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BackgroundThere is evidence that cognitive training interventions can positively impact executive functions, and that some studies have demonstrated that athletes typically exhibit greater accuracy and faster response times on select cognitive tasks. While the engagement of executive functions is suggested to be part of high-level sporting activities, it is unclear whether such training approaches could directly benefit athletic performance. ObjectiveThe objective of this study was to evaluate the impact of a combined virtual reality (VR)– and tablet-based cognitive training intervention on adolescent tennis players’ performance. Here, we examined differences in Universal Tennis Rating (UTR) between players who supplemented their regular tennis training with a cognitive training intervention and a group that continued regular tennis training alone. This custom cognitive training program targeted specific cognitive control abilities including attention, working memory, and goal management. MethodsData were collected from a cohort of tennis players in a randomized controlled trial design led by the dedicated research team. Participants (N=23, age: mean 14.8, SD 2.4 years) from the Czech Lawn Tenis Klub (Prague, Czech Republic) were invited to participate in this study. These individuals were randomized into an intervention + training-as-usual group (n=13) or training-as-usual group (control group; n=10), with the change in UTR score being the primary metric of interest. ResultsThere was no difference in UTR between the 2 groups at baseline (intervention: mean 8.32, SD 2.7; control: mean 7.60, SD 2.3). Following the treatment period, individuals in the intervention group showed a significant improvement in their UTR (an increase of 0.5; t12=4.88, P

BackgroundType 2 diabetes (T2D) is a leading cause of premature morbidity and mortality globally and affects more than 100 million people in the world’s most populous country, India. Nutrition is a critical and evidence-based component of effective blood glucose control and most dietary advice emphasizes carbohydrate and calorie reduction. Emerging global evidence demonstrates marked interindividual differences in postprandial glucose response (PPGR) although no such data exists in India and previous studies have primarily evaluated PPGR variation in individuals without diabetes. ObjectiveThis prospective cohort study seeks to characterize the PPGR variability among individuals with diabetes living in India and to identify factors associated with these differences. MethodsAdults with T2D and a hemoglobin A1c of ≥7 are being enrolled from 14 sites around India. Participants wear a continuous glucose monitor, eat a series of standardized meals, and record all free-living foods, activities, and medication use for a 14-day period. The study’s primary outcome is PPGR, calculated as the incremental area under the curve 2 hours after each logged meal. ResultsData collection commenced in May 2022, and the results will be ready for publication by September 2025. Results from our study will generate data to facilitate the creation of machine learning models to predict individual PPGR responses and to facilitate the prescription of personalized diets for individuals with T2D. ConclusionsThis study will provide the first large scale examination variability in blood glucose responses to food in India and will be among the first to estimate PPGR variability for individuals with T2D in any jurisdiction. Trial RegistrationClinical Trials Registry-India CTRI/2022/02/040619; https://tinyurl.com/mrywf6bf International Registered Report Identifier (IRRID)DERR1-10.2196/59308

ABSTRACT Background and Aims An exploratory focus group study was conducted to better understand the needs of patients living with generalized myasthenia gravis (gMG). Methods US‐based adults with gMG and caregivers of patients with gMG participated in a Patient Engagement Research Council between August 2022 and January 2023. The study consisted of a 15‐min prework survey, followed by virtual focus groups facilitated using a semi‐structured interview guide. Data concepts were identified using conversational analysis and by direct observation. All transcripts were coded based on concepts using a qualitative research analysis program (MaxQDA). Results 16 participants (13 patients, three caregivers) were recruited. Participants reported impact on daily activities, fatigue, and psychosocial problems. Many participants experienced delayed diagnosis and difficulty accessing specialist care. Participants described multiple barriers related to their gMG, including barriers to treatment, access‐related issues, and communication disconnect between patients and healthcare professionals. Achieving stable disease was the most important goal. There was a preference for the autonomy of self‐administered medications at home versus infusions. Study insights led to recommendations to guide patient and healthcare professional education. Conclusion The study illustrates the need to improve access to specialist care, achieve earlier diagnosis, prioritize patients' preferences in disease management, and develop treatments that improve outcomes without additional burden. Patient or Public Contribution The data collected in this study was provided by the focus group participants, which included patients and caregivers of those with myasthenia gravis.

Abstract Background and Aims Due to the high symptom and treatment burden in myasthenia gravis (MG), understanding patient and care partner perspectives and preferences is crucial. Methods This study used voice analysis and virtual focus groups to understand patient and care partner experiences with MG‐related symptoms, treatments, and preferences. The voice analysis via social media listening used artificial intelligence‐powered tools to gather and structure public digital conversations on MG. Focus groups included people living with MG and care partners who completed a questionnaire and participated in a 1‐h virtual session facilitated using a semi‐structured interview guide. Qualitative data were aggregated, transcribed, and thematically analyzed. Results The voice analysis examined 11,554 posts from 8321 individuals, discussing MG symptoms, treatments, and burden. Of 7563 symptom‐related posts, 5902 (78%) conveyed negative, 1427 (19%) neutral, and 234 (3%) positive sentiment. The most frequently mentioned symptoms were categorized as dysarthria, muscle weakness, and dysphagia. MG treatment sentiment analysis identified 6667 posts (67%) as neutral, 2887 (29%) as negative, and 350 (4%) as positive. For the focus groups, 15 individuals (12 patients and 3 care partners) completed the questionnaire and 14 participated in the virtual focus group sessions. The 15 participants who completed the questionnaire prioritized treatment convenience, symptom control for improved quality of life, and preventing potential MG crises in their current treatment. New treatment expectations included increased effectiveness, less frequent dosing, faster onset, and fewer side effects. Participants were also receptive to wearable medication delivery systems placed on the body and valued direct involvement in treatment decisions. Conclusion Patients and care partners are often negatively impacted by MG symptoms and value convenient and fast‐acting treatments that control symptoms with minimal side effects. Considering patient preferences may help optimize treatment decisions and improve patients' overall well‐being and satisfaction in their care.

Abstract Myasthenia gravis (MG) is a rare, autoimmune, antibody-mediated, neuromuscular disease. This study analyzed digital conversations about MG to explore unprovoked perspectives. Advanced search, data extraction, and artificial intelligence-powered algorithms were used to harvest, mine, and structure public domain digital conversations about MG from US Internet Protocol addresses (August 2021 to August 2022). Thematic analyses examined topics, mindsets, and sentiments/key drivers via natural language processing and text analytics. Findings were described by sex/gender and treatment experience with steroids or intravenous immunoglobulin (IVIg). The 13,234 conversations were extracted from message boards (51%), social media networks (22%), topical sites (21%), and blogs (6%). Sex/gender was confirmed as female in 5703 and male in 2781 conversations, and treatment experience was with steroids in 3255 and IVIg in 2106 conversations. Topics focused on diagnosis (29%), living with MG (28%), symptoms (24%), and treatment (19%). Within 3176 conversations about symptoms, eye problems (21%), facial muscle problems (18%), and fatigue (18%) were most commonly described. Negative sentiments about MG were expressed in 59% of conversations, with only 2% considered positive. Negative conversations were dominated by themes of impact on life (29%), misdiagnosis problems (27%), treatment issues (24%), and symptom severity (20%). Impact on life was a key driver of negativity in conversations by both men (27%) and women (34%), and treatment issues was a dominant theme in conversations by steroid-treated (29%) and IVIg-treated (31%) patients. Of 1382 conversations discussing treatment barriers, 36% focused on side effects, 33% on lack of efficacy, 21% on misdiagnosis, and 10% on cost/insurance. Side effects formed the main barrier in conversations by both steroid-treated and IVIg-treated patients. Capturing the patient voice via digital conversations reveals a high degree of concern related to burden of disease, misdiagnosis, and common MG treatments among those with MG, pointing to a need for treatment options that can improve quality of life.

Background: To make basic sciences easy and accessible to enhance their clinical importance. Objective: basic sciences in medical education have a pivotal role in forming foundation of a medical students. However, students have become disinterested because of the inaccessibility of the study system and methods. Through this study, an attempt was made to highlight this problem and find a suitable solution. Material and Methods: Data were collected from 265 students. Data were collected using a questionnaire that was analyzed using SPSS version 20 (IBM, Chicago, IL, USA). Descriptive statistics were used for categorical and quantitative variables. The total scores on each subscale pertaining to basic science subjects, anatomy, physiology, and biochemistry were calculated. Results: Medical students reported mixed responses on the clinical significance of anatomy (moderate) and physiology (low to moderate), while biochemistry was reported to be the most clinically useful. More than 50% of the respondents considered the syllabus of the basic medical sciences to be vast, in contrast to their limited clinical usefulness. Traditional teaching of basic medical sciences as individual disciplines, unrelated to each other and other clinical subjects (7), made them very difficult to recall and applicable in clinical years of the students, included in our survey Conclusion: The majority of the respondents in our study were of the view that the knowledge of basic medical sciences is very important in order to become a good clinician, but the majority also thought that only working knowledge of these subjects is required in clinical years. Therefore, there is no need for deeper understanding of structures and functions.

Introduction: Chronic Kidney Disease (CKD) has become an impending health concern due to the massive rise in the number of patients with diabetes mellitus and hypertension. Monitoring CKD patients typically requires regular invasive testing, and a simple diagnostic test that does not involve venipuncture would greatly benefit patients and healthcare professionals. Extensive research is being conducted to explore the use of saliva as a Non invasive tool for evaluation of systemic diseases like CKD. However, most of these studies have focused on End Stage Renal Disease (ESRD) patients. Aim: To investigate the correlation between salivary urea and creatinine levels and their serum counterparts in CKD patients and healthy controls. Additionally, the study aimed to assess the efficacy of salivary urea and creatinine compared to serum urea and creatinine in predicting CKD. Materials and Methods: The present cross-sectional study was conducted between January 2021 and July 2022 in the Department of Biochemistry, in collaboration with the Department of Medicine, at Heritage Institute of Medical Sciences in Varanasi, Uttar Pradesh, India. The study included a total of 60 participants: 30 CKD patients (stage 1-3) and 30 age-matched healthy controls. Serum and salivary urea were analysed using the Urease-Glutamate Dehydrogenase (GLDH) method, and creatinine was measured using the Modified Jaffe’s method on the Dirui-300B autoanalyser. Data were statistically analysed using Pearson’s correlation coefficient. The sensitivity, specificity, and Area Under the Curve (AUC) of salivary urea and creatinine were evaluated in comparison to their serum counterparts. Results: The participants consisted of 30 CKD patients with a mean age of 54.8±8.8 years and 30 age-matched healthy controls with a mean age of 52.42±8.4 years. A significant difference in salivary urea and creatinine levels was observed between the control and CKD groups. There was a strong and significant correlation (p-value

Introduction: Anxiety, depression, and poor sleep quality are the most common mental health issues in post-acute Coronavirus Disease-2019 (COVID-19) syndrome. Healthcare professionals (HCPs) were overburdened and unable to focus on their own health issues. Previous epidemic diseases, such as Severe Acute Respiratory Syndrome (SARS) in 2003, also accompanied psychiatric issues in HCPs. In light of this, the purpose of this study was to identify the symptoms of COVID19 that continue to affect HCPs and their associations with fatigue, poor sleep, anxiety, depression, and activity levels, in order to provide better care and treatment for them. Aim: To analyse the impact of post-acute COVID-19 syndrome on the mental health of HCPs and compare the results with non COVID-19 infected participants. Materials and Methods: A cross-sectional study was conducted at PGIMS, Rohtak in Haryana, India from October 2021 to September 2022. A total of 280 participants between 25-45 years of age, including doctors, nurses, and dentists involved in direct COVID-19 patient care, were included in the survey. They were divided equally into a non COVID-19 infected group and a post-acute COVID-19 syndrome group, with atleast three months having passed since infection. The survey included scales addressing anxiety, depression, and sleep quality, including the Zung Self-rating Anxiety Scale (SAS), Zung Self-rating Depression Scale (SDS), and Pittsburgh Sleep Quality Index (PSQI). The mean scores were compared between both groups using an Independent sample t-test. Results: The data of 240 participants were analysed and compared between both groups. The mean age was 32.41 years in the post-acute COVID-19 syndrome group and 31.24 years in the non COVID-19 infected group. The post-acute COVID-19 syndrome group consisted of a large proportion of doctors (60, 42.9%) and nurses (53, 37.9%), whereas the non COVID-19 infected group included doctors (47, 33.5%) and nurses (56, 40%). The results showed statistically significant differences for anxiety (p-value=0.001) and sleep quality (p-value =0.001), while no significant differences were found for depression (p-value>0.05). Conclusion: Anxiety and poorer sleep quality occur in healthcare workers suffering from post-acute COVID-19 syndrome. Creating multidisciplinary rehabilitation health teams in hospitals with clinician psychologists, physiotherapists, nurses, and psychiatrists is essential to address mental health issues in the post-COVID-19 population.

Objective: To determine the association of platelet count with the severity of COVID-19 infection. Study Design: Retrospective longitudinal study. Place and Duration of Study: Mayo Hospital, Lahore Pakistan, from Aug 2020 and Aug 2021. Methodology: Data was recorded in a proforma. The severity of COVID-19 infection, based on physical examination and saturation measured on a pulse oximeter recorded at the time of presentation to the hospital, was noted. A platelet count was obtained from a complete blood count at the presentation time. Platelet counts were compared in patients with non-severe infection and severe infection. Results: The mean age of the patients was 50.11±14.20 years. Out of 200 patients, 134(67%) were male and 66(33%) were female. Sixty-three (31.5%) patients had non-severe, while 137(68.5%) had severe COVID-19 symptoms. A significant association was seen between the severity of illness and platelet count at the time of presentation, with a p-value of 0.047. Conclusion: This study shows that in COVID-19 patients, thrombocytopenia at the time of presentation to the hospital is associated with severe disease.

Abstract The prevalence of edentulism is pandemic and people resort to complete dentures for the restoration of missing teeth and esthetics. However, the determination of the correct occlusal vertical dimensions (OVD) constitutes to play an important role in overall patient satisfaction. The objective of this study was to apply anthropometric methods to correlate the length of index finger (2D) to measure the OVD from base of the nose to the base of the chin (Sn–Me) and to assess satisfaction by comparing both the methods. A total of 80 edentulous patients were randomized and controlled for this trial into experimental and control groups. A correlation was found between Sn–Me and finger measurements, dentures’ satisfaction was assessed after a 1-week follow-up and marked according to the Visual Analog Scale. Our findings established that finger measurements are greater among males, and in both genders, positive, and statistically significant correlations exist between the facial and finger length measurements. Moreover, 97.0% patients from experimental group were satisfied with the use of complete dentures through the new anthropometric method. Hence measuring the length of index finger can be an adjunct method for the restoration of OVD and is a relatively time-effective and simple method with a satisfactory follow-up. Trial registration: ID: NCT05153213 ( https://clinicaltrials.gov/ct2/show/NCT05153213 ).

Objective Poor medication adherence remains highly prevalent and adversely affects health outcomes. Patients frequently describe properties of the pills themselves, like size and shape, as barriers, but this has not been evaluated objectively. We sought to determine the extent to which oral medication properties thought to be influential translate into lower objectively-measured adherence.Design Retrospective cohort study.Setting US nationwide commercial claims database, 2016–2019.Participants Among patients initiating first-line hypertension, diabetes or hyperlipidaemia treatment based on clinical guidelines, we measured pill size, shape, colour and flavouring, number of pills/day and fixed-dose combination status as properties.Outcome measures Outcomes included discontinuation after the first fill (ie, never filling again over a minimum of 1-year follow-up) and long-term non-adherence (1-year proportion of days covered

Introduction: Obesity is on the rise in Pakistan. This study aims to assess the association of depression and obesity in patients who have undergone bariatric surgery at our center. Aims & Objectives: To assess the association of depression and obesity in patients who have undergone bariatric surgery at our center. Place and duration of study: This one-year mixed descriptive study was conducted at Sir Ganga Ram Hospital, Lahore between January 2021 and January 2022 Material & Methods: Ninety bariatric surgery patients files were screened to see whether data regarding depression screening and follow-up was complete as per DSM-V formulated depression questionnaire. Patients were then randomly selected and asked for short interviews to understand themes and experiences regarding their mood to understand the association between obesity and depression. Results: Statistically significant difference existed in the depression scores at each follow-up from the previous score and from baseline, showing decreased weight resulted in lower scores. Themes of (i) financial constraints and economic struggles, (ii) depression linked to eating habits, (iii) anger and irritability as a predominant symptom of low mood, and (iv) using religion as mental health therapy were picked during the interviews. Conclusion: Bariatric and metabolic surgery should be offered to patients as per guidelines for patients who require it. Depression and mental health disorders are prevalent in the obese population, and these should be screened for and appropriately dealt with in both the pre-operative and post-operative phase. Surgical candidacy decision should not be based on the presence or absence of mental health disorders.

Objective: To study the association between hepatitis C virus viral load by real-time PCR and core antigen value of HCV and define an antiviral treatment monitoring cut-off value for HCV core antigen. Study Design: Cross-sectional validation study. Place and Duration of Study: Department of Infectious Diseases, Chughtai Lab Lahore Pakistan, from Jun 2017 to Mar 2018. Methodology: To establish the association between these two parameters, we took a hundred positive plasma samples for HCV RNA and subjected them to an HCV Core antigen test. Furthermore, the samples were divided into three categories based on their viral load; 10000 IU/ml. Results: Our results showed that the hepatitis C virus core antigen was concordant with hepatitis C virus RNA by PCR when the viral load was above 2000 IU/ml. Below the HCV RNA load of 2000 IU/ml, the HCV core antigen had a sensitivity of 94.95% and specificity of 88.89%. Conclusion: In patients having a viral load above 2,000 IU/ml, the hepatitis C virus core antigen value can be used as a marker for diagnosis and monitoring antiviral therapy. After the antiviral treatment, HCV RNA real-time PCR should be performed to validate viral clearance.

Randomised controlled clinical trials are widely considered the preferred method for evaluating the efficacy or effectiveness of interventions in healthcare. Adaptive trials incorporate changes as the study proceeds, such as modifying allocation probabilities or eliminating treatment arms that are likely to be ineffective. These designs have been widely used in drug discovery studies but can also be useful in health services and implementation research and have been minimally used. In this article, we use an ongoing adaptive trial and two completed parallel group studies as motivating examples to highlight the potential advantages, disadvantages, and important considerations when using adaptive trial designs in health services and implementation research. We also investigate the impact on power and the study duration if the two completed parallel group trials had instead been conducted using adaptive principles. Compared with traditional trial designs, adaptive designs can often allow the evaluation of more interventions, adjust participant allocation probabilities (eg, to achieve covariate balance), and identify participants who are likely to agree to enrol. These features could reduce resources needed to conduct a trial. However, adaptive trials have potential disadvantages and practical aspects that need to be considered, most notably: outcomes that can be rapidly measured and extracted (eg, long term outcomes that take considerable time to measure from data sources can be challenging), minimal missing data, and time trends. In conclusion, adaptive designs are a promising approach to help identify how best to implement evidence based interventions into real world practice in health services and implementation research.

Abstract Gut barrier dysfunction is often implicated in pathology following alcohol intoxication and burn injury. MicroRNAs (miRNAs) are negative regulators of gene expression that play a central role in gut homeostasis, although their role after alcohol and burn injury is poorly understood. We performed an integrated analysis of miRNA and RNA sequencing data to identify a network of interactions within small intestinal epithelial cells (IECs) which could promote gut barrier disruption. Mice were gavaged with ~ 2.9 g/kg ethanol and four hours later given a ~ 12.5% TBSA full thickness scald injury. One day later, IECs were harvested and total RNA extracted for RNA-seq and miRNA-seq. RNA sequencing showed 712 differentially expressed genes (DEGs) (padj

Abstract The a priori T cell repertoire and immune response against SARS-CoV-2 viral antigens may explain the varying clinical course and prognosis of patients having a mild COVID-19 infection as opposed to those developing more fulminant multisystem organ failure and associated mortality. Using a novel SARS-Cov-2-specific artificial antigen presenting cell (aAPC), coupled with a rapid expansion protocol (REP) as practiced in tumor infiltrating lymphocytes (TIL) therapy, we generate an immune catalytic quantity of Virus Induced Lymphocytes (VIL). Using T cell receptor (TCR)-specific aAPCs carrying co-stimulatory molecules and major histocompatibility complex (MHC) class-I immunodominant SARS-CoV-2 peptide-pentamer complexes, we expand virus-specific VIL derived from peripheral blood mononuclear cells (PBMC) of convalescent COVID-19 patients up to 1000-fold. This is achieved in a clinically relevant 7-day vein-to-vein time-course as a potential adoptive cell therapy (ACT) for COVID-19. We also evaluate this approach for other viral pathogens using Cytomegalovirus (CMV)-specific VIL from donors as a control. Rapidly expanded VIL are enriched in virus antigen-specificity and show an activated, polyfunctional cytokine profile and T effector memory phenotype which may contribute to a robust immune response. Virus-specific T cells can also be delivered allogeneically via MHC-typing and patient human leukocyte antigen (HLA)-matching to provide pragmatic treatment in a large-scale therapeutic setting. These data suggest that VIL may represent a novel therapeutic option that warrants further clinical investigation in the armamentarium against COVID-19 and other possible future pandemics.

Abstract Trophic coherence, a measure of a graph’s hierarchical organisation, has been shown to be linked to a graph’s structural and dynamical aspects such as cyclicity, stability and normality. Trophic levels of vertices can reveal their functional properties, partition and rank the vertices accordingly. Trophic levels and hence trophic coherence can only be defined on graphs with basal vertices, i.e. vertices with zero in-degree. Consequently, trophic analysis of graphs had been restricted until now. In this paper we introduce a hierarchical framework which can be defined on any simple graph. Within this general framework, we develop several metrics: hierarchical levels, a generalisation of the notion of trophic levels, influence centrality, a measure of a vertex’s ability to influence dynamics, and democracy coefficient, a measure of overall feedback in the system. We discuss how our generalisation relates to previous attempts and what new insights are illuminated on the topological and dynamical aspects of graphs. Finally, we show how the hierarchical structure of a network relates to the incidence rate in a SIS epidemic model and the economic insights we can gain through it.

Abstract N-acetyltransferase 10 (NAT10), is an acetyltransferase that regulates RNA stability and translation processes. Association of NAT10 with several diseases including cancer, makes it a promising therapeutic target. Remodelin is the only known NAT10 inhibitor, but the structural information related to its binding with NAT10 is still obscure. Here, we predicted the human NAT10 structure using homology modeling that was not available previously and used human NAT10 to identify the novel binding site(s) of Remodelin. The alignment of the modeled human NAT10 showed 24% identity and 37% positivity with crystal structure of tRNA (Met) cytidine acetyltransferase. Molecular docking showed binding of Remodelin with NAT10 in acetyl-CoA binding pocket. Additionally, we screened a library of FDA-approved drugs for the identification of novel inhibitors of NAT10 activity. Binding score showed that four drugs namely, Fosaprepitant (− 11.709), Leucal (− 10.46), Fludarabine (− 10.347) and Dantrolene (− 9.875) bind to NAT10 and have better binding capability when compared with Acetyl-CoA (− 5.691) and Remodelin (− 5.3). Acetyl-CoA, Remodelin, and others exhibit hits for hydrophobic, hydrophilic and hydrogen interactions. Interestingly, Remodelin and others interact with the amino acid residues ILE629, GLY639, GLY641, LEU719, and PHE722 in the Acetyl-CoA binding pocket of NAT10 similar to Acetyl-CoA. Our findings revealed that Fosaprepitant, Leucal, Fludarabine, and Dantrolene are promising molecules that can be tested and developed as potential inhibitors of NAT10 acetyltransferase activity.

Abstract During cancer, a major challenge faced by oncologists is the treatment of metastasis; a leading cause of cancer-related deaths around the world. Metastasis involves a highly ordered sequence of events starting with the detachment of tumor cells from the extracellular matrix (E.C.M.). In normal cells, detachment from E.C.M. triggers programmed cell death, termed anoikis. However, tumor cells dodge their way to anoikis and spread to distant sites for initiating the metastatic program. In this work, we explored the impact of E.C.M. detachment on the expression of some major oncogenic histone methyltransferases. Results showed both EZH2 expression and its enzymatic activity were significantly increased in E.C.M. detached cancer cells when compared to the attached cells. Inhibition of EZH2 results in a significant reduction in cell proliferation, spheroids size, and induction in apoptosis in E.C.M. detached cells. Furthermore, we observed a reduction in EZH2 expression levels in single cells when compared to clusters of E.C.M. detached cells. Finally, we combined the EZH2 inhibition with AMPK, known to be highly expressed in E.C.M. detached cancer cells and observed antagonistic effects between the two pathways. The observed results clearly showed that E.C.M. detached cancer cells require oncogenic EZH2 and can be targeted by EZH2 inhibitors.

Abstract Respiratory protection is key in infection prevention of airborne diseases, as highlighted by the COVID-19 pandemic for instance. Conventional technologies have several drawbacks (i.e., cross-infection risk, filtration efficiency improvements limited by difficulty in breathing, and no safe reusability), which have yet to be addressed in a single device. Here, we report the development of a filter overcoming the major technical challenges of respiratory protective devices. Large-pore membranes, offering high breathability but low bacteria capture, were functionalized to have a uniform salt layer on the fibers. The salt-functionalized membranes achieved high filtration efficiency as opposed to the bare membrane, with differences of up to 48%, while maintaining high breathability (> 60% increase compared to commercial surgical masks even for the thickest salt filters tested). The salt-functionalized filters quickly killed Gram-positive and Gram-negative bacteria aerosols in vitro, with CFU reductions observed as early as within 5 min, and in vivo by causing structural damage due to salt recrystallization. The salt coatings retained the pathogen inactivation capability at harsh environmental conditions (37 °C and a relative humidity of 70%, 80% and 90%). Combination of these properties in one filter will lead to the production of an effective device, comprehensibly mitigating infection transmission globally.

BackgroundGaps between rational thought and actual decisions are increasingly recognized as a reason why people make suboptimal choices in states of heightened emotion, such as stress. These observations may help explain why high-risk medications continue to be prescribed to acutely ill hospitalized older adults despite widely accepted recommendations against these practices. Role playing and other efforts, such as simulation training, have demonstrated benefits to help people avoid decisional gaps but have not been tested to reduce overprescribing of high-risk medications. ObjectiveThis study aims to evaluate the impact of a simulation-based training program designed to address decisional gaps on prescribing of high-risk medications compared with control. MethodsIn this 2-arm pragmatic trial, we are randomizing at least 36 first-year medical resident physicians (ie, interns) who provide care on inpatient general medicine services at a large academic medical center to either intervention (simulation-based training) or control (online educational training). The intervention comprises a 40-minute immersive individual simulation training consisting of a reality-based patient care scenario in a simulated environment at the beginning of their inpatient service rotation. The simulation focuses on 3 types of high-risk medications, including benzodiazepines, antipsychotics, and sedative hypnotics (Z-drugs), in older adults, and is specifically designed to help the physicians identify their reactions and prescribing decisions in stressful situations that are common in the inpatient setting. The simulation scenario is followed by a semistructured debriefing with an expert facilitator. The trial’s primary outcome is the number of medication doses for any of the high-risk medications prescribed by the interns to patients aged 65 years or older who were not taking one of the medications upon admission. Secondary outcomes include prescribing by all providers on the care team, being discharged on 1 of the medications, and prescribing of related medications (eg, melatonin, trazodone), or the medications of interest for the control intervention. These outcomes will be measured using electronic health record data. ResultsRecruitment of interns began on March 29, 2021. Recruitment for the trial ended in Q42021, with follow-up completed by Q12022. ConclusionsThis trial will evaluate the impact of a simulation-based training program designed using behavioral science principles on prescribing of high-risk medications by junior physicians. If the intervention is shown to be effective, this approach could potentially be reproducible by others and for a broader set of behaviors. Trial RegistrationClinicalTrials.gov NCT04668248; https://clinicaltrials.gov/ct2/show/NCT04668248 International Registered Report Identifier (IRRID)PRR1-10.2196/31464

Background Type 2 diabetes mellitus is a multifactorial disease that escalates the risk of other associated complications such as diabetic neuropathy, retinopathy, and nephropathy. Diabetic nephropathy is a microvascular condition that leads to end-stage renal disease (ESRD). There are several genes involved in disease development and it is a challenging task to investigate all of these. Nonetheless, identifying individual gene roles can assist in evaluating the combinatorial effects with other genes. Angiotensin-1 converting enzyme 2 (ACE2), is the key regulator of blood pressure in the Renin-Angiotensin-Aldosterone System that hydrolyzes angiotensin II (vasoconstrictor) into angiotensin 1–7 (vasodilator). The association of different variants of the ACE2 with the risk of type 2 diabetes mellitus has been determined in various populations with susceptibility to other complications. This study was aimed to investigate the association of Angiotensin-1 converting enzyme 2 polymorphism, G8790A, with the increased risk of type 2 diabetes mellitus (T2DM) development with the complication of diabetic nephropathy (DN) in the Pakistani population. Methods In this case-control study, a total of 100 healthy controls and 100 patients of type 2 diabetes mellitus aged > 40 years, having disease duration ≥ 10 years were compared. The G8790A polymorphism in ACE2 was analyzed by allele-specific polymerase chain reaction (AS-PCR). The urinary albumin excretion (UAE), urinary creatinine, and albumin to creatinine ratios (ACR) were determined to assess renal function status. Pearson bivariate correlation coefficients were calculated to investigate the relationship among all the parameters. Crude and adjusted odds ratios were found to determine any risk association between ACE2 G8790A polymorphisms and disease development. The p-values < 0.05 were considered significant. Results A homogeneity was obtained regarding the distribution of data by sex, BMI, diastolic blood pressure, pulse rate and urinary creatinine levels between case and control groups. The ACR showed a significant correlation with UAE (r = 0.524, p = 0.001), urinary creatinine (r = -0.375, p = 0.001) and random blood sugar levels (r = 0.323, p = 0.005) with the complication of diabetic nephropathy in T2DM patient. Females with the AA genotype had a 10-fold increased risk for the development of type 2 Diabetes (OR = 9.5 [95% CI = 2.00–21.63] pConclusion The study finding indicated that female AG/AA genotype and male A genotype of G8790A polymorphism in the ACE2 gene were associated with type 2 diabetes mellitus as a genetic risk factor but are not associated with diabetic nephropathy in the Pakistani population.

Purpose To evaluate the predictive ability of a deep learning-based algorithm to determine long-term best-corrected distance visual acuity (BCVA) outcomes in neovascular age-related macular degeneration (nARMD) patients using baseline swept-source optical coherence tomography (SS-OCT) and OCT-angiography (OCT-A) data. Methods In this phase IV, retrospective, proof of concept, single center study, SS-OCT data from 17 previously treated nARMD eyes was used to assess retinal layer thicknesses, as well as quantify intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelium detachments (PEDs) using a novel deep learning-based, macular fluid segmentation algorithm. Baseline OCT and OCT-A morphological features and fluid measurements were correlated using the Pearson correlation coefficient (PCC) to changes in BCVA from baseline to week 52. Results Total retinal fluid (IRF, SRF and PED) volume at baseline had the strongest correlation to improvement in BCVA at month 12 (PCC = 0.652, p = 0.005). Fluid was subsequently sub-categorized into IRF, SRF and PED, with PED volume having the next highest correlation (PCC = 0.648, p = 0.005) to BCVA improvement. Average total retinal thickness in isolation demonstrated poor correlation (PCC = 0.334, p = 0.189). When two features, mean choroidal neovascular membranes (CNVM) size and total fluid volume, were combined and correlated with visual outcomes, the highest correlation increased to PCC = 0.695 (p = 0.002). Conclusions In isolation, total fluid volume most closely correlates with change in BCVA values between baseline and week 52. In combination with complimentary information from OCT-A, an improvement in the linear correlation score was observed. Average total retinal thickness provided a lower correlation, and thus provides a lower predictive outcome than alternative metrics assessed. Clinically, a machine-learning approach to analyzing fluid metrics in combination with lesion size may provide an advantage in personalizing therapy and predicting BCVA outcomes at week 52.

Understanding the complexities of sexual relationships is essential to understand the risky sexual behaviours among young people in Ugandan universities. Nine focus group discussions conducted with 31 males and 33 female students in 2014 utilising the grounded theory approach explored the role of sexual relationships in their lives. 'Relationships in campus are situationships' emerged as the core category and referred to the variety of sexual interactions within relationships among young people in a Ugandan university. The study findings indicated that sexual interactions often follow a sexual script that undergoes transitions to negotiate various situations. The sexual scripts in these situationships were strongly influenced by local socio-cultural norms and global aspirations among young people. Students often discussed these sexual scripts within a wider discourse on transactional sexual relationships. The motivations for transactional sexual relationships ranged from 'fulfilling aspirations' of various kinds on the one hand to 'being forced into trading sex' to overcome socio-economic vulnerabilities. Sexual relationships were facilitated by the perception of a university as a sexualized space in which one may enjoy a period of emerging adulthood characterized by exploration in relationships, access to alcohol and prolonged delay in assuming the traditional adult roles of marriage and family. The sexual scripts at the cultural level were grounded in traditional gender roles although at the same time, were under transition during university life with the growing influence of globalization and consumerism in the Ugandan society. Young men and young women must be engaged to critically challenge the implicit assumptions about sexual interactions within various situations that may put them at risk for poor sexual health outcomes.

Introduction Achieving optimal diabetes control requires several daily self-management behaviours, especially adherence to medication. Evidence supports the use of text messages to support adherence, but there remains much opportunity to improve their effectiveness. One key limitation is that message content has been generic. By contrast, reinforcement learning is a machine learning method that can be used to identify individuals’ patterns of responsiveness by observing their response to cues and then optimising them accordingly. Despite its demonstrated benefits outside of healthcare, its application to tailoring communication for patients has received limited attention. The objective of this trial is to test the impact of a reinforcement learning-based text messaging programme on adherence to medication for patients with type 2 diabetes.Methods and analysis In the REinforcement learning to Improve Non-adherence For diabetes treatments by Optimising Response and Customising Engagement (REINFORCE) trial, we are randomising 60 patients with suboptimal diabetes control treated with oral diabetes medications to receive a reinforcement learning intervention or control. Subjects in both arms will receive electronic pill bottles to use, and those in the intervention arm will receive up to daily text messages. The messages will be individually adapted using a reinforcement learning prediction algorithm based on daily adherence measurements from the pill bottles. The trial’s primary outcome is average adherence to medication over the 6-month follow-up period. Secondary outcomes include diabetes control, measured by glycated haemoglobin A1c, and self-reported adherence. In sum, the REINFORCE trial will evaluate the effect of personalising the framing of text messages for patients to support medication adherence and provide insight into how this could be adapted at scale to improve other self-management interventions.Ethics and dissemination This study was approved by the Mass General Brigham Institutional Review Board (IRB) (USA). Findings will be disseminated through peer-reviewed journals, clinicaltrials.gov reporting and conferences.Trial registration number Clinicaltrials.gov (NCT04473326).

Management of a difficult airway can be a nightmare for even an experienced anaesthesiologist. Video laryngoscopes have been mentioned in the difficult airway cart as a requisite equipment according to 2016 All India difficult airway guidelines. Ambuscope is a recently introduced flexible videoscope which is portable, light weight and single use device. This was a case of 25-year-old male who presented with loss of vision in both eyes and diffuse swelling of the face in the Ophthalmology Department. A diagnosis of post Coronavirus Disease-19 (COVID-19), Rhino-orbito-cerebral mucormycosis was made. Further patient was scheduled for emergency surgical debridement and bilateral orbital exentration under general anaesthesia. Airway assessment revealed mouth opening of one finger, Mallampati (MPG) score of 4, thyromental distance of 4.5 cm and a receding mandible with normal neck flexion and extension. Ambuscope™ 3 was employed for facilitating endotracheal intubation after anaesthesia induction. Ambuscope is a useful aid in confirming the position of endotracheal tubes and tracheostomy tubes in the operating room and intensive care unit. They are a disposable, convenient and practical alternative to fibreoptic bronchoscopes in patients of difficult airway. AmbuscopeTM 3 has tip movements with 150° up and 130° down. These unique features make this equipment user-friendly in anticipated and unanticipated difficult airway scenarios. Flexible endoscopes have carved a niche for themselves in the armamentarium of the anaesthesiologist airway cart to be equipped for any challenge.

Objective Long-term adherence to evidence-based medications in cardiometabolic diseases remains poor, despite extensive efforts to develop and test interventions and deploy clinician performance incentives. The limited success of interventions may be due to ignored factors such as patients’ experience of medication-taking. Despite being potentially addressable by clinicians, these factors have not been sufficiently explored, which is particularly important as patients use increasing numbers of medications. The aim is to explore patient perspectives on medication-taking, medication properties that are barriers to adherence, and coping strategies for their medication regimen.Design Individual, in-person, semistructured qualitative interviews.Setting Urban healthcare system.Participants Twenty-six adults taking ≥2 oral medications for diabetes, hypertension or hyperlipidaemia with non-adherence. Interviews were digitally recorded and transcribed. Data were analysed using developed codes to generate themes. Representative quotations were selected to illustrate themes.Results Participants’ mean age was 55 years, 46% were female and 39% were non-white. Six key themes were identified: (1) medication-taking viewed as a highly inconvenient action (that patients struggle to remember to do); (2) negative implications because of inconvenience or illness perceptions; (3) actual medication regimens can deviate substantially from prescribed regimens; (4) certain medication properties (especially size and similar appearance with others) may contribute to adherence deviations; (5) development of numerous coping strategies to overcome barriers and (6) suggestions to make medication-taking easier (including reducing drug costs, simplifying regimen or dosing frequency and creating more palatable medications).Conclusion Patients with poor adherence often find taking prescription medications to be undesirable and take them differently than prescribed in part due to properties of the medications themselves and coping strategies they have developed to overcome medication-taking challenges. Interventions that reduce the inconvenience of medication use and tailor medications to individual needs may be a welcome development.

Objectives Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.Setting Prospective, international, multicentre, observational cohort study.Participants Patients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome 30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.Results This study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).Conclusions Patients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration number NCT04323644

Introduction Medication adherence for patients with chronic conditions such as gout, a debilitating form of arthritis that requires daily medication to prevent flares, is a costly problem. Existing interventions to improve medication adherence have only been moderately effective. Habit formation theory is a promising strategy to improve adherence. The cue-reward-repetition principle posits that habits are formed by repeatedly completing an activity after the same cue and having the action rewarded every time. Over time, cues become increasingly important whereas rewards become less salient because the action becomes automatic. Leveraging the cue-reward-repetition principle could improve adherence to daily gout medications.Methods and analysis This three-arm parallel randomised controlled trial tests an adaptive intervention that leverages the repetition cue-reward principle. The trial will began recruitment in August 2021 in Boston, Massachusetts, USA. Eligible patients are adults with gout who have been prescribed a daily oral medication for gout and whose most recent uric acid is above 6 mg/dL. Participants will be randomised to one of three arms and given electronic pill bottles. In the two intervention arms, participants will select a daily activity to link to their medication-taking (cue) and a charity to which money will be donated every time they take their medication (reward). Participants in Arm 1 will receive reminder texts about their cue and their charity reward amount will be US$0.50 per day of medication taken. Arm 2 will be adaptive; participants will receive a US$0.25 per adherent-day and no reminder texts. If their adherence is

Bordetella pertussis is a Gram-negative bacterium known to cause pertussis or whooping cough. The disease affects the respiratory system and is contagious. Pertussis causes high mortality among infants aged less than one-year-old, although it can affect anyone of any age. Globally, 16 million cases of pertussis were reported in 2008, 95% of which were in developing nations, and approximately 195,000 children died from the disease. Under a computational subtractive genomics approach, the total proteome of a pathogen is gently trimmed down to a few potential drug targets. First, from NCBI, we obtained the pathogen proteins followed by CD hit for removal of duplicate proteins. The BLAST step was applied to find non-similar proteins, and then, we applied BLAST to these non-similar bacterial proteins with DEG to find essential bacterial proteins. After this, to find the location, these vital proteins were screened via PSORTb; the majority of proteins were in cytoplasm. The KASS server was used to determine the involvement of these proteins in the metabolic pathways of bacteria, and KEGG was applied to find the unique metabolic pathways of the pathogen. Finally, we applied BLAST to these vital, unique, and non-similar proteins with FDA-approved drug targets, and four proteins of the B. pertussis strain B1917 were identified that might be powerful drug targets. A variety of therapeutic molecules could be designed to target these proteins in order to treat infections caused by bacteria.

Introduction India is home to 20% of the world’s children and yet, little is known on the magnitude and trends of child maltreatment nationwide. The aims of this review are to provide a prevalence of child maltreatment in India with considerations for any effects of gender; urbanisation (eg, urban vs rural) and legislation (Protection of Children from Sexual Offences (POCSO) Act 2012).Methods and analysis A rapid review will be undertaken of all quantitative peer-reviewed studies on child maltreatment in India between 2005 and 2020. Four electronic databases will be systematically searched: PubMed, EMBASE, Cochrane and PsychInfo. The primary outcomes will include all aspects of child maltreatment: physical abuse, sexual abuse, emotional abuse, emotional neglect and physical neglect. Study participants will be between 0 and 18 years and will have reported maltreatment experiences using validated, reliable tools such as the Adverse Childhood Experiences Questionnaire as well as child self-reports and clinician reports. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and the methodological appraisal of the studies will be assessed by the Newcastle-Ottawa Quality assessment scale. A narrative synthesis will be conducted for all included studies. Also, if sufficient data are available, a meta-analysis will be conducted. Effect sizes will be determined from random-effects models stratified by gender, urbanisation and the pre-2012 and post-2012 POCSO Act cut-off. I2 statistics will be used to assess heterogeneity and identify their potential sources and τ2 statistics will indicate any between-study variance.Ethics and dissemination As this is a rapid review, minimal ethical risks are expected. The protocol and level 1 self-audit checklist were submitted and approved by the Usher Research Ethics Group panel in the Usher Institute (School of Medicine and Veterinary Sciences) at the University of Edinburgh (Reference B126255). Findings from this review will be disseminated widely through peer-reviewed publications and in various media, for example, conferences, congresses or symposia.PROSPERO registration number CRD42019150403.

Introduction: Recent studies suggest that saliva could be functionally equivalent to serum in reflecting the physiological state of the body. Studies are being conducted to develop saliva as a tool for the screening and monitoring of chronic systemic diseases like Diabetes mellitus. Dyslipidaemia is most commonly assessed by laboratory lipid profile analysis in serum sample. This study is a step towards validation of saliva as a tool for the screening and monitoring of dyslipidaemia. Aim: To measure, compare and correlate the serum and salivary lipid profile parameters {Total Cholesterol (TC), High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL)} in Type 2 Diabetes mellitus patients and healthy individuals. Materials and Methods: The case control study was carried out for a period of one year i.e., from March 2019 to February 2020. The study comprised of 200 participants between the ages 31- 70 years. The participants included 100 diabetic subjects with a history of diabetes for at least three years and 100 age matched subjects as controls. TC, HDL and LDL was estimated by using kits based on spectrophotometric principle. Statistical analysis was done on Statistical Package for Social Sciences (SPSS) Version 16.0. Mean, Standard deviation, Pearson’s correlation coefficient, along with regression analysis was carried out and compared between the groups. Results: There is a significant difference between the salivary TC, HDL and LDL levels in healthy individuals and diabetics. A strong and significant positive correlation of serum TC (Pearson correlation coefficient ‘r’=0.87 for controls, 0.66 for diabetics, p

Introduction: Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disease which hampers the physical activity of an individual due to presence of pain, stiffness and fatigue. As it is progressive in nature, regular exercise of sufficient intensity is needed to maintain muscle strength. Aim: To find the effectiveness of hand strengthening exercise programme with therapeutic putty on grip strength and functional movement in chronic rheumatoid hand. Materials and Methods: A total of 206 female patients of chronic RA female patients were randomly divided in two groups- control and experimental groups and data. Control group received care which included active hand exercises with hot water fomentation while experimental group received strengthening exercises with therapeutic putty and hot water fomentation. Grip strength was measured by hand dynamometer, key pinch strength of dominant hand was measured by digital pinch meter, pain severity was assessed by Brief pain inventory scale and hand function was measured by SF-SACRAH (Score for Assessment and Quantification of Chronic Rheumatic Affections of Hands) at 0 week, after 4 week, 8 week and 12 week for both groups. Treatment effects were compared by one-way ANOVA followed by post-hoc analysis. The results were analysed by Statistical Package for Social Sciences (SPSS) version 16.0. Results: After 12 weeks of exercise programme, a significant improvement (p

An airship is lighter than an air vehicle with enormous potential in applications such as communication, aerial inspection, border surveillance, and precision agriculture. An airship model is made up of dynamic, aerodynamic, aerostatic, and propulsive forces. However, the computation of aerodynamic forces remained a challenge. In addition to aerodynamic model deficiencies, airship mass matrix suffers from parameter variations. Moreover, due to the lighter-than-air nature, it is also susceptible to wind disturbances. These modeling issues are the key challenges in developing an efficient autonomous flight controller for an airship. This article proposes a unified estimation method for airship states, model uncertainties, and wind disturbance estimation using Unscented Kalman Filter (UKF). The proposed method is based on a lumped model uncertainty vector that unifies model uncertainties and wind disturbances in a single vector. The airship model is extended by incorporating six auxiliary state variables into the lumped model uncertainty vector. The performance of the proposed methodology is evaluated using a nonlinear simulation model of a custom-developed UETT airship and is validated by conducting a kind of error analysis. For comparative studies, EKF estimator is also developed. The results show the performance superiority of the proposed estimator over EKF; however, the proposed estimator is a bit expensive on computational grounds. However, as per the requirements of the current application, the proposed estimator can be a preferred choice.

The development of spontaneous pneumomediastinum and subcutaneous emphysema are few of the rare clinical manifestations observed in coronavirus disease-19 (COVID-19) patients which are yet to be fully understood. Most cases of spontaneous pneumomediastinum arises due to factors causing high intra-alveolar pressure. Herein, we report a case of a COVID-19 positive elderly male, who presented with spontaneous pneumomediastinum and subcutaneous emphysema unrelated to high-pressure ventilatory measures, detected on chest computed tomography (CT). Despite acute medical care, the patient progressed towards a more serious clinical course. Male gender and diffuse alveolar damage caused by COVID-19 seems to be the most relevant association in this case. However, we have enlightened other possible pathological mechanisms and their association with severity index of COVID-19.

BackgroundQuality of care in family planning traditionally focuses on promoting awareness of the broad array of contraceptive options rather than on the quality of interpersonal communication offered by family planning (FP) providers. There is a growing emphasis on person-centered contraceptive counselling, care that is respectful and focuses on meeting the reproductive needs of a couple, rather than fertility regulation. Despite the increasing global focus on person-centered care, little is known about the quality of FP care provided in low- and middle- income countries like India. This study involves the development and psychometric testing of a Quality of Family Planning Counselling (QFPC) measure, and assessment of its associations with contraceptives selected by clients subsequently.MethodsWe analyzed cross-sectional survey data from N = 237 women following their FP counselling in 120 public health facilities (District Hospitals and Community Health Centers) sampled across the state of Uttar Pradesh in India. The study captured QFPC, contraceptives selected by clients post-counselling, as well as client and provider characteristics. Based on formative research and using Principal Component Analysis, we developed a 13-item measure of quality of FP counselling. We used adjusted regression models to assess the association between QFPC and contraceptive selected post-counselling.ResultsThe QFPC measure demonstrated good internal reliability (Cronbach alpha = 0.80) as well as criterion validity, as indicated by client reports of high QFPC being significantly more likely for clients with trained versus untrained counsellors. We found that each point increase in QFPC, including increasing quality of counselling, is associated with higher odds of clients selecting an intrauterine device (IUD) (aRR:1.03; 95% CI:1.01-1.05) and sterilization (aRR:1.06; 95% CI:1.03-1.08), compared to no method selected.ConclusionsHigh-quality FP counselling is associated with clients subsequently selecting more effective contraceptives, including IUD and sterilization, in India. High-quality counselling is also more likely among FP-trained providers, highlighting the need for focused training and monitoring of quality care.Trial registrationCTRI/2015/09/006219. Registered 28 September 2015.

PurposeTo investigate changes in retinal thickness, drusen volume, and visual acuity following subthreshold nanosecond laser (SNL) treatment in patients with age-related macular degeneration (ARMD).DesignRetrospective chart review.MethodsPatients with intermediate ARMD treated with a single session of SNL (2RT®, Ellex R&D Pty Ltd, Adelaide, Australia) were included. Swept-source optical coherence tomography (OCT) imaging (Triton; Topcon Medical Systems, Tokyo, Japan) was performed within 6 months before and after SNL treatment. Retinal layers were segmented using the artificial intelligence-enabled Orion® software (Voxeleron LLC, San Francisco, USA). The macular region was analyzed according to the Early Treatment Diabetic Retinopathy Study map. Mean difference and standard deviation in baseline and post-treatment retinal layer thicknesses are reported.Results37 eyes from 25 patients were included in this study (mean age 74.7±9.2 years). An average of 51±6 spots were applied around the macula of each study eye, with a mean spot power of 0.33±0.04mJ. Increases in total retinal thickness were observed within the outer temporal and inferior sectors (PConclusionsAt 6 months post-SNL treatment, there were sectoral increases in OPL, photoreceptor complex, and sub-RPE space thicknesses and sectoral decreases in INL and ONL thicknesses. This pilot study demonstrates the utility of OCT combined with artificial intelligence-enabled software to track retinal changes that occur following SNL treatment in intermediate ARMD.

Abstract The use of anti-cancer adjuvant therapy is rationalized by potentiating the efficacy, and/or protecting from major side effects of chemotherapeutics. Thymoquinone (TQ) is a naturally occurring compound with cumulative evidence of anti-cancer properties. In this study, we assessed the chemomodulatory potential of TQ to gemcitabine (GCB) against human breast adenocarcinoma (MCF-7), and ductal carcinoma (T47D) cells. TQ showed cytotoxic effects against MCF-7 and T47D with IC50’s of 64.9 ± 14 µM and 165 ± 2 µM, respectively. The IC50’s of GCB against MCF-7 and T47D were 0.9 ± 0.18 µM and 14.3 ± 2.8 µM and were significantly reduced after combination with TQ to 0.058 ± 12 µM and 2.3 ± 0.2 µM, respectively. The CI- values were indicative of synergism in MCF-7 and T47D cells (0.15 and 0.30, respectively). Further investigation showed that GCB caused significant anti-proliferative effect reflected by increasing cell population in S-phase in both cell lines. TQ potentiated GCB-induced anti-proliferative activity in both cell lines. GCB induced considerable apoptosis in T47D cell line, and TQ significantly increased GCB-induced apoptotic effects by 1.5 to 3.6 folds. Interestingly, GCB, TQ and their combination induced significant autophagic cell death in the apoptosis defected MCF-7 cells. In addition, TQ, GCB and their combination depleted breast cancer associated stem cell (CD44(+)/CD24(−)/(low)) clone within MCF-7 and T47D cells by 3.8% to 27.5%. In conclusion, TQ showed promising chemomodulatory effects to GCB against breast cancer cells via inducing apoptosis, necrosis and autophagy, in addition to depleting tumor associated resistant stem cell fraction.

Abstract Background Breast cancer brain metastases (BCBM) develop in about 20–30% of breast cancer (BC) patients. BCBM are associated with dismal prognosis not at least due to lack of valuable molecular therapeutic targets. The aim of the study was to identify new molecular biomarkers and targets in BCBM by using complementary state-of-the-art techniques. Methods We compared array expression profiles of three BCBM with 16 non-brain metastatic BC and 16 primary brain tumors (prBT) using a false discovery rate (FDR) p 2. Biofunctional analysis was conducted on the differentially expressed probe sets. High-density arrays were employed to detect copy number variations (CNVs) and whole exome sequencing (WES) with paired-end reads of 150 bp was utilized to detect gene mutations in the three BCBM. Results The top 370 probe sets that were differentially expressed between BCBM and both BC and prBT were in the majority comparably overexpressed in BCBM and included, e.g. the coding genes BCL3, BNIP3, BNIP3P1, BRIP1, CASP14, CDC25A, DMBT1, IDH2, E2F1, MYCN, RAD51, RAD54L, and VDR. A number of small nucleolar RNAs (snoRNAs) were comparably overexpressed in BCBM and included SNORA1, SNORA2A, SNORA9, SNORA10, SNORA22, SNORA24, SNORA30, SNORA37, SNORA38, SNORA52, SNORA71A, SNORA71B, SNORA71C, SNORD13P2, SNORD15A, SNORD34, SNORD35A, SNORD41, SNORD53, and SCARNA22. The top canonical pathway was entitled, role of BRCA1 in DNA damage response. Network analysis revealed key nodes as Akt, ERK1/2, NFkB, and Ras in a predicted activation stage. Downregulated genes in a data set that was shared between BCBM and prBT comprised, e.g. BC cell line invasion markers JUN, MMP3, TFF1, and HAS2. Important cancer genes affected by CNVs included TP53, BRCA1, BRCA2, ERBB2, IDH1, and IDH2. WES detected numerous mutations, some of which affecting BC associated genes as CDH1, HEPACAM, and LOXHD1. Conclusions Using complementary molecular genetic techniques, this study identified shared and unshared molecular events in three highly aberrant BCBM emphasizing the challenge to detect new molecular biomarkers and targets with translational implications. Among new findings with the capacity to gain clinical relevance is the detection of overexpressed snoRNAs known to regulate some critical cellular functions as ribosome biogenesis.

Abstract Protein stability is a requisite in the field of biotechnology, cell biology and drug design. To understand effects of amino acid substitutions, computational models are preferred to save time and expenses. As a systemically important, highly abundant, stable protein, the knowledge of Cu/Zn Superoxide dismutase1 (SOD1) is important, making it a suitable test case for genotype-phenotype correlation in understanding ALS. Here, we report performance of eight protein stability calculators (PoPMuSiC 3.1, I-Mutant 2.0, I-Mutant 3.0, CUPSAT, FoldX, mCSM, BeatMusic and ENCoM) against 54 experimental stability changes due to mutations of SOD1. Four different high-resolution structures were used to test structure sensitivity that may affect protein calculations. Bland-Altman plot was also used to assess agreement between stability analyses. Overall, PoPMuSiC and FoldX emerge as the best methods in this benchmark. The relative performance of all the eight methods was very much structure independent, and also displayed less structural sensitivity. We also analyzed patient’s data in relation to experimental and computed protein stabilities for mutations of human SOD1. Correlation between disease phenotypes and stability changes suggest that the changes in SOD1 stability correlate with ALS patient survival times. Thus, the results clearly demonstrate the importance of protein stability in SOD1 pathogenicity.

ABSTRACT The central retinal vein occlusion is caused by age related changes in the retinal vessels. Bilateral central retinal vein occlusion is a relatively rare event. Only less than 10% cases are bilateral. While simultaneous bilateral central retinal vein occlusion is very rare. We are presenting a case report regarding a middle aged hypertensive patient who presented with bilateral central retinal vein occlusion in the Department of Ophthalmology, Madina Teaching Hospital, Faisalabad. A 55 years old middle aged female presented with bilateral sudden blurring of vision with finger counting vision in both eyes. After detailed clinical work up a diagnosis of bilateral central retinal vein occlusion secondary to systemic hypertension was made. Her hypertension was controlled with the help of internist and constant follow up was advised.

The use of glass to magnify image was reported by an Arabian scientist,ibn al-Haytham. He mentioned this in his book, written in 11th century. The name of his book was Alhazen’s book of optics. After hundred years this book was translated from Arabic to Latin. It took another hundered year to invent spectacles. This step of invention is attributed to an unknown Italian scientist. But that unknown Italian scientist kept this art to himself and sold glasses and did not share it with his colleagues.

The definitive characterization of common cancer stem cell (CSCs) subpopulations in breast cancer subtypes with distinct genotypic and phenotypic features remains an ongoing challenge. In this study, we have used a non-biased genome wide screening approach to identify transcriptional networks that may be specific to the CSC subpopulations in both luminal and basal breast cancer subtypes. In depth studies of three CSC-enriched breast cancer cell lines representing various subtypes of breast cancer revealed a striking hyperactivation of the mevalonate metabolic pathway in comparison to control cells. The upregulation of metabolic networks is a key feature of tumour cells securing growth and proliferative capabilities and dysregulated mevalonate metabolism has been associated with tumour malignancy and cellular transformation in breast cancer. Furthermore, accumulating evidence suggests that Simvastatin therapy, a mevalonate pathway inhibitor, could affect breast cancer progression and reduce breast cancer recurrence. When detailing the mevalonate pathway in breast cancer using a single-cell qPCR, we identified the mevalonate precursor enzyme, HMGCS1, as a specific marker of CSC-enriched subpopulations within both luminal and basal tumour subtypes. Down-regulation of HMGCS1 also decreased the CSC fraction and function in various model systems, suggesting that HMGCS1 is essential for CSC-activities in breast cancer in general. These data was supported by strong associations between HMGCS1 expression and aggressive features, such as high tumour grade, p53 mutations as well as ER-negativity in lymph node positive breast cancer. Importantly, loss of HMGCS1 also had a much more pronounced effect on CSC-activities compared to treatment with standard doses of Simvastatin. Taken together, this study highlights HMGCS1 as a potential gatekeeper for dysregulated mevalonate metabolism important for CSC-features in both luminal and basal breast cancer subtypes. Pharmacological inhibition of HMGCS1 could therefore be a superior novel treatment approach for breast cancer patients via additional CSC blocking functions.

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are adverse cutaneous drug reaction that has been associated with various drugs like antibiotics, anticonvulsant and non-steroidal anti-inflammatory agents. Fluconazole has rarely been associated with SJS and TEN. A 39-year-old male patient of SJS due to fluconazole, who was subsequently diagnosed to suffer from Acquired Immunodeficiency Syndrome (AIDS) is being reported. The low CD4+ T Cell count in this patient is a likely contributing factor for the precipitation of SJS due to fluconazole. There is a paucity of reports of SJS due to fluconazole in HIV positive patients, though TEN has been described in few patients. This case highlights that fluconazole causing SJS/TEN is more likely in a HIV positive patient. This patient’s HIV positive status was diagnosed subsequent to the diagnosis of SJS.

BACKGROUND:Many factors contribute to suboptimal diabetes control including insufficiently-intensive treatment and non-adherence to medication and lifestyle. Determining which of these is most relevant for individual patients is challenging. Patient engagement techniques may help identify contributors to suboptimal adherence and address barriers (using motivational interviewing) and help facilitate choices among treatment augmentation options (using shared decision-making). These methods have not been used in combination to improve diabetes outcomes. OBJECTIVE:To evaluate the impact of a telephone-based patient-centered intervention on glycosylated hemoglobin (HbA1c) control for individuals with poorly-controlled diabetes. DESIGN:Two-arm pragmatic randomized control trial within an explanatory sequential mixed-methods design. SUBJECTS:1,400 participants 18-64 years old with poorly-controlled type 2 diabetes. INTERVENTION:The intervention was delivered over the telephone by a clinical pharmacist and consisted of a 2-step process that integrated brief negotiated interviewing and shared decision-making to identify patient goals and options for enhancing diabetes management. MAIN MEASURES:The primary outcome was change in HbA1c. Secondary outcomes were medication adherence measures. Outcomes were evaluated using intention-to-treat principles; multiple imputation was used for missing values in the 12-month follow-up. We used information from pharmacist notes to elicit factors to potentially explain the intervention's effectiveness. KEY RESULTS:Participants had a mean age of 54.7 years (SD:8.3) and baseline HbA1c of 9.4 (SD:1.6). Change in HbA1c from baseline was -0.79 (SD:2.01) in the control arm and -0.75 (SD:1.76) in the intervention arm (difference:+0.04, 95%CI: -0.22, 0.30). There were no significant differences in adherence. In as-treated analyses, the intervention significantly improved diabetes control (-0.48, 95%CI: -0.91, -0.05). Qualitative findings provided several potential explanations for the findings, including insufficiently addressing patient barriers. CONCLUSIONS:A novel telephone-based patient-centered intervention did not improve HbA1c among individuals with poorly-controlled diabetes, though as-treated analyses suggest that the intervention was effective for those who received it. TRIAL REGISTRATION:ClinicalTrials.gov NCT02910089.

The ongoing episode of coronavirus disease 19 (COVID-19) has imposed a serious threat to global health and the world economy. The disease has rapidly acquired a pandemic status affecting almost all populated areas of the planet. The causative agent of COVID-19 is a novel coronavirus known as SARS-CoV-2. The virus has an approximate 30 kb single-stranded positive-sense RNA genome, which is 74.5% to 99% identical to that of SARS-CoV, CoV-pangolin, and the coronavirus the from horseshoe bat. According to available information, SARS-CoV-2 is inferred to be a recombinant virus that originated from bats and was transmitted to humans, possibly using the pangolin as the intermediate host. The interaction of the SARS-CoV-2 spike protein with the human ACE2 (angiotensin-converting enzyme 2) receptor, and its subsequent cleavage by serine protease and fusion, are the main events in the pathophysiology. The serine protease inhibitors, spike protein-based vaccines, or ACE2 blockers may have therapeutic potential in the near future. At present, no vaccine is available against COVID-19. The disease is being treated with antiviral, antimalarial, anti-inflammatory, herbal medicines, and active plasma antibodies. In this context, the present review article provides a cumulative account of the recent information regarding the viral characteristics, potential therapeutic targets, treatment options, and prospective research questions.