Serum and gene expression profile of tumor necrosis factor-alpha and interleukin-6 in hypertensive diabetic patients: effect of amlodipine administration.
Pro-inflammatory cytokines are critical factors in type 2 diabetes-associated atherosclerosis. We aim to analyze in hypertensive type 2 diabetic patients the serum concentrations and the mRNA expression levels in peripheral blood mononuclear cells (PBMC) of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), as well as to evaluate the effect of amlodipine administration. Twenty-one hypertensive diabetic patients and 10 healthy non-diabetic controls were included in the study. Serum levels of cytokines were measured by chemiluminescent immunometric assay, and mRNA expression levels by RT-PCR. The mean serum concentrations of TNF-alpha and IL-6 in diabetic patients showed a 6.1-fold and 2.9-fold increase with respect to non-diabetic control subjects, respectively (p less than 0.0001). Likewise, there was a 3.3- and a 4-fold increase in the PBMC mRNA expression level of TNF-alpha and IL-6 (p less than 0.0001) in diabetic subjects. After amlodipine administration, a significant decrease (p less than 0.01) was observed in the serum TNF-alpha and IL-6 levels. In addition, pre-treatment mRNA expression of TNF-alpha and IL-6 also decreased, with a mean percent reduction of 26 percent (p less than0.01) and 25 percent (p less than 0.001), respectively. In conclusion, serum concentrations and PBMC mRNA expression levels of TNF-alpha and IL-6 are significantly elevated in hypertensive type 2 diabetic patients. Administration of amlodipine is associated with a significant reduction of the increased levels of these inflammatory parameters, both at the protein as well as at the transcriptional level. These modulatory effects of amlodipine on proinflammatory cytokine level and expression may be related to its suggested anti-atherosclerotic actions.


Anti-PD1 antibody enhances the anti-tumor efficacy of MUC1-MBP fusion protein vaccine via increasing Th1, Tc1 activity and decreasing the proportion of MDSC in the B16-MUC1 melanoma mouse model.
In previous studies, we have obtained a notable anti-tumor efficacy of the recombinant MUC1-MBP vaccine in the process of mouse B16-MUC1 melanoma treatment. However, the tumor cannot be eliminated completely. We found that the tumor inhibition rate decreased from 81.67% (five immunizations) to 43.67% (eight immunizations) after more than five immunizations, indicating persistent vaccine stimulation may activate immunosuppressive factors. In the present study, we revealed that programmed cell death 1 (PD1), an inhibitory molecule suppressing T cell function, expressed on splenic and tumor-infiltrating T cells were up-regulated by the vaccine. Therefore, to optimize the anti-tumor efficacy of the vaccine, we employed combination immunotherapy with MUC1-MBP vaccine and αPD1 (anti-PD1 antibody). Results showed that combination immunotherapy induced a more remarkable anti-tumor efficacy, the tumor clearance being increased to 80% from 20% which obtain by MUC1-MBP vaccine immunizations. To investigate the possible underlying mechanism, IFN-γ secretion and cytotoxic T lymphocyte (CTL) cytotoxicity were measured by enzyme-linked immunosorbent assay (ELISA) and xCELLigence real-time cell analyzer (RTCA) respectively. T cell subsets and immunosuppressive cells in the mouse spleen and tumor microenvironment were analyzed by FACS. Results showed that the proportion of splenic CD8+T cells and tumor infiltration was increased and the activity of CTL killing, T helper 1 (Th1), Type 1 CD8+T (Tc1) was enhanced, indicating that the anti-tumor efficacy enhanced by combination immunotherapy was mainly through boosting CD8+T cells mediated anti-tumor cellular immunity. Additionally, combination immunotherapy significantly decreased the splenic and tumor-infiltrating myeloid derived suppressor cells (MDSCs). These results demonstrated that combination immunotherapy with MUC1-MBP vaccine and αPD1 was capable to invoke a more potent anti-tumor immune response and provide a foundation for further research.


Low personal exposure to benzene and 1,3-butadiene in the Swedish petroleum refinery industry.
Petroleum refinery workers are exposed to the carcinogens benzene and 1,3-butadiene. Declining exposures have been reported internationally but information on current exposure in the Swedish refinery industry is limited. The aim was to examine refinery workers' personal exposure to benzene and 1,3-butadiene and increase awareness of exposure conditions by collaboration with involved refineries. Altogether 505 repeated personal exposure measurements were performed among workers at two refineries. Full-shift measurements were conducted in different exposure groups using Perkin Elmer diffusive samplers filled with Carbopack X. Mean levels were calculated using mixed-effects models. A large fraction of measurements below the limit of detection (LOD) required imputation of computer-generated data. Mean benzene exposure among process technicians was 15.3 µg/m3 (95% CI 10.4-22.5 µg/m3) and 13.7 µg/m3 (95% CI 8.3-22.7 µg/m3) for Refinery 1 and 2, respectively. Process technicians working outdoors had higher exposure than maintenance workers (20.7 versus 5.9 µg/m3, p < 0.01). Working in the harbour and tank park (Refinery 1), compared with the process area, was associated with higher exposure. The 1,3-butadiene exposure was low, 5.4 and 1.8 µg/m3, respectively. The total variation was generally attributed to within-worker variability. Low benzene and 1,3-butadiene levels were found among refinery workers. Mean benzene exposure was about 1% of the Swedish occupational limit (1500 µg/m3) and for 1,3-butadiene, exposure was even lower. A large fraction of values below the LOD can be managed by carefully modelled, computer-generated data.


Demographic and laboratory data may predict positive temporal artery biopsy.
Temporal artery biopsy is performed in patients suspected of having giant cell arteritis. This study was conducted to evaluate clinical and laboratory criteria correlating with positive biopsy results in an effort to limit the number of negative biopsies performed. A retrospective review was performed of patients who underwent temporal artery biopsy at two urban medical centers from 2002 to 2009. A multivariate analysis of patient demographics, clinically relevant signs and symptoms, laboratory data, and pathologic outcomes was performed. Temporal artery biopsy histologically confirmed giant cell arteritis in 24% of cases. The mean age of those with disease was 77.8 y and those without were 73.1 y; age was found to be statically significant (P = 0.0227); 76% were female and 24% were male; gender was not significant (P = 0.9594); 42% were Caucasian (39% had a positive temporal artery biopsy), 27% were Hispanic (17% positive), and 31% of the patients were African-American (3% positive); ethnicity was significant (P = 0.0005). The PPV of elevated ESR was 27%; sensitivity was 100%; specificity was 16%. A history of headache or visual disturbance was not predictive of a positive biopsy Fewer negative biopsy results may be achieved by screening patients with normal ESR or lower risk patients with other modalities.


Comparison between standard and ultrasound-integrated approach for risk stratification of syncope in the emergency department.
This prospective cohort enrolled all patients above 16 years of age presenting to the in the emergency department (ED) for a reported syncope was designed to test the accuracy of a point-of-care ultrasound (POCUS) integrated approach in risk stratification. The emergency physician responsible for the patient care was asked to classify the syncope risk after the initial clinical assessment and after performing POCUS evaluation. All risk group definitions were based on the 2018 European Society of Cardiology guidelines. Thirty days after the index event, all participants were followed up to assess the frequency of short-term serious outcomes as defined in the San Francisco Syncope Rule (SFSR) cohorts. We estimated the accuracy of clinical and POCUS-integrated evaluation in predicting SFSR outcomes. Between February 2016 and January 2018, 196 patients were enrolled [109 women (55.6%)]. Median age was 64 years (interquartile range 31 years). After a follow-up of 30 days, 19 patients experienced 20 SFSR outcomes. Positive and negative likelihood ratios were 1.73 (95% CI 0.87-3.44) and 0.84 (95% CI 0.62-1.12) for the clinical evaluation, and 5.93 (95% CI 2.83-12.5) and 0.63 (95% CI 0.45-0.9) for the POCUS-integrated evaluation. The POCUS-integrated approach would reduce the diagnostic error of the clinical evaluation by 4.5 cases/100 patients. This cohort study suggested that the integration of the clinical assessment with POCUS results in patients presenting to the ED for non-high-risk syncope may increase the accuracy of predicting the risk of SFSR outcomes and the usefulness of the clinical assessment alone.


Global exponential stability of delayed Markovian jump fuzzy cellular neural networks with generally incomplete transition probability.
The problem of global exponential stability in mean square of delayed Markovian jump fuzzy cellular neural networks (DMJFCNNs) with generally uncertain transition rates (GUTRs) is investigated in this paper. In this GUTR neural network model, each transition rate can be completely unknown or only its estimate value is known. This new uncertain model is more general than the existing ones. By constructing suitable Lyapunov functionals, several sufficient conditions on the exponential stability in mean square of its equilibrium solution are derived in terms of linear matrix inequalities (LMIs). Finally, a numerical example is presented to illustrate the effectiveness and efficiency of our results.


Bone microstructure in men assessed by HR-pQCT: Associations with risk factors and differences between men with normal, low, and osteoporosis-range areal BMD.
The primary objective of this study was to analyze the relationships between bone microstructure and strength, and male osteoporosis risk factors including age, body mass index, serum 25-hydroxyvitamin D level, and testosterone level. A secondary objective was to compare microstructural and strength parameters between men with normal, low, and osteoporosis-range areal bone mineral density (aBMD). Seventy-eight healthy male volunteers (mean age 62.4 ± 7.8 years, range 50-84 years) were recruited. The participants underwent dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) of the ultra-distal radius and tibia. From the HR-pQCT images, volumetric bone mineral density (BMD) and cortical and trabecular bone microstructure were evaluated, and bone strength and cortical load fraction (Ct.LF) were estimated using micro-finite element analysis (μFEA). Age was more strongly correlated with bone microstructure than other risk factors. Age had significant positive correlations with cortical porosity at both ultra-distal radius and tibia (r = 0.36, p = 0.001, and r = 0.47, p < 0.001, respectively). At the tibia, age was negatively correlated with cortical BMD, whereas it was positively correlated with trabecular BMD. In μFEA, age was negatively correlated with Ct.LF, although not with bone strength. Compared with men with normal aBMD, men with low or osteoporosis-range aBMD had significantly poor trabecular bone microstructure and lower bone strength at the both sites, while there was no significant difference in cortical bone. Cortical bone microstructure was negatively affected by aging, and there was a suggestion that the influence of aging may be particularly important at the weight-bearing sites.


Pigtail catheter drainage and surgery in severe acute pancreatitis.
Severe acute pancreatitis is initially managed with conservative treatment. Patients who failed conservative management were effectively treated with pigtail drainage. Factors predicting surgery remain uncertain. A total of 58 patients with severe acute pancreatitis presenting to JIPMER Hospital were studied and managed with a step-up approach. In this prospective observational study, patients were divided into three groups based on the final mode of treatment received: conservative, pigtail alone, and surgery groups. Of 58 patients, 30 patients were managed with conservative treatment, 20 patients with pigtail alone, and 8 patients underwent surgical treatment after pigtail failure. Overall sepsis reversal was achieved in 22 of 28 (78.5%) patients: 18 were in the pigtail alone group, and 4 were in surgery group, which was statistically significant (P = 0.03). Respiratory failure was the most common organ failure, 68.9%, and overall mortality was 8.62 in this study. On univariate analysis, absence of sepsis reversal within 2 weeks of pigtail insertion is a predictor of need of surgery. Other significant findings were higher catheter-related complications in the surgery group (P = 0.01) and a 100% unimicrobial infection in the surgery group (P = 0.02). Overall mortality was 8.6%, which did not differ significantly between the groups. The step-up approach avoided unnecessary intervention, and 52% patients recovered by conservative treatment alone. Sepsis reversal within 2 weeks of pigtail insertion can be used as a predictor of surgery in the early course of severe acute pancreatitis managed by the step-up approach.


Decision-making experiences of family members of older adults with moderate dementia towards community and residential care home services: a grounded theory study protocol.
Caring and supporting older people with dementia have become a major public health priority. Recent reports have also revealed a diminishing number of family carers to provide dementia care in the future. Carers who are engaged in the caring role are known to bear significant psychological, practical and economic challenges as the disease advances over time. Seemingly, evidence indicates that the burden of care can be relieved by formal services. This study aims to explore decision-making experiences of family members of older adults with moderate dementia towards the use of community support (CS) and residential care home (RCH) services. A large multi-site constructivist grounded theory in a range of non-government organizations and a private aged home will frame this Hong Kong study. Purposive sampling will begin the recruitment of family members, followed by theoretical sampling. It is estimated that more than 100 family members using CS and RCH services will participate in an interview. The process of successive constant comparative analysis will be undertaken. The final product, a theory, will generate an integrated and comprehensive conceptual understanding which will explain the processes associated with decision-making of family members for dementia sufferers. Deeper understanding of issues including, but not exclusive to, service needs, expectations and hopes among family carers for improving service support to serve dementia sufferers in CS and RCH services will also be revealed. Importantly, this study seeks to illustrate the practical and strategic aspects of the theory and how it may be useful to transfer its applicability to various service settings to better support those who deliver formal and informal care to the dementia population.


Study of the use of a spironolactone and angiotensin-converting enzyme inhibitor combination: a population-based analysis.
To analyse the conditions of use of the drug combination in outpatients. The first section consisted of a population-based analysis using computerized records from the French national health insurance system. The study population consisted of adult patients, receiving long-term treatment with spironolactone (SPIR) and angiotensin-converting enzyme inhibitor (ACEI). For each patient, the reimbursement of serum potassium and creatinine determinations was searched for in the database during the 6-month period preceding the date of the last dispensation. The second section comprised a written questionnaire on use practises, sent to practitioners who prescribed the drug combination to randomly selected patients. Analysis of the answers to the questionnaire made it necessary to develop a reference system. In the third section, procedure one was repeated at a later stage, following an information campaign, in order to measure its impact. The exhaustive population under procedure 1 consisted of 3620 patients (71 +/- 11 years). During the 6 months prior to the index date, 51% of patients underwent at least one determination of both serum potassium and serum creatinine. The randomised population under procedure two consisted of 441 patients (70 +/- 13 years) and their 375 practitioners. When compared with the reference system, SPIR-ACEI was used for the recommended indications, at the appropriate SPIR-ACEI dosages, and under minimal monitoring of biological parameters in only 65 patients (15%). After the information campaign, results were disappointing because only 55% of patients underwent the minimal laboratory monitoring. The use of the drug combination in general practice was mainly inappropriate.


Natural killer cell awakening: unleash cancer-immunity cycle against glioblastoma.
Due to the negligence of the complex tumor immune microenvironment, traditional treatment for glioblastoma has reached its limitation and cannot achieve a satisfying outcome in the past decade. The emergence of immunotherapy based on the theory of cancer-immunity cycle has brought a new dawn to glioblastoma patients. However, the results of most phase II and phase III clinical trials are not optimistic due to the simple focus on T cells activation rather than other immune cells involved in anti-tumor immunity. NK cells play a critical role in both innate and adaptive immunity, having the ability to coordinate immune response in inflammation, autoimmune disease and cancer. They are expected to cooperate with T cells to maximize the anti-tumor immune effect and have great potential in treating glioblastoma. Here, we describe the traditional treatment methods and current immunotherapy strategies for glioblastoma. Then, we list a microenvironment map and discuss the reasons for glioblastoma inhibitory immunity from multiple perspectives. More importantly, we focus on the advantages of NK cells as potential immune regulatory cells and the ways to maximize their anti-tumor immune effect. Finally, our outlook on the directions and potential applications of NK cell-based therapy combining with the advance technologies is presented. This review depicts NK cell awakening as the precondition to unleash the cancer-immunity cycle against glioblastoma and elaborate this idea from biology to clinical treatment.


Experimental models for evaluation of radioactive tumor-localizing agents.
Although subject to limitations, there is a need for carefully controlled laboratory studies using animal tumor models in research on tumor-localizing agents. This paper reviews the literature relating to the more important transplantable tumor systems, spontaneous or induced, as to origin, host, site, and radioactive agent used. The historical background of animal tumor models is discussed, including such technical aspects as source of tumor, techniques of transplantation, transplantation sites, and maintenance of transplants. Also, considered are the use of animal tumor models as predictive systems, expression of experimental results of quantitative studies of tissue uptake and comparative radionuclide tumor and distributional studies, and suggestions for future studies, such as the need of more intensive study of existing tumor models for a better understanding of the relationship between animal and human tumors, the need for the development of new tumor model systems, and for standardization of experimental protocols and procedures. A total of 48 t,mor models (26 in mice, 11 in rats, 7 in hamsters, 2 in rabbits, and 2 in dogs) are presented in seven tables dividing the models into tumors of epithelial tissue, connective tissue, hematopoietic tissues, melanin-forming tissue, neural tissues, undetermined site of origin or undifferentiated histologic pattern, and miscellaneous background. The use of animal tumor models in cancer research, which utilizes radionuclides, permits the investigator to do many things not permissible with human beings, but the extrapolation of animal results to human beings must be approached with caution, Although malignant disease, whether in animals or man, must be individualized, certain trends in animal studies can be observed. It is the goal of the laboratory investigator to be able to indicate to the clinician those trends or phenomena that, when repeatedly observed in animal model systems, may be applicable to an understanding of malignant disease in man.


Obstructed intestine as a reservoir for systemic infection.
Intestinal motility, absorption, and secretion are altered after intestinal obstruction, but at what point the normal bacterial barrier function of the viable gut fails after intestinal obstruction is unclear. Thus, we tested whether after simple intestinal obstruction bacteria would translocate across the viable intestinal wall to cause systemic infection. Within 6 hours of intestinal ligation 1 cm proximal or distal to the ileocecal valve, bacteria had translocated to the mesenteric lymph nodes, and by 24 hours after intestinal obstruction, bacteria had spread to the liver, spleen, and blood stream. Bacterial translocation rarely occurred in the animals undergoing laparotomy and sham intestinal ligation, indicating that bacterial translocation was not due to surgical stress. Based on the results of these studies, bacterial translocation induced by intestinal obstruction appears to be due to disruption of the ecology of the normal gut microflora, leading to intestinal overgrowth with certain enteric bacilli and mucosal damage. Although the exact mechanism(s) by which simple mechanical obstruction injures the intestine is not known, the fact that mucosal injury did not occur in germ-free mice suggests that bacteria may play a role in the pathogenesis of obstruction-induced intestinal injury.


A holistic approach for the assessment of the indoor environmental quality, student productivity, and energy consumption in primary schools.
The perception of the indoor environmental quality (IEQ) through questionnaires in conjunction with in-field measurements related to the indoor air quality (IAQ), the thermal comfort and the lighting environment were studied in nine naturally ventilated schools of Athens, Greece. Cluster analysis was carried out in order to determine the ranges of indoor air pollutants, temperature (T), relative humidity (RH), and ventilation rates at which the students were satisfied with the indoor environment. It was found that increased levels of particulate matter did not have a negative effect on students' perception while students seemed to link the degradation of IAQ with temperature variations. Statistically significant correlations were further found between measurement results and students' perception of the IEQ. Students' sick building syndrome (SBS) symptoms and performance of schoolwork were also investigated as a function of the levels of indoor air pollutants and ventilation, and there were found significant positive correlations between particulate matter (PM) and certain health symptoms. Students' learning performance seemed to be affected by the ventilation rates and carbon dioxide (CO₂) concentrations while certain health effects positively correlated to the levels of PM and CO₂. The energy consumption of schools was rather low compared to other national findings, and both the electricity and oil consumption for heating positively correlated to the levels of indoor air pollutants.


Modeling interactions between a β-O-4 type lignin model compound and 1-allyl-3-methylimidazolium chloride ionic liquid.
Aiming at understanding the molecular mechanism of the lignin dissolution in imidazolium-based ionic liquids (ILs), this work presents a combined quantum chemistry (QC) calculation and molecular dynamics (MD) simulation study on the interaction of the lignin model compound, veratrylglycerol-β-guaiacyl ether (VG) with 1-allyl-3-methylimidazolium chloride ([Amim]Cl). The monomer of VG is shown to feature a strong intramolecular hydrogen bond, and its dimer is indicated to present important π-π stacking and intermolecular hydrogen bonding interactions. The interactions of both the cation and anion of [Amim]Cl with VG are shown to be stronger than that between the two monomers, indicating that [Amim]Cl is capable of dissolving lignin. While Cl- anion forms a hydrogen-bonded complex with VG, the imidazolium cation interacts with VG via both the π-π stacking and intermolecular hydrogen bonding. The calculated interaction energies between VG and the IL or its components (the cation, anion, and ion pair) indicate the anion plays a more important role than the cation for the dissolution of lignin in the IL. Theoretical results provide help for understanding the molecular mechanism of lignin dissolution in imidazolium-based IL. The theoretical calculations on the interaction between the lignin model compound and [Amim]Cl ionic liquid indicate that the anion of [Amim]Cl plays a more important role for lignin dissolution although the cation also makes a substantial contribution.


Quantitative distributions of aspartate aminotransferase and glutaminase activities in the rat cochlea.
The intra-cochlear distributions of aspartate aminotransferase and glutaminase, prominent enzymes of aspartate and glutamate metabolism, have been studied by quantitative microchemical techniques. Also measured was choline acetyltransferase, the enzyme synthesizing acetylcholine, and a marker for the olivocochlear bundle. Aspartate aminotransferase activity was highest in the stria vascularis, about half this high in the organ of Corti synaptic (hair cell) zones, somewhat lower in the organ of Corti non-synaptic (Hensen's cell) zones, lower yet in Reissner's and lowest in the tectorial membrane. Glutaminase, on the other hand, had its highest activity in synaptic zones, about a third of that activity in the organ of Corti non-synaptic zones, and a barely detectable activity in Reissner's and tectorial membranes, and stria vascularis. Seven days after transection of the olivocochlear bundle, no significant difference was found between lesion- and control-side aspartate aminotransferase or glutaminase activities, even though no choline acetyltransferase activity remained in the lesion-side of the organ of Corti. Both the distribution of aspartate aminotransferase activity and the lesion results would seem to implicate it in energy more so than neurotransmitter metabolism. The distribution of glutaminase activity could be consistent with a role in neurotransmission; however, the lesion data were unable to demonstrate a specific association with the olivocochlear bundle.


Immune-Mediated Therapies in Lymphoma.
To review types of lymphoma, risk factors, and evaluate novel immune-mediated therapies, including side effects and management of immune-mediated toxicities. Published literature, national statistics, and Web sites. Novel biologic agents are being developed with the potential to improve outcomes. However, these novel agents pose unique and sometimes serious adverse events. The immune-mediated adverse events require a multidisciplinary approach and early identification. It is imperative providers and nurses are educated on the management of the unique toxicities caused by lymphoma treatment.


Impact of country self citation on the ranking of the top 50 countries in clinical neurology.
To examine the factors that influence country self-citation rate (SCR) in clinical neurology and to assess the impact of self-citation on the ranking of the top 50 countries. SCImago Journal & Country Rank was used to collect data for the 50 most cited countries in clinical neurology during 1996-2019. Country SCR was correlated with several productivity parameters and examined statistically. Countries that dropped in their ranking after the exclusion of self-citations were identified. The median (range) country SCR for the 50 most cited countries was 11.3%.(5.3%- 47%). Country SCR correlated significantly with total citable documents and total cites numbers and rankings. The exclusion of self-citations led to a drop in the ranking of 8(16%) countries only. No significant difference between the total and net total cites rankings was observed. Self-citation can be appropriate and reflect an expansion on earlier research. Highly cited productive countries tend to have high country SCR. Excluding self-citations had minimal impact on the ranking of the top 50 countries. Our findings indicate that self-citation is unlikely to influence country standing amongst the top 50 and does not support the argument for eliminating self-citations from citation-based metrics. A more globalization through international collaboration in research is encouraged.


Skin tumorigenic potential of aflatoxin B1 in mice.
Aflatoxin B1 (AFB1) has been classified as a category I human carcinogen, which is responsible for a high incidence of hepatocellular carcinoma. Since exposure to AFB1 can occur through skin contact in addition to ingestion and inhalation, the carcinogenic potential of topically applied AFB1 on mouse skin was investigated. Our results show that single topical application of AFB1 (80 nmol) as a tumor initiator, followed by twice weekly application of 12-tetradecanoyl phorbol myristate acetate (TPA, 4 nmol), resulted in tumor formation after 13 weeks. However, no tumorigenic potential was observed when AFB1 (16 nmol) was used either as a complete carcinogen or as a tumor promoter (4 nmol). Histological analysis of skin showed squamous cell carcinoma in the AFB1/TPA treated group. The application of AFB1 as a complete carcinogen, an initiator or a promoter after 24 weeks demonstrated widespread degenerative and necrotic changes in hepatic tissue as well, suggesting liver to be the target organ following percutaneous absorption. Additionally, twice weekly topical application of AFB1 caused significant induction of cutaneous CYP IA monoxygenases without any effect on hepatic levels while glutathione-S-transferase activity was induced more in the liver than skin. The topical application of AFB1 also resulted in increased hepatic and cutaneous lipid peroxidation with concomitant depletion of glutathione content. It is likely that due to higher induction of hepatic GST activity, products of lipid peroxidation may be detoxified and therefore unable to cause DNA damage making mice resistant to hepatic tumor formation. The overall results indicate a tumor initiating potential of AFB1 in mice and suggest that continued dermal exposure of AFB1, even at low doses, might lead to degenerative changes in hepatocytes.


Effective Analysis of Inpatient Satisfaction: The Random Forest Algorithm.
To identify the factors influencing inpatient satisfaction by fitting the optimal discriminant model. A cross-sectional survey of inpatient satisfaction was conducted with 3888 patients in 16 large public hospitals in Zhejiang Province. Independent variables were screened by single-factor analysis, and the importance of all variables was comprehensively evaluated. The relationship between patients' overall satisfaction and influencing factors was established, the relative risk was evaluated by marginal benefit, and the optimal model was fitted using the receiver operating characteristic curve. Patients' overall satisfaction was 79.73%. The five most influential factors on inpatient satisfaction, in this order, were: patients' right to know, timely nursing response, satisfaction with medical staff service, integrity of medical staff, and accuracy of diagnosis. The prediction accuracy of the random forest model was higher than that of the multiple logistic regression and naive Bayesian models. Inpatient satisfaction is related to healthcare quality, diagnosis, and treatment process. Rapid identification and active improvement of the factors affecting patient satisfaction can reduce public hospital operating costs and improve patient experiences and the efficiency of health resource allocation. Public hospitals should strengthen the exchange of medical information between doctors and patients, shorten waiting time, and improve the level of medical technology, service attitude, and transparency of information disclosure.


Characteristics of cancer patients participating in presurgical lifestyle intervention trials exploring effects on tumor biology.
Poor diet and insufficient physical activity are strongly associated with an increased risk of several cancers. Preclinical studies suggest that lifestyle modifications may exert favorable effects on tumor biology. Randomized controlled trials in the presurgical setting serve as an ideal means to translate this research to humans; however, little is known about the characteristics of patients who enroll in these presurgical trials versus those who do not. Screening databases from three presurgical lifestyle intervention trials for breast and prostate cancer patients conducted at Duke University Medical Center (NCT00049309) and the University of Alabama at Birmingham (NCT02224807 and NCT01886677) were combined for analysis. Demographic and anthropometric differences between enrolled vs. non-enrolled individuals were assessed using Chi-square for categorical variables and t-tests for continuous variables. There was no difference in participation rate when comparing minority status or overweight and obese patients. However, obese females were slightly more likely to enroll than women who were overweight (p = 0.110), a trend not seen in men. Women were also less likely than men to participate if their study site was >25 miles from their home (p = 0.034). Patients who had completed a college degree were somewhat less likely to enroll than those with less educational attainment (p = 0.072). Of those who did not enroll, 80% cited a lack of time. Similar to other clinical trials, lack of time is a leading barrier to enrollment, and travel/distance appears to be a greater barrier for women in presurgical studies. Larger presurgical lifestyle intervention trials will require tailored strategies to enhance recruitment.


[Serum screening in pregnant women for Down syndrome and open neural-tube defects; testing against the Health Council criteria for genetic screening].
To check whether serum screening for Down syndrome and open neural tube defects satisfies the criteria set by the 'Committee Genetic screening' of the Dutch Health Council. Theoretical evaluation. Serum screening (the combined serum assessment of alpha-fetoprotein, human chorionic gonadotrophin and unconjugated oestriol, taking into consideration maternal age) was assessed against the Dutch Health Council criteria. The absolute criteria could be subdivided into a group of general conditions not related to a particular screening programme, and a group of programme-specific conditions. Population serum screening satisfied some of the absolute criteria, while the programme-specific conditions should be realised in an actual screening programme. Psychological and community consequences of such a screening have not yet been investigated in the Dutch population.


Methylation of guar gum for improving mechanical and barrier properties of biodegradable packaging films.
Improving functional properties of biopolymers for use as environment friendly packaging is an area of current interest. Biodegradable films with improved barrier and mechanical properties were prepared from methylated guar gum. Methylation resulted in structural modification of guar gum (GG) promoting greater crystallization thereby enhancing thermal stability towards decomposition. Reduction in radius of gyration (Rg), weight average molecular weight (Mw), and an increase in polydispersity index (PDI) were also observed due to methylation. Methylated guar gum (MGG) films exhibited 40% lower water vapor transmission rate (WVTR) as compared to control purified guar gum (PGG) films. Films prepared by partial replacement of PGG with MGG (10, 25, 50, 75 and 100% w/w) showed gradual improvement in percent elongation. The study gives an insight on the role of methylation in enhancing barrier and mechanical properties of GG based biodegradable films for possible application in food packaging.


Superelongation in helical muscles of leeches.
The fine structure of leech body wall muscles, has been analysed under great length variations. All the measurable parameters of the fibre (distance between thick filaments, sarcomere and A band width, percentage of actin crowns around myosin filaments, fibre radius) at different elongations were tested with equations describing the geometrical model of helical fibres. Anaesthetized and nonanaesthetized worms behave in different ways and can be utilized to verify the 'changing partner hypothesis'. The fit between theoretical and experimental data suggests that a double change of partner actually takes place in extremely stretched fibres.


The major antigen of elastin-associated microfibrils is a 31-kDa glycoprotein.
The major antigen derived from elastic fiber microfibrils was identified as a Mr = 31,000 glycoprotein, using immunoblotting and immunohistochemical techniques with antisera raised to "reductive guanidine extracts" of fetal bovine nuchal ligament, and to subfractions of these. A second, elastic fiber-derived, but unidentified, antigen of large molecular size (Mr greater than 200,000) was present in these extracts. Antisera raised to the purified 31-kDa glycoprotein were shown, by immunoelectron microscopy, to localize specifically to the elastin-associated microfibrils. Thus, the macro-molecule was called "microfibril-associated glycoprotein" or MAGP. MAGP is an acidic glycoprotein with a distinctive amino acid composition, being exceptionally rich in glutamic acid, rich in cystine, and low in glycine. MAGP was extractable from tissue homogenates using NaCl, urea, or guanidine hydrochloride solutions, only if a strong reducing agent was present. Thus, disulfide bonding is important for the strong association of MAGP with elastic fibers. Immunoblotting with anti-MAGP antiserum identified two additional reactive species, of Mr = 60,000 and Mr approximately 300,000, in tissue extracts. As only the 31-kDa species was detected in fibroblast culture medium, these additional species were probably aggregates, rather than precursors. MAGP did not react with antilysyl oxidase antiserum on immunoblots or by enzyme-linked immunosorbent assay. MAGP is the first macromolecule to have been established to be a constituent of elastin-associated microfibrils in both developing and mature elastic tissues.


Transcriptome and metabolome analysis of stress tolerance to aluminium in Vitis quinquangularis.
Transcriptional and metabolic regulation of aluminium tolerance of Chinese wild Vitis quinquangularis after Al treatment for 12 h: genes and pathways related to stress resistance are activated to cope with Al stress. The phytotoxicity of aluminium (Al) has become a major issue in inhibiting plant growth in acidic soils. Chinese wild Vitis species have excellent stress resistance. In this study, to explore the mechanism underlying Al tolerance in Chinese wild Vitis quinquangularis, we conducted a transcriptome analysis to understand the changes in gene expression and pathways in V. quinquangularis leaves after Al treatment for 12 h (Al_12 h). Compared with the control (CK) treatment, 2266 upregulated differentially expressed genes (DEGs) and 2943 downregulated DEGs were identified after Al treatment. We analysed the top 60 upregulated DEGs and found that these genes were related mostly to cell wall organization or biogenesis, transition metal ion binding, etc. Another analysis of all the upregulated DEGs showed that genes related to the ABC transport pathway, salicylic acid (SA), jasmonic acid (JA) and abscisic acid (ABA) hormone signalling pathway were expressed. Transcriptome and metabolome analysis revealed that genes and metabolites (phenylalanine, cinnamate and quercetin) related to the phenylalanine metabolic pathway were expressed. In summary, the results provide a new contribution to a better understanding of the metabolic changes that occur in grapes after Al stress as well as to research on improving the resistance of grape cultivars.


Neuroprotection of paliperidone on SH-SY5Y cells against β-amyloid peptide(25-35), N-methyl-4-phenylpyridinium ion, and hydrogen peroxide-induced cell death.
Antipsychotic drugs (APDs) were widely used in treating schizophrenia. Some APDs were reported to have neuroprotective effects against neurotoxicants in the cell level. Thus, one typical APD (haloperidol) and three atypical APDs (paliperidone, olanzapine, and risperidone) were tested whether they provide neuroprotection against stressor-induced cell death of SH-SY5Y. Hydrogen peroxide, N-methyl-4-phenylpyridinium ion, and β-amyloid peptide were used to treat cells with or without preconditioning by APDs; cell survival and indicators of oxidative stress were measured, respectively. Paliperidone has the lowest baseline cytotoxicity compared with other APDs at 24 h; in addition, the paliperidone group showed a better survival than the other APD groups (P < 0.05). In stressor challenging, with a fixed concentration of stressors, olanzapine provided the best neuroprotection at 100 μM against Aβ(25-35) and MPP(+) (P < 0.05). In contrast, paliperidone works finely at low concentrations (10 and 50 μM) against Aβ(25-35) and MPP(+) and solely protected SH-SY5Y from hydrogen peroxide. At 100 μM, paliperidone completely diminished cell reduction induced by different stressors, regardless of their dosages. Paliperidone was demonstrated with a higher oxidative stress-scavenging properties than other APDs in several aspects, such as generated bulk glutathione, low HNE, and protein carbonyl productions. Contradictorily, olanzapine, at 24 h, also enhanced HNE and protein carbonyl productions, which may underlie its induced cytotoxicity. Different APDs exhibit variations against different stressors. Paliperidone might be useful not only in alleviating oxidative stress induced by Aβ(25-35) and MPP(+) but also in providing neuroprotection against hydrogen peroxide.


A review of the use and psychometric properties of the Cognistat/Neurobehavioral Cognitive Status Examination in adults post-cerebrovascular accident.
This Rehabilitation Measures Database summary provides a review of the psychometric properties of the Cognistat/Neurobehavioral Cognitive Status Examination in individuals with cognitive impairment. A full review of the Cognistat/Neurobehavioral Cognitive Status Examination as well as reviews of over 300 other instruments can be found at www.rehabmeasures.org. (PsycINFO Database Record


Designer exosomes enabling tumor targeted efficient chemo/gene/photothermal therapy.
Exosomes, endogenous nanosized particles (50-150 nm) secreted and absorbed by cells, have been recently used as diagnostic and therapeutic platforms in cancer treatment. The integration of exosome-based delivery with multiple therapeutic modalities could result in better clinical outcomes and reduced-sided effects. Here, we combined the targeting and biocompatibility of designer exosomes with chemo/gene/photothermal therapy. Our platform consists of exosomes loaded with internalized doxorubicin (DOX, a model cancer drug) and coated with magnetic nanoparticles conjugated with molecular beacons capable of targeting miR-21 for responsive molecular imaging. The coated magnetic nanoparticle enables enrichment of the exosomes at the tumor site by external magnetic field guidance. After the exosomes are gathered at the tumor site, the application of near-infrared radiation (NIR) induces localized hyperthermia and triggers the release of cargoes loaded inside the exosome. The released molecular beacon can target the miR-21 for both imaging and gene silencing. Meanwhile, the released doxorubicin serves to kill the cancer cells. About 91.04 % of cancer cells are killed after treatment with Exo-DOX-Fe3O4@PDA-MB under NIR. The ability of the exosome-based method for cancer therapy has been demonstrated by animal models, in which the tumor size is reduced dramatically by 97.57 % with a magnetic field-guided tumor-targeted chemo/gene/photothermal approach. Thus, we expected this designer exosome-mediated multi-mode therapy to be a promising platform for the next-generation precision cancer nanomedicines.


Irreversible inactivation of 3-hydroxy-3-methylglutaryl-CoA reductase by H2O2.
A concentration-dependent inactivation of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase was found on preincubation of rat liver microsomal preparations with H2O2 and at lower concentrations in the presence of KCN which inhibited the contaminating catalase. The inactivation was not affected in the presence quenchers of hydroxyl radicals and singlet oxygen and was also obtained when H2O2 was added during the reaction. HMG-CoA, but not NADPH, partially protected the enzyme from H2O2-inactivation. Even at high concentration DTT was unable to reverse this inactivation. The soluble 50 kDa-enzyme was similarly inactivated by H2O2, and the tryptic-digest of the inactivated protein indicated the presence of a disulfide-containing peptide. The results support the view that H2O2 by directly acting on the catalytic domain possibly converts an active thiol group to an inaccessible disulfide and irreversibly inactivates HMG-CoA reductase.


Simultaneous determination of pharmaceuticals and metabolites in fish tissue by QuEChERS extraction and UHPLC Q/Orbitrap MS analysis.
In recent years, the occurrence, fate, and adverse effects of pharmaceutically active compounds (PhACs) in aquatic organisms have become a noteworthy issue. In the present study, a rapid and sensitive multiresidue analytical method was developed for the determination of 18 parent PhACs and 5 metabolites in sea bream (Sparus aurata), by combining a modified QuEChERS (quick, easy, cheap, effective, rugged and safe) procedure with ultra-high performance liquid chromatography-Orbitrap-mass spectrometry (UHPLC-Orbitrap-MS). The method development involved optimization of extraction solvent, extraction salts, clean-up sorbents, and amount of sample evaluation, while identification on Orbitrap MS was based on accurate mass and further confirmation with MS/MS fragmentation. The developed method was validated, and linearity was higher than 0.99. Recoveries in all cases ranged between 62 and 107% (at 10, 50, and 100 ng g-1), while intra-day and inter-day precision, expressed as relative standard deviation, RSD, was lower than 4% and 7%, respectively. In addition, limits of quantification (LOQs) ranged between 0.5 and 19 ng g-1. The compounds presented a low matrix effect, between - 13 and 4%, while the expanded uncertainty U% estimated at the three spiking levels 10, 50, and 100 ng g-1 was found below 49% in all cases. Finally, the validated method was applied to sea bream samples from an aquaculture farm located in the Mediterranean Sea, with one positive finding for the antibiotic trimethoprim at a concentration of 26 ng g-1, presenting negligible human health risk.


[Cognitive Behavioral Therapies, a co-coconstruction of care].
The decline of the medical paternalism tend to promote the emergence of person centered approaches. Cognitive behavioral therapies allow the enhancement of empowerment and contribute to the expansion of experiential knowledge. Various therapeutic strategies are summarized as well as their benefits and especially their leading role in the generation of experiential knowledge.


[Combined use of psychological and physical loading tests in the diagnosis of ischemic heart disease].
Reactions of heart ectopic activity in psychological exercise were similar to those in bicycle ergometry, but the values of pulse and arterial pressure increase were lower. The advantages of the psychological exercise test in detecting disorders of cardiac rhythm in patients, particularly in those hypersensitive to psychogenic effects, is noted. The importance of using psychological exercises in patients with high tolerance to physical exercises, by means of which latent forms of arrhythmias cannot always be detected, is pointed out.


A luminescent polyoxoniobate lanthanide derivative {Eu3(H2O)9[Nb48O138(H2O)6]}27- .
A europium-containing isopolyoxoniobate with the formula (CN3H6)7K3H17{Eu3(H2O)9Nb48O138(H2O)6}·40H2O is synthesized under the protection of citric acid. ESI-MS spectra show that the polyoxoanion structural unit {Eu3(H2O)9[Nb48O138(H2O)6]}27- is intact in aqueous solution. Moreover, its solid-state luminescence displays a red emission with the long lifetime of 258 μs.


Genome-wide identification and expression analysis of the Brassica oleracea L. chitin-binding genes and response to pathogens infections.
Chitinase family genes were involved in the response of Brassica oleracea to Fusarium wilt, powdery mildew, black spot and downy mildew. Abstract Chitinase, a category of pathogenesis-related proteins, is believed to play an important role in defending against external stress in plants. However, a comprehensive analysis of the chitin-binding gene family has not been reported to date in cabbage (Brassica oleracea L.), especially regarding the roles that chitinases play in response to various diseases. In this study, a total of 20 chitinase genes were identified using a genome-wide search method. Phylogenetic analysis was employed to classify these genes into two groups. The genes were distributed unevenly across six chromosomes in cabbage, and all of them contained few introns (≤ 2). The results of collinear analysis showed that the cabbage genome contained 1-5 copies of each chitinase gene (excluding Bol035470) identified in Arabidopsis. The heatmap of the chitinase gene family showed that these genes were expressed in various tissues and organs. Two genes (Bol023322 and Bol041024) were relatively highly expressed in all of the investigated tissues under normal conditions, exhibiting the expression characteristics of housekeeping genes. In addition, under four different stresses, namely, Fusarium wilt, powdery mildew, black spot and downy mildew, we detected 9, 5, 8 and 8 genes with different expression levels in different treatments, respectively. Our results may help to elucidate the roles played by chitinases in the responses of host plants to various diseases.


The prevalence of hepatitis C virus infection in β-thalassemia patients in Pakistan: a systematic review and meta-analysis.
Hepatitis C virus infection is the most commonly reported bloodborne infection in Pakistan. Frequent blood transfusions in β-thalassemia patients expose them to a high risk of HCV infection. The purpose of this paper is to summarise the current data on the prevalence of HCV infection in β-thalassemia patients in Pakistan by using a systematic review and meta-analysis. PubMed, EMBASE, Web of Sciences, the Cochrane Library, Directory of Open Access Journal and local databases were systematically searched for studies published between January 1st, 1995 and May 31st, 2019. Meta-analysis was performed using the DerSimonian and Laird random-effects models with inverse variance weighting. The presence of publication bias was tested by Egger test, and the methodological quality of each included article was evaluated by the STROBE. We identified a total of 229 potential studies, of which 27 studies were finally considered in the meta-analysis. The pooled prevalence of HCV in β-thalassemia patients in Pakistan was 36.21% (95% CI: 28.98-43.75%) based on 5789 β-thalassemia patients, but there was considerable heterogeneity. Meta-analysis estimated the HCV prevalence among the β-thalassemia patients at 45.98% (95% CI: 38.15-53.90%) in Punjab, 31.81% (95% CI: 20.27-44.59%) in Sindh, and 28.04% (95% CI: 13.58-45.26%) in Khyber Pakhtunkhwa. Meta-regression analysis showed that geographical location was a key source of heterogeneity. The pooled prevalence of HCV in β-thalassemia patients in Pakistan was more than one in three, and higher than in neighbouring countries. It varies regionally within the country. With the use of standard prevention procedures during blood transfusion, the risk of HCV transmission in β-thalassemia patients could be controlled and the prevalence of HCV in β-thalassemia patients reduced.


Clinical Characteristics, Course, and Long-Term Outcomes in Patients with Talaromyces marneffei Infection: A 10-Year Retrospective Cohort Study.
Talaromyces marneffei (T. marneffei), a dimorphic fungus, causes local or disseminated infection in humans. We aimed to analyze the clinical characteristics, prognostic factors, and survival outcomes of patients with T. marneffei infection and compare the differences between human immunodeficiency virus (HIV)-positive and HIV-negative subgroups. We retrospectively analyzed 241 patients with T. marneffei infection at the First Affiliated Hospital of Guangxi Medical University between January 2012 and January 2022. The overall population was stratified into HIV-positive (n = 98) and HIV-negative (n = 143) groups according to HIV status. Kaplan-Meier analysis and multivariate Cox regression models were used to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). With a median follow-up time of 58.9 months, 120 patients (49.8%) experienced disease progression and 85 patients (70.8%) died. The 5-year rates of OS and PFS were 61.4% (95% CI 55.0-68.6%) and 47.8% (95% CI 41.5-55.1%), respectively. As an independent factor, patients who were HIV positive had better PFS (HR 0.50, 95% CI 0.31-0.82; p < 0.01) than patients who were HIV negative. Compared with patients who were HIV positive, patients who were HIV negative were older and had more probabilities of underlying diseases, chest involvement, bone destruction, and higher count of neutrophils (all p < 0.05). Hemoglobin (PFS: HR 0.62; 95% CI 0.39-1.00; p < 0.05; OS: HR 0.45; 95% CI 0.22-0.89; p = 0.02) and lymphocyte count (PFS: HR 0.06; 95% CI 0.01-0.26; p < 0.01; OS: HR 0.08; 95% CI 0.01-0.40; p < 0.01) were independent prognostic factors for PFS and OS in patients who were HIV negative. Patients with T. marneffei infection have a poor prognosis. Patients who are HIV positive and HIV negative have relatively independent clinical characteristics. Multiple organ involvement and disease progression are more common in patients who are HIV negative.


Vascular tracers alter hemodynamics and airway pressure in anesthetized sheep.
The technique of vascular labeling was developed to mark sites of increased microvascular permeability. We used the vascular labeling technique in anesthetized sheep and found that hemodynamics and airway pressure were adversely affected by intraarterial infusions of two vascular tracers. Monastral blue (nine sheep) immediately caused systemic arterial hypotension, pulmonary arterial hypertension, and bronchoconstriction. All three physiological responses were partially blocked by a cyclooxygenase inhibitor (indomethacin) but not by an H1-antihistamine (chlorpheniramine). Colloidal gold (nine sheep) caused immediate, but less dramatic, pulmonary arterial hypertension which was not attenuated by the blocking agents. We conclude that these two vascular tracers caused detrimental physiological side effects in sheep at the usual doses used to label injured microvessels in other species.


Cancer stem cells, hypoxia and metastasis.
The successful growth of a metastasis, by definition, requires the presence of at least 1 cancer stem cell. Metastasis is a complex process, and an important contributor to this process is the influence of the tissue microenvironment, both cell-cell and cell-matrix interactions and the pathophysiologic conditions in tumors, such as hypoxia. A number of studies have suggested that normal stem cells may reside in "niches," where cell-cell and cell-matrix interactions can provide critical signals to support and maintain the undifferentiated phenotype of the stem cells. In this article, the evidence that these niches may be hypoxic is described, and the potential role that hypoxia may play in maintaining the stem cell phenotype in cancers is discussed. Recent work has suggested that there may be a linkage between the stem cell phenotype and that induced by the process of epithelial-mesenchymal transition (EMT). EMT plays an important role in cell movement and organ formation during embryogenesis, and it is currently hypothesized to be a major mechanism by which epithelial cancers may generate cells that can form metastases. Recent evidence suggests that the expression of certain genes involved in EMT is influenced by low oxygen levels, again suggesting a linkage between stem cells and hypoxia. Whether this supposition is correct remains an open question that will only be answered by further experimentation, but the potential role of hypoxia is critical because of its widespread existence in tumors and its known role in resistance to both radiation and drug treatment.


First record of the family Schizodactylidae (Orthoptera: Ensifera) from Thailand, with the description of a new species.
A new species of dune cricket in the family Schizodactylidae, Schizodactylus salweenensis sp. nov. is described from Salween River, Mae Hong Son Province, northwestern Thailand based on both males and females. The Schizodactylidae is recorded for the first time in Thailand. The new species is most similar to Schizodactylus tuberculatus Ander, 1938 and Schizodactylus burmanus Uvarov, 1935 in the morphology of male subgenital plate, but mainly differs in the shape of subgenital plate apex, and the spurs of hind tibiae. The type series was collected from sand dunes along the river. This cricket reaches adulthood during the rainy season.


Quality of life and psychological well-being during and after left ventricular assist device support.
Left ventricular assist devices (LVAD) are increasingly being used to treat patients in end-stage heart failure to facilitate survival to cardiac transplant or as a bridge to myocardial recovery. The technical innovation of the LVAD has a significant benefit on the patients' physical functioning. However, within the United Kingdom, there has been no systematic evaluation of the psychological adjustment and quality of life (QoL) of patients currently living with an LVAD, or of the differences in QoL for patients who are either explanted or transplanted. To assess the differences in QoL and psychological adjustment for current LVAD patients, patients who have been transplanted from an LVAD and patients in whom the device has been explanted. Twenty-two patients involved in an LVAD programme were recruited (18 men and four women; age range 18-60). Eight patients had an LVAD in situ, six patients had the LVAD explanted and eight had undergone transplantation. QoL and psychological functioning were assessed using previously validated measures. Although there were no significant differences between the three groups, there was a trend for the LVAD patients to have higher levels of anxiety and depression and a lower QoL compared with transplanted or explanted patients. For patients with an LVAD in situ, there was a trend for QoL and psychological functioning to be poorer than for transplanted and explanted patients. Larger studies will be needed to confirm these findings, but psychological assessment and interventions to reduce psychological morbidity and improve QoL will be important in these patients, particularly in view of the increasing numbers of LVADs being implanted and the possibility of their use for long-term "destination" therapy.


Altered Indoleamine 2,3-Dioxygenase Production and Its Association to Inflammatory Cytokines in Peripheral Blood Mononuclear Cells Culture of Type 2 Diabetes Mellitus.
To analyze indoleamine 2,3-dioxygenase (IDO) production in the cell culture supernatant of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from type 2 DM (T2DM) patients and investigate IDO's association to pro- and anti-inflammatory cytokines. PBMC samples were collected from 21 T2DM patients and 17 normoglycemic participants, then stimulated with PHA for 3 days. Cytokine and IDO concentrations were measured in the PBMC culture supernatants. In vitro production of TNF-α, IL-6, interferon-γ, and IL-10 were measured using multiplex immunoassay. IDO concentration was assessed using ELISA. To assess how PHA stimulation altered IDO production and to minimize the unstimulated baseline effect of T2DM, we subtracted the PHA-stimulated IDO concentration from the unstimulated one. IBM SPSS version 23 was used for statistical analysis. The IDO concentrations in the PBMC culture supernatants were significantly higher in T2DM patients regardless of whether they were unstimulated (P < .001) or PHA-stimulated (P = .012). Reduced IDO production was observed in 52.8% of T2DM patients and was associated with older age and lower interferon-γ levels. Conversely, 42.8% of T2DM patients showed increased IDO concentrations, which were correlated with the IL-6/IL-10 ratio (r = 0.683, P = .021) and interferon-γ/IL-10 ratio (r = 0.517, P = .077). The interferon-γ level was reduced in the PBMC culture supernatant of T2DM patients with reduced IDO production. Reduced IDO production in T2DM patients following PHA stimulation was associated with older age and, notably, higher baseline IDO concentrations. Since IDO is primarily produced by dendritic cells, reduced IDO production after PHA stimulation may indicate dendritic cell dysfunction.


Nutritional management of cystic fibrosis - an update for the 21st century.
Nutritional management is an essential part of multidisciplinary care for infants, children and adults with cystic fibrosis (CF). In 2016 two updated nutritional consensus guidelines were published [1,2]. This review will explore some of the key points in the nutritional management of people with CF in the 21st Century.


Single-crystal structure of the 2H-related perovskites (A(3-x)Nax)NaBO6 (A = La, Pr, Nd; B = Rh, Pt).
Single crystals of La(2.47)Na(1.53)RhO6, Pr(2.45)Na(1.55)RhO6, Nd(2.45)Na(1.55)RhO6, La2Na2PtO6, and Nd2Na2PtO6 were grown from carbonate and "wet" hydroxide fluxes. All were found to crystallize in the trigonal space group R3c and adopt the K4CdCl6 structure.


A cross-sectional study of implicit rationing of care in publicly funded nursing homes in Shanghai, China.
To investigate the level of implicit care rationing and its association with training needs in nursing homes in Shanghai, China. Nursing homes in Shanghai are confronted with a lack of care resources. Implicit care rationing can emerge due to inadequate training of care workers. A cross-sectional survey was conducted between 10 September and 17 November 2020. A total of 374 care workers from 16 randomly were selected nursing homes from each of the administrative districts participated the surveys. The Basel Extent of Rationing of Nursing Care-Nursing Home instrument and the training needs analysis were adopted to measure implicit care rationing and training needs, respectively. Multiple regression techniques were used to explore the factors associated with implicit care rationing. Activities related to social care, documentation and activation/rehabilitation (mean rating = 2.8, 1.89 and 1.93 respectively) were mostly likely to be rationed. Training needs of activities of daily living (ADL), activation/rehabilitation and documentation were significantly related to their implicit rationing (β = 0.864, 0.21 and 0.166, respectively, p < .01). Training needs are crucial determinants of implicit care rationing. Quality control systems are needed to ensure care comprehensiveness. The current training system should be re-designed according to results of training needs analysis.


Binding of the antiretroviral drug, d-aspartate-β-hydroxamate on the NMDA receptor.
d-Aspartate-β-hydroxamate (d-A β H) exhibits antiretroviral properties in vitro and in vivo. It has glutamate agonist properties at the N-methyl-d-aspartate (NMDA) receptor in neuronal cell cultures. This study characterizes its binding properties to the NMDA receptor by measuring its stimulating effect on N-(1-(2-thienyl)[(3)H]cyclohexyl)piperidine ([(3)H]TCP) binding to the ionic channel in rat brain membranes. d-A β H stimulated [(3)H]TCP binding in a dose-dependent manner but to a lower extent than glutamate, suggesting only partial glutamate agonist properties. In the presence of antagonists of the different effector sites of the NMDA receptor the affinity of d-A β H was competitively decreased by CGS-19755 and 7-chlorokynurenate and unaffected by arcaine. Among several d-A β H analogues VHS.125 behaved as a full NMDA agonist, but l- or d-glutamate γ-monohydroxamate (d-GH or l-GH) were without effect. This study shows that d-A β H has potential neurotoxic effects due to its direct interaction with the NMDA receptor and that analogues such as d-GH or l-GH may rather be used in humans.


Biosynthesis of fatty acid-derived hydrocarbons: perspectives on enzymology and enzyme engineering.
Enormous fuel consumption and growing environmental concerns have been spurring development of renewable biofuels. Among various biofuels, fatty acid-derived biohydrocarbons are ideal alternatives to non-renewable fossil fuels due to their closest properties to petroleum-based fuels. In the past decade, novel hydrocarbon-producing enzymes have continuously been discovered and engineered. Here, we review the recent advances in biosynthesis of fatty acid-derived hydrocarbons with emphasis on enzymology and enzyme engineering, based on which some outlooks are provided.


Quantitative sensory testing.
Quantitative sensory testing is a reliable way of assessing large and small sensory nerve fiber function. Sensory deficits may be quantified and the data used in parametric statistical analysis in research studies and drug trials. It is an important addition to the neurophysiologic armamentarium, because conventional sensory nerve conduction tests only the large fibers. QST is a psychophysical test and lacks the objectivity of NCS. The results are subject to changes owing to distraction, boredom, mental fatigue, drowsiness, or confusion. When patients are consciously or unconsciously biased toward an abnormal QST result, no psychophysical testing can reliably distinguish these patients from those with organic disease. QST tests the integrity of the entire sensory neuraxis and is of no localizing value. Dysfunction of the peripheral nerves or central nervous system may give rise to abnormalities in QST. As is true for other neurophysiologic tests, QST results should always be interpreted in light of the patient's clinical presentation. Quantitative sensory testing has been shown to be reasonably reproducible over a period of days or weeks in normal subjects. Because longitudinal QST studies of patients in drug trials are usually performed over a period of several months to a few years, reproducibility studies on the placebo-control group should be included. For individual patients, more studies are needed to determine the maximum allowable difference between two QSTs that can be attributed to experimental error. The reproducibility of thermal thresholds may not be as good as that of vibration threshold. Different commercially available QST instruments have different specifications (thermode size, stimulus characteristics), testing protocols, algorithms, and normal values. Only QST instruments and their corresponding methodologies that have been shown to be reproducible should be used for research and patient care. The data in the literature do not allow conclusions regarding the superiority of any QST instruments. The future of QST is promising; however, many factors can affect QST results. As is true for other neurophysiologic tests, QST is susceptible to many extraneous factors and to misuse when not properly interpreted by the clinician.


Presence of functional receptors for corticotropin releasing hormone in caecal circular smooth muscle cells of guinea pig.
The presence of specific binding sites for corticotropin releasing hormone (CRH) in caecal circular smooth muscle cells of guinea pig was investigated by binding and pharmacological studies. The specific binding of 125I-CRH to these muscle cells reached an equilibrium after 90 minutes. Several peptides structurally unrelated to CRH did not affect the specific binding of 125I-CRH to these muscle cells. Unlabeled CRH completely inhibited the specific binding of 125I-CRH in a concentration-dependent manner, with an IC50 value of 13.5 nM. A CRH receptor antagonist, alpha-helical CRH (9-41), inhibited the specific binding of 125I-CRH in a concentration-dependent manner with a lower affinity than CRH. In pharmacological study, CRH inhibited the contractile response of these muscle cells to 1 nM cholecystokinin-octapeptide in a concentration-dependent manner, with an IC50 value of 14.1 nM. A CRH receptor antagonist, alpha-helical CRH (9-41), significantly antagonized this inhibitory effect produced by CRH. These results strongly suggest the presence of functional receptors for CRH that mediate relaxation of caecal circular smooth muscle cells of guinea pig.


Prolonged nursing habit: a profile of patients and their families.
No association of the prolonged nursing-habit with the family background was found with the exception of predominantly lower socioeconomic conditions. All subjects demonstrated prolonged bottle-feeding or breast-feeding. Milk was reported to be the liquid most often used in the bottle. Parents reported that they did not know when weaning should occur, and when oral hygiene should be instituted. The nearly symmetrical caries pattern, the teeth most often affected and the order in which they are attacked and destroyed are conditions which are similar to those described in earlier studies.


Waist to Height Ratio and Metabolic Syndrome as lung dysfunction predictors.
Metabolic Syndrome (MetS) has been related to pulmonary diseases but its relationship with lung age has not been sufficiently studied. In addition, anthropometric variables have been associated with pulmonary dysfunction, highlighting the waist-to-height ratio (WHtR). The aim was to evaluate the relationship between MetS and: lung age, anthropometric variables and the alteration of lung function. A cross-sectional study was carried out in 1901 workers, evaluating lung function through lung age (Morris & Temple equation) and spirometric values. The diagnosis of MetS was based on the harmonized criteria. We measured anthropometric variables (WHtR, waist circumference, body mass index, waist to hip ratio), blood pressure and biochemical variables (glucose, cholesterol total, HDL, triglycerides). Workers suffering from MetS showed an accelerated lung aging (59.4 ± 18.7 years vs 49 ± 18.4 years). The WHtR ≥ 0.55 was significantly related to an increase in lung age (β = 6.393, p < 0.001). In addition, a significant linear trend was found between clinical categories of WHtR and lung dysfunction, restrictive and mixed pattern. MetS caused an accelerated lung aging and favored the presence of restrictive lung impairment. In addition, WHtR ≥ 0.55 has been shown as the best predictor for pulmonary health.


Bifunctional Metal Nanocrystals for Catalyzing and Reporting on Chemical Reactions.
Bifunctional nanocrystals with integrated plasmonic and catalytic activities hold great promise for analyzing chemical reactions by in situ surface-enhanced Raman spectroscopy. This Minireview gives a brief introduction to the general strategies for designing such nanocrystals, followed by four typical examples, including their fabrication, characterization, and potential limitation. We then use the reduction of 4-nitrothiophenol and oxidation of 4-aminothiophenol as two model systems to demonstrate the capabilities of these bifunctional nanocrystals to monitor chemical reactions for the elucidation of reaction mechanisms and measurement of kinetics. We conclude with perspectives on further development of these bifunctional nanocrystals into a viable platform for investigating other types of catalytic reactions.


A closer look at the bad deal trial: beyond clinical equipoise.
Some commentators have recently proposed that "clinical equipoise," although widely accepted, is not necessary for morally acceptable research on human subjects. If this concept is rejected, however, we may find that trials not in the best medical interests of their subjects--"bad deal trials"--could be justified. To avoid exploiting participants, we must find a way to distribute the risks fairly, even if it means embracing radical changes in the way clinical research is conducted.


Mast cell-driven skin inflammation is impaired in the absence of sensory nerves.
Mast cells (MCs) and nerves can induce cutaneous inflammatory responses, both independently and by interacting with each other. However, little is known about the role of skin nerves and neuropeptides in the regulation of MC-mediated skin inflammation, and the contribution of MCs in neurogenic inflammation is still controversial. The aim of this study was to investigate the effects of cutaneous sensory nerves on MC-driven inflammatory responses. Passive cutaneous anaphylaxis, a model for type I allergic skin responses, was studied in the presence or absence of sensory nerves by using a murine model of selective cutaneous denervation. Passive cutaneous anaphylaxis was significantly impaired in the absence of sensory nerves. This effect was not a result of an alteration of mast cell numbers in denervated skin. Moreover, IgE-mediated activation of mast cells was markedly decreased in denervated compared with normal skin. Notably, pretreatment of mice with selective antagonists of the neuropeptides substance P and/or calcitonin gene-related peptide also resulted in decreased inflammatory responses after MC activation. These data suggest that sensory skin nerves augment MC-driven inflammatory responses by releasing neuropeptides that increase MC degranulation.


Ideas crystallized on immunoglobulin superfamily-integrin interactions.
Interactions between immunoglobulin superfamily (IgSF) members and integrins are central to lymphocyte homing, leukocyte emigration into tissues at inflammatory sites, and in cell-cell interactions that lead to immune responses. Recent X-ray crystal structures reveal that the interaction of a divalent cation found in the integrin structure with an acidic residue from the IgSF partner may be important in binding.


Levobunolol 0.5% and timolol 0.5% to prevent intraocular pressure elevation after neodymium:YAG laser posterior capsulotomy.
To evaluate the prophylactic effect of levobunolol 0.5%, timolol 0.5%, or vehicle in reducing the incidence of postoperative intraocular pressure (IOP) spikes of 5 and 10 mm Hg or more in patients having neodymium:YAG (Nd:YAG) laser posterior capsulotomy. Miami Vision Center, Coral Gables, Florida; Cullen Eye Institute, Baylor College of Medicine, Houston, Texas; Cincinnati Eye Institute, Cincinnati, Ohio; South Texas Cataract and Glaucoma Center, San Antonio, Texas; Mid-South Eye Foundation, Memphis, Tennessee, USA. This prospective, double-masked, randomized study comprised 144 patients having Nd:YAG laser posterior capsulotomy in one eye. One drop of the test medication was administered preoperatively and one drop on the evening after surgery; IOP was measured preoperatively and 1,2,3 and 24 hours postoperatively. Intraocular pressure elevations of 5 mm Hg or more were seen in 1 of 60 patients (2%) in the levobunolol group, 4 of 54 (7%) in the timolol group, and 10 of 28 (36%) in the vehicle group. These elevations occurred significantly more frequently in the vehicle group than in the levobunolol (P < .001) or timolol (P < .004) groups. Elevations of 10 mm Hg or more were found in 2 of 28 patients (7%) treated with vehicle but were not observed in the patients treated with levobunolol or timolol. Levobunolol 0.5% or timolol 0.5% administered preoperatively and again in the evening after Nd:YAG laser capsulotomy effectively blunted the IOP rise that frequently follows laser surgery.


A clinicopathologic study of autosomal dominant optic atrophy.
Of a family with 40 members, 12 had autosomal dominant optic atrophy. The affected members were aware of reduced vision from the first decade. Visual loss was moderate to severe, 6/12 (20/40) to 3/60 (10/200). The affected members showed similar centrocecal scotomata. Most affected patients had severe unclassified color defects. Electroretinography measurements were normal in all but one patient who had a small reduction in the scotopic response. The pathologic changes in a patient with autosomal dominant optic atrophy showed diffuse atrophy of the ganglion cell layer of the retina with a loss of myelin and nerve tissue within the optic nerves. We suggest that autosomal dominant atrophy is a primary degeneration of retinal ganglion cells.


[Redistribution of concanavalin A receptors on the surfaces of enucleated cell fragments].
Normal mouse fibroblasts in culture were enucleated by centrifugation in a cytochalasin B-containing medium and then incubated with Con A. Bound Con A was determined by the indirect immunofluorescence technique. Such incubation led to the redistribution of the Con A receptors on the surface from the periphery towards the center both in enucleated cells and in small cytoplasmic fragments. Thus the capping of the cross-linked receptors was shown to be independent of the nucleus presence in the cell. Large cytoplasts contained both microfilaments and microtubules. Meanwhile small fragments demonstrated only microfilaments. Colcemide that destroys microtubules did not affect the redistribution of the Con A receptors. It is suggested that microfilaments rather than microtubules are responsible for the redistribution in question.


Retrospective lifetime estimation of failed and explanted diamond-like carbon coated hip joint balls.
Diamond-like carbon (DLC) coatings are known to have extremely low wear in many technical applications. The application of DLC as a coating has aimed at lowering wear and to preventing wear particle-induced osteolysis in artificial hip joints. In a medical study femoral heads coated with diamond-like amorphous carbon, a subgroup of DLC, articulating against polyethylene cups were implanted between 1993 and 1995. Within 8.5 years about half of the hip joints had to be revised due to aseptic loosening. The explanted femoral heads showed many spots of local coating delamination. Several of these explanted coated TiAlV femoral heads have been analyzed to investigate the reason for this failure. Raman analysis and X-ray photoelectron spectroscopy (XPS) depth profiling showed that the coating consists of diamond-like amorphous carbon, several Si-doped layers and an adhesion-promoting Si interlayer. Focused ion beam (FIB) transverse cuts revealed that the delamination of the coatings is caused by in vivo corrosion of the Si interlayer. Using a delamination test set-up dissolution of the silicon adhesion-promoting interlayer at a speed of more than 100 μm year(-1) was measured in vitro in solutions containing proteins. Although proteins are not directly involved in the corrosion reactions, they can block existing small cracks and crevices under the coating, hindering the exchange of liquid. This results in a build-up of crevice corrosion conditions in the crack, causing a slow dissolution of the Si interlayer.


Resveratrol-induced SIRT1 activation inhibits glycolysis-fueled angiogenesis under rheumatoid arthritis conditions independent of HIF-1α.
This study investigated the impacts of SIRT1 activation on rheumatoid arthritis (RA)-related angiogenesis. HUVECs were cultured by different human serum. Intracellular metabolites were quantified by UPLC-MS. Next, HUVECs and rat vascular epithelial cells under different inflammatory conditions were treated by a SIRT1 agonist resveratrol (RSV). Cytokines and biochemical indicators were detected by corresponding kits. Protein and mRNA expression levels were assessed by immunoblotting and PCR methods, respectively. Angiogenesis capabilities were evaluated by migration, wound-healing and tube-formation experiments. To down-regulate certain signals, gene-specific siRNA were applied. Metabolomics study revealed the accelerated glycolysis in RA serum-treated HUVECs. It led to ATP accumulation, but did not affect GTP levels. RSV inhibited pro-angiogenesis cytokines production and glycolysis in both the cells, and impaired the angiogenesis potentials. These effects were mimicked by an energy metabolism interrupter bikini in lipopolysaccharide (LPS)-primed HUVECs, largely independent of HIF-1α. Both RSV and bikinin can inhibit the activation of the GTP-dependent pathway Rho/ROCK and reduce VEGF production. Abrogation of RhoA signaling reinforced HIF-1α silencing-brought changes in LPS-stimulated HUVECs, and overshadowed the anti-angiogenesis potentials of RSV. Glycolysis provides additional energy to sustain Rho/ROCK activation in RA subjects, which promotes VEGF-driven angiogenesis and can be inhibited by SIRT1 activation.


Analysis of Mortality from Asbestos-Related Diseases in Brazil Using Multiple Health Information Systems, 1996-2017.
In Brazil, asbestos was intensively used from the 1960s until its ban in 2017. Mesothelioma, asbestosis, and pleural plaques are typical asbestos-related diseases (ARD-T). To create an ARD-T national database, death records from 1996-2017 were retrieved from several health information systems (HIS). All national HIS containing coded diagnoses (ICD-10) and death information were obtained. Linkage was performed to create a single database of ARD-T death records, either as underlying or contributory causes, in adults aged 30 years and older. A total of 3,057 ARD-T death records were found, 2,405 (76.4%) of which being malignant mesotheliomas (MM). Pleural MM (n = 1,006; 41.8%) and unspecified MM (n = 792; 32.9%) prevailed. Male to female MM ratio (M:F) was 1.4:1, and higher ratios were found for non-malignant ARD-T: 3.5:1 for asbestosis and 2.4:1 for pleural plaques. Male crude annual mesothelioma mortality (CMmm x1,000,000) was 0.98 in 1996 and 2.26 in 2017, a 131.1% increment, while for females it was 1.04 and 1.25, a 20.2% increase, correspondingly. The small number of deaths with asbestosis and pleural plaques records precluded conclusive interpretations. Even with the linkage of several HIS, ARD-T in death records remained in low numbers. MM mortality in men was higher and showed a rapid increase and, along with non-malignant ARD-T, higher M:F ratios suggested a predominant pattern of work-related exposure. The monitoring of workplace and environmental asbestos exposure needs to be improved, as well as the workers surveillance, following the recent Brazilian ban.


A novel lipase-catalyzed method for preparing ELR-based bioconjugates.
Herein we present a novel one-pot method for the chemical modification of elastin-like recombinamers (ELRs) in a mild and efficient manner involving enzymatic catalysis with Candida antarctica lipase B. The introduction of different functionalities into such ELRs could open up new possibilities for the development of advanced biomaterials for regenerative medicine and, specifically, for controlled drug delivery given their additional ability to respond to stimuli other than pH or temperature, such as glucose concentration or electromagnetic radiation. Candida antarctica lipase B immobilized on a macroporous acrylic resin (Novozym 435) was used to enzymatically couple different aminated substrates to a recombinamer containing carboxylic groups along its amino acid chain by way of an amidation reaction. A preliminary study of the kinetics of this amidation in response to different reaction conditions, such as solvent, temperature or reagent ratio, was carried out using a phenylazobenzene derivative (azo-NH2) as a model. The optimal amidation conditions were used to couple other amine reagents, such as phenylboronic acid (FB-NH2) or polyethylene glycol (PEG-NH2), thus allowing us to obtain photoresponsive, glucose-responsive or PEGylated ELRs that could potentially be useful as sensors in devices for controlled drug delivery.


Emotional intelligence and eating disorders: a systematic review.
Prior research indicates that deficits in emotional abilities are key predictors of the onset and maintenance of eating disorders (ED). As a relatively new emotion-related construct, emotional intelligence (EI) comprises a set of basic emotional abilities. Preliminary research suggests that deficits in EI are linked with disordered eating and other impulsive behaviours. Also, previous research reveals that emotional and socio-cognitive abilities, as well as ED symptomatology, varies across lifespan development. However, while the findings suggest promising results for the development of potential effective treatments for emotional deficits and disordered eating, it is difficult to summarise the relationship between EI and ED due to the diversity of theoretical approaches and variety of EI and ED measures. Our study, therefore, aimed to systematically review the current evidence on EI and ED in both the general and clinical populations and across different developmental stages. The databases examined were Medline, PsycInfo and Scopus, and 15 eligible articles were identified. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were used. All the studies reviewed indicated negative associations between EI and the dimensions of ED. Additionally, several mechanisms involved, namely adaptability, stress tolerance and emotional regulation were highlighted. The systematic review suggests promising but challenging preliminary evidence of the associations between EI and the dimensions of ED across diverse stages of development. In addition, future research, practical implications and limitations are discussed. Systematic review.


Inhibition of gamma-secretase by the CK1 inhibitor IC261 does not depend on CK1delta.
CK1 and gamma-secretase are interesting targets for therapeutic intervention in the treatment of cancer and Alzheimer's disease. The CK1 inhibitor IC261 was reported to inhibit gamma-secretase activity. The question is: Does CK1 inhibition directly influence gamma-secretase activity? Therefore we analyzed the SAR of 15 analogues and their impact on gamma-secretase activity. The most active compounds were investigated on CK1delta activity. These findings exclude a direct influence of CK1delta on gamma-secretase, because any change in the substitution pattern of IC261 diminished CK1 inhibition, whereas gamma-secretase inhibition is still exerted by several analogues.


Exercise decreases PP2A-specific reversible thiol oxidation in human erythrocytes: Implications for redox biomarkers.
New readily accessible systemic redox biomarkers are needed to understand the biological roles reactive oxygen species (ROS) play in humans because overtly flawed, technically fraught, and unspecific assays severely hamper translational progress. The antibody-linked oxi-state assay (ALISA) makes it possible to develop valid ROS-sensitive target-specific protein thiol redox state biomarkers in a readily accessible microplate format. Here, we used a maximal exercise bout to disrupt redox homeostasis in a physiologically meaningful way to determine whether the catalytic core of the serine/threonine protein phosphatase PP2A is a candidate systemic redox biomarker in human erythrocytes. We reasoned that: constitutive oxidative stress (e.g., haemoglobin autoxidation) would sensitise erythrocytes to disrupted ion homeostasis as manifested by increased oxidation of the ion regulatory phosphatase PP2A. Unexpectedly, an acute bout of maximal exercise lasting ~16 min decreased PP2A-specific reversible thiol oxidation (redox ratio, rest: 0.46; exercise: 0.33) without changing PP2A content (rest: 193 pg/ml; exercise: 191 pg/ml). The need for only 3-4 μl of sample to perform ALISA means PP2A-specific reversible thiol oxidation is a capillary-fingertip blood-compatible candidate redox biomarker. Consistent with biologically meaningful redox regulation, thiol reductant-inducible PP2A activity was significantly greater (+10%) at rest compared to exercise. We establish a route to developing new readily measurable protein thiol redox biomarkers for understanding the biological roles ROS play in humans.


Inverse Tendency between Ex Vivo Expansion Potential of Hematopoietic Progenitors and Time to Engraftment after Hematopoietic Stem Cell Transplantation.
The CD34(+) cell dose and infused number of committed progenitor cells in transplantation are important factors in hematologic engraftment. However, the relationship between expansion potential of progenitor cells and hematologic engraftment remains controversial. We evaluated whether expansion potential of progenitor cells is a predictive factor of post-transplantation hematologic engraftment. Mononuclear cells isolated from mobilized peripheral blood and bone marrow were cultured with cytokine cocktail for 7 days. Progenitor cells and committed progenitors were analyzed using stem cell markers (CD34 and CD133) and lineage specific markers. Hematologic engraftment was defined as neutrophil counts over 500/microL and platelet counts over 20,000/microL without transfusion. Acute and chronic graft-versus-host disease (GVHD) were investigated. There was inverse tendency between the number and fold expansion of progenitor cells or committed (granulocytic or megakaryocytic) progenitors and time to engraftment. Especially, fold expansion of CD34(+)/CD33(+) cells was significantly correlated with time to neutrophil engraftment in bone marrow transplantation (r=-0.56, P=0.04). The infused number and fold expansion of lymphoid progenitors were not related to the occurrence of acute or chronic GVHD. We could not prove that expansion potential of progenitor cells and committed progenitor cells is correlated to hematologic engraftment although there is a correlation between CD34(+)/ CD33(+) cells and time to neutrophil engraftment. But, a further study on the value of expansion potential is required because there is an inverse tendency.


A comparative dose-response study of cartilage-derived morphogenetic protein (CDMP)-1, -2 and -3 for tendon healing in rats.
Cartilage-derived morphogenetic proteins (CDMPs), belonging to the bone morphogenetic protein (BMP) family, are known to be cartilage and bone inducers as well as to induce tendon and ligament-like tissue. In this study we investigated the influence of CDMP-1, -2 or -3 at four different doses (0, 0.4, 2 and 10 microg) on tendon healing in a rat model, as well as differences in osteogenesis between the different CDMPs and doses.In 110 rats, a 3 mm segment of the Achilles tendon was removed via a 2 mm skin incision. CDMP-1, -2 or -3 was injected into the defect 6 h postoperative. The rats were killed 8 days after operation. The tendon regenerates were tested biomechanically. There was a significant dose-related increase in strength and stiffness with all three CDMPs, but no difference between the CDMPs was found. Another 50 rats were used to compare the highest dose of the CDMPs with controls and osteogenic protein 1 (OP-1), as regards cartilage or bone formation after 4 weeks. Cartilage occurred in all groups, including the controls. Some specimens in all groups contained bone, except the controls. No difference between the CDMPs could be demonstrated. The CDMP-1, CDMP-3 and OP-1 groups contained significantly more calcium than controls. Only the CDMP-2 group and the controls contained significantly less calcium than the OP-1 group.In conclusion, the three CDMPs appeared similar as regards improvement of tendon repair and osteogenicity in this setting.


MicroRNA-664a-5p promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by directly downregulating HMGA2.
Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs) has been regarded as a central issue in fracture healing. MicroRNAs (miRNAs, miRs) participate in diverse physiological processes such as osteoblastic differentiation of BMSCs. In this study, we found that miR-664a-5p was upregulated during osteogenic differentiation of human BMSCs, and this upregulation positively correlated with the expression of osteogenic genes Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and osteocalcin (OCN). Overexpression of miR-664a-5p promoted the osteogenic differentiation of BMSCs, whereas a knockdown of miR-664a-5p suppressed it. Additionally, high-mobility group A2 (HMGA2) mRNA was identified as a direct target of miR-664a-5p that mediates the function of this miRNA. Overexpression of HMGA2 obviously attenuated miR-664a-5p-induced osteogenic differentiation of BMSCs. Thus, the newly identified miR-664a-5p-HMGA2 pathway expands our understanding of the mechanisms underlying the osteogenic differentiation of human BMSCs, may provide deeper insights into the regulation of this differentiation, and can point to new effective methods for treating osteoporosis.


Facial paralysis: timing of repair and management of the nonflaccidly paralyzed face.
To explore recent advances in therapeutic interventions for nonflaccid facial paralysis (NFFP), including new evidence for surgical and nonsurgical treatments. Timing of treatment is also discussed, along with possible future treatments. NFFP remains a difficult disease to treat. Chemodenervation with botulinum toxin remains a first-line treatment to suppress aberrant and antagonistic movements during voluntary use of muscles. More permanent treatments such as selective neurectomy, myectomy, and nerve and muscle transfers have been shown to offer promising results for the nonflaccidly paralyzed face. NFFP is commonly seen in patients who have incomplete recovery from facial paralysis, and carries high psychosocial morbidity. A large array of treatments have been described in the literature, both procedural and nonprocedural. Both treatment type and timing are important in optimal patient recovery.


Exploring different organic manures in the production of quality basil seedlings.
In recent years, the demand of people for medicinal and aromatic plants has dramatically increased. For this reason, a large number of researches are being conducted to make these plants more quality. In this sense, this study explored the effects of domestic peat, bat guano, chicken and sheep manures, and vermicompost on the growth, quality traits, and nutrient contents of basil (Ocimum basilicum L.). For this purpose, an experiment in greenhouse conditions was arranged in a completely randomized design with four replications. The treatments included control (100% Peat/Perlite) and three doses (2%, 4%, 6%) for each of four organic manures. In total, there were 13 treatments. The study showed that there were significant differences among treatments for aesthetic appearance score, height, and fresh and dry weights of plants with the exception of crown width. Control and "94% Peat/Perlite + 6% Bat guano" had the lowest and highest values of all growth and quality traits. Overall, it concluded that "94% Peat/Perlite + 6% Bat guano" should be used in planting basil. Further studies including different organic manures and their combinations are required to obtain better growth and quality traits as well as physiological traits of basil.


Consistency between patients and families in recognizing cancer chemotherapy side effects: A questionnaire survey.
Although the side effects of cancer chemotherapy impair a patient's quality of life, family members' awareness of side effects may relieve patient anxiety and distress. We investigated whether patients and their families were consistent in recognizing the occurrence and severity of symptomatic side effects of chemotherapy treatment for cancer. This was a prospective observational study. We administered a questionnaire survey to patients and family members to assess the frequency of occurrence (1: never, 2: almost never, 3: sometimes, 4: frequently, 5: almost always, 6: unknown) and the degree of severity (1: mild, 2: moderate, 3: severe, 4: extremely severe, 5: unknown) of physical and psychological symptoms associated with cancer chemotherapy. Weighted Kappa and Cramer coefficients were used to assess consistency between the two groups. We surveyed 20 pairs of patients (5 men, 15 women) and their families (10 men, 10 women); 17 pairs lived together. The median age was 65.5 years (interquartile [IQR], 58.75, 69.25) for patients and 61.00 years (IQR, 47.25, 71.25) for family members. Of patients, 17 had solid cancer, and three had leukemia. Family members mostly recognized objectively visible symptoms such as hair loss and development of spots and keratinization. However, it was difficult for families to detect invisible subjective symptoms such as weakness, dysesthesia, depressed mood, and unarticulated anxiety. The results indicated that recognition of invisible subjective symptoms in patients undergoing chemotherapy was difficult even for family members. Therefore, a multidisciplinary approach in which various medical professionals actively communicate with both patients and families is important. Information sharing in collaboration with patients and families could increase understanding of the patient's condition and optimize patient care.


Combining insights from quantile and ordinal regression: child malnutrition in Guatemala.
Chronic child undernutrition is a persistent problem in developing countries and has been the focus of hundreds of studies where the primary intent is to improve targeting of public health and economic development policies. In national level cross-sectional studies undernutrition is measured as child stunting and the goal is to assess differences in prevalence among population subgroups. Several types of regression modeling frameworks have been used to study childhood stunting but the literature provides little guidance in terms of statistical properties and the ease with which the results can be communicated to the policy community. We compare the results from quantile regression and ordinal regression models. The two frameworks can be linked analytically and together yield complementary insights. We find that reflecting on interpretations from both models leads to a more thorough analysis and forces the analyst to consider the policy utility of the findings. Guatemala is used as the country focus for the study.