while the moderating role of moral identity appeared only in women. These findings imply different methods for men and women to enhance their prosocial behaviors, including the need to pay more attention to developing moral reasoning in men while putting more emphasis on evoking moral emotion and moral traits in women. Together, these results supported the assumptive model and provided a comprehensive framework to explain prosocial behaviors. | moderated mediation;moral elevation;moral identity;moral judgment;prosocial behavior | pubmed |
Different neuromuscular parameters influence dynamic balance in male and female football players. | To analyse the relationship between several parameters of neuromuscular performance with unilateral dynamic balance measured through the Y-Balance test, as well as to determine the possible sex-related differences. The Y-Balance test, isokinetic (concentric and eccentric) knee flexion and extension strength, isometric hip abduction and adduction strength, lower extremity joint range of motion (ROM) (hip, knee and ankle) and core stability were assessed in male (n = 88) and female (n = 44) professional football players. A stepwise multivariate linear least square regression with backward elimination analysis was carried out to identify a group of factors that were independently associated with balance performance in both sexes. Passive hip flexion and ankle dorsiflexion with knee flexed ROM were the main factors that retained a significant association to dominant (R<sup>2</sup> = 23.1) and non-dominant (R<sup>2</sup> = 33.5) balance scores for males. For females, core stability, hip abduction isometric peak torque, passive hip abduction and ankle dorsiflexion with knee flexed ROM variables retained a significant association with balance scores for both, dominant (R<sup>2</sup> = 38.2) and non-dominant (R<sup>2</sup> = 46.9) legs. Training interventions aimed at improving or maintaining unilateral dynamic balance in male football players should include, among other things, stretching exercises for the posterior chain of the lower extremity. However, females should also include exercises for strength and mobility of the hip abductors and core stability (especially in the frontal plane). This knowledge would allow clinicians and sport practitioners to develop more effective and tailored unilateral dynamic balance training interventions in male and female football players, possibly improving performance and reducing the risk of injury. III. | Injury;Performance;Strength;Trunk stability;Y-Balance | pubmed |
Incidence of hyponatraemia following the use of three different intravenous fluids in paediatric surgery. | It is a common practice to administer 4.3% dextrose in 0.18% saline peri-operatively and for routine fluid maintenance in the paediatric age group. Concerns have been expressed about the risk of hyponatraemia associated with the administration of hypotonic intravenous fluids, hence the need to re-evaluate our practice. This study aims to evaluate the relative incidence of intra-operative hyponatraemia following the use of isotonic and hyopotonic intravenous fluids. This randomised double-blind clinical trial recruited consecutive American Society of Anaesthesiologists physical status Class I and II children aged between 6 months and 17 years scheduled for various minor elective surgical procedures. The patients received one of 3 intravenous infusions for intra-operative fluid management. Group I received 4.3% dextrose in 0.18 saline (n = 25), Group II received normal saline (n = 20) and Group III received Ringer's lactate (n = 20). Blood samples were collected before the surgery and at the end of surgery for serum electrolytes. One patient in each group developed moderate hyponatraemia intraoperatively. This constituted a 4% (1/25) incidence of intra-operative hyponatraemia among patients who had hypotonic maintenance fluid and a 5% (2/40) incidence in the isotonic maintenance groups. The incidence of hyponatraemia was therefore comparable between patients who had hypotonic and isotonic intra-operative maintenance fluids (P = 1.000). We conclude that healthy children who have intraoperative hypotonic maintenance fluids during minor elective surgeries are not exposed to the additional risk of hyponatraemia compared to those who have isotonic fluids. The study of a larger sample size is recommended to further validate our findings. | Hyponatraemia;intra-operative;intravenous fluids;paediatrics;surgery | pubmed |
How the gene behind Huntington's disease could be neutralized. | Brain;Gene therapy;Neurodegeneration;Therapeutics | pubmed |
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Thalassemia: a prevalent disease yet unknown term among college students in Saudi Arabia. | Thalassemia is a life-threatening blood disorder that has a high prevalence in Saudi Arabia despite the implementation of mandatory premarital testing and the availability of genetic counseling. This study aimed to assess college students' knowledge of thalassemia. A cross-sectional survey of a random sample of 920 senior students enrolled at King Abdulaziz University was conducted. A self-administered questionnaire was used to collect information about thalassemia and socio-demographic characteristics. Of the 920 students, 445 (48%) had ever heard of thalassemia. Despite the mandatory premarital testing for thalassemia, only 50% of married students stated having heard of the disease. The mean thalassemia knowledge score was 4.4 ± 2.2 out of a maximum of 12. Knowledge was significantly influenced by university faculty, gender, and education outside of Saudi Arabia. Those who had heard of thalassemia had misconceptions about the disease characteristics and pattern of inheritance such as associating thalassemia with low iron levels. A substantial proportion of the participants had a low knowledge of thalassemia. This lack of awareness requires a reassessment of the goals and success of the premarital testing program, including the genetic counseling services, and also indicates the importance of emphasizing thalassemia in school curricula and promoting and scaling up existing thalassemia campaigns in the region. | Knowledge;Premarital testing;Prevention;Thalassemia | pubmed |
Hijacking of the AP-1 Signaling Pathway during Development of ATL. | Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a fatal malignancy known as adult T-cell leukemia (ATL). One way to address the pathology of the disease lies on conducting research with a molecular approach. In addition to the analysis of ATL-relevant signaling pathways, understanding the regulation of important and relevant transcription factors allows researchers to reach this fundamental objective. HTLV-1 encodes for two oncoproteins, Tax and HTLV-1 basic leucine-zipper factor, which play significant roles in the cellular transformation and the activation of the host's immune responses. Activating protein-1 (AP-1) transcription factor has been linked to cancer and neoplastic transformation ever since the first representative members of the Jun and Fos gene family were cloned and shown to be cellular homologs of viral oncogenes. AP-1 is a dimeric transcription factor composed of proteins belonging to the Jun (c-Jun, JunB, and JunD), Fos (c-Fos, FosB, Fra1, and Fra2), and activating transcription factor protein families. Activation of AP-1 transcription factor family by different stimuli, such as inflammatory cytokines, stress inducers, or pathogens, results in innate and adaptive immunity. AP-1 is also involved in various cellular events including differentiation, proliferation, survival, and apoptosis. Deregulated expression of AP-1 transcription factors is implicated in various lymphomas such as classical Hodgkin lymphomas, anaplastic large cell lymphomas, diffuse large B-cell lymphomas, and adult T-cell leukemia. Here, we review the current thinking behind deregulation of the AP-1 pathway and its contribution to HTLV-induced cellular transformation. | AP-1;HBZ;HTLV-1;JunD;antisense transcription;leukemia | pubmed |
Effects of Legal Access to Cannabis on Scheduled II-V Drug Prescriptions. | Co-prescribing of scheduled drugs is endemic in the United Sates, increasing health risks to patients and the burden on healthcare systems. We conducted a pragmatic historical cohort study to measure the effect of enrollment in a state-authorized United States' Medical Cannabis Program (MCP) on scheduled II-V drug prescription patterns. Eighty-three chronic pain patients, who enrolled in the New Mexico MCP between April 1, 2010 and October 3, 2015, were compared with 42 nonenrolled patients over a 24-month period (starting 6 months before enrollment for the MCP patients) using the Prescription Monitoring Program. The outcome variables include baseline levels and pre- and postenrollment monthly trends in the number of drug prescriptions, distinct drug classes, dates prescription drugs were filled, and prescribing providers. Twenty-eight MCP patients (34%) and 1 comparison group patient (2%) ceased the use of all scheduled prescription medications by the last 6 months of the observation period. Age- and sex-adjusted regressions show that, although no statistically significant differences existed in pre-enrollment levels and trends, the postenrollment trend among MCP patients is statistically significantly negative for all 4 measures (decreases in counts of -0.02 to -0.04, P values between <.001 and .017), whereas the postenrollment trend is 0 among the comparison group. Controlling for time-invariant patient characteristics suggested that MCP patients showed statistically significantly lower levels across all 4 measures by 10 months postenrollment. Legal access to cannabis may reduce the use of multiple classes of dangerous prescription medications in certain patient populations. | Marijuana;Prescription Monitoring Program;cannabis;opioids;scheduled medications;substitution | pubmed |
Recombinant Flag-tagged E1E2 glycoproteins from three hepatitis C virus genotypes are biologically functional and elicit cross-reactive neutralizing antibodies in mice. | Hepatitis C virus (HCV) is a globally disseminated human pathogen for which no vaccine is currently available. HCV is highly diverse genetically and can be classified into 7 genotypes and multiple sub-types. Due to this antigenic variation, the induction of cross-reactive and at the same time neutralizing antibodies is a challenge in vaccine production. Here we report the analysis of immunogenicity of recombinant HCV envelope glycoproteins from genotypes 1a, 1b and 2a, with a Flag tag inserted in the hypervariable region 1 of E2. This modification did not affect protein expression or conformation or its capacity to bind the crucial virus entry factor, CD81. Importantly, in immunogenicity studies on mice, the purified E2-Flag mutants elicited high-titer, cross-reactive antibodies that were able to neutralize HCV infectious particles from two genotypes tested (1a and 2a). These findings indicate that E1E2-Flag envelope glycoproteins could be important immunogen candidates for vaccine aiming to induce broad HCV-neutralizing responses. | E1E2;Envelope glycoproteins;Flag tag;Hepatitis C virus;Neutralization;Vaccine | pubmed |
The hospital anxiety and depression scale, in patients with multiple sclerosis. | Multiple sclerosis (MS) is a long-lasting disabling disease with psychological implications. Hospital Anxiety and Depression Scale (HADS) is a questionnaire developed to screen anxiety and depression among patients in hospital settings. The objective of this report was to study the metric properties of the Portuguese version of HADS regarding MS. This was a cross-sectional study. Three hundred and eighty individuals with a diagnosis of MS, according to the revised McDonald criteria, were recruited from an outpatient Neuroimmunology Clinic of the city of Porto. Participants had a mean age of 40.04 years (SD =10.86), 63.9% of them were female. HADS consists of two subscales - anxiety and depression - scored separately, with seven items each. The results of our study show the appropriateness of HADS for the identification of mood changes in people with MS and show good metric properties. It seems to be a useful tool for the scrutiny of mood disorders in Portuguese patients with MS. The questionnaire is also sensitive to disease when compared to people with other severe illnesses, and with people without the disease. | HADS;anxiety;depression;multiple sclerosis | pubmed |
Social Information Links Individual Behavior to Population and Community Dynamics. | When individual animals make decisions, they routinely use information produced intentionally or unintentionally by other individuals. Despite its prevalence and established fitness consequences, the effects of such social information on ecological dynamics remain poorly understood. Here, we synthesize results from ecology, evolutionary biology, and animal behavior to show how the use of social information can profoundly influence the dynamics of populations and communities. We combine recent theoretical and empirical results and introduce simple population models to illustrate how social information use can drive positive density-dependent growth of populations and communities (Allee effects). Furthermore, social information can shift the nature and strength of species interactions, change the outcome of competition, and potentially increase extinction risk in harvested populations and communities. | Allee effect;coexistence;density dependence;environmental change;facilitation;population dynamics;public information;social interactions;species interactions | pubmed |
Hyperechoic breast images: all that glitters is not gold! | Hyperechogenicity is a sign classically reported to be in favour of a benign lesion and can be observed in many types of benign breast lesions such as hamartoma, lipoma, angiolipoma, haemangioma, haematoma, fat necrosis, fibrosis and galactocele, among others. However, some rare malignant breast lesions can also present a hyperechoic appearance. Most of these hyperechoic malignant lesions present other characteristics that are more typically suggestive of malignancy such as posterior shadowing, a more vertical axis or irregular margins that help to guide the diagnosis. Post magnetic resonance imaging, second-look ultrasound may visualise hyperechoic malignant lesions that would not have been identified at first sight and radiologists must know how to recognise these lesions. • Some rare malignant breast lesions can present a hyperechoic appearance. • Malignant lesions present other characteristics that are suggestive of malignancy. • An echogenic mass with fat density on mammography does not require biopsy. | Breast cancer;Breast ultrasound;Histology;Hyperechogenicity;Malignancy | pubmed |
Stability and oscillatory behavior of microbial consortium in continuous conversion of crude glycerol to 1,3-propanediol. | Microbial consortium is an alternative for bioconversion of crude glycerol to value-added products whereas concerns about the process stability in long-term operation existed. The aim of this study is to evaluate the feasibility of using an anaerobic microbial consortium as inoculum for continuous conversion of crude glycerol to 1,3-propanediol (1,3-PDO). Performances of continuous fermentations with the consortium inoculum were evaluated under different dilution rates and glycerol feed concentrations. The highest 1,3-PDO production of 57.86 g/L was achieved with a productivity of 5.55 g/(L·h). Analyses of kinetic data showed that the consortium maintained a consistent pattern for 1,3-PDO production under different operating conditions despite changes in community composition. The continuous fermentation by the consortium was able to operate for a longer period of time (31 volume changes) than that using pure culture (24 volume changes) with the average 1,3-PDO concentration of 53.52 g/L and productivity of 6.69 g/(L·h) under glycerol-excess condition, which could be contributed to the intraspecies diversity among Clostridium butyricum in the consortium. Under glycerol-limited conditions, however, a spontaneous oscillation of the consortium was observed after continuous operation for about 120 h, along with severe fluctuations of the microbial community. The oscillatory behavior could be reduced by increasing the dilution rates and was likely the metabolic feature of C. butyricum. | 1,3-Propanediol;Clostridium butyricum;Continuous fermentation;Microbial consortium;Oscillation;Stability | pubmed |
The first case of genetically confirmed sparganosis (Spirometra erinaceieuropaei) in European reptiles. | Sparganosis is a zoonosis caused by the spargana (larvae) of Spirometra sp. (Diphyllobothriidae). Reptiles are particularly important vectors for the transmission of this parasite in Asia; however, their role in sparganosis spread in European wildlife is unrecognized. We investigated the infection of reptiles with Spirometra sp. in NE Poland, where several mammalian hosts have been identified recently and in the past. Of the 59 dead reptiles, plerocercoids were found in two grass snakes (Natrix natrix) from the Białowieża Primeval Forest (BPF). The Spirometra erinaceieuropaei species was genetically confirmed using the evolutionary conserved nuclear 18S rRNA gene, and then compared to GenBank deposits. The sequences were identical to previously investigated Spirometra sp. found in Eurasian badger and wild boar from BPF. Our finding is the first genetically confirmed record of Spirometra sp. in reptiles in Europe. Since reptiles are often a component of mammalian diet, they can be a source of Spirometra tapeworm infection in European wildlife; however, further studies are needed to investigate the prevalence of infection in reptiles and other non-mammalian hosts. | DNA analyses;Natrix natrix;Non-mammalian host;Plerocercoid;Sparganum;Zoonosis | pubmed |
Changes in peroxisome proliferator-activated receptor alpha target gene expression in peripheral blood mononuclear cells associated with non-alcoholic fatty liver disease. | To identify differences in the expression of peroxisome proliferator-activated receptor alpha (PPARα) target genes in human peripheral blood mononuclear cells (PBMCs) associated with non-alcoholic fatty liver disease (NAFLD) among Chinese individuals. Thirty healthy subjects were selected as the control group (CN), and 43 patients newly diagnosed with NAFLD were subdivided into two groups, non-obese group (NF, n = 21) and obese group (OF, n = 22). Expression of PPARα and its target genes was determined in PBMCs. The levels of liver cell damage markers, total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), glucose, and insulin were determined in serum. Compared to the CN group, the blood pressure and homeostasis model assessment for insulin resistance (HOMA-IR) were increased in the other groups (P < 0.05), while the systolic blood pressure (SBP) and liver cell damage markers were significantly increased in the OF group (P < 0.05). In the OF group, PPARα target gene expression was 2.03-3.31 times higher than that in the CN group, and a negative correlation was found between PPARα target gene expression and abdominal circumference (AC), body mass index (BMI), diastolic blood pressure (DBP). Additionally, solute carrier family 25 (carnitine/acylcarnitine translocase) member 20 (SLC25A20) and acyl-coenzyme A dehydrogenase 2 long chain (ACADVL) were negatively correlated with HOMA-IR; PPARα, acetyl-coenzyme A dehydrogenase 2 (ACAA2), and carnitine palmitoyltransferase 1A (CPT1A) were positively correlated with HOMA-IR. There is an up-expression of PPARα target genes in the PBMCs of NAFLD patients, possibly leading to changes in β-oxidation and insulin resistance. | Insulin resistance;NAFLD;Obesity;PBMC;PPARα | pubmed |
Towards chemically neutral carbon cleaning processes: plasma cleaning of Ni, Rh and Al reflective optical coatings and thin Al filters for free-electron lasers and synchrotron beamline applications. | The choice of a reflective optical coating or filter material has to be adapted to the intended field of application. This is mainly determined by the required photon energy range or by the required reflection angle. Among various materials, nickel and rhodium are common materials used as reflective coatings for (soft) X-ray mirrors. Similarly, aluminium is one of the most commonly used materials for extreme ultraviolet and soft X-ray transmission filters. However, both of these types of optics are subject to carbon contamination, which can be increasingly problematic for the operation of the high-performance free-electron laser and synchrotron beamlines. As an attempt to remove this type of contamination, an inductively coupled plasma source has been used in conjunction with N<sub>2</sub>/O<sub>2</sub>/H<sub>2</sub> and N<sub>2</sub>/H<sub>2</sub> feedstock gas plasmas. Results from the chemical surface analysis of the above materials before and after plasma treatment using X-ray photoelectron spectroscopy are reported. It is concluded that a favorable combination of an N<sub>2</sub>/H<sub>2</sub> plasma feedstock gas mixture leads to the best chemical surface preservation of Ni, Rh and Al while removing the carbon contamination. However, this feedstock gas mixture does not remove C contamination as rapidly as, for example, an N<sub>2</sub>/O<sub>2</sub>/H<sub>2</sub> plasma which induces the surface formation of NiO and NiOOH in Ni and RhOOH in Rh foils. As an applied case, the successful carbon removal from ultrathin Al filters previously used at the FERMI FEL1 using an N<sub>2</sub>/H<sub>2</sub> plasma is demonstrated. | FEL and synchrotron radiation beamline optics;carbon contamination;free-electron lasers (FELs);inductively coupled plasma;plasma cleaning chemistry | pubmed |
Diverse effects of the common hippopotamus on plant communities and soil chemistry. | The ecological importance of the common hippopotamus (Hippopotamus amphibius) in aquatic ecosystems is becoming increasingly well known. These unique megaherbivores are also likely to have a formative influence on the terrestrial ecosystems in which they forage. In this study, we employed a novel exclosure design to exclude H. amphibius from experimental plots on near-river grasslands. Our three-year implementation of this experiment revealed a substantial influence of H. amphibius removal on both plant communities and soil chemistry. H. amphibius significantly reduced grassland canopy height, increased the leafiness of common grasses, reduced woody plant abundance and size, and increased the concentrations of several soil elements. Many of the soil chemistry changes that we experimentally induced by exclusion of H. amphibius were mirrored in the soil chemistry differences between naturally occurring habitats of frequent (grazing lawns) and infrequent (shrub forest) use by H. amphibius and other grazing herbivores. In contrast to existing hypotheses regarding grazing species, we found that H. amphibius had little effect on local plant species richness. Simultaneous observations of exclosures designed to remove all large herbivores revealed that H. amphibius removal had ecologically significant impacts, but that the removal of all species of large herbivores generated more pronounced impacts than the removal of H. amphibius alone. In aggregate, our results suggest that H. amphibius have myriad effects on their terrestrial habitats that likely improve the quality of forage available for other herbivores. We suggest that ongoing losses of this vulnerable megaherbivore are likely to cause significant ecological change. | Exclosure;Grazing lawn;Megaherbivore;Nutrient cycling;Vegetation structure | pubmed |
Clinical impact of computed tomography in the emergency department in nontraumatic chest and abdominal conditions. | To evaluate the clinical impact of CT scan in modifying the clinical management in patients referred to the emergency department. We prospectively evaluated 300 patients (177 males, 63 ± 18 years old) admitted in the emergency department (ED) of a single institution, who underwent a CT examination for thoracic and/or abdominal complains. Demographic and clinical data were collected. Hypothesized outcome prior to CT scan and final management (i.e., discharge, short observation in the ED, hospitalization, and department of admission) were compared. After CT examination, a major variation in diagnosis occurred in 37% of cases and clinical management changed in 43%, occurring in 51% of patients who underwent abdominal CT, in 40% of chest CT, and in 29% of chest/abdominal CT (P = 0.015). Department of hospitalization changed in 26% of cases (P < 0.001). Clinical impact of CT scan was significantly associated (P = 0.001) with the color code at admission. In particular, the more severe was the clinical condition, the lower was the variation of management after CT examination. This work confirms the crucial role of CT examination in the management of nontraumatic patients admitted to the ED, both in terms of better clarifying the diagnosis and in influencing the clinical management. | Clinical impact;Computed tomography;Emergency department;Outcome | pubmed |
Improved Dehydrogenation Properties of LiBH<sub>4</sub> Using Catalytic Nickel- and Cobalt-based Mesoporous Oxide Nanorods. | Lithium borohydride (LiBH<sub>4</sub> ) with a theoretical hydrogen storage capacity of 18.5 wt % has attracted intense interest as a high-density hydrogen storage material. However, high dehydrogenation temperatures and limited kinetics restrict its practical applications. In this study, mesoporous nickel- and cobalt-based oxide nanorods (NiCo<sub>2</sub> O<sub>4</sub> , Co<sub>3</sub> O<sub>4</sub> and NiO) were synthesized in a controlled manner by using a hydrothermal method and then mixed with LiBH<sub>4</sub> by ball milling. It is found that the dehydrogenation properties of LiBH<sub>4</sub> are remarkably enhanced by doping the as-synthesized metal oxide nanorods. When the mass ratio of LiBH<sub>4</sub> and oxides is 1:1, the NiCo<sub>2</sub> O<sub>4</sub> nanorods display the best catalytic performance owing to the mesoporous rod-like structure and synergistic effect of nickel and cobalt active species. The initial hydrogen desorption temperature of the LiBH<sub>4</sub> -NiCo<sub>2</sub> O<sub>4</sub> composite decreases to 80 °C, which is 220 °C lower than that of pure LiBH<sub>4</sub> , and 16.1 wt % H<sub>2</sub> is released at 500 °C for the LiBH<sub>4</sub> -NiCo<sub>2</sub> O<sub>4</sub> composite. Meanwhile, the composite also exhibits superior dehydrogenation kinetics, which liberates 5.7 wt % H<sub>2</sub> within 60 s and a total of 12 wt % H<sub>2</sub> after 5 h at 400 °C. In comparison, pure LiBH<sub>4</sub> releases only 5.3 wt % H<sub>2</sub> under the same conditions. | hydrogen storage;lithium borohydride;mesoporous materials;nanorods;synergistic effect | pubmed |
The Effect of Sintering Time on the Marginal Fit of Zirconia Copings. | This study analyzed the effect of different sintering times on the marginal adaptation of zirconia ceramic copings. Thirty copings of pre-sintered 3Y-TZP blanks were milled and subsequently sintered in a special furnace for three different durations (n = 10 per group). The sintering time was 1 hour, 15 minutes for IPS e.max ZirCAD, 4 hours 20 minutes for Speed ZrO<sub>2,</sub> and 7 hours 20 minutes for the conventional ZrO<sub>2</sub> group. The marginal gaps of specimens were measured at 18 spots on the master die by employing a digital microscope. One-way ANOVA test compared the mean differences among the 3 groups (α = 0.05). The mean values for the marginal gap of the IPS e.max ZirCAD, Speed ZrO<sub>2</sub> , and conventional ZrO<sub>2</sub> groups were 41.06 ± 14.03, 43.03 ± 11.67, and 39.88 ± 15.23 μm, respectively. There was no statistically significant difference among the groups regarding the marginal gap. Different sintering times did not alter the marginal fit of the zirconia copings. The mean values of the marginal gap were within the clinically acceptable level for all three groups. | Marginal fit;sintering time;zirconia | pubmed |
Tungsten-loaded SMP foam nanocomposites with inherent radiopacity and tunable thermo-mechanical properties. | Shape memory polymer (SMP) foams have been developed for use in neurovascular occlusion applications. These materials are predominantly polyurethanes that are known for their biocompatibility and tunable properties. However, these polymers inherently lack X-ray visibility, which is a significant challenge for their use as implantable materials. Herein, low density, highly porous shape memory polyurethane foams were developed with tungsten nanoparticles dispersed into the foam matrix, at increasing concentrations, to serve as a radiopaque agent. Utilizing X-ray fluoroscopy sufficient visibility of the foams at small geometries was observed. Thermal characterization of the foams indicated altered thermal response and delayed foam actuation with increasing nanoparticle loading (because of restricted network mobility). Mechanical testing indicated decreased toughness and strength for higher loading because of disruption of the SMP matrix. Overall, filler addition imparted x-ray visibility to the SMP foams and allowed for tuned control of the transition temperature and actuation kinetics for the material. | aneurysm;dispersion;glass transition temperature;nanocomposite;radiopacity | pubmed |
Improving Outcomes by Implementing a Pressure Ulcer Prevention Program (PUPP): Going beyond the Basics. | A multidisciplinary process improvement program was initiated at the University of Miami Hospital (UMH) in 2009 to identify the prevalence of hospital-acquired pressure ulcers (HAPU) at the institution and to implement interventions to reduce the incidence of HAPU. This deliberate and thoughtful committee-driven process evaluated care, monitored results, and designed evidence-based strategic initiatives to manage and reduce the rate of HAPU. As a result all inpatient beds were replaced with support surfaces, updated care delivery protocols were created, and monitored, turning schedules were addressed, and a wound, ostomy, and continence (WOC) nurse and support staff were hired. These initial interventions resulted in a decrease in the prevalence of HAPU at UMH from 11.7% of stage II to IV ulcers in the second quarter, 2009 to 2.1% the third quarter. The rate remained at or near the 2009 UMH benchmark of 3.1% until the first quarter of 2012 when the rate rose to 4.1%. At that time new skin products were introduced into practice and continuing re-education was provided. The rate of HAPU dropped to 2.76% by the second quarter of 2012 and has remained steadily low at 1%-2% for nine consecutive quarters. | hospital-acquired pressure ulcers;pressure ulcer prevention;pressure ulcer prevention education;skin care | pubmed |
Reconstituted Keratin Biomaterial with Enhanced Ductility. | Nowadays the waste from protein fibres represents an important renewable source for a new generation of biomaterials and promising competitors for carbohydrate based biomaterials. Regenerated keratin biomaterials are biodegradable <i>in vivo</i> and <i>in vitro</i>, biocompatible, and support cell attachment and proliferation; however, their major drawback has been their weak mechanical properties such as ductility. The following study was conducted in an attempt to improve the ductility of reconstituted keratin films obtained from Australian merino wool fibres. Keratin was extracted from wool fibres according to an established protocol proposed by Yamauchi, and then dialyzed and desalted by multiple diafiltration wash cycles. The resulting keratin film was transparent, biodegradable, and, opposite to its predecessors, mechanically durable, possessing a Young modulus about 12.5 MPa with 35% extensibility. The polypeptide chains were found to rearrange themselves in the β-sheet state in this keratin film, which was shown to be semi-crystalline. This film, unlike its predecessors, did not support human cell proliferation. These properties of the diafiltered keratin film have led us to think that diafiltration resulted in producing a totally new keratin film, which is envisaged to find applications in various areas. | biodegradability;cell attachment;keratin;mechanical properties;recycling | pubmed |
Hg-contaminated terrestrial spiders pose a potential risk to songbirds at Caddo Lake (Texas/Louisiana, USA). | Methylmercury (MeHg) is an environmental contaminant that can have adverse effects on wildlife. Because MeHg is produced by bacteria in aquatic ecosystems, studies of MeHg contamination of food webs historically have focused on aquatic organisms. However, recent studies have shown that terrestrial organisms such as songbirds can be contaminated with MeHg by feeding on MeHg-contaminated spiders. In the present study, the authors examined the risk that MeHg-contaminated terrestrial long-jawed orb weaver spiders (Tetragnatha sp.) pose to songbirds at Caddo Lake (Texas/Louisiana, USA). Methylmercury concentrations in spiders were significantly different in river, wetland, and open-water habitats. The authors calculated spider-based wildlife values (the minimum spider MeHg concentrations causing physiologically significant doses in consumers) to assess exposure risks for arachnivorous birds. Methylmercury concentrations in spiders exceeded wildlife values for Carolina chickadee (Poecile carolinensis) nestlings, with the highest risk in the river habitat. The present study indicates that MeHg concentrations in terrestrial spiders vary with habitat and can pose a threat to small-bodied nestling birds that consume large amounts of spiders at Caddo Lake. This MeHg threat to songbirds may not be unique to Caddo Lake and may extend throughout the southeastern United States. | Caddo Lake;Methylmercury;Songbird;Terrestrial spider | pubmed |
Stress and alcohol use in rural Chinese residents: A moderated mediation model examining the roles of resilience and negative emotions. | Little research has been done on alcohol use and dependence among rural residents in China, a sub-population that might be under increased stress due to the rapid modernization and urbanization processes. We aimed to assess rural residents' levels of stress, negative emotions, resilience, alcohol use/dependence and the complex relationships among them. Survey data from a large random sample (n=1145, mean age=35.9, SD=7.7, 50.7% male) of rural residents in Wuhan, China were collected using Audio Computer-Assisted Self-Interview. The sample had high prevalence of frequently perceived stress (47%) and high prevalence of ever (54.4%), past 30-day (40.4%), and binge drinking (13.8%). Approximately 11% met the criterion for intermediate to severe alcohol dependence. Mediation analysis indicated that the association between perceived stress (predictor) and alcohol dependence (outcome) was fully mediated by anxiety (indirect effect=.203, p<.01) and depression (indict effect=.158, p<.05); moderation analysis indicated that association between stress and two negative emotions (mediators) was significantly modified by resilience (moderator); an integrative moderated mediation analysis indicated that the indirect effect from stress to alcohol dependence through negative emotions was also moderated by resilience. Negative emotions play a key role in bridging stress and alcohol dependence, while resilience significantly buffers the impact of stress on depression, reducing the risk of alcohol dependence. Resilience training may be an effective component for alcohol intervention in rural China. | Alcohol dependence;Mediated moderation;Negative emotions;Resilience;Rural China | pubmed |
Immediate video feedback on ramp, wheelie, and curb wheelchair skill training for persons with spinal cord injury. | We hypothesized that the effects of immediate video feedback (IVF) on training ramp, wheelie, and curb wheelchair skills for persons with spinal cord injury (SCI) would be equivalent to or better than the traditional wheelchair skill training. Participants were manual wheelchair users with recent SCI (thoracic 1-lumbar 1) who were matched (9 pairs) on motor function level, age, and sex and randomly assigned to a control group (conventional training) or an experimental group (IVF training). Participants learned three wheelchair skills and then went through the wheelchair skill competency test, retention test, and transfer test. Paired t-tests were used to examine the differences in training time (minutes), spotter intervention needed (counts), and successful rate in performance between the two groups. A 2 (groups) x 3 (skills) x 3 (tests) repeated-measures analysis of variance and Bonferroni adjustment test were used to examine differences between groups on wheelchair skills and tests. No differences were found between two groups in training times (minutes) on three wheelchair skills (experimental vs control: ramp 14.92 +/- 5.80 vs 11.69 +/- 7.85; wheelie 17.79 +/- 6.03 vs 19.92 +/- 13.42; and curb 38.35 +/-23.01 vs 48.59 +/- 15.21). This study demonstrated that IVF for training manual wheelchair skills may produce similar results as the conventional training and may be an alternative training method for wheelchair skills. | conventional training;learning;manual wheelchair;physical therapy;rehabilitation;skill performance;spinal cord injury;verbal instruction;video feedback;wheelchair skill training | pubmed |
Dinuclear rare-earth metal alkyl complexes supported by indolyl ligands in μ-η(2) :η(1) :η(1) hapticities and their high catalytic activity for isoprene 1,4-cis-polymerization. | Two series of new dinuclear rare-earth metal alkyl complexes supported by indolyl ligands in novel μ-η(2) :η(1) :η(1) hapticities are synthesized and characterized. Treatment of [RE(CH2 SiMe3 )3 (thf)2 ] with 1 equivalent of 3-(tBuN=CH)C8 H5 NH (L1 ) in THF gives the dinuclear rare-earth metal alkyl complexes trans-[(μ-η(2) :η(1) :η(1) -3-{tBuNCH(CH2 SiMe3 )}Ind)RE(thf)(CH2 SiMe3 )]2 (Ind=indolyl, RE=Y, Dy, or Yb) in good yields. In the process, the indole unit of L1 is deprotonated by the metal alkyl species and the imino C=N group is transferred to the amido group by alkyl CH2 SiMe3 insertion, affording a new dianionic ligand that bridges two metal alkyl units in μ-η(2) :η(1) :η(1) bonding modes, forming the dinuclear rare-earth metal alkyl complexes. When L1 is reduced to 3-(tBuNHCH2 )C8 H5 NH (L2 ), the reaction of [Yb(CH2 SiMe3 )3 (thf)2 ] with 1 equivalent of L2 in THF, interestingly, generated the trans-[(μ-η(2) :η(1) :η(1) -3-{tBuNCH2 }Ind)Yb(thf)(CH2 SiMe3 )]2 (major) and cis-[(μ-η(2) :η(1) :η(1) -3-{tBuNCH2 }Ind)Yb(thf)(CH2 SiMe3 )]2 (minor) complexes. The catalytic activities of these dinuclear rare-earth metal alkyl complexes for isoprene polymerization were investigated; the yttrium and dysprosium complexes exhibited high catalytic activities and high regio- and stereoselectivities for isoprene 1,4-cis-polymerization. | homogeneous catalysis;isoprene;ligand effects;polymerization;rare-earth metals | pubmed |
Improvement in muscle strength after an anterior cruciate ligament injury corresponds with a decrease in serum cytokines. | The purpose of this communication was to identify if a decrease in serum cytokine concentrations associates with an improvement in muscle strength after an anterior cruciate ligament (ACL) injury. To establish groups with contrasting serum cytokine concentrations, subjects scheduled for ACL reconstructive surgery were separated into one of two groups (gender matched) based on their time from injury occurrence: (1) Early (<21-d from injury occurrence; n=22) or (2) Late (⩾21-d from injury occurrence; n=22). Before surgery, each subject provided a fasting blood sample and performed single-leg peak isometric force testing on the injured (INJ) and non-injured (NI) limbs. Compared to the NI limb, peak isometric force in the INJ limb was decreased (p<0.05) in both groups (Early, ∼35%; Late, ∼18%). The deficit in peak isometric force, however, was increased (p<0.05) in the Early compared to Late group. Similarly, serum granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, and IL-13 were increased (all p<0.05) in the Early group. These unique findings show a concurrent increase in muscular weakness and serum cytokine concentrations shortly after (<21-d) an ACL injury. Importantly, muscular weakness persisted thereafter (⩾21-d) but at an attenuated level and parallel to a decrease in circulating cytokine concentrations. We conclude that a decrease in serum cytokines associates with a reduction in muscular weakness after an ACL injury. | Anterior cruciate ligament;Cytokines;Injury;Muscle weakness;Surgery | pubmed |
Does the speaker matter? Online processing of semantic and pragmatic information in L2 speech comprehension. | The present study investigated how pragmatic information is integrated during L2 sentence comprehension. We put forward that the differences often observed between L1 and L2 sentence processing may reflect differences on how various types of information are used to process a sentence, and not necessarily differences between native and non-native linguistic systems. Based on the idea that when a cue is missing or distorted, one relies more on other cues available, we hypothesised that late bilinguals favour the cues that they master during sentence processing. To verify this hypothesis we investigated whether late bilinguals take the speaker's identity (inferred by the voice) into account when incrementally processing speech and whether this affects their online interpretation of the sentence. To do so, we adapted Van Berkum, J.J.A., Van den Brink, D., Tesink, C.M.J.Y., Kos, M., Hagoort, P., 2008. J. Cogn. Neurosci. 20(4), 580-591, study in which sentences with either semantic violations or pragmatic inconsistencies were presented. While both the native and the non-native groups showed a similar response to semantic violations (N400), their response to speakers' inconsistencies slightly diverged; late bilinguals showed a positivity much earlier than native speakers (LPP). These results suggest that, like native speakers, late bilinguals process semantic and pragmatic information incrementally; however, what seems to differ between L1 and L2 processing is the time-course of the different processes. We propose that this difference may originate from late bilinguals' sensitivity to pragmatic information and/or their ability to efficiently make use of the information provided by the sentence context to generate expectations in relation to pragmatic information during L2 sentence comprehension. In other words, late bilinguals may rely more on speaker identity than native speakers when they face semantic integration difficulties. | Bilingualism;ERPs;LPP;N400;Pragmatics;Semantics;Sentence comprehension | pubmed |
Resource specialists lead local insect community turnover associated with temperature - analysis of an 18-year full-seasonal record of moths and beetles. | Insect responses to recent climate change are well documented, but the role of resource specialization in determining species vulnerability remains poorly understood. Uncovering local ecological effects of temperature change with high-quality, standardized data provides an important first opportunity for predictions about responses of resource specialists, and long-term time series are essential in revealing these responses. Here, we investigate temperature-related changes in local insect communities, using a sampling site with more than a quarter-million records from two decades (1992-2009) of full-season, quantitative light trapping of 1543 species of moths and beetles. We investigated annual as well as long-term changes in fauna composition, abundance and phenology in a climate-related context using species temperature affinities and local temperature data. Finally, we explored these local changes in the context of dietary specialization. Across both moths and beetles, temperature affinity of specialists increased through net gain of hot-dwelling species and net loss of cold-dwelling species. The climate-related composition of generalists remained constant over time. We observed an increase in species richness of both groups. Furthermore, we observed divergent phenological responses between cold- and hot-dwelling species, advancing and delaying their relative abundance, respectively. Phenological advances were particularly pronounced in cold-adapted specialists. Our results suggest an important role of resource specialization in explaining the compositional and phenological responses of insect communities to local temperature increases. We propose that resource specialists in particular are affected by local temperature increase, leading to the distinct temperature-mediated turnover seen for this group. We suggest that the observed increase in species number could have been facilitated by dissimilar utilization of an expanded growing season by cold- and hot-adapted species, as indicated by their oppositely directed phenological responses. An especially pronounced advancement of cold-adapted specialists suggests that such phenological advances might help minimize further temperature-induced loss of resource specialists. Although limited to a single study site, our results suggest several local changes in the insect fauna in concordance with expected change of larger-scale temperature increases. | climate change;community temperature index;community turnover;diet specialists;ecological specialization;light trap;phenology shift | pubmed |
Rapid and facile recombinant expression of bovine rhodopsin in HEK293S GnTI(-) cells using a PiggyBac inducible system. | Rhodopsin is a class A G protein-coupled receptor (GPCR) that provides important insights into the structure and function of the GPCR superfamily. Bovine rhodopsin is widely used as a model for GPCRs and was the first GPCR whose X-ray crystal structure was solved. One of the advantages of rhodopsin is that it is abundant in native tissue, and as a result, milligram quantities can be purified from the retinal rod cells of bovine eyes. Nonetheless, the study of GPCR conformation and dynamics, e.g., by electron paramagnetic resonance or (19)F nuclear magnetic resonance spectroscopy, typically requires mutagenesis to enable site-directed labeling of the protein. Mutations are also of great importance as they can stabilize the receptor and can be necessary to study different receptor conformations. Recombinant production of rhodopsins for biophysical studies has been achieved in different systems, including mammalian, insect, and yeast cells in culture, and from Drosophila melanogaster and Caenorhabditis elegans tissue. The piggyBac (PB) transposon system is used for gene delivery into a variety of cell types (e.g., HEK293 and CHO cells, fibroblasts, stem cells) and living organisms (e.g., honeybees, pigs, chicken, mice). Recently, the PB transposon has been described as an efficient tool for inducible protein expression in HEK293T and HEK293S N-acetylglucosaminyltransferase I-deficient (GnTI(-)) cells. This chapter describes a protocol for using the PB-based system for inducible expression of bovine rhodopsin in HEK293S GnTI(-) cells. Using this protocol, we expressed and purified 26 rhodopsin mutants to be used for site-directed spin labeling. | HEK293S GnTI(−);Recombinant mammalian expression;Rhodopsin mutants;Site-directed spin labeling (SDSL) | pubmed |
Complex formation and functional interaction between adenosine A1 receptor and type-1 metabotropic glutamate receptor. | The adenosine A1 receptor (A1R) is a G protein-coupled receptor (GPCR) for adenosine, a ubiquitous neuromodulator, and thus regulates neuronal excitability, as well as arousal and sensitivity to pain. In addition, we have previously described a new mode of action for A1R: in cerebellar Purkinje cells, its activation attenuates neuronal responses to glutamate, as mediated by the type-1 metabotropic glutamate receptor (mGluR1). mGluR1 is also a GPCR, and elicits such responses as long-term depression of the postsynaptic response to glutamate, a cellular basis for cerebellar motor learning. Here, we explore in greater detail the interaction between A1R and mGluR1 using non-neuronal cells. Co-immunoprecipitation and Förster resonance energy transfer (FRET) analysis reveal that A1R and mGluR1 form a complex. Furthermore, we found that mGluR1 activation inhibits A1R signaling, as measured by changes in intracellular cAMP. These findings demonstrate that A1R and mGluR1 have the intrinsic ability to form a heteromeric complex and mutually modulate signaling. This interaction may represent a new form of intriguing GPCR-mediated cellular responses. | Adenosine receptor;FRET;GPCR;Metabotropic glutamate receptor;cAMP | pubmed |
Positive and negative affective processing exhibit dissociable functional hubs during the viewing of affective pictures. | Recent resting-state functional magnetic resonance imaging (fMRI) studies using graph theory metrics have revealed that the functional network of the human brain possesses small-world characteristics and comprises several functional hub regions. However, it is unclear how the affective functional network is organized in the brain during the processing of affective information. In this study, the fMRI data were collected from 25 healthy college students as they viewed a total of 81 positive, neutral, and negative pictures. The results indicated that affective functional networks exhibit weaker small-worldness properties with higher local efficiency, implying that local connections increase during viewing affective pictures. Moreover, positive and negative emotional processing exhibit dissociable functional hubs, emerging mainly in task-positive regions. These functional hubs, which are the centers of information processing, have nodal betweenness centrality values that are at least 1.5 times larger than the average betweenness centrality of the network. Positive affect scores correlated with the betweenness values of the right orbital frontal cortex (OFC) and the right putamen in the positive emotional network; negative affect scores correlated with the betweenness values of the left OFC and the left amygdala in the negative emotional network. The local efficiencies in the left superior and inferior parietal lobe correlated with subsequent arousal ratings of positive and negative pictures, respectively. These observations provide important evidence for the organizational principles of the human brain functional connectome during the processing of affective information. | affective pictures;connectome;fMRI;graph theory;small-world | pubmed |
FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients. | There is no standard second-line chemotherapy after progression on first-line therapy including gemcitabine and platinum combination in advanced gall bladder cancer patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. In this observational study, patients with performance status ≤2, who progressed on first-line therapy, were enrolled from May 2010 to June 2014. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. A total of 66 patients were enrolled in this study. The median age of patients was 52.5 years (32-66 years),of which 24 (36.36%) were males and 42 (63.63%) were females. The median number of cycles could be given were 9.5 (2-12). Only 43.93% patients in this study completed full 12 cycles of chemotherapy. Sixteen patients (24.24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 39 (59.09%) patients, with complete response in none, partial response in 16 (24.24%), stable disease in 23 (34.84%) and progressive disease in 27 (40.90%) patients. The median progression free survival was 3.9 months; median overall survival was 7.6 months. The main Grade 3/4 side effects seen were hematological in 31.81% (n = 21) and gastrointestinal in 25.75% (n = 17) patients. Majority of patients (46%) had Grade 1/2 peripheral neuropathy. FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment in advanced gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent. | FOLFOX-4;carcinoma gall bladder;gemcitabine;platinum;second line | pubmed |
Prognostic value of ERCC1 and ERCC2 gene polymorphisms in patients with gastric cancer receiving platinum-based chemotherapy. | We conducted a prospective study to analyze whether ERCC1 rs11615 and rs3212986 and ERCC2 rs13181 and rs1799793 gene polymorphisms could serve as potential biomarkers for the prognosis of gastric cancer. A total of 228 patients with pathologically proven gastric cancer and receiving platinum-based chemotherapy were recruited from our hospital between October 2009 and October 2011. The ERCC1 rs11615 and rs3212986 and ERCC2 rs13181 and rs1799793 polymorphisms were genotyped using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Conditional logistic regression analysis revealed that patients carrying the CA and AA genotypes of ERCC1 rs3212986 polymorphism showed a poorer response to chemotherapy compared to the CC genotype (CA vs. CC: OR = 0.28, 95% CI = 0.06-0.98, P = 0.04; AA vs. CC: OR = 0.49, 95% CI = 0.06-0.98, P = 0.01). Moreover, the CA+AA genotype of ERCC1 rs3212986 polymorphism showed a significantly poorer response to chemotherapy (CA+AA vs. CC: OR = 0.49, 95% CI = 0.27-0.90). Patients with the AA genotype of ERCC1 rs3212986 polymorphism had a longer overall survival time when compared with the CC genotype (34.91 months vs. 51.19 months, log-rank P = 0.003). The AA genotype of ERCC1 rs3212986 polymorphism in gastric cancer patients was correlated with a higher risk of death from varying causes by the Cox proportional hazards model, compared to the CC genotype (HR = 6.19, 95% CI = 1.42-30.60). In conclusion, the ERCC1 rs3212986 polymorphism was found to influence the response to chemotherapy and overall survival of gastric cancer patients. | ERCC1;ERCC2;gastric cancer;polymorphism;treatment outcome | pubmed |
The effect of paired associative stimulation on fatigue resistance. | Paired associative stimulation (PAS) is a non-invasive stimulation method developed to induce bidirectional changes in the excitability of the cortical projections to the target muscles. However, very few studies have shown an association between changes in motor evoked potentials (MEP) after PAS and behavioral changes in healthy subjects. In the present study we hypothesized that the functional relevance of PAS can be seen during fatiguing exercise, since there is always a central contribution to the development of fatigue. Transcranial magnetic stimulation was applied over the motor cortex to measure changes in the MEPs of the soleus muscle before and after PAS. Furthermore, fatigue resistance was tested during 15s sustained maximal isometric contractions before and after PAS. On average, fatigue resistance did not change after PAS, however the change in excitability correlated significantly with the change in fatigue resistance. Functionality of PAS intervention was not demonstrated in this study. However, the observed relationship between excitability and fatigue resistance suggests that PAS might have affected central fatigue during short maximal contractions. | Central fatigue;Fatigue;Motor cortex;Paired associative stimulation;Transcranial magnetic stimulation | pubmed |
Tolerance of skin grafts to postoperative radiotherapy. | The aim was to evaluate the integrity and functional outcomes of skin grafts following external beam radiotherapy (EBRT). A prospective study of 15 patients, in whom EBRT was planned after their wound coverage with split-thickness skin graft (STSG). Parameters evaluated include defect size, time to postoperative radiotherapy, total radiotherapy dose, delays and interruptions in radiotherapy, wound complications, and the need for further surgical interventions. In all the 15 (6 men, 9 women) patients of STSG, radical doses of EBRT, that is, 50-70 Gy in 25-35 fractions are delivered over around 6 weeks. All STSGs were placed on healthy vascular tissue beds. Median time to initial radiotherapy after grafting was 3 weeks (range 3-6 weeks). There were no interruptions in radiotherapy treatment. In one patient, there was partial skin graft loss after radiotherapy that was adequately managed with conservative treatment. No patient requires further surgical intervention. Adjuvant postoperative radiotherapy can be delivered to STSGs without significant complications. Postoperative radiotherapy can be started as early as 3-4 weeks after skin grafting. Skin grafts should be placed on well-vascularized healthy tissues. Minor skin graft loss resulting from postoperative radiotherapy can usually be treated conservatively. | External beam radiotherapy;split-thickness skin grafts;tolerance of skin graft | pubmed |
MCmatlab: an open-source, user-friendly, MATLAB-integrated three-dimensional Monte Carlo light transport solver with heat diffusion and tissue damage. | While there exist many Monte Carlo (MC) programs for solving the radiative transfer equation (RTE) in biological tissues, we have identified a need for an open-source MC program that is sufficiently user-friendly for use in an education environment, in which detailed knowledge of compiling or UNIX command-line cannot be assumed. Therefore, we introduce MCmatlab, an open-source codebase thus far consisting of (a) a fast three-dimensional MC RTE solver and (b) a finite-element heat diffusion and Arrhenius-based thermal tissue damage simulator, both run in MATLAB. The kernel for both of these solvers is written in parallelized C and implemented as MATLAB MEX functions, combining the speed of C with the familiarity and versatility of MATLAB. We compare the RTE solver to Steven Jacques' mcxyz, which it is inspired by, and present example results generated by the thermal model. MCmatlab is easy to install and use and can be used by students and experienced researchers alike for simulating tissue light propagation and, optionally, thermal damage. | Monte Carlo methods;absorption;photothermal effects;scattering;three-dimensional modeling;tissue optics | pubmed |
Supporting patients learning to live with diabetes: a phenomenological study. | This article describes a study of the phenomenon of supporting patients who are learning to live with diabetes, from a diabetes specialist nurse (DSN) perspective. Guided by principles of reflective lifeworld research, data from six interviews (four in groups and two individual) with 16 DSNs were analysed. The results show that, in order to support learning, DSNs use a self-critical approach with the insight that they should not take over responsibility for their patients' diabetes. The DSNs support, encourage and challenge the patients to self-reflect and take responsibility based on patients' own goals and needs. To provide support, DSNs need to assume a tactful, critically challenging approach, dare to confront patients' fears and other emotions and have the insight to know that the responsibility for learning and integration of the condition lies with the patient. To be able to support patients in this way, it is necessary that the DSN is mentored and supported in this role. | Diabetes;Diabetes specialist nurse;Lifeworld;Patient support;Phenomenology;Reflection;Sweden | pubmed |
Homogeneous Coating with an Anion-Exchange Ionomer Improves the Cycling Stability of Secondary Batteries with Zinc Anodes. | Limited cycling stability of secondary cells with zinc anodes arises mainly from the high solubility of oxidized zinc species in the alkaline electrolyte resulting in electrode shape change and loss of active material during repeated discharge and charge. We propose and successfully employ a homogeneous coating with an anion-exchange ionomer (AEI) on model electrodes with electron-conductive host structures to confine the oxidized zinc species. Ideally, the confinement of oxidized zinc species reduces the shape change of the electrode and keeps the active material as close as possible at its place of origin. In this work, the confinement concept for the oxidized zinc species is elucidated by means of electrochemical studies and X-ray photoelectron spectroscopy: as intended, an interlayer of zinc oxide forms between the AEI and the surface of the zinc electrode. This interlayer implies that the hydroxide ions are able to pass and react as intended, whereas the migration of oxidized zinc species into the bulk electrolyte is hindered. The coating with an AEI yields a higher amount of restored zinc during electrodeposition in comparison to an uncoated zinc electrode-applying an AEI coating increases the achievable cycle number by up to six times. We investigate the morphology of the cycled electrodes and derive thereby the needs for further material classes that might be employed in the confinement concept. This approach demonstrates the benefit of ion-selective coatings, allowing for the permeation of hydroxide ions but not of oxidized zinc species, a concept which improves rechargeable batteries with zinc anodes, such as zinc-oxygen batteries. | XPS;anion-exchange ionomer;cycling stability;metal air battery;surface coating;zinc anode | pubmed |
Detection of viable Escherichia coli in environmental water using combined propidium monoazide staining and quantitative PCR. | The objectives of this study were to specifically detect viable Escherichia coli in environmental waters by targeting the ycjM gene in a propidium monoazide (PMA)-qPCR assay. PMA is a viability dye that can inhibit the amplification of DNA from dead cells, thus allowing for the detection and quantification of only viable cells. The ycjM primers were used to target E. coli that directly originated from the feces of warm blooded animals, and avoid false positive detection caused by "naturalized" E. coli that can exist in the environment. In this study, tap water and environmental waters were inoculated with E. coli isolated from animal feces. Following cell collection, samples were treated with PMA, followed by DNA isolation and qPCR detection. For pure cultures, 5 μM PMA with a 10-min light exposure was efficient at inhibiting the amplification of DNA from 10<sup>5</sup> CFU/mL dead E. coli cells, with a detection limit of 10<sup>2</sup> CFU/100 mL viable cells. For tap and environmental waters collected in the winter, a 10 μM PMA was required and as low as 10<sup>3</sup> CFU/100 mL viable cells could be detected in the presence of 10<sup>5</sup> CFU/100 mL dead cells. For water samples collected during the summer, 10<sup>2</sup> CFU/10 mL viable cells could be detected in the presence of 10<sup>4</sup> CFU/10 mL dead cells, after a 20 μM PMA treatment. No significant differences were found among the PMA-qPCR assay and two other standard culture-based methods for detection of viable E. coli in environmental water. In conclusion, with proper pretreatment of environmental water samples, this PMA-qPCR assay that targets the ycjM gene could quantify viable E. coli cells that directly come from the feces of warm-blooded animals, and therefore effectively and accurately indicate the quality of environmental water. | E. coli;Environmental waters;PMA;Viable cells;qPCR;ycjM | pubmed |
Genetics of Primary Congenital Hypothyroidism. | Congenital hypothyroidism (CH) is one of the most common preventable forms of mental retardation and since the implementation of neonatal screening programs in the mid-1970s, early detection and treatment have proven to be very successful in preventing brain damage. CH may be of thyroidal (= primary) or of hypothalamic-pituitary (= central) origin. Primary CH may be due to abnormal thyroid gland formation (dysgenesis) or defective thyroid hormone syntheses by a structurally normal gland (dyshormonogenesis). While thyroid dysgenesis is the most common form of CH, accounting for approximately 85% of cases, genetic defects are only found in a very low proportion of patients. On the other hand, thyroid dyshormonogenesis is less common, but is usually a genetic condition with autosomal recessive inheritance. In this review we provide an overview of all known monogenetic causes of primary CH, including promising new candidate genes. In addition, alternative genetic mechanisms are discussed. | Congenital hypothyroidism;Genetics;Thyroid dysgenesis;Thyroid dyshormonogenesis | pubmed |
Directed evolution of the bacterial endo-β-1,4-glucanase from Streptomyces sp. G12 towards improved catalysts for lignocellulose conversion. | With the aim to develop biocatalysts for enhanced hydrolysis of (hemi)cellulose into monosaccharides, random diversity by directed evolution was introduced in the gene coding for the endo-β-1,4-glucanase from Streptomyces sp. G12 which had been recombinantly expressed in Escherichia coli and named rCelStrep. The main objectives were therefore to set up a complete strategy for creation and automated screening of rCelStrep evolved direct mutants and to apply it to generate and screen a library of 10,000 random mutants to select the most active variants. The diversity was introduced in the gene by error-prone polymerase chain reaction. A primary qualitative screening on solid plates containing carboxymethylcellulose as the substrate allowed selecting 2200 active clones that were then subjected to a secondary quantitative screening towards AZO-CMC for the selection of 76 improved variants that were cultured in flasks and characterized. Five rCelStrep mutants exhibiting the highest hydrolytic activities than the wild-type enzyme were further characterized and applied to the bioconversion of the pretreated Arundo donax lignocellulosic biomass. It is worth of noting that one of the five tested mutants exhibited a 30% improvement in bioconversion yields compared to the wild-type enzyme, despite the absence of the carbohydrate binding module domain in this variant. Homology models of the three-dimensional structures of the catalytic and binding modules of rCelStrep were obtained and localization of mutations on these models allowed us to speculate on the structure-function relationships of the mutants. | Arundo donax;Cellulase;Directed evolution;High-throughput screening;Saccharification | pubmed |
Normal glutathione levels in autopsied brain of chronic users of heroin and of cocaine. | Animal studies suggest that exposure to either of the two widely used drugs of abuse, heroin or cocaine, causes depletion of the antioxidant, reduced glutathione, a hallmark of oxidative stress, in the brain. However, the relevance of the animal findings to the human is uncertain and clinical trials with the antioxidant GSH precursor n-acetylcysteine have produced mixed results in cocaine dependence. Our major objective was to compare glutathione levels, determined by an HPLC-coulometric procedure, in autopsied brain of chronic heroin (n = 11) and cocaine users (n = 9), who were positive for the drugs in the brain, to those of matched controls (n = 16). Six brain regions were examined, including caudate, hippocampus, thalamus and frontal, temporal and insular cortices. In contrast to experimental animal findings, we found no statistically significant difference between mean levels of reduced or oxidized glutathione in the drug user vs. control groups. Moreover, no correlation was found between levels of drugs in the brain and those of glutathione. Acknowledging the many generic limitations of an autopsied human brain study and the preliminary nature of the findings, our data nevertheless suggest that any oxidative stress caused by heroin or cocaine in chronic users of the drugs might not be sufficient to cause substantial loss of stores of glutathione in the human brain, at least during early withdrawal. These findings, requiring replication, might also have some relevance to future clinical trials employing glutathione supplement therapy as an anti-oxidative strategy in chronic users of the two abused drugs. | Cocaine;Glutathione;Heroin;Human brain;Oxidative stress;Postmortem | pubmed |
Surface imprinted polymers based on amino-hyperbranched magnetic nanoparticles for selective extraction and detection of chlorogenic acid in Honeysuckle tea. | Novel water-compatible magnetic molecularly imprinted polymers were developed. The magnetic core was firstly grafted by methyl acrylate and ethanediamine to increase the number of amino groups, which could immobilize more templates and form high-density recognition sites. Dopamine was adopted as functional monomer and crosslinker to retighten templates and prepare hydrophilic polymers. The characterization, adsorption capability, selectivity, and reusability were investigated in detail. The limit of detection and quantification of the method were 0.01μgmL<sup>-1</sup> and 0.038μgmL<sup>-1</sup>. The experimental results exhibited that the resultant nanomaterials had high crystallinity, satisfactory magnetic property, fast kinetics, favorable adsorption capacity, excellent specificity, and pleasing recovery after a mild elution. In addition, the recoveries of the proposed method at four spiked levels analysis were between 98.4% to 101.3%. The obtained imprinted nanoparticles were used as sorbents for selective separation and determination of chlorogenic acid in Honeysuckle tea. | Chlorogenic acid;Immobilized template strategy;Magnetic separation;Surface imprinting | pubmed |
Inferring distributional shifts of epidemiologically important North and Central American sandflies from Pleistocene to future scenarios. | Nine sandfly species (Diptera: Psychodidae) are suspected or proven vectors of Leishmania spp. in the North and Central America region. The ecological niches for these nine species were modelled in three time periods and the overlaps for all time periods of the geographic predictions (G space), and of ecological dimensions using pairwise comparisons of equivalent niches (E space), were calculated. Two Nearctic, six Neotropical and one species in both bioregions occupied a reduced number of distribution areas. The ecological niche projections for most sandfly species other than Lutzomyia shannoni and Lutzomyia ovallesi have not expanded significantly since the Pleistocene. Only three species increase significantly to 2050, whereas all others remain stable. Lutzomyia longipalpis shared a similar ecological niche with more species than any other, although both L. longipalpis and Lutzomyia olmeca olmeca had conserved distributions over time. Climate change, at both regional and local levels, will play a significant role in the temporal and spatial distributions of sandfly species. | ENM interactions;North and Central America;Phlebotomine sandflies;Pleistocene;climate change | pubmed |
Edge chipping resistance of ceramics bonded to a dentine analogue. | To evaluate the edge chip resistance (R<sub>eA</sub>) of two CAD/CAM monolithic ceramics (GC- IPS e.max CAD and YZ- Zenostar Zr Translucent) bonded to a dentine analogue substrate (G10- NEMA G10). Plate-shaped specimens were prepared from GC and YZ ceramics and were either bonded (B) to G10 or attached (NB) to a universal testing machine for edge chipping test. Samples from all groups (GC-B, GC-NB, YZ-B and YZ-NB) were indented (n = 25) at different edge distances (d = 0.1, 0.2, 0.3, 0.4, 0.5 and 0.6 mm) to produce chips. Force (F, in N) and d values were recorded and R<sub>eA</sub> (in N/mm) were calculated. Data were statistically analyzed using Pearson´s correlation, Student t, ANOVA and Tukey tests (α = 0.05). A strong correlation (R ≥ 0.98) was found between F and d values for all groups. R<sub>eA</sub> values increased with increasing d, irrespective of ceramic type (GC and YZ) or fixation method (B and NB). Significant differences (p < 0.05) in mean R<sub>eA</sub> values were found between B and NB ceramics at lower d (0.1-0.3 mm) that did not persist (p > 0.05) at greater d (0.5 and 0.6 mm), meaning, bonding (B) to G10 protected both materials against chipping close to the edge. The larger the distance from the occlusal contact to the restoration edge, the greater the chance to avoid ceramic chipping in monolithic restorations. For d ≤ 0.3 mm, such F vs d relation is less critical for edge resistance of YZ and for resin bonded monolithic ceramics. | CAD/CAM;Dental ceramics;Edge chipping;Fracture resistance | pubmed |
Internal pilot design for balanced repeated measures. | Repeated measures are common in clinical trials and epidemiological studies. Designing studies with repeated measures requires reasonably accurate specifications of the variances and correlations to select an appropriate sample size. Underspecifying the variances leads to a sample size that is inadequate to detect a meaningful scientific difference, while overspecifying the variances results in an unnecessarily large sample size. Both lead to wasting resources and placing study participants in unwarranted risk. An internal pilot design allows sample size recalculation based on estimates of the nuisance parameters in the covariance matrix. We provide the theoretical results that account for the stochastic nature of the final sample size in a common class of linear mixed models. The results are useful for designing studies with repeated measures and balanced design. Simulations examine the impact of misspecification of the covariance matrix and demonstrate the accuracy of the approximations in controlling the type I error rate and achieving the target power. The proposed methods are applied to a longitudinal study assessing early antiretroviral therapy for youth living with HIV. | UNIREP;fixed effects inference;linear mixed model;power;sample size | pubmed |
We Miss You, Allen. | Allen Anderson | pubmed |
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Mitochondrial CoQ deficiency is a common driver of mitochondrial oxidants and insulin resistance. | Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance. | Coenzyme Q;Insulin;Insulin resistance;Mitochondria;Oxidants;Ubiquinone;cell biology;human;human biology;medicine;mouse | pubmed |
The regulatory roles of Notch in osteocyte differentiation via the crosstalk with canonical Wnt pathways during the transition of osteoblasts to osteocytes. | Osteocytes comprise more than 90% of the cells in bone and are differentiated from osteoblasts via an unknown mechanism. Recently, it was shown that Notch signaling plays an important role in osteocyte functions. To gain insights into the mechanisms underlying the functions of Notch in regulating the transition of osteoblasts to osteocytes, we performed a luciferase assay by cloning the proximal E11 and dentin matrix acidic phosphoprotein 1 (DMP1) promotor regions into pGluc-Basic 2 vectors, which were subsequently transfected into the IDG-SW3 (osteocytes), MC3T3 (osteoblasts) and 293T (non-osteoblastic cells) cell lines. Two approaches were used to activate Notch signaling in vitro. One was a Notch1 extracellular antibody-coated cell culture plate, and the other was transfection of a Hairy/Enhancer of Split 1 (Hes1) overexpression vector. The interaction between the Notch and Wnt signaling pathways was probed by assessing the expression of a series of phosphorylated proteins involved in the cascade of both signaling pathways. Our data suggested that Notch signaling regulates E11 expression through Hes1 activity, while Hes1 solely did not initiate the expression of DMP1. The regulatory function of E11 by Hes1 was not observed in the 293T cell line, indicating a cell context-dependent manner of the Notch signaling pathway. Additionally, we found that Notch inhibited Wnt signaling at the late differentiation stage of osteocytes by both directly repressing phosphorylated Akt and preventing the nuclear aggregation of β-catenin. These findings provide profound understandings of Notch's regulatory function in osteocyte differentiation. | Cell differentiation;Cell signaling;Notch;Osteoblast;Osteocytes;Wnt | pubmed |
Prognostic comparison of goal-oriented hemoperfusion and routine hemoperfusion combined with continuous venovenous hemofiltration for paraquat poisoning. | Objective To investigate the impact of goal-oriented hemoperfusion (HP) with monitoring of the paraquat concentration on the prognosis of patients with acute paraquat poisoning. Methods This prospective observational study involved patients with acute paraquat poisoning admitted from March 2012 to September 2015. The patients received either goal-oriented or routine HP. All other treatments were the same between the two groups. The primary endpoint was 28-day mortality after poisoning. The secondary endpoints were the incidence of organ dysfunction within 7 days and 7-day mortality. Results Eighty-four patients were enrolled (49 in the control group and 35 in the goal-oriented group). The two groups were similar in terms of clinical characteristics. There was no significant difference in the incidence of organ dysfunction between the two groups within 1 week of admission. Mortality on day 7 was significantly lower in the goal-oriented than control group, but there was no difference on day 28. However, 28-day mortality was significantly lower in the goal-oriented group among patients with an oral dose of ≤50 ml. Conclusions HP with monitoring of the urine paraquat concentration as goal-oriented therapy can reduce the early mortality of paraquat poisoning. | Paraquat;dynamic monitoring;hemoperfusion;mortality;prognosis;urine paraquat test | pubmed |
Further evidence of novel APOB mutations as a cause of familial hypercholesterolaemia. | APOB mutations are a rare cause of familial hypercholesterolaemia (FH) and, until recently, routine genetic diagnosis only included the study of two small APOB fragments. In previous years, 5 novel functional mutations have been described in APOB fragments not routinely studied, our group having functionally characterized 2 of them. The main aim of this work was to identify and characterize novel alterations in APOB to assess the genetic cause of hypercholesterolemia in patients with a clinical diagnosis of FH. We performed next generation sequencing of 48 Portuguese clinical FH patients, who were apparently mutation negative. All variants found in APOB were annotated. For functional studies, LDL from index patients and relatives was separated and marked with FITC-LDL for flow cytometry assays in lymphocytes and U937 growth assays. A total of 11 potential pathogenic variants were identified. Variants p.(Pro994Leu) and p.(Thr3826Met) in exons 19 and 26 were found in 4 patients, and in vitro analysis was performed for these variants. An exon 26 alteration (p.(Thr3826Met)) showed a decrease in binding and internalization of LDL, and in U937 growth assays that was similar to the effect with p.(Arg3527Gln). An alteration in exon 19 had a neutral effect. The spectrum of functional alterations in APOB outside the fragments routinely screened is slowly growing. Screening of all 29 exons of APOB is advised for FH routine diagnosis, but functional characterization is necessary for pathogenicity assessment. It is expected that the number of patients with functional APOB mutations will increase in the near future. | APOB variants;Familial hypercholesterolemia;Functional studies | pubmed |
The Body Position Spatial Task, a Test of Whole-Body Spatial Cognition: Comparison Between Adults With and Without Parkinson Disease. | The Body Position Spatial Task (BPST) is a novel measure of whole-body spatial cognition involving multidirectional steps and turns. Individuals with Parkinson disease (PD) are affected by motor and cognitive impairments, particularly in spatial function, which is important for mental imagery and navigation. Performance on the BPST may inform understanding of motor-cognitive and spatial cognitive function of individuals with PD. We conducted this study to determine feasibility and validity of the BPST with standard, validated, and reliable measures of spatial cognition and motor-cognitive integration and to compare BPST performance in adults with and without PD. A total of 91 individuals with mild-moderate PD and 112 neurotypical (NT) adults of similar age were recruited for the study to complete the BPST and other measures of mobility and cognition. Correlations were used to determine construct and concurrent validity of BPST with valid measures of spatial cognition and motor-cognitive integration. Performance was compared between PD and NT adults using independent t-tests. BPST was feasible to administer. Analyses show evidence of construct validity for spatial cognition and for motor-cognitive integration. Concurrent validity was demonstrated with other tests of mobility and cognition. Relationships were stronger and more significant for individuals with PD than for NT individuals. BPST performance was not significantly different between groups. Tests that integrate cognitive challenge in mobility contexts are necessary to assess the health of spatial cognitive and motor-cognitive integration. The BPST is a feasible and valid test of whole-body spatial cognition and motor-cognitive integration in individuals with PD. | Parkinson’s;allocentric;egocentric;gait;mobility;neurodegenerative;older adults;spatial cognition;visuospatial | pubmed |
Lafoensia pacari A. St.-Hil.: Wound healing activity and mechanism of action of standardized hydroethanolic leaves extract. | Lafoensia pacari A. St.-Hil., (Lythraceae) is a native tree of Brazilian Cerrado and commonly known in Brazil as "mangava-brava". Its leaves are used in Brazilian folk medicine in wound healing, cutaneous mycoses, and in the treatment of gastritis and ulcers. The present study was designed to evaluate the wound healing activity and mechanism of action of the hydroethanolic extract of Lafoensia pacari A. St.-Hil. leaves (HELp), and to advance in its chemical profiling. HELp was prepared by maceration in 70% hydroethanolic solution (1:10, w/v). The phytochemical analyses were investigated using colorimetry and electrospray ionization/mass spectrometric detection (ESI-MS<sup>n</sup>). Its in vitro cytotoxicity was evaluated in CHO-K1 and L929 cells, while the in vivo acute toxicity was performed in mice. The potential in vivo wound healing activity was assessed using excision and incision rat models and histopathology of the wounded skin (excision model) was carried out. The in vitro wound healing activity of HELp was demonstrated by scratch assay in L-929 cells, by measuring proliferation/migration rate and p-ERK 1/2 protein expression using western blot analysis. HELp's in vivo anti-inflammatory activity was evaluated by lipopolysaccharide (LPS) induced peritonitis in mice, along with the determination of nitric oxide (NO) and cytokines (TNF-α and IL-10) in the peritoneal lavages. Its potential in vitro antibacterial activity was performed using microbroth dilution assay, while in vitro antioxidant activities was by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and ferric reducing antioxidant power (FRAP) assays. The phytochemical analysis of HELp revealed the presence of polyphenols with ellagic acid, punicalagin, punicalin, kaempferol, quercetin-3-O-xylopyranoside and quercetin-3-O-rhamnopyranoside being the most prominent. HELp showed no toxicity on CHO-k1 and L929 cell lines. Topical treatment with HELp (10 and 30 mg/g of gel) presented increased rates of wound contraction at all the days evaluated with complete wound re-epithelialization at 22.0 ± 1.5 (p < 0.05) and 21.7 ± 1.6 (p < 0.01) days, respectively. Topical application of HELp (10, 30 or 100 mg/g of gel) in incised wounds caused an increase in tensile break strength at all concentrations resulting in moderate re-epithelialization and neovascularization, increased cell proliferation an accelerated remodeling phase of the wound, in a manner comparable to standard drug (Madecassol<sup>®</sup>, 10 mg/g). In the scratch assay with L929 cells, HELp (0.1 and 0.03 mg/mL) and PDGF (5 ng/mL) resulted in the increased proliferation/migration rate of fibroblasts and higher expression of p-ERK 1/2 protein. In LPS-induced peritonitis, HELp (100 and 200 mg/kg p.o.) decreased total leukocyte migration, comparable to the dexamethasone (0.5 mg/kg p.o.). In RAW 264.7 macrophages activated by LPS, HELp produced anti-inflammatory activity dependent on increased concentrations of IL-10, reduction in NO production, without altering the TNF-α levels. HELp also presented potent antioxidant activity in the DPPH and FRAP, but lacks in vitro antibacterial activity. The present study results support the popular use of the leaves of L. pacari in the treatment of wounds. Its wound healing activity is multi-targeted and involves inhibition of the proliferative and anti-inflammatory phases, antioxidant and positive modulation of the remodeling phase that might be involved different secondary metabolites, with emphasis on the ellagic acid, punicalagin, punicalin, kaempferol, quercetin-3-O-xylopyranoside and quercetin-3-O-rhamnopyranoside. | Cytotoxicity;Lafoensia pacari;Leaves;Phytochemistry;Wound healing | pubmed |
Repeated exposure to 3,4-methylenedioxypyrovalerone and cocaine produces locomotor sensitization with minimal effects on brain monoamines. | Synthetic cathinones, known as "bath salts" on the illicit drug market, pose a significant public health concern. 3,4-Methylenedioxypyrovalerone (MDPV), one of several popular constituents of illicit bath salts, produces similar pharmacological actions to cocaine, albeit with greater potency and efficacy. The present study sought to characterize behavioral and neurochemical effects of repeated exposure to MDPV alone and in combination with cocaine. Male Sprague-Dawley rats were randomly assigned to one the following four treatments, administered once daily for seven days: 1 mg/kg MDPV, 5 mg/kg cocaine, 1 mg/kg MDPV +5 mg/kg cocaine, or saline. Locomotor activity was assessed for 1 h immediately before and 1 h immediately after injections on days 1 and 6. Brains were harvested 20 min after the final injection on day 7 and brain tissue punches were obtained to determine monoamine content within the anterior striatum, medial prefrontal cortex, and nucleus accumbens using High-Performance Liquid Chromatography (HPLC). Drug-induced increases in horizontal activity were significantly greater on treatment day 6 compared to treatment day 1 in all three drug treatment groups in comparison to the saline control group. MDPV produced significantly higher increases in activity compared to either saline or cocaine, although concurrent treatment with MDPV and cocaine produced sub-additive effects. Neurochemical analyses provided no evidence of alterations in total monoamine content following repeated administration of MDPV, cocaine, or the MDPV + COC mixture. Further investigations targeting possible changes in DA receptor sensitivity following repeated exposure to MDPV may help elucidate the mechanistic changes responsible for MDPV-induced behavioral sensitization. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.' | Behavioral sensitization;Cocaine;Dopamine;Locomotor activity;MDPV;Medial prefrontal cortex;Monoamines;Nucleus accumbens;Rats;Serotonin;Striatum | pubmed |
Future of human mitochondrial DNA editing technologies. | ATP and other metabolites, which are necessary for the development, maintenance, and functioning of bodily cells are all synthesized in the mitochondria. Multiple copies of the genome, present within the mitochondria, together with its maternal inheritance, determine the clinical manifestation and spreading of mutations in mitochondrial DNA (mtDNA). The main obstacle in the way of thorough understanding of mitochondrial biology and the development of gene therapy methods for mitochondrial diseases is the absence of systems that allow to directly change mtDNA sequence. Here, we discuss existing methods of manipulating the level of mtDNA heteroplasmy, as well as the latest systems, that could be used in the future as tools for human mitochondrial genome editing. | AsCpf1;SpCas9;mitoRGEN;mitoRetron;mitoTALE | pubmed |
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