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Abstract Background High-protein diets are often enriched with branched-chain amino acids (BCAAs) known to enhance protein synthesis and provide numerous physiological benefits, but recent studies reveal their association with obesity and diabetes. In support of this, protein or BCAA supplementation is shown to disrupt glucose metabolism while restriction improves it. However, it is not clear if these are primary, direct effects of BCAAs or secondary to other physiological changes during chronic manipulation of dietary BCAAs. Methods Three-month-old C57Bl/6 mice were acutely treated with either vehicle/BCAAs or BT2, a BCAA-lowering compound, and detailed in vivo metabolic phenotyping, including frequent sampling and pancreatic clamps, were conducted. Results Using a catheter-guided frequent sampling method in mice, here we show that a single infusion of BCAAs was sufficient to acutely elevate blood glucose and plasma insulin. While pre-treatment with BCAAs did not affect glucose tolerance, a constant infusion of BCAAs during hyperinsulinemic–euglycemic clamps impaired whole-body insulin sensitivity. Similarly, a single injection of BT2 was sufficient to prevent BCAA rise during fasting and markedly improve glucose tolerance in high-fat-fed mice, suggesting that abnormal glycemic control in obesity may be causally linked to high circulating BCAAs. We further show that chemogenetic over-activation of AgRP neurons in the hypothalamus, as present in obesity, significantly impairs glucose tolerance that is completely normalized by acute BCAA reduction. Interestingly, most of these effects were demonstrated only in male, but not in female mice. Conclusion These findings suggest that BCAAs per se can acutely impair glucose homeostasis and insulin sensitivity, thus offering an explanation for how they may disrupt glucose metabolism in the long-term as observed in obesity and diabetes. Our findings also reveal that AgRP neuronal regulation of blood glucose is mediated through BCAAs, further elucidating a novel mechanism by which brain controls glucose homeostasis.

Abstract The Pythia8/Angantyr model for heavy ion collisions was recently updated with a mechanism for global colour reconnection. The colour reconnection model used is QCD colour algebra inspired and enhances baryon production due to the formation of string junctions. In this paper, we present updates to the junction formation and string fragmentation mechanisms, connected to heavy quark fragmentation. This allows for the simulation of heavy quark fragmentation, using junction formation, in heavy ion collisions. The framework is validated for proton collisions, and we show results for charm baryon production in proton-lead collisions.

India has put efforts into the prevention and control of tuberculosis (TB) for more than 50 years. Nikshay Poshan Yojna (NPY) is one of the schemes of conditional cash transfers (CCTs) by the Government of India. The CCT schemes mostly address the demand side constraints. Governments could use this in developing nations as a tool to divert financial resources toward societal development. In India, NPY is more directed toward providing monetary support for a nutritional diet and reducing the catastrophic expenditure of TB patients. Several studies highlighted challenges in implementing cash transfer schemes and provided different operational models. A country like India should address the challenges with defined strategies to ensure its last-mile reach. A present commentary discussing challenges and possible solutions that policy-makers can adapt and set up a support structure to ensure that supportive actions are implemented in response to patient and system side issues.

Abstract We present the results from our investigation of angular correlations between baryons pairs in the Pythia8 event generator. We show how colour reconnection models and hadronization mechanisms influence such angular correlations and in particular address the effect of gluons on the baryon production mechanism in the Lund string fragmentation model. We conclude by discussing the new theoretical ideas in comparison with the ALICE $$\textrm{pp} $$ pp collision results for the baryon angular correlations. We propose a hypothesis for suppressing baryons produced in gluon jets and show how that may influence the angular correlations.

The changing notion of “companion animals” and their increasing global status as family members underscores the dynamic interaction between gut microbiota and host health. This review provides a comprehensive understanding of the intricate microbial ecology within companion animals required to maintain overall health and prevent disease. Exploration of specific diseases and syndromes linked to gut microbiome alterations (dysbiosis), such as inflammatory bowel disease, obesity, and neurological conditions like epilepsy, are highlighted. In addition, this review provides an analysis of the various factors that impact the abundance of the gut microbiome like age, breed, habitual diet, and microbe-targeted interventions, such as probiotics. Detection methods including PCR-based algorithms, fluorescence in situ hybridisation, and 16S rRNA gene sequencing are reviewed, along with their limitations and the need for future advancements. Prospects for longitudinal investigations, functional dynamics exploration, and accurate identification of microbial signatures associated with specific health problems offer promising directions for future research. In summary, it is an attempt to provide a deeper insight into the orchestration of multiple microbial species shaping the health of companion animals and possible species-specific differences.

Abstract Chimeric antigen receptor T-cell therapy (CAR-T) has been successful in treating relapsed/refractory B-cell lymphomas. However, its role in the treatment of diseases involving the central nervous system (CNS) is not well studied. We performed a multicenter retrospective cohort study to evaluate the outcomes of patients with secondary CNS lymphoma (SCNSL) who received CAR-T. Eligibility required active CNSL at the time of apheresis. The objectives included evaluation of overall survival (OS), progression-free survival (PFS), identification of predictors of complete response (CR) post-CAR-T, and assessment of risk factors for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Sixty-one patients were included in the analysis. The overall response rate was 68% with a CR rate of 57%. In the multivariable analysis, patients who experienced any grade CRS had higher odds of achieving CR (OR = 3.9, 95% CI = 1.01–15.39, p = 0.047). The median PFS was 3.3 months (95% CI = 2.6–6.0 months) with 6- and 12-month PFS rates of 35% and 16%, respectively. The median OS was 7.6 months (95% CI = 5.0–13.5 months) with 6- and 12-month OS rates of 59% and 41%, respectively. Any grade CRS and ICANS were 70% (n = 43) and 57% (n = 34), respectively with grade ≥ 3 CRS and ICANS rates of 16% and 44%. Factors associated with increased risk of CRS and ICANS included receiving axi-cel or having leptomeningeal ± parenchymal + CNS involvement, respectively. Despite achieving high response rates, most patients experience early relapse or death following CAR-T in SCNSL. The current study provides a benchmark for future trials exploring novel therapeutic options in SCNSL.

Abstract We present an updated version of the QCD-based colour reconnection model in Pythia8, where we constrain the range in impact parameter for which reconnections are allowed. In this way, we can introduce more realistic colour reconnections in the Angantyr model for heavy ion collisions, where previously only reconnections within separate nucleon sub-collisions have been allowed. We investigate how the new impact parameter constraint influences final states in $$\textrm{pp}$$ pp collisions, and retune parameters of the multi-parton interaction parameters in Pythia to compensate so that minimum bias data are reproduced. We also study multiplicity distributions in $$\textrm{p}A$$ p A collisions and find that, in order to counteract the loss in multiplicity due to the introduction of global colour reconnections, we need to modify some parameters in the Angantyr model while keeping the parameters tuned to $$\textrm{pp}$$ pp fixed. With Angantyr we can then extrapolate to $$AA$$ AA collisions without further parameter tuning and retaining a reasonable description of the basic multiplicity distributions.

Rapid and accurate detection of the pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for COVID-19, is critical for mitigating the COVID-19 pandemic. Current state-of-the-art pathogen tests for COVID-19 diagnosis are done in a liquid medium and take 10–30 min for rapid antigen tests and hours to days for polymerase chain reaction (PCR) tests. Herein we report novel accurate pathogen sensors, a new test method, and machine-learning algorithms for a breathalyzer platform for fast detection of SARS-CoV-2 virion particles in the aerosol in 30 s. The pathogen sensors are based on a functionalized molecularly-imprinted polymer, with the template molecules being the receptor binding domain spike proteins for different variants of SARS-CoV-2. Sensors are tested in the air and exposed for 10 s to the aerosols of various types of pathogens, including wild-type, D614G, alpha, delta, and omicron variant SARS-CoV-2, BSA (Bovine serum albumin), Middle East respiratory syndrome–related coronavirus (MERS-CoV), influenza, and wastewater samples from local sewage. Our low-cost, fast-responsive pathogen sensors yield accuracy above 99% with a limit-of-detection (LOD) better than 1 copy/μL for detecting the SARS-CoV-2 virus from the aerosol. The machine-learning algorithm supporting these sensors can accurately detect the pathogens, thereby enabling a new and unique breathalyzer platform for rapid COVID-19 tests with unprecedented speeds.

BackgroundAchieving the target for eliminating tuberculosis (TB) in India by 2025, 5 years ahead of the global target, critically depends on strengthening the capacity of human resources as one of the key components of the health system. Due to the rapid updates of standards and protocols, the human resources for TB health care suffer from a lack of understanding of recent updates and acquiring necessary knowledge. ObjectiveDespite an increasing focus on the digital revolution in health care, there is no such platform available to deliver the key updates in national TB control programs with easy access. Thus, the aim of this study was to explore the development and evolution of a mobile health tool for capacity building of the Indian health system’s workforce to better manage patients with TB. MethodsThis study involved two phases. The first phase was based on a qualitative investigation, including personal interviews to understand the basic requirements of staff working in the management of patients with TB, followed by participatory consultative meetings with stakeholders to validate and develop the content for the mobile health app. Qualitative information was collected from the Purbi Singhbhum and Ranchi districts of Jharkhand and Gandhinagar, and from the Surat districts of Gujarat State. In the second phase, a participatory design process was undertaken as part of the content creation and validation exercises. ResultsThe first phase collected information from 126 health care staff, with a mean age of 38.4 (SD 8.9) years and average work experience of 8.9 years. The assessment revealed that more than two-thirds of participants needed further training and lacked knowledge of the most current updates to TB program guidelines. The consultative process determined the need for a digital solution in easily accessible formats and ready reckoner content to deliver practical solutions to address operational issues for implementation of the program. Ultimately, the digital platform named Ni-kshay SETU (Support to End Tuberculosis) was developed to support the knowledge enhancement of health care workers. ConclusionsThe development of staff capacity is vital to the success or failure of any program or intervention. Having up-to-date information provides confidence to health care staff when interacting with patients in the community and aids in making quick judgments when handling case scenarios. Ni-kshay SETU represents a novel digital capacity-building platform for enhancing human resource skills in achieving the goal of TB elimination.

Within organizational settings, communication dynamics are influenced by various factors, such as email content, historical interactions, and interpersonal relationships. We introduce the Email MultiModal Architecture (EMMA) to model these dynamics and predict future communication behavior. EMMA uses data related to an email sender’s social network, performance metrics, and peer endorsements to predict the probability of receiving an email response. Our primary analysis is based on a dataset of 0.6 million corporate emails from 4320 employees between 2012 and 2014. By integrating features that capture a sender’s organizational influence and likability within a multimodal structure, EMMA offers improved performance over models that rely solely on linguistic attributes. Our findings indicate that EMMA enhances email reply prediction accuracy by up to 12.5% compared to leading text-centric models. EMMA also demonstrates high accuracy on other email datasets, reinforcing its utility and generalizability in diverse contexts. Our findings recommend the need for multimodal approaches to better model communication patterns within organizations and teams and to better understand how relationships and histories shape communication trajectories.

Tuberculosis (TB) is a major killer and cause of human suffering worldwide and imposes a substantial reduction in patients’ health-related quality of life (HRQoL). HRQoL indicates the consciousness of patients regarding their physical and mental health. It is, therefore, very relevant in comprehending and measuring the exact impact of the disease state. Therefore, we undertook this review to summarize the available evidence on the impact of TB and its treatment on HRQoL. An in-depth understanding of HRQoL in TB patients can identify the existing management gaps. We undertook a systematic search through PubMed and CENTRAL. Data were extracted and tabulated for study design, targeted population, QoL instrument used, QoL domain assessed, and key findings. We included studies that assessed the effect of TB on the QoL both during and after treatment. There are no specific HRQoL assessment tools for utilization among TB patients. HRQoL is markedly impaired in patients with TB. The factors affecting HRQoL differ with active and latent TB, socio-demographics, socio-economic status, presence of co-infections, etc. This review’s findings can help to frame appropriate policies for tackling HRQoL issues in TB patients.

Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma demonstrated an improved 2-year progression-free survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, multicenter study investigated the effect of cumulative maintenance BV dose on 2-year PFS. Data were collected from patients who received at least one cycle of BV maintenance after ASCT with one of the following high-risk features: primary refractory disease (PRD), extra-nodal disease (END), or relapse 75% of the planned total cumulative dose, cohort 2 with 51-75% of dose, and cohort 3 with ≤50% of dose. The primary outcome was 2-year PFS. A total of 118 patients were included. Fifty percent had PRD, 29% had RL

Background: Parkinson’s disease (PD) is a neurodegenerative disorder associated with inferior clinical outcomes after surgical management of many orthopedic conditions. The purpose of this systematic review was to define the clinical, functional, and patient-reported outcomes of shoulder arthroplasty (SA) in patients with PD. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was completed using the Ovid platform for searches in MEDLINE, EMBASE, Cochrane Central, and Cochrane Systematic Reviews, with additional searches in Web of Science and Scopus. Included studies were full-length, English-language, clinical investigations reporting on SA in patients with PD with at least one clinical outcome. Results: Seven studies including 7126 patients (7134 SA) met inclusion criteria with a mean age of 72.6 (range, 69.5–75.8 years), 58.9% female, and the average follow-up duration was 65 months (range, 17–119 months). Anatomic total shoulder arthroplasty (aTSA) was the most reported implant surgery (n = 3455, 48.4%) followed by hemiarthroplasty (HA) (n = 2840, 39.8%), and reverse shoulder arthroplasty (RSA) (n = 839,1.8%). SA consistently improved pain. Forward elevation, abduction, and external rotation had a pooled mean increase of 36°, 20°, and 6°, respectively. Complications occurred at a pooled rate of 22.5%, with stiffness (7.1%), need for revision (5.3%), and instability (4.7%) as the most common complications reported. Reoperations inclusive of revisions occurred at a lower pooled rate of 5.6%, with aTSA (n = 201; 9.0%) having the highest rate, followed by HA (n = 158; 7.1%), and then RSA (n = 42; 1.9%). Conclusions: The results of the present systematic review demonstrate that SA in patients with PD results in consistent pain relief. However, inferior improvements in clinical outcomes may be expected when compared with patients without PD, likely due to the neurodegenerative manifestations of this disorder. In addition, RSA had a lower reoperation rate than HA and aTSA in patients with PD.

Introduction: Patient satisfaction in health care describes the degree to which patients' needs 'meet their expectations and provide an acceptable standard of care'. Therefore, their opinion should be incorporated to understand factors affecting patients' satisfaction with the health-care setting. The recent COVID-19 pandemic has posed a significant challenge for the field of dentistry owing to its working characteristics. It is difficult for dentists to provide optimum satisfaction to patients receiving dental care with such changes proposed. A study aiming to evaluate the patient's satisfaction receiving treatment in the Department of Dentistry during the pandemic was planned. Materials and Methods: A cross-sectional observational study from September to November 2020 was conducted. A self-administered printed questionnaire drafted in English/Gujarati was provided to 225 patients on completion of their dental treatment. Thirteen close-ended questions were included in determining the patient's satisfaction. Descriptive statistical analysis was used to describe the parameters of the questionnaire. The Chi-square test was used to find a significant association between parameters, and P < 0.05 was considered statistically significant. Results: About 74.3% of the participants were satisfied with dentist–patient communication. Positive response (80%) by patients where they were able to get an appointment as per their suitability and were informed in advance by the department if there were any changes. One hundred and sixty-eight (84%) patients responded that the waiting area was hygienic. One hundred and thirty-seven (68.5%) patients assured that their arrival was intimated to the respective dentist by supporting staff and that they were taken into an operatory for treatment within 10 min of arrival. Participants said that they were informed about the delay from their allotted appointment schedule with reasons; hence, better compliance (79%) was obtained from them. Conclusions: This cross-sectional study indicated that with proper communication, a positive response by participants over satisfaction was obtained even due to changing treatment patterns due to pandemic.

Tuberculosis (TB) is the second leading cause of death due to infectious diseases globally, and delay in the TB care cascade is reported as one of the major challenges in achieving the goals of the TB control programs. The main aim of this study was to investigate the delay and responsible factors for the delay in the various phases of care cascade among TB patients in two Indian states, Jharkhand and Gujarat. This cross-sectional study was conducted among 990 TB patients from the selected tuberculosis units (TUs) of two states. This study adopted a mixed-method approach for the data collection. The study targeted a diverse profile of TB patients, such as drug-sensitive TB (DSTB), drug resistance TB (DRTB), pediatric TB, and extra-pulmonary TB. It included both public and private sector patients. The study findings suggested that about 41% of pulmonary and 51% of extra-pulmonary patients reported total delay. Delay in initial formal consultation is most common, followed by a delay in diagnosis and treatment initiation in pulmonary patients. While in extra-pulmonary patients, delay in treatment initiation is most common, followed by the diagnosis and first formal consultation. DR-TB patients are more prone to total delay and delay in the treatment initiation among pulmonary patients. Addiction, co-morbidity and awareness regarding monetary benefits available for TB patients contribute significantly to the total delay among pulmonary TB patients. There were system-side factors like inadequacy in active case findings, poor infrastructure, improper adverse drug reaction management and follow-up, resulting in delays in the TB care cascade in different phases. Thus, the multi-disciplinary strategies covering the gambit of both system and demand side attributes are recommended to minimize the delays in the TB care cascade.

Introduction: Mortality and morbidity due to infectious disease have got reduced in the last couple of decades. Diphtheria is one of the infectious diseases which can be preventable with a complete immunization. Objective: To understand trends and identify factors affecting the outbreak of diphtheria in Banaskantha district of Gujarat. Method: A retrospective study based on the available case records for the years 2019, 2020 and 2021(till June). The study was conducted after the reported diphtheria cases in a district. The study was a public health response and intended to provide specific geographical recommendations to the district. The data was recorded from the reported case record and immunization registers. The data were analyzed for defined variables. Results: Out of the 366 cases identified during years 2019-2021.Almost 74% cases have occurred during 2019, with a 7.7% mortality rate. Total 48% of cases were among the age group of 5-10 years, with an increasing number of cases during August-December with specific geographical distribution. Among all the cases, 164 (44.5%) have never taken any vaccine in their lifetime or are unaware of the vaccination status, and 87.9% of cases have not taken third dose of DPT or Pentavalent Vaccine, which is associated statistically with the mortality. Conclusion: The prevalence of diphtheria cases was high in children who have not taken all three doses of DPT or Pentavalent vaccine. These have shown an essential role of immunization, focusing on the vaccine for all doses and need to create a customized awareness communication plan.

IntroductionAdherence to tuberculosis (TB) medication is one of the critical challenges to tuberculosis elimination in India. Digital adherence technologies (DAT) have the potential to facilitate medication adherence and monitor it remotely. Tuberculosis Monitoring Encouragement Adherence Drive (TMEAD) is one such DAT piloted in Nasik, Maharashtra, from April 2020 to December 2021. The study aims to assess the adherence and cost-effectiveness of TMEAD compared to the standard of care among patients with drug-sensitive tuberculosis (DSTB) residing in the urban areas of Nasik, Maharashtra, India.MethodsA quasi-experimental study was conducted among new cases of TB as per the National TB Elimination Programme (NTEP) residing in the urban geography of Nasik. The intervention and control arms were purposively selected from non-contaminating TB units (TUs). A total of 400 DSTB patients (200 in the intervention group and 200 in the control group) were enrolled. After enrolment, patients in the intervention arm were provided with the TMEAD device and followed for 24 weeks to assess treatment outcomes. Adherence was measured as those patients who have completed 80% of prescribed doses, as reported during patient follow-up, and further validated by analyzing the trace of rifampicin in urine among 20% of patients from both arms. A budget impact analysis was done to assess the impact of the TMEAD program on the overall state health budget.ResultsOut of 400 enrolled DSTB patients, 261 patients completed treatment, 108 patients were on treatment, 15 patients died, and 16 patients were defaulters over the study period. The study reported overall treatment adherence of 94% among those who completed treatment. Patient reports indicated high levels of treatment adherence in the intervention group (99%) as compared to the control group (90%). Adherence assessed through analyzing trace of rifampicin in the urine sample for the intervention arm was 84% compared to the control arm (80%). Per beneficiary (discounted) cost for TMEAD was Indian rupees (INR) 6,573 (USD 83). The incremental cost-effectiveness ratio of the intervention is INR 11,599 (USD 146), which shows that the intervention is highly cost-effective.ConclusionThis study revealed that patient-reported treatment adherence was high in TMEAD when compared to standard therapy of care for DSTB patients and the intervention is cost-effective. TMEAD could complement the national strategy to end TB by improving adherence to the treatment regimen in India.

Prostaglandins are naturally occurring hormones that play a significant role in the commencement of labour. Prostaglandins have been utilised in clinical practise to ripen the cervix and elicit uterine contractions synthetically since the 1960s. When a woman's cervix is immature (when her Bishop score is less than six), they are more likely to utilise them. Cervical ripening and labour induction are aided by prostaglandins, which work on cervical collagen to relax and dilate the cervix in anticipation of giving birth. It's possible that prostaglandins have a role in inducing uterine contractions. The benefits of prostaglandins in inducing labour are discussed in this article.

The greatest threat to humanity is climate change. Carbon dioxide, methane, and nitrous oxide are the three main greenhouse gases that microbes make and consume. Some microbes can cause diseases in humans, animals, and plants that can be made worse by climate change. To reduce the warming trajectory and cascade consequences brought on by heat, drought, and severe storms, microbial research is required.

Albendazole (ABZ) is a weakly basic drug that undergoes extensive presystemic metabolism after oral administration and converts to its active form albendazole sulfoxide (ABZ_SO). The absorption of albendazole is limited by poor aqueous solubility, and dissolution is the rate-limiting step in the overall exposure of ABZ_SO. In this study, PBPK modeling was used to identify formulation-specific parameters that impact the oral bioavailability of ABZ_SO. In vitro experiments were carried out to determine pH solubility, precipitation kinetics, particle size distribution, and biorelevant solubility. A transfer experiment was conducted to determine the precipitation kinetics. A PBPK model for ABZ and ABZ_SO was developed using the Simcyp™ Simulator based on parameter estimates from in vitro experiments. Sensitivity analyses were performed to assess the impact of physiological parameters and formulation-related parameters on the systemic exposure of ABZ_SO. Model simulations predicted that increased gastric pH significantly reduced ABZ absorption and, subsequently, ABZ_SO systemic exposure. Reducing the particle size below 50 µm did not improve the bioavailability of ABZ. Modeling results illustrated that systemic exposure of ABZ_SO was enhanced by increasing solubility or supersaturation and decreasing the drug precipitation of ABZ at the intestinal pH level. These results were used to identify potential formulation strategies to enhance the oral bioavailability of ABZ_SO.

Type 2 diabetes (T2D) is a challenging health concern worldwide. A lifestyle intervention to treat T2D is difficult to adhere, and the effectiveness of approved medications such as metformin, thiazolidinediones (TZDs), and sulfonylureas are suboptimal. On the other hand, bariatric procedures such as Roux-en-Y gastric bypass (RYGB) are being recognized for their remarkable ability to achieve diabetes remission, although the underlying mechanism is not clear. Recent evidence points to branched-chain amino acids (BCAAs) as a potential contributor to glucose impairment and insulin resistance. RYGB has been shown to effectively lower plasma BCAAs in insulin-resistant or T2D patients that may help improve glycemic control, but the underlying mechanism for BCAA reduction is not understood. Hence, we attempted to explore the mechanism by which RYGB reduces BCAAs. To this end, we randomized diet-induced obese (DIO) mice into three groups that underwent either sham or RYGB surgery or food restriction to match the weight of RYGB mice. We also included regular chow-diet-fed healthy mice as an additional control group. Here, we show that compared to sham surgery, RYGB in DIO mice markedly lowered serum BCAAs most likely by rescuing BCAA breakdown in both liver and white adipose tissues. Importantly, the restored BCAA metabolism following RYGB was independent of caloric intake. Fasting insulin and HOMA-IR were decreased as expected, and serum valine was strongly associated with insulin resistance. While gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are postulated to mediate various surgery-induced metabolic benefits, mice lacking these hormonal signals (GLP-1R/Y2R double KO) were still able to effectively lower plasma BCAAs and improve glucose tolerance, similar to mice with intact GLP-1 and PYY signaling. On the other hand, mice deficient in fibroblast growth factor 21 (FGF21), another candidate hormone implicated in enhanced glucoregulatory action following RYGB, failed to decrease plasma BCAAs and normalize hepatic BCAA degradation following surgery. This is the first study using an animal model to successfully recapitulate the RYGB-led reduction of circulating BCAAs observed in humans. Our findings unmasked a critical role of FGF21 in mediating the rescue of BCAA metabolism following surgery. It would be interesting to explore the possibility of whether RYGB-induced improvement in glucose homeostasis is partly through decreased BCAAs.

BackgroundA global rollout of vaccinations is currently underway to mitigate and protect people from the COVID-19 pandemic. Several individuals have been using social media platforms such as Twitter as an outlet to express their feelings, concerns, and opinions about COVID-19 vaccines and vaccination programs. This study examined COVID-19 vaccine–related tweets from January 1, 2020, to April 30, 2021, to uncover the topics, themes, and variations in sentiments of public Twitter users. ObjectiveThe aim of this study was to examine key themes and topics from COVID-19 vaccine–related English tweets posted by individuals, and to explore the trends and variations in public opinions and sentiments. MethodsWe gathered and assessed a corpus of 2.94 million COVID-19 vaccine–related tweets made by 1.2 million individuals. We used CoreX topic modeling to explore the themes and topics underlying the tweets, and used VADER sentiment analysis to compute sentiment scores and examine weekly trends. We also performed qualitative content analysis of the top three topics pertaining to COVID-19 vaccination. ResultsTopic modeling yielded 16 topics that were grouped into 6 broader themes underlying the COVID-19 vaccination tweets. The most tweeted topic about COVID-19 vaccination was related to vaccination policy, specifically whether vaccines needed to be mandated or optional (13.94%), followed by vaccine hesitancy (12.63%) and postvaccination symptoms and effects (10.44%) Average compound sentiment scores were negative throughout the 16 weeks for the topics postvaccination symptoms and side effects and hoax/conspiracy. However, consistent positive sentiment scores were observed for the topics vaccination disclosure, vaccine efficacy, clinical trials and approvals, affordability, regulation, distribution and shortage, travel, appointment and scheduling, vaccination sites, advocacy, opinion leaders and endorsement, and gratitude toward health care workers. Reversal in sentiment scores in a few weeks was observed for the topics vaccination eligibility and hesitancy. ConclusionsIdentification of dominant themes, topics, sentiments, and changing trends about COVID-19 vaccination can aid governments and health care agencies to frame appropriate vaccination programs, policies, and rollouts.

Introduction: Facility Based Newborn Care (FBNC) is a critical intervention to improve child survival & to reduce neonatal mortality rate Neonatal Mortality Rate (NMR) is major challenge.Objectives: Toanalyze morbidity profile of neonates admitted in special newborn care units of a tertiary level hospitals and medical college attached hospitals of Gujarat State. Method: A cross sectional descriptive study where record based secondary data collected & analysed for key indicators from all Govt. supported Sick Newborn Care Unit (SNCUs) which are in Medical college attached hospitals, district hospitals and grant in aid trust hospitals. April 2014 to March 2016 was the study period. Results: The study found near proportions of (53%) inborn, (47%) out born admission and 44% admission of female. Out of 69,662 admissions, 67% were discharged, 16% died, 10% leaving against medical advice, and 7% referred to higher centers. Major reasons for admission were respiratory distress syndrome (RDS) (22%) and infection (21%). Conclusion: Strengthening of appropriate facility care is essential to address neonatal mortality. The health interventions needed to tackle NMR differ from those needed for infant mortality rate and under-five mortality rate.

Alzheimer’s disease (AD) is the most common type of dementia that affects millions of individuals worldwide. It is an irreversible neurodegenerative disorder that is characterized by memory loss, impaired learning and thinking, and difficulty in performing regular daily activities. Despite nearly two decades of collective efforts to develop novel medications that can prevent or halt the disease progression, we remain faced with only a few options with limited effectiveness. There has been a recent growth of interest in the role of nutrition in brain health as we begin to gain a better understanding of what and how nutrients affect hormonal and neural actions that not only can lead to typical cardiovascular or metabolic diseases but also an array of neurological and psychiatric disorders. Vitamins and minerals, also known as micronutrients, are elements that are indispensable for functions including nutrient metabolism, immune surveillance, cell development, neurotransmission, and antioxidant and anti-inflammatory properties. In this review, we provide an overview on some of the most common vitamins and minerals and discuss what current studies have revealed on the link between these essential micronutrients and cognitive performance or AD.

Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with a complex pathophysiology. Type 2 diabetes (T2D) is a strong risk factor for AD that shares similar abnormal features including metabolic dysregulation and brain pathology such as amyloid and/or Tau deposits. Emerging evidence suggests that circulating branched-chain amino acids (BCAAs) are associated with T2D. While excess BCAAs are shown to be harmful to neurons, its connection to AD is poorly understood. Here we show that individuals with AD have elevated circulating BCAAs and their metabolites compared to healthy individuals, and that a BCAA metabolite is correlated with the severity of dementia. APPSwe mouse model of AD also displayed higher plasma BCAAs compared to controls. In pursuit of understanding a potential causality, BCAA supplementation to HT-22 neurons was found to reduce genes critical for neuronal health while increasing phosphorylated Tau. Moreover, restricting BCAAs from diet delayed cognitive decline and lowered AD-related pathology in the cortex and hippocampus in APP/PS1 mice. BCAA restriction for two months was sufficient to correct glycemic control and increased/restored dopamine that were severely reduced in APP/PS1 controls. Treating 5xFAD mice that show early brain pathology with a BCAA-lowering compound recapitulated the beneficial effects of BCAA restriction on brain pathology and neurotransmitters including norepinephrine and serotonin. Collectively, this study reveals a positive association between circulating BCAAs and AD. Our findings suggest that BCAAs impair neuronal functions whereas BCAA-lowering alleviates AD-related pathology and cognitive decline, thus establishing a potential causal link between BCAAs and AD progression.

Involvement of adrenal gland in kidney cancer represents a unique site of metastasis with a distinct clinical course. The cases are typically resistant to immune therapy and need local therapy management. A case series of patients with adrenal metastases was reviewed to highlight the nuances of clinical course and therapy. We reviewed renal cancer carcinoma (RCC) cases with adrenal metastases at Karmanos Cancer Center, Detroit MI. Medical records were reviewed to collect relevant case information. Next-generation sequencing, tumor mutation burden testing, and programmed death ligand bio-markers were evaluated in five cases. Twelve cases were reviewed; all were males with a median age of 49.5 years. Three patients presented with adrenal metastases only and were treated with local therapy. Three received interleukin-2 (IL-2). One patient relapsed with bilateral adrenal lesions after 11 years of remission, post-IL-2 therapy. Five cases received immune checkpoint inhibitor (ICI) and one received antivascular therapy. ICI therapy was followed by ablation of residual adrenal metastases in three patients. Genomic profiling was available in five cases. All were BAP1 and PD-L1 negative.Patho-genic mutations in PBRM1, SETD2, and VHL were noted. All patients with residual adrenal metastases responded to antivascular therapies or to local ablation. One patient died 17 years after diagnosis and 11 patients are alive at a median follow-up of 9.5 years. Adrenal metastases in RCC have a distinct clinical course. They can represent a sanctuary site of relapse/residual disease following treatment with immune therapy. Management with local therapy can induce durable remissions. Systemic management with antivascular therapies also demonstrated favorable responses. Further investigation should focus on the unique clinical course and optimal management of adrenal metastases in kidney cancer.

Background Prior data demonstrate significant heterogeneity regarding coronary artery disease risk factors and outcomes among Asians in the United States, but no studies have yet examined coronary artery disease treatment patterns or outcomes among disaggregated Asian American subgroups. Methods and Results From a total of 772 882 patients with known race/ethnicity and sex who received care from a mixed‐payer healthcare organization in Northern California between 2006 and 2015, a retrospective analysis was conducted on 6667 adults with coronary artery disease. Logistic regression was used to examine medical and procedural therapies and outcomes by race/ethnicity, with adjustment for age, sex, income, and baseline comorbidities. Compared with non‐Hispanic whites, Chinese were more likely to undergo stenting (50.9% versus 60.8%, odds ratio [OR] 1.39 [95% CI, 1.04–1.87], p=0.005), whereas Filipinos were more likely to receive bypass surgery (6.9% versus 20.5%, OR 2.65 [95% CI, 1.75–4.01], P

Non-steroidal anti-inflammatory drugs (NSAIDs) are generally utilized for numerous inflammatory ailments. The long-term utilization of NSAIDs prompts adverse reactions such as gastrointestinal ulceration, renal dysfunction and hepatotoxicity; however, selective COX-2 inhibitors prevent these adverse events. Various scientific approaches have been employed to identify safer COX-2 inhibitors, as in any case, a large portion of particular COX-2 inhibitors have been retracted from the market because of severe cardiovascular events. This study aimed to develop and synthesize a novel series of indomethacin analogues with potential anti-inflammatory properties and fewer side effects, wherein carboxylic acid moiety was substituted using DCC/DMAP coupling. This study incorporates the docking of various indomethacin analogues to detect the binding interactions with COX-2 protein (PDB ID: 3NT1). MD simulation was performed to measure the stability and flexibility of ligand–protein interactions at the atomic level, for which the top-scoring ligand–protein complex was selected. These compounds were evaluated in vitro for COX enzymes inhibition. Likewise, selected compounds were screened in vivo for anti-inflammatory potential using the carrageenan-induced rat paw oedema method and their ulcerogenic potential. The acute toxicity of compounds was also predicted using in silico tools. Most of the compounds exhibited the potent inhibition of both COX enzymes; however, 3e and 3c showed the most potent COX-2 inhibition having IC50 0.34 µM and 1.39 µM, respectively. These compounds also demonstrated potent anti-inflammatory potential without ulcerogenic liability. The biological evaluation revealed that the compound substituted with 4-nitrophenyl was most active.

Abstract We present a new model for building up complete exclusive hadronic final states in high energy nucleus collisions. It is a direct extrapolation of high energy pp collisions (as described by Pythia), and thus bridges a large part of the existing gap between heavy ion and high energy physics phenomenology. The model is inspired by the old Fritiof model and the notion of wounded nucleons. Two essential features are the treatment of multi-parton interactions and diffractive excitation in each NN sub-collision. Diffractive excitation is related to fluctuations in the nucleon partonic sub-structure, and fluctuations in both projectile and target are here included for the first time. The model is able to give a good description of general final-state properties such as multiplicity and transverse momentum distributions, both in pA and AA collisions. The model can therefore serve as a baseline for understanding the non-collective background to observables sensitive to collective behaviour. As Pythia does not include a mechanism to reproduce the collective effects seen in pp collisions, such effects are also not reproduced by the present version of Angantyr. Effects of high string density, shown to be able to reproduce e.g. higher strangeness ratios and the ridge in pp, will be added in future studies.

This paper demonstrates how the innovative application of a Collective Intelligence approach enhanced Local Skills Improvement Planning information for employers, education and skills training organisations and regional economic policy organisations. This took place within a Knowledge Transfer Partnership between a Chamber of Commerce and a University. This aimed to develop and deploy regional business intelligence for enhanced policy and decision-making in enterprise and economic development. The project converged knowledge from several research centres including economics, entrepreneurship and innovation, data science, and Artificial Intelligence. The paper presents a project case study which provides two contributions to applied knowledge. Firstly, it demonstrates how a Collective Intelligence (CI) approach can be applied to achieve rapid results in resolving the real-world problem of local skills information availability. Useful real-time data was gathered from employers in three sectors on skills requirements, supply and training. This was analysed using Artificial Intelligence tools, then shared publicly via an automated Internet portal, providing a scalable model for wider use. Secondly, it explores and evaluates how the knowledge exchange (KE) process can function effectively and quickly in applying CI-based innovation in practical ways which create new value, within a Knowledge Transfer Partnership between a University and Chamber of Commerce.environment.

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

Purpose: The purpose was to elaborate difficulties encountered during the transition from external dacryocystorhinostomy (Ex-DCR) to endonasal endoscopic DCR (EN-DCR) by an oculoplasty surgeon and to evaluate the outcome of EN-DCR. Materials and Methods: A retrospective study of consecutive 24 patients who presented with epiphora and underwent EN-DCR between August 2008 and December 2009. All procedures except for one case were performed under general anesthesia and under the direct visualization of the rigid fiberoptic endoscope (Hopkin II, 30°, Karl Storz, Germany, endoscope). Success was measured by both improvement of the epiphora and patency of the lacrimal system on irrigation. Results: The total of 25 EN-DCRs were performed of which the first 12 together with an otorhinolaryngologist. Of 24 patients 18 were females and 6 were males. The mean age was 43.8 ± 20.2 years. In one patient, the procedure was performed bilaterally. After an average follow-up 15.92 ± 4.57 months, success was achieved in 92% of all patients. No significant intra- and post-operative complications were detected. Conclusion: The success rate of EN-DCR was 92%. The success rate of EN-DCR compares favorably with Ex-DCR. We are of the opinion that the surgery is best learned in conjunction with an otorhinolaryngologist ENT surgeon who has expertize in endoscopic nasal surgery. Although the learning curve of EN-DCR is steep and requires thorough knowledge of nasal anatomy it is to be performed by an oculoplastic surgeon to keep up with the times.

Introduction: Menarche is a psychological, social as well as behavioural transition for an adolescent girl from girlhood to womanhood. Menstrual hygiene is most important, still neglected area of concern. The objective of the study was to find out menstrual pattern, knowledge and practice for menstrual hygiene among adolescent girls. Method: A cross sectional study was undertaken in a rural area of Sabarkantha district. Randomly selected 250 adolescent girls were inter-viewed using predesigned pretested questionnaire. Results: It was evident that 35.6% participants were aware about menstruation before their menarche and important sources of information were mothers in 54.2% girls. 14.8% respondents used only sanitary napkin during menstruation. 83.8% changed absorbent 1 to 2 times a day. Conclusion: This study has highlighted the need of adolescent girls to have accurate and adequate information about menstruation before the menarche.

We have formulated a new model for collisions with nuclei, called Angantyr, which is now included in PYTHIA8 event generator. The model is inspired by the old Fritiof model, but also includes effects of hard partonic interactions. It uses a Glauber model to calculate the number of wounded nucleons, but includes fluctuations in the nucleon-nucleon(NN) interaction to separate non-diffractively and diffractively wounded nucleons. The MC simulates final states without assuming a thermalised plasma. In this manner we are providing an event generator to be used to simulate events from pp to AA with the same underlying physics approach. Collective effects due to high string density are not included in the present version, but will be added in future work.

We report a case of acute promyelocytic leukemia (APL) presenting with severely fibrotic marrow. There are four other reports of similar cases in the literature. Our patient was treated with All-Transretinoic Acid- (ATRA-) containing induction chemotherapy, followed by consolidation and maintenance therapy. He achieved a complete morphologic remission with adequate count recovery in a timely fashion, and later a molecular remission was documented. The patient remains in molecular remission and demonstrates normal blood counts now more than 4 years after induction. Since the morphological appearance may not be typical and the bone marrow may not yield an aspirate for cytogenetic analysis, awareness of such entity is important to make a correct diagnosis of this potentially curable disease.

Background Tuberculosis (TB) continues to pose a serious threat to the public health system in India. Although the National Tuberculosis Elimination Program (NTEP) is providing a wide range of interventions from early diagnosis to complete treatment to reduce morbidity and mortality from TB, adverse drug reactions (ADR) remain a challenge in treatment adherence and completion. Methods An observational cross-sectional study was conducted in selected districts of Gujarat state. A total of 593 reported TB patients were recruited with an adjusted unified distribution based on the type of cases, site of diseases, and service facility through a simple random sampling method. A semi-structured questionnaire tool was used to collect socio-demographic, clinical, and ADR-related data from the TB patients. Data was analyzed for the frequency, percentage, chi-squared, and adjusted odds ratio to find the association between the variables. Results The majority of the study participants were male (87.2%), aged 15 to 60 (57.8%), daily laborers (22.4%), and married (64.2%). Over 75% of individuals had pulmonary TB, with 87% having experienced their first episode, 83% being new cases, and 44.7% having a history of addiction. ADR with mild symptoms was reported by more than a quarter (29%) of TB patients during the intensive phase (77%). The association between ADR experience and drug susceptibility was significant (p Conclusion The study highlighted a need to enhance health care providers’ capacity and program structure for managing ADRs among TB patients. In order to completely eliminate TB across the country, it also emphasized the attention for a holistic and all-encompassing strategy for managing TB patients at the field level.

A 20 year old male presented with fever associated with eruption of papules, plaques and vesiculobullous lesions on the chest, back, extremities, palms, soles, and genital mucosa of 20 days duration. Histopathological examination revealed epidermal clefts, edema and vacuolar degeneration of keratinocytes, basal cell degeneration, and dermal perivascular lymphocytic infiltrate. On the basis of clinical features and histology, a diagnosis of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) was made. Treatment with doxycycline (100 mg BD for 4 weeks) and oral prednisolone 60 mg/day tapered to 25 mg in 4 weeks led to initial response that was followed by a relapse on tapering steroid. Addition of methotrexate (7.5 mg increased to 15 mg in 2 weeks) led to a dramatic response.

Background Tuberculosis (TB) continues to pose a serious threat to the public health system in India. Although the National Tuberculosis Elimination Program (NTEP) is providing a wide range of interventions from early diagnosis to complete treatment to reduce morbidity and mortality from TB, adverse drug reactions (ADR) remain a challenge in treatment adherence and completion. Methods An observational cross-sectional study was conducted in selected districts of Gujarat state. A total of 593 reported TB patients were recruited with an adjusted unified distribution based on the type of cases, site of diseases, and service facility through a simple random sampling method. A semi-structured questionnaire tool was used to collect socio-demographic, clinical, and ADR-related data from the TB patients. Data was analyzed for the frequency, percentage, chi-squared, and adjusted odds ratio to find the association between the variables. Results The majority of the study participants were male (87.2%), aged 15 to 60 (57.8%), daily laborers (22.4%), and married (64.2%). Over 75% of individuals had pulmonary TB, with 87% having experienced their first episode, 83% being new cases, and 44.7% having a history of addiction. ADR with mild symptoms was reported by more than a quarter (29%) of TB patients during the intensive phase (77%). The association between ADR experience and drug susceptibility was significant (p Conclusion The study highlighted a need to enhance health care providers’ capacity and program structure for managing ADRs among TB patients. In order to completely eliminate TB across the country, it also emphasized the attention for a holistic and all-encompassing strategy for managing TB patients at the field level.