Miracle-dz/UniFAR-FTUs huggingface dataset:
Butyrate Modulates Diabetes-Linked Gut Dysbiosis: Epigenetic and Mechanistic Modifications.

Diabetic dysbiosis has been described as a novel key player in diabetes and diabetic complications. However, the cellular/molecular alteration associated with dysbiosis remain poorly characterized. For that, control, non-obese type 2 diabetic MKR mice and MKR mice treated with butyrate were used to delineate the epigenetic, cellular and molecular mechanisms by which dysbiosis associated with diabetes induces colon shortening, inflammation attesting to gastrointestinal disturbance. Our results show that dysbiosis is associated with T2DM and characterized by reduced Bacteroid fragilis population and butyrate-forming bacteria. The reduction of butyrate-forming bacteria and inadequate butyrate secretion result in alleviating HDAC3 inhibition and alter colon permeability. The observed changes are also associated with increased ROS production, a rise in NOX4 proteins, and a shift in the inflammatory markers, where IL-1 is increased and IL-10 and IL-17 are reduced. Treatment with butyrate restores the homeostatic levels of NOX4 and IL-1. In summary, our data suggest that in T2DM, dysbiosis associates with a reduction in butyrate content leading to increased HDAC3 activity. Butyrate treatment restores the homeostatic levels of the inflammatory markers and reduces ROS production known to mediate diabetes-induced colon disturbance. Taken together our results suggest that butyrate could be a potential treatment to attenuate diabetic complications.
Replicable brain signatures of emotional bias and memory based on diffusion kurtosis imaging of white matter tracts

Diffusion MRI (dMRI) is sensitive to anisotropic diffusion within bundles of nerve axons and can be used to make objective measurements of brain networks. Many brain disorders are now recognised as being caused by network dysfunction or are secondarily associated with changes in networks. There is therefore great potential in using dMRI measures that reflect network integrity as a future clinical tool to help manage these conditions. Here, we used dMRI to identify replicable, robust and objective markers that meaningfully reflect cognitive and emotional performance. Using diffusion kurtosis analysis and a battery of cognitive and emotional tests, we demonstrated strong relationships between white matter structure across networks of anatomically and functionally specific brain regions with both emotional bias and emotional memory performance in a large healthy cohort. When the connectivity of these regions was examined using diffusion tractography, the terminations of the identified tracts overlapped precisely with cortical loci relating to these domains, drawn from an independent spatial meta‐analysis of available functional neuroimaging literature. The association with emotional bias was then replicated using an independently acquired healthy cohort drawn from the Human Connectome Project. These results demonstrate that, even in healthy individuals, white matter dMRI structural features underpin important cognitive and emotional functions. Our robust cross‐correlation and replication supports the potential of structural brain biomarkers from diffusion kurtosis MRI to characterise early neurological changes and risk in individuals with a reduced threshold for cognitive dysfunction, with further testing required to demonstrate clinical utility.
Patterns of allele distribution in a hybrid population of the Cryptococcus neoformans species complex

The sister yeast species Cryptococcus neoformans (serotype A) and Cryptococcus deneoformans (serotype D) are causative agents of deadly cryptococcosis and fungal meningoencephalitis. These haploid yeasts can hybridise in nature, giving rise to AD hybrids that are predominantly diploid or aneuploid. Despite their increasing prevalence in clinical settings, much remains unknown about the allelic distribution patterns in AD hybrid strains.
A Behavioral Activation Mobile Health App for Smokers With Depression: Development and Pilot Evaluation in a Single-Arm Trial

Background The integration of Behavioral Activation Treatment for Depression (BAT-D) into smoking cessation interventions is a promising approach to address depression as a barrier to quitting. However, this approach has only been tested as a face-to-face intervention, which has low reach. Objective The aims of the study were to develop a BAT-D mobile health app with high potential reach and determine its feasibility, acceptability, and preliminary effects on theory-based behavioral processes of behavioral activation, reduced depressive symptoms, and smoking cessation. Methods Following a user-centered design process consisting of competitive analysis, focus groups, and prototype testing, we conducted a single-arm pilot trial of Actify! , a BAT-D app for depressed smokers. Participants used SmokefreeTXT along with Actify! to provide cessation content that had not yet been built into the app for this initial phase of pilot testing. Participants in the trial were current, daily smokers with mild to moderate depressive symptoms. We examined use outcomes for all enrolled participants and process and cessation outcomes at 6 weeks postenrollment for study completers (16/17, 94% retention). Results Regarding acceptability, average number of log-ins per participant was 16.6 (SD 13.7), and 63% (10/16) reported being satisfied overall with the app. Posttreatment interviews identified some usability challenges (eg, high perceived burden of planning and scheduling values-based activities). There was a significant decrease in depressive symptoms from baseline to follow-up (mean change in Patient Health Questionnaire–9 scores was –4.5, 95% CI –7.7 to –1.3; P=.01). Additionally, carbon monoxide (CO)-confirmed, 7-day point prevalence abstinence (PPA) at 6-week follow-up was 31% (5/16), and the 30-day PPA was 19% (3/16). Conclusions Results demonstrate promising engagement with Actify! and potential for impact on theory-based change processes and cessation outcomes. Preliminary quit rates compare favorably to previous trials of smoking cessation apps for the general population (ie, short-term, self-reported 30-day quit rates in the 8% to 18% range) and a previous trial of face-to-face BAT-D for depressed smokers (ie, CO-confirmed, 7-day PPA rate of 17% at end of treatment).
The Effects of Anthocyanins and Their Microbial Metabolites on the Expression and Enzyme Activities of Paraoxonase 1, an Important Marker of HDL Function

High circulating HDL concentrations and measures of various HDL functions are inversely associated with cardiovascular disease (CVD) risk. Paraoxonase 1 (PON1) contributes to many of the athero-protective functions of HDL, such as promoting the reverse cholesterol transport process and reducing the levels of oxidized LDL. PON1 activities are influenced by several factors, the most important being diet and genetic polymorphisms. Reported data from randomized controlled trials have shown that anthocyanin consumption increased PON1 activity. However, the underlying molecular mechanisms by which anthocyanins increase PON1 activity are not understood. Therefore, the aim of this research was to investigate the ability of anthocyanins and their metabolites to increase PON1 gene expression and/or enzyme activities as potential mechanisms. The effect of the two predominant dietary anthocyanins and 18 of their recently identified microbial metabolites including their phase-II conjugates on PON1 gene expression was studied using a PON1-Huh7 stably-transfected cell line and reporter gene assay. The effects of these compounds on PON1 arylesterase and lactonase activities were investigated using two isoforms of the PON1 enzyme that are the phenotypes of the 192Q/R polymorphism. None of the compounds caused even modest changes in PON1 promoter activity (p ≥ 0.05). Further, none of the compounds at physiological concentrations caused any significant changes in the arylesterase or lactonase activity of either of the iso-enzymes. Cyanidin reduced the lactonase activity of the PON1-R192R enzyme at high concentrations (−22%, p < 0.001), but not at physiologically achievable concentrations. In conclusion, none of the data reported here support the notion that anthocyanins or their metabolites affect PON1 transactivation or enzyme activities.
Running head : SOCIOMETRIC STATUS IN YOUTH SPORT 1 1 2 3 4 5 An Exploration of Sociometric Status and Peer Relations in Youth Sport 6

25 More than 10 years ago, it was suggested that sociometry and systematic observation were two 26 potentially useful but under-utilized methods for the study of peers in youth sport (Smith, 2003). 27 Despite this call, the methods used to study peers in sport remain largely focused on athletes’ 28 perceptions through questionnaires and interviews. Thus, the purpose of this exploratory, 29 descriptive study was to investigate the utility of sociometry in relation to sport competence and 30 observed athlete behavior in youth sport. Three adolescent female volleyball teams were 31 videotaped during three practice sessions, and sport competence and sociometric status were 32 assessed using questionnaires. An observational coding system was developed and used to code 33 athlete behaviors and data were compared across sociometric status groups. Results revealed 34 significant differences between sociometric status groups on peer ratings of sport competence, 35 but not on athlete behavior. However, interesting findings emerged with respect to how status 36 groups interacted with teammates and coaches. Thus, sport competence seems to be an important 37 factor in gaining acceptance among youth peer groups. Further, sociometry and behavioral 38 observation appear to be useful techniques that should continue to be employed in the study of 39 peer relations in youth sport. 40 41
Impact of pharmaceutical care interventions on the occurrence and resolution of side/adverse drug effects associated with antiretroviral drug therapy

Pharmaceutical care (PC) has been shown to improve the outcome of drug therapy in many disease conditions. HIV/AIDS is one of the disease conditions that are fraught with many problems that can benefit from this new emphasis of pharmacy practice also known as ‘pharmacists care’. Adverse drug reactions or effects are unintended and undesirable effects of drugs other than their known and expected actions which can be unpleasant and sometimes fatal. This study is designed to evaluate the impact of pharmaceutical care activities on the occurrence of side/adverse drug reactions in HIV/AIDS patients receiving antiretroviral drugs. The components of the American society of health-system pharmacists (ASHP) guidelines on ‘standardized method for pharmaceutical care’ was used as a data collection instrument to evaluate, document and intervene in the antiretroviral therapy of about one thousand four hundred and seventy three (1,473) patients. The study identified about sixty (60) different types of side/adverse effects occurring among these patients through observation and patient complaints. The study also showed significant reduction in the incidence of side/adverse drug effects following the Pharmacist’s intervention activities, p ≥ 0.5. The study showed that pharmacists’ interventions in antiretroviral drug therapy through Pharmaceutical care can significantly reduce the incidence of side/adverse drug effects in HIV/AIDS patients receiving antiretroviral drugs.
Nanoparticles as carriers for drug delivery of macromolecules across the blood-brain barrier

ABSTRACT Introduction: Current therapies of neurodegenerative or neurometabolic diseases are, to a large extent, hampered by the inability of drugs to cross the blood-brain barrier (BBB). This very tight barrier severely restricts the entrance of molecules from the blood into the brain, especially macromolecular substances (i.e. neurotrophic factors, enzymes, proteins, as well as genetic materials). Due to their size, physicochemical properties, and instability, the delivery of these materials is particularly difficult. Areas covered: Recent research showed that biocompatible and biodegradable nanoparticles possessing tailored surface properties can enable a delivery of drugs and specifically of macromolecules across the blood-brain barrier by using carrier systems of the brain capillary endothelium (Trojan Horse strategy). In the present review, the state-of-art of nanoparticle-mediated drug delivery of different macromolecular substances into the brain following intravenous injection is summarized, and different nanomedicines that are used to enable the transport of neurotrophic factors and enzymes across the blood-brain barrier into the CNS are critically analyzed. Expert opinion: Brain delivery of macromolecules by an intravenous application using nanomedicines is now a growing area of interest which could be really translated into clinical application if dedicated effort will be given to industrial scale-up production.
Biomarkers for healing in adults with venous leg ulcers

To the Editor: I read with great interest the article by Stacey et al. The authors conducted a prospective study for 13 weeks to evaluate the healing effect of wound fluid biomarkers in 42 patients with chronic venous leg ulcers. Among 13 biomarkers, granulocyte-macrophage colony-stimulating factor and matrix metalloprotease-13 were selected as the best predictors of wound healing by a multivariate logistic regression model. Receiver operating characteristic (ROC) curve analysis indicated 92% accuracy (95% confidence interval [CI]: 85–100%) for granulocyte-macrophage colony-stimulating factor, and 78% accuracy (95% CI: 65–90) for matrix metalloprotease-13 in discriminating between healing and non-healing wounds. I have some concerns about their study with special reference to statistical approach and additional information of specific enzyme for wound healing. First, the total number of events for logistic regression analysis is closely related to statistical power. If the number of events per variable (EPV) value is less than 10, prediction ability of events might decrease. In case of evaluating relative significance of independent variables (13 biomarkers in this report), EPV value less than 10 is also acceptable. Second, the authors adopted ROC curve analysis to compare the diagnostic performance of biomarkers. They presented “accuracy” values and I suppose that comparisons of the sensitivity and specificity might be performed using the McNemar and chi-square tests for determining the positive and negative predictive values. Generally, ROC analysis presents the area under the curve (AUC) of each ROC curve. If the authors intend to compare AUCs of each ROC curves, statistical approach differs according to null hypothesis. In addition, the size of the sample is important for keeping statistical power. Taken together, more information might be required to accept their validation study. Recently, Turner et al investigated the role of Granzyme K (GzmK) in inflammation and remodeling in response to thermal injury. GzmK induced IL-6 expression in keratinocytes, and keratinocytes showed impaired wound healing. GzmK might influence wound healing by augmenting inflammation and impeding epithelialization. GzmK markedly elevates in response to sepsis and infection, and GzmK in combination with classically activated macrophages in wound fluid should be evaluated for verifying the healing effect. CONFLICTS OF INTEREST
The value of kinetic glomerular filtration rate estimation on medication dosing in acute kidney injury

Background In acute kidney injury (AKI), medication dosing based on Cockcroft-Gault creatinine clearance (CrCl) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rates (eGFR) are not valid when serum creatinine (SCr) is not in steady state. The aim of this study was to determine the impact of a kinetic estimating equation that incorporates fluctuations in SCrs on drug dosing in critically ill patients. Methods We used data from participants enrolled in the NIH Acute Respiratory Distress Syndrome Network Fluid and Catheters Treatment Trial to simulate drug dosing category changes with the application of the kinetic estimating equation developed by Chen. We evaluated whether kinetic estimation of renal function would change medication dosing categories (≥60, 30–59, 15–29, and <15mL/min) compared with the use of CrCl or CKD-EPI eGFR. Results The use of kinetic CrCl and CKD-EPI eGFR resulted in a large enough change in estimated renal function to require medication dosing recategorization in 19.3% [95 CI 16.8%–21.9%] and 23.4% [95% CI 20.7%–26.1%] of participants, respectively. As expected, recategorization occurred more frequently in those with AKI. When we examined individual days for those with AKI, dosing discordance was observed in 8.5% of total days using the CG CrCl and 10.2% of total days using the CKD-EPI equation compared with the kinetic counterparts. Conclusion In a critically ill population, use of kinetic estimates of renal function impacted medication dosing in a substantial proportion of AKI participants. Use of kinetic estimates in clinical practice should lower the incidence of medication toxicity as well as avoid subtherapeutic dosing during renal recovery.
How I Perform Resurfacing Shoulder Replacement

Surface replacement arthroplasty of the shoulder is a well accepted and frequently performed procedure. There are reports of good long-term results to support this. As with all surgical procedures, however, the results depend on a thorough understanding of the surgical technique. This article discusses the most common pitfalls and suggests solutions developed over 25 years of use.
The impact of HIV and AIDS on education as perceived by secondary school learners in Masilonyana District in the Free State Province

This paper reports on secondary school learners' perceptions of the impact of human immunodeficiency virus and acquired immune deficiency syndrome (HIV and AIDS) on education. A questionnaire on the impact of HIV and AIDS on education was constructed and it was content validated against the theoretical assumptions supported by the literature on HIV and AIDS. Empirical investigation and findings reveal that learners perceive that HIV and AIDS have impact on educators, on learners themselves, on school environment, and on school enrolments and performance.
Guidelines for the Management of Safety When Using Volunteers and Patients for Practical Training in Ultrasound Scanning

Practical experience of ultrasound scanning forms an essential component of all training in clinical ultrasound. Those in training may observe experienced and qualified practitioners carrying out scanning, and, more importantly, use ultrasound equipment under the guidance and supervision of a tutor, or other senior clinical colleague. During training, they develop an understanding of the machine controls and settings and a working knowledge of the purpose and outcome of altering the machine settings. They also develop practical skills in carrying out a wide range of clinical studies, obtaining images of optimum diagnostic quality and interpreting and reporting findings.
The prevalence of SEN virus infection in blood donors and chronic hepatitis B and C patients in Chaharmahal Va Bakhtiari province

SEN virus (SEN-V) is a blood-borne, circular, nonenveloped and single-stranded DNA virus. Phylogenetic analysis demonstrated 9 different genotypes for this virus. SEN-V could be related to post-transfusion hepatitis and infections with this virus in blood donors and hepatitis patients differ markedly by geographic region. The purpose of present study was to determine the prevalence of H and D genotypes of SEN-V (SENV-H and SENV-D) infection in blood donors and patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) for the first time in Chaharmahal Va Bakhtiari province located in southwest Iran. SEN-V DNA was analyzed in 240 serum samples of the patients with chronic HBV and HCV (172 HBV and 68 HCV) and 60 non-professional blood donors from the blood transfusion organization, hospital and clinical and pathological laboratories in Chaharmahal Va Bakhtiari province. SEN-V DNA was amplified by specific primers for SENV-H and SENV-D genotypes using polymerase chain reaction (PCR) method after extraction of DNA from sera and PCR products were visualized in a 1% agarose gel electrophoresis. SENV-H genotype was found to be positive in 54/172 (31.39%), 23/68 (33.82%), and 8/60 (13.33%) and SENV-D genotype was detected in 48/172 (27.91%), 27/68 (39.7%), and 6/60 (10%) of patients with chronic HBV, HCV and healthy blood donors, respectively. These results showed that high prevalence of SEN-V infection in patients with chronic HBV and HCV compared healthy blood donors in Chaharmahal Va Bakhtiari province using T test statistical analysis (P<0.05). According to these findings examination of serum samples for control and prevention of SEN-V infection in hepatitis patients and healthy blood donors seems to be necessary .
Bone Ultrasound

Another misleading feature is the apparent inverse proportionality between the velocity and the density. It might be assumed from the above equation that bones which had been subject to demineralisation and the conseqent reduction in density, would exhibit higher than normal velocities. This is manifestly not true and indeed, it can be shown that if any particular bone sample is progressively demineralised with nitric acid, for example, then its velocity varies roughly linearly with density apparently in complete contradiction to the theory (Fig. 1). This can be understood if it is appreciated that the bulk modulus term, K, is itself also a function of density and therefore a density term appears both in the numerator and denominator. It is travelled is known. In the laboratory, this is readily achieved by using mechanical calipers on the specimen but in-vivo the thickness of bone is not readily distinguishable from that of the surrounding tissue. If a measurement of the velocity, v, is achieved then it is normally accepted that this is related to the material properties through a simple equation:
Training in urology: The development of a tracking feedback system for flexible scopes

During the training of new doctors in cystoscopy a problem could occur. When the trainee controls the cystoscope, the supervising doctor is focussed on the scope images on a monitor. Because the supervising doctor is not holding the scope, location feedback is absent. This makes it difficult to determine whether the entire inner surface of the bladder has been inspected. This problem of missing critical parts of the surface during a cystoscopy is not described in literature, thus the prevalence of this problem is explored using a questionnaire. A possible solution has been developed, using an assistive tracking system that provides qualitative feedback on inspection performance. The result is an external tracking device consisting of sensors and a computer display that provides real-time bladder location feedback. In an experiment, participants were asked to inspect a bladder model with a cystoscope equipped with and without the system. This proved position feedback significantly increased the inspected area size during the procedure. The improvement in inspected area size was 5%. In a second study, focused on the effect of training, participants were divided into two groups, with and without the system. Participants had to perform a task six times to see the effect the system had on training. These results were inconclusive. The questionnaire that was sent and answered by 100 urologists in the Netherlands indicates that urologists find the system promising. Subsequent steps are general improvement of the system, integration with existing technology, expanding to other scope types and repeating experiments with more participants and in a clinical setting.