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To evaluate whether health facility-based HIV interventions align with UNAIDS 90-90-90 targets, we performed a systematic review through the lens of UNAIDS targets. We searched 11 databases, retrieving 5201 citations with 26 eligible studies classified by country income and UNAIDS target. We analyzed whether reporting of study outcome metrics was in line with UNAIDS targets using a standardized extraction form and results were summarized in a narrative synthesis given data heterogeneity. We also assessed the quality of randomized trials with the Cochrane Risk of Bias Tool and observational studies with the Newcastle-Ottawa Scale. Stratification of interventions by country income level revealed themes in successful interventions that provide insight for scale-up in similar resource contexts. Few studies reported outcomes using metrics according to UNAIDS targets. Standardization of reporting according to the UNAIDS framework could facilitate comparability of interventions and inform country-level progress on an international scale.

Performance Appraisal is the process of assessing the accomplishments of workforce & to ac­knowledge their capabilities for facilitating development. Performance evaluation is one of the areas in Human resource management which is considerably affected by the spread of pandemic severe acute respiratory syndrome corona virus 2. This virus outbreak posed new challenges for the companies across the globe. As a result in order to tackle this uncertainty various organiza­tions have taken measures to cut down the expenses like deferment in the appraisal cycle or for muted salary increments. Thus one of the objectives of this paper is to study the impact of Covid -19 on performance appraisal of employees. Further this pandemic is equally challenging for the managers also. As social distancing and working remotely have become a new normal, employees work remotely from each other and from managers, and this will be more common in the fu­ture. Managers are now searching for new ways to ‘do visibility’ without always being physically present. It has also become the vital demand of the situation as managers must be aware of the circumstances in which employees are working in. Therefore another objective of this paper is to suggest an approach to manage the performance evaluations of remote working employees. It is recommended that managers should adopt the choice based approach for performance evaluation instead of control based approach. The review is formed on articles and reports from various internet sources and journals. Further some ways of managing the performance assessment of remotely working employees and scope for the future are also discussed.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Silicon (Si) is an omnipresent and second most abundant element in the soil lithosphere after oxygen. Silicon being a beneficial element imparts several benefits to the plants and animals. In many plant species, including the cereals the uptake of Si from the soil even exceeds the uptake of essential nutrients. Cereals are the monocots which are known to accumulate a high amount of Si, and reaping maximum benefits associated with it. Cereals contribute a high amount of Si to the human diet compared to other food crops. In the present review, we have summarized distribution of the dietary Si in cereals and its role in the animal and human health. The Si derived benefits in cereals, specifically with respect to biotic and abiotic stress tolerance has been described. We have also discussed the molecular mechanism involved in the Si uptake in cereals, evolution of the Si transport mechanism and genetic variation in the Si concentration among different cultivars of the same species. Various genetic mutants deficient in the Si uptake have been developed and many QTLs governing the Si accumulation have been identified in cereals. The existing knowledge about the Si biology and available resources needs to be explored to understand and improve the Si accumulation in crop plants to achieve sustainability in agriculture.

BackgroundIndia’s tobacco-free film and TV rules were implemented from 2012. To assess the effect of the rules, we studied tobacco depictions in top-grossing Bollywood films released between 2006 and 2017 and rule compliance after 2012.MethodsTobacco incidents and brand appearances were coded in 240 top-grossing Bollywood films (2006–2017) using the Breathe California method. Trends in number of tobacco incidents per film per year were studied before and after implementation of the rules using Poisson regression analysis. Compliance with rules over the years was studied using Pearson product-moment correlations.ResultsForty-five films were U-rated (all ages), 162 were UA-rated (below age 12 years must be adult-accompanied), and 33 were A-rated (age 18+ years only). Before implementation of the rules, the number of tobacco incidents per film was increasing by a factor of 1.1/year (95% CI 1.0 to 1.2, p=0.002). However, beginning year 2013, the number of incidents per film started falling significantly by a factor of 0.7/year (95% CI 0.6 to 0.9; p=0.012) compared with the previous increasing trend. The percentage of youth-rated (U and UA) films with any tobacco incidents also declined from a peak of 76% in 2012 to 35% in 2017. The percentage of films complying with the rules (audio-visual disclaimers, health spots, static warnings) did not change significantly from 2012 to 2017.ConclusionIndia’s 2012 rules were followed by a reduction in tobacco depictions in Bollywood films. Enhanced monitoring of compliance is needed to ensure the continued effectiveness of the rules.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of extra-nodal non-Hodgkin’s lymphoma. Corticosteroids cause transient regression of PCNSL at the radiological and histological level. A growing number of case reports describe histologically confirmed neuroinflammation (sentinel lesions) heralding the development of PCNSL. We present two further cases of sentinel lesions contextualised by a review of past literature. Our aims are to collate existing knowledge on sentinel lesions in PCNSL and explore their pathophysiological significance. Two cases were identified (n = 2) from a cohort of 104 patients with PCNSL referred to a tertiary neurosurgery centre. A literature search identified previously reported cases (n = 14). Median age was 57.5 (range; 26–72); pre-biopsy corticosteroid administration was reported in 50% of cases (n = 8); mean time between biopsies was 10 months (range; 3–60). Common MRI features were homogenous enhancement (10;71.4%) and T2-hyperintensity (11;100%). Histochemical analysis of sentinel lesion biopsy revealed inflammatory CD3/4/5/8-positive T-cells (14; 100%), demyelination (13; 81.3%), rare/scattered CD20-postive B-cells (11;78.6%) and CD68-positive macrophages (10;71.4%). Repeat biopsy confirmed PCNSL in all cases. Waxing and waning CNS inflammation has been identified in 16 patients ultimately diagnosed with PCNSL. Neuro-specialists should be aware of this atypical presentation and maintain a high index of suspicion for lymphoma despite histopathology negative for lymphoma when clinical or radiological features indicate PCNSL.

Background Thoracic paravertebral block (TPVB) has emerged as an effective and feasible mode of providing analgesia in laparoscopic cholecystectomy. Though a variety of local anaesthetic combinations are used for providing TPVB, literature is sparse on use of dexmedetomidine in TPVB. We aimed to compare levobupivacaine and levobupivacaine-dexmedetomidine combination in ultrasound guided TPVB in patients undergoing laparoscopic cholecystectomy. Methodology 70 ASA I/II patients, aged 18–60 years, scheduled to undergo laparoscopic cholecystectomy under general anaesthesia were enrolled and divided into two groups. Before anaesthesia induction, group A patients received unilateral right sided ultrasound guided TPVB with 15 ml 0.25% levobupivacaine plus 2 ml normal saline while group B patients received unilateral right sided ultrasound guided TPVB with 15 ml 0.25% levobupivacaine plus 2 ml solution containing dexmedetomidine 1 μg.kg-1. Patients were monitored for pain using Numeric Rating Scale (NRS) at rest, on movement, coughing and comfort scores post surgery. Total analgesic consumption in first 48 hour postoperative period, time to first request analgesic and pain scores were recorded. Results Total amount of rescue analgesia (injection tramadol plus injection tramadol intravenous equivalent dose) consumed during 48 hours postoperatively in group A was 146.55 mg while in group B was 111.30 mg (p = 0.026). Mean time for demanding rescue analgesia was 273 minutes in group A while in group B was 340 minutes (p = 0.00). Conclusion TPVB using dexmedetomidine 1 μg.kg-1 added to levobupivacaine 0.25% in patients undergoing laparoscopic cholecystectomy significantly reduced total analgesic consumption in first 48 hours and provided longer duration of analgesia postoperatively compared to levobupivacaine 0.25% alone.

Many people in different African countries are suffering from different diseases many of which result in serious life threat and public health problems with high risk of infection and mortality. Due to less accessibility and high cost of modern drugs, people of this continent often depend on traditional medicine using medicinal plants to manage the diseases. Africa has large tropical rain forests, which are very rich in medicinal plants. Many of them have been scientifically proven for their medicinal values. These medicinal plants which constitute a large repertoire of endophytes have not been significantly explored for the isolation of these microorganisms and their bioactive secondary metabolites. This review summarizes the research on endophytes isolated from medicinal plants of Africa, their pharmacological potential and some of their biotechnological aspects. Novel compounds reported from endophytes from Africa with their biological activities have also been reviewed. Information documented in this review might serve as starting point for future researches on endophytes in different African countries.

Despite great success as a targeted breast cancer therapy, trastuzumab use may be complicated by heart failure and loss of left ventricular contractile function. This review summarizes the risk factors, imaging, and prevention of cardiotoxicity associated with trastuzumab and other HER2-targeted therapies. Cardiovascular disease risk factors, advanced age, and previous anthracycline treatment predispose to trastuzumab-induced cardiotoxicity (TIC), with anthracycline exposure being the most significant risk factor. Cardiac biomarkers such as troponins and pro-BNP and imaging assessments such as echocardiogram before and during trastuzumab therapy may help in early identification of TIC. Initiation of beta-adrenergic antagonists and angiotensin converting enzyme inhibitors may prevent TIC. Cardiotoxicity rates of other HER2-targeted treatments, such as pertuzumab, T-DM1, lapatinib, neratinib, tucatinib, trastuzumab deruxtecan, and margetuximab, appear to be significantly lower as reported in the pivotal trials which led to their approval. Risk assessment for TIC should include cardiac imaging assessment and should incorporate prior anthracycline use, the strongest risk factor for TIC. Screening and prediction of cardiotoxicity, referral to a cardio-oncology specialist, and initiation of effective prophylactic therapy may all improve prognosis in patients receiving HER2-directed therapy. Beta blockers and ACE inhibitors appear to mitigate risk of TIC. Anthracycline-free regimens have been proven to be efficacious in early HER2-positive breast cancer and should now be considered the standard of care for early HER2-positive breast cancer. Newer HER2-directed therapies appear to have significantly lower cardiotoxicity compared to trastuzumab, but trials are needed in patients who have experienced TIC and patients with pre-existing cardiac dysfunction.

Background Protein tyrosine phosphatase 1B (PTP1B) inhibitors are potential candidates for the treatment of peripheral insulin resistance and diabetes mellitus. Similar to peripheral action within the brain also, PTP1B activation impairs insulin signaling pathways. Activation of PTP1B in brain also accentuates neuroinflammation, oxidative stress and decreases neurotrophic factors in various brain dysfunctions including cognitive decline. Objectives The main objective of our study was to elucidate the role of alendronate, a potent PTP1B inhibitor (blood brain barrier crossing bisphosphonate) in central insulin resistance and associated memory deficits. Methodology To induce central insulin resistance, streptozotocin (3 mg/kg) intracerebroventricular (ICV) was administered in two alternate days (1st and 3rd). After 21 days, memory was assessed via using the passive avoidance and Morris water maze paradigm. At the end of behavioral studies, animals were sacrificed to assess a variety of biochemical and molecular parameters in the hippocampus and cerebral cortex region of the brain. Treatment drug alendronate (3 mg/kg/day, p.o) and standard drug donepezil (3 mg/kg/i.p.) were administered from the 3rd day of STZ administration till the end of the study. Inhibition of PTP1B activates phosphoinsotide-3 kinase (PI3 K) (down-stream regulator of insulin signaling pathway).Thus, to illuminate the mechanism of action of alendronate, PI3 K inhibitor, wortmannin was administered in presence of alendronate in one group. Results Administration of alendronate to ICV streprozotocin treated rats resulted in modulation of the insulin signaling pathway and associated behavioral, biochemical and molecular changes in central insulin resistance. However, the protective effect of alendronate was entirely vanished when it was administered in the presence of wortmannin. Conclusion Alendronate can be an important treatment strategy in central insulin signaling pathway dysfunction and associated cognitive deficits. Protective effect of alendronate is via modulation of PI3-K/Akt signaling pathway.

A steatotic liver is increasingly vulnerable to ischemia reperfusion injury (IRI), and the underlying mechanisms are incompletely defined. Caspases are endo-proteases, which provide critical regulatory connections between cell death and inflammation. Caspase 1 is driven by inflammasomes which are key signaling platforms, that detect sterile stressors (DAMPs), releasing the highly pro-inflammatory cytokine interleukin IL-8 and IL-1β. To delineate the involvement of Caspase 1 and 11 in hepatocellular injury in steatotic liver undergoing IRI. Male C57BL6/Wild Type and Caspase 1Null, Caspase 11−/− and Caspase 1−/−/11−/− mice were fed a high fat diet (HFD) for 12 weeks. These mice were subjected to 40 min of ischemia followed by 2–24 h of reperfusion. Hepatocellular injury was assessed by histopathologic injury scoring, serum ALT and propidium iodide (PI) uptake, mRNA levels of Caspase 1, IL-1β by RT PCR, Caspase 1 activity assay and Caspase 1. Specific Caspase 1, inhibitor experiments were carried out. All groups gained similar body weight after a 12-week HFD. Cleaved Caspase 1 protein levels, Caspase 1 mRNA levels were significantly higher in steatotic liver undergoing IRI. Executor of pyroptosis cleaved GSDMD levels were higher in HFD fed mouse compared to lean. In addition, genetic deletion of Caspase 1, Casp1Null mouse expressing Caspase-11 and Caspase 1/11 double knock out demonstrated significant reduction in serum ALT (p

Immune checkpoint inhibitors (ICIs) are a breakthrough in therapy for many solid malignancies. ICIs suppress the inhibitory signaling of several immune cell subtypes by the blocking the ligation of...

We evaluated the clinical histories, motor and pulmonary functions, cardiac phenotypes and GAA genotypes of an Indian cohort of twenty patients with late onset Pompe disease (LOPD) in this multi-centre study. A mean age at onset of symptoms and diagnosis of 9.9 ±9.7 years and 15.8 ±12.1 years respectively was identified. All patients had lower extremity limb-girdle muscle weakness. Seven required ventilatory support and seven used mobility assists. Of the four who used both assists, two received ventilatory support prior to wheelchair use. Cardiac involvement was seen in eight patients with various combinations of left ventricular hypertrophy, tricuspid regurgitation, cardiomyopathy,dilated ventricles with biventricular dysfunction and aortic regurgitation. Amongst 20 biochemically diagnosed patients (low residual GAA enzyme activity) GAA genotypes of 19 patients identified homozygous variants in eight and compound heterozygous in 11: 27 missense, 3 nonsense, 2 initiator codon, 3 splice site and one deletion. Nine variants in 7 patients were novel. The leaky Caucasian, splice site LOPD variant, c. −32 −13T > G mutation was absent. This first study from India provides an insight into a more severe LOPD phenotype with earlier disease onset at 9.9 years compared to 33.3 years in Caucasian patients, and cardiac involvement more than previously reported. The need for improvement in awareness and diagnosis of LOPD in India is highlighted

Background and aims Tolerance is transplantation's holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long-term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance. Approach and results We conducted a multicenter, single-arm trial of immunosuppression withdrawal over 36-48 weeks. Liver tests were monitored biweekly (year 1), monthly (year 2), and bimonthly (years 3-4). For-cause biopsies were done at investigators' discretion but mandated when alanine aminotransferase or gamma glutamyltransferase exceeded 100 U/L. All subjects underwent final liver biopsy at trial end. The primary efficacy endpoint was operational tolerance, defined by strict biochemical and histological criteria 1 year after stopping immunosuppression. Among 88 subjects (median age 11 years; 39 boys; 57 deceased donor grafts), 33 (37.5%; 95% confidence interval [CI] 27.4%, 48.5%) were operationally tolerant, 16 were nontolerant by histology (met biochemical but failed histological criteria), and 39 were nontolerant by rejection. Rejection, predicted by subtle liver inflammation in trial entry biopsies, typically (n = 32) occurred at ≤32% of the trial-entry immunosuppression dose and was treated with corticosteroids (n = 32) and/or tacrolimus (n = 38) with resolution (liver tests within 1.5 times the baseline) for all but 1 subject. No death, graft loss, or chronic, severe, or refractory rejection occurred. Neither fibrosis stage nor the expression level of a rejection gene set increased over 4 years for either tolerant or nontolerant subjects. Conclusions Immunosuppression withdrawal showed that 37.5% of selected pediatric liver-transplant recipients were operationally tolerant. Allograft histology did not deteriorate for either tolerant or nontolerant subjects. The timing and reversibility of failed withdrawal justifies future trials exploring the efficacy, safety, and potential benefits of immunosuppression minimization.

Objective To assess the activity and safety of sequential lutetium-177 (Lu-177)-PSMA-617 and docetaxel vs docetaxel on a background of androgen deprivation therapy (ADT) in men with de novo metastatic hormone-naive prostate cancer (mHNPC).Patients and Methods UpFrontPSMA (NCT04343885) is an open-label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: prostate cancer with a histological diagnosis within 12 weeks of screening commencement; prostate-specific antigen (PSA) >10 ng/mL at diagnosis; 15; and absence of extensive discordant fluorodeoxyglcuose (FDG)-positive, PSMA-negative disease. Ga-68-PSMA-11 and F-18-FDG positron-emission tomography (PET)/CT undergo central review to determine eligibility. Patients are randomized 1:1 to experimental treatment, Arm A (Lu-177-PSMA-617 7.5GBq q6w x 2 cycles followed by docetaxel 75 mg/m(2) q3w x 6 cycles), or standard-of-care treatment, Arm B (docetaxel 75 mg/m(2) q3w x 6 cycles). All patients receive continuous ADT. Patients are stratified based on disease volume on conventional imaging and duration of ADT at time of registration. The primary endpoint is the proportion of patients with undetectable PSA (

The genome-wide architecture of chromatin-associated proteins that maintains chromosome integrity and gene regulation is not well defined. Here we use chromatin immunoprecipitation, exonuclease digestion and DNA sequencing (ChIP–exo/seq)1,2 to define this architecture in Saccharomyces cerevisiae. We identify 21 meta-assemblages consisting of roughly 400 different proteins that are related to DNA replication, centromeres, subtelomeres, transposons and transcription by RNA polymerase (Pol) I, II and III. Replication proteins engulf a nucleosome, centromeres lack a nucleosome, and repressive proteins encompass three nucleosomes at subtelomeric X-elements. We find that most promoters associated with Pol II evolved to lack a regulatory region, having only a core promoter. These constitutive promoters comprise a short nucleosome-free region (NFR) adjacent to a +1 nucleosome, which together bind the transcription-initiation factor TFIID to form a preinitiation complex. Positioned insulators protect core promoters from upstream events. A small fraction of promoters evolved an architecture for inducibility, whereby sequence-specific transcription factors (ssTFs) create a nucleosome-depleted region (NDR) that is distinct from an NFR. We describe structural interactions among ssTFs, their cognate cofactors and the genome. These interactions include the nucleosomal and transcriptional regulators RPD3-L, SAGA, NuA4, Tup1, Mediator and SWI–SNF. Surprisingly, we do not detect interactions between ssTFs and TFIID, suggesting that such interactions do not stably occur. Our model for gene induction involves ssTFs, cofactors and general factors such as TBP and TFIIB, but not TFIID. By contrast, constitutive transcription involves TFIID but not ssTFs engaged with their cofactors. From this, we define a highly integrated network of gene regulation by ssTFs. A ChIP–exo method is used to define the genome-wide positional organization of proteins associated with gene transcription, DNA replication, centromeres, subtelomeres and transposons, revealing distinct protein assemblies for constitutive and inducible gene expression.

The kinetic patterns of CpG methylation of the cis-regulatory region of heat stress-related genes on exposed to heat stress (at 42 °C) between the Sahiwal and Frieswal cattle was compared in the present study. Using an in vitro whole blood culture model, cells were continuously exposed to heat stress (at 42 °C) for 6 h. Methylation levels of five genes, viz., GPX1, HSP70, HSP90, c-FOS, and JUN were estimated by SyberGreen-based quantitative methylation-specific PCR (qMSP) assay. CpG methylation kinetics at different time points of heat stress (0.5, 1, 2, 4, 6 h) were analyzed using mixed ANOVA. The initial methylation level, estimated at 37 °C, of HSP70 was significantly high in the Sahiwal breed. A significant (p

Bacterial sporulation is a conserved process utilized by members of Bacillus genus and Clostridium in response to stress such as nutrient or temperature. Sporulation initiation is triggered by stress signals perceived by bacterial cell that leads to shutdown of metabolic pathways of bacterial cells. The mechanism of sporulation involves a complex network that is regulated at various checkpoints to form the viable bacterial spore. Engulfment is one such check point that drives the required cellular rearrangement necessary for the spore assembly and is mediated by bacterial proteolytic machinery that involves association of various Clp ATPases and ClpP protease. The present study highlights the importance of degradation of an anti-sigma factor F, SpoIIAB by ClpCP proteolytic machinery playing a crucial role in culmination of engulfment process during the sporulation in Bacillus anthracis.

Background: Citrus limon, a Mediterranean-grown citrus species of plants belonging to the Rutaceae family, occupies a place of an impressive range of food and medicinal uses with considerable value in the economy of the fruit of the country. Citrus fruits are economically important with large-scale production of both the fresh fruits and industrially processed products. The extracts and phytochemicals obtained from all parts of C. limon have shown immense therapeutic potential because of their anticancer, anti-tumor and anti-inflammatory nature, and also serve as an important ingredient in the formulation of several ethnic herbal medicines. These properties are mediated by the presence of different phytochemicals, vitamins and nutrients in the citrus fruits. Material and Methods: The methods involved in the preparation of the present article included the collection of information from various scientific databases, indexed periodicals, and search engines such as Medline Scopus google scholar PubMed, PubMed central web of science, and science direct. Results: This communication presents an updated account of different pharmacological aspects of C. limon associated with its anti-oxidative, antiulcer, antihelmintic, insecticidal, anticancer, cytotoxic, and estrogenic activities. In addition, C. limon extracts possess hepatoprotective, anti-hyperglycemic, and antimicrobial properties. The present article includes the structure and function of different key chemical constituents from different parts of C. limon. Also, the possible molecular mechanisms of actions of bioactive compounds from C. limon are displayed. Conclusion: The traditional and ethno-medicinal literature revealed that C. limon is very effective in different pathologies. Most of these compounds possessing antioxidant properties would be implicated in offering health benefits by acting as potential nutraceuticals to humans with special reference to disease management of health and disease.

Mobile health (mHealth) technologies for HIV care are developed to provide diagnostic support, health education, risk assessment and self‐monitoring. They aim to either improve or replace part of the therapeutic relationship. Part of the therapeutic relationship is affective, with the emergence of feelings and emotion, yet little research on mHealth for HIV care focuses on affect and HIV testing practices. Furthermore, most of the literature exploring affect and care relations with the introduction of mHealth is limited to the European and Australian context. This article explores affective dimensions of HIV self‐testing using a smartphone app strategy in Cape Town, South Africa and Montréal, Canada. This study is based on observation notes, 41 interviews and 1 focus group discussion with study participants and trained HIV healthcare providers from two quantitative studies evaluating the app‐based self‐test strategy. Our paper reveals how fear, apathy, judgement, frustration and comfort arise in testing encounters using the app and in previous testing experiences, as well as how this relates to care providers and test materials. Attending to affective aspects of this app‐based self‐testing practice makes visible certain affordances and limitations of the app within the therapeutic encounter and illustrates how mHealth can contribute to HIV care.

Across two studies, this research examines the effects of positive versus negative framing of health messages on food consumption, in the relatively short and long run. Specifically, it studies the effects of multiple exposures to health messages over time (Study 1), using daily food consumption diary data. It replicates and extends those findings in a cross-sectional, single exposure setting to tease out the individual effects of positive and negative framing with consumption intentions as the dependent variable (Study 2). With this combination of an externally and internally valid setup, our research provides robust evidence of the associations of message effectiveness and behavioral outcomes. Our findings suggest that negative messages are more effective than positive messages in the short term but importantly, in the long term as well, suggesting that transforming consumption in the long term can be a viable social marketing objective with the appropriate message tactics. JEL Classification: M31, M37

In cattle production systems, an intense selection pressure for production traits has resulted in the decline of fertility traits. To optimize an efficient reproduction system, the inclusion of both male and female fertility traits in the selection process is very much essential. RAPD (Random Amplified Polymorphic DNA) was developed as a molecular biology tool and has been extensively used, to study intra- and interspecific genetic diversity. The present study was undertaken to utilize RAPD primers to investigate the association between DNA markers and semen quality traits viz. Sperm concentration, total sperm count ejaculate and initial sperm motility and thereby to identify good/poor semen producers. DNA isolated from the blood samples of healthy bulls was subjected to RAPD-PCR. The multiple regression analysis followed by independent t test was carried out to identify suitable markers. Based on the results, only 12 bands were identified as marker suitable for any of the quality trait. This includes, OPA2 ~ 760, OPA2 ~ 700, OPA6 ~ 1,200, OPA9 ~ 400, OPA9 ~ 380, OPA12 ~ 970, OPA14 ~ 715, OPA14 ~ 605, OPA16 ~ 485, OPA17 ~ 860 and OPA18 ~ 480. Multiple regression analysis selected, OPA2 ~ 760 and OPA2 ~ 1,750 for sperm concentration and OPA2 ~ 760, OPA2 ~ 700, OPA9 ~ 620, OPA4 ~ 670 and OPA18 ~ 1,015 for total sperm count/ejaculate. But the t test revealed a significant association between OPA2 ~ 760 and total sperm count. Further, discriminant function analysis also identified this marker in the first step itself. The results of the present study can be exploited as a low-cost alternative strategy for identification of good /poor semen producers in crossbred bulls at an early age.

Introduction: General anesthesia causes pulmonary atelectasis within few minutes of induction. This can have significant impact on postoperative outcome of cancer patients undergoing prolonged reconstructive surgeries. Objective: The purpose of this study was to evaluate the impact of sonographically detected perioperative atelectasis on the need for postoperative oxygen supplementation, bronchodilator therapy and assisted chest physiotherapy in patients undergoing free flap surgeries for head and neck carcinoma. Methods: Twenty eight head and neck cancer patients underwent bilateral pulmonary ultrasonographic assessments before and after lung surgery. Lung ultrasound scores, serum lactate, and PaO2/FiO2 ratio were measured both at the beginning and at end of the surgery. Patients were scanned in the supine position and the number of single and confluent B lines was noted. These values were correlated with the need for oxygen therapy, requirement of bronchodilators and total weaning time to predict the postoperative outcome. Other factors affecting weaning were also studied. Results: Among twenty eight patients, seven had mean lung ultrasound score of ≥10.5 which correlated with prolonged weaning time (144.56±33.5min vs. 66.7±15.7min; p = 0.005). The change in lung ultrasound score significantly correlated with change in PaO2/FiO2 ratio (r = −0.56, p = 0.03). Elevated total leukocyte count >8200 ΜL and serum lactate >2.1 mmoL/L also predicted prolonged postoperative mechanical ventilation. Conclusion: This preliminary study detected significant levels of perioperative atelectasis using point of care lung ultrasonography in head and neck cancer patients undergoing long duration surgical reconstructions. Higher lung ultrasound scores highlighted the need for frequent bronchodilator nebulizations as well as assisted chest physiotherapy and were associated with delayed weaning. We propose more frequent point of care lung ultrasonographic evaluations and use of recruitment maneuvers to reduce the impact of perioperative pulmonary atelectasis. Resumo Introdução: A anestesia geral causa atelectasia pulmonar poucos minutos após sua indução. Isso pode ter um impacto significativo no resultado pós-operatório de pacientes com câncer submetidos a cirurgias reconstrutivas prolongadas. Objetivo: Avaliar o impacto das atelectasias perioperatórias detectadas por ultrassonografia na necessidade de suplementação pós-operatória de oxigênio, terapia broncodilatadora e fisioterapia respiratória assistida em pacientes com carcinoma de cabeça e pescoço submetidos a cirurgias com uso de retalho livre. Método: Foram submetidos a avaliações ultrassonográficas pulmonares bilaterais antes e após a cirurgia 28 pacientes com câncer de cabeça e pescoço. Os escores de ultrassonografia pulmonar, lactato sérico, razão PaO2/FiO2 foram medidos no início e no fim da cirurgia. Os pacientes foram avaliados na posição supina e o número de linhas B confluentes e únicas foi observado. Esses valores foram correlacionados com a necessidade de oxigenoterapia, necessidade de broncodilatadores e tempo total de desmame para predizer o resultado pós-operatório. Outros fatores que afetam o desmame também foram estudados. Resultados: Entre os 28 pacientes, sete apresentaram escore médio de ultrassonografia pulmonar ≥ 10,5, que se correlacionou com o tempo de desmame prolongado (144,56 ± 33,5 minutos vs. 66,7 ± 15,7 minutos; p = 0,005). A mudança no escore de ultrassonografia pulmonar correlacionou-se significantemente com a mudança na razão PaO2/FiO2 (r = −0,56, p = 0,03). A contagem total elevada de leucócitos > 8200 uLe o nível de lactato sérico >2,1 mmoL/L também previram ventilação mecânica pós-operatória prolongada. Conclusão: Este estudo preliminar detectou um nível significante de atelectasia perioperatória com ultrassonografia pulmonar no local de atendimento em pacientes com câncer de cabeça e pescoço submetidos a reconstruções cirúrgicas de longa duração. Escores mais altos de ultrassonografia pulmonar enfatizaram a necessidade de nebulizações broncodilatadoras frequentes e fisioterapia respiratória assistida e foram associados a desmame tardio. Propomos avaliações ultrassonográficas pulmonares mais frequentes no local de atendimento e o uso de manobras de recrutamento para reduzir o impacto das atelectasias pulmonares perioperatórias.

Quality of biotherapeutic products is of paramount importance for ensuring patient safety. Analytical tools that can facilitate rapid quality assessment of the therapeutic product at the point of care are very much in demand. In this article, we apply chemometrics based analysis of Raman spectra towards quantitative prediction of protein aggregation in lyophilized biotherapeutic products. Two commercially available therapeutic proteins, erythropoietin (EPO) and human growth hormone (HGH), have been used to demonstrate the applicability of the proposed approach. Thermally induced protein aggregation was monitored by size exclusion chromatography as well as Raman spectroscopy with a 785 nm wavelength laser. Partial least square (PLS) regression was used to analyse the Raman spectra and create a model for quantitative determination of aggregate. Satisfactory performance was observed with both EPO and HGH with R2 of 0.91 and 0.94, cross-validation correlation coefficient of 0.85 and 0.89, and Root Mean Square Error computed from cross calibration (RMSEcv) of 5.25 and 1.92, respectively. The developed approach can enable rapid and accurate assessment of aggregation in lyophilized samples of biotherapeutic products. The study also demonstrates novel use of Raman spectroscopy for protein quantification through a vial.

Background: Adverse drug reactions (ADRs) to psychotropic drugs are common. There are very few reports of ADR prole of psychotropic drugs. Pharmacovigilance of psychotropic drugs is essential to improve patient care and create awareness among physicians. Objective: To study the pattern of ADRs among patients in the OPD of Psychiatry of Tertiary Care Hospital. Materials and Methods: This prospective study was conducted at a Tertiary Care Teaching Hospital and all the patients who developed ADR to atypical antipyschotics and antidepressant drugs formed the study population. Details were documented from OPD prescription slips and lled in ADR reporting form and Causality assessment was done based on WHO Causality scale. Data were subjected to descriptive analysis. Results: During the study period, 100 patients developed a total of 180 ADRs. Based on causality assessment in these cases as per WHO Causality scale, most were judged as probable, followed by possible and then certain. The most common ADRs observed were extrapyramidal symptoms. Antipsychotics are the most common group of drugs found responsible for most of the ADRs; olanzapine being the individual drug which caused the maximum number of ADRs. Conclusion: Active surveillance from the part of clinicians and pharmacologists will help build a database for ADRs in Indian setting.

Phytoglobins (Pgbs) are multifaceted stress-responsive proteins implicated in regulating various physiological and stress-responsive pathways in plants. Previous work has demonstrated NO dioxygenase and peroxidase-like activity of Arabidopsis phytoglobin 3 (AHb3) and its potential role in defense against Sclerotinia sclerotiorum. The work reported here highlights the significance of the other two classes of Arabidopsis phytoglobins (AHb1 and AHb2) in response to S. sclerotiorum. Constitutive expression of AHb1 (OEAHb1) and AHb2 (OEAHb2) conferred marginal tolerance towards S. sclerotiorum whereas respective knockdown (RNAi) lines displayed enhanced susceptibility, with AHb1 RNAi (RNAi-1) lines being more susceptible in comparison to AHb2 RNAi (RNAi-2) lines. Interestingly, transgenic lines with a simultaneous reduction in the transcripts of AHb1 and AHb2 (RNAi-F) displayed greater disease spread in comparison to individual knockdown lines indicative of their additive effect. The enhanced susceptibility upon pathogen challenge correlated with the elevated NO and H2O2 levels in these lines. Furthermore, detailed structural analysis hints towards an alternate mechanism of NO dioxyegnation by AHbs. Taken together, the current investigation illustrates the NO dioxygenase and peroxidase-like activity of AHbs and highlights their role in defense against stem rot pathogen S. sclerotiorum.

The refractory epilepsy adds to the global burden of epilepsy as about 25 % of all patients with epilepsy present drug-resistant epilepsy. The P-glycoprotein (P-gp) plays a vital role in the mechanism of resistance in epilepsy. The AED levels in the brain are regulated by the P-gp transport. The upregulation of P-gp results in low concentration of AEDs inside the brain parenchyma and thus leads to resistance. There are three main conditions which lead to decrease transport of AEDs in refractory epilepsy. First being AEDs as substrate of P-gp; secondly, the elevated expression of P-gp in patients with drug resistant epilepsy as compared to drug-responsive patients; thirdly, the low brain AED concentration in refractory epilepsy in comparison to drug-responsive epilepsy. Therefore, determination of P-gp substrate should be a criterion for the selection of new AED for management of refractory epilepsy. This review highlights various tools which help in identification of P-gp substrates and also illustrates a concept of using various novel non-P-gp substrates which can cross the blood brain barrier and leads to enhanced accumulation inside the brain. Hence, these non P-gp substrates can be used as an add on treatment for the management of resistant epilepsy.

Chikungunya virus; the pathogen for chikungunya febrile and arthritic disease, having 11.8 kb positive-sense RNA genome encodes polyproteins for structural and non-structural regions. The polyprotein (P1234) corresponding to the non-structural part from 5′ end gets auto-cleaved by the action of nsP2 protease, which leads to the generation of individual functional enzymatic proteins like nsP4, nsP1, nsP2 and nsP3. Thus, nsP2 protein initiates viral replication. Targeting nsP2 to block virus replication has always been the foremost strategy to develop antivirals. Plant-based molecules are one of the top choices to develop as inhibitor due to their less toxicity and wide availability. Using a combination of receptor-based docking and MD simulations, we identified a flavanone glycoside- naringin, which binds to nsP2 protease at nM affinity. The biomolecular interaction between naringin and nsP2 was established through SPR. As discerned through FTIR and intrinsic fluorescence studies, upon binding with naringin, a global structural change in nsP2 occurs. This structural modulation in nsP2 due to binding of naringin is likely to interfere with the normal functioning of this enzyme during the viral life cycle. In conclusion, this report highlights the potential of naringin as an anti-viral agent against Chikungunya.

PEGylation of therapeutic proteins has long been recognized as a safe and effective approach to enhance pharmacokinetic properties of proteins by increasing the in-vivo half-life and thereby the bioavailability. Despite all the benefits linked to PEGylation, high cost of PEGylated products has hindered accessibility of these products to patients. Continuous processing offers a solution to this predicament with its proven capability to improve economics without sacrificing product quality. In this study, we report the development of an integrated continuous PEGylation and purification process for a therapeutic protein, PEG-GCSF. The methodology to achieve this consisted of developing the batch PEGylation and purification protocols followed by their conversion into an integrated continuous process. A batch process involving rapid and highly productive PEGylation (reaction completion within one hour of reaction time) followed by cation exchange chromatography was developed. Enabling technologies like coiled flow inversion reactor, inline concentrator and counter-current chromatography, were utilized for the successful conversion of the batch process to continuous mode. The final integrated continuous process consisted of continuous PEGylation in a coiled flow inverter reactor followed by four column continuous counter-current cation exchange chromatography. Continuous chromatography was performed in a novel displacement mode, wherein all the multi-PEGylated impurities were removed in the loading flow-through and the pure mono-PEGylated protein was obtained in a single step salt elution. In combination with our previously established GCSF manufacturing train, the end-to-end continuous manufacturing process starting from inclusion bodies to unformulated PEG-GCSF drug substance was successfully run for 12 h. All attributes were found to be consistent over the period of operation with product purity99 % and high molecular weight impurities0.5 %. We hope that the current study will lay the foundation for implementation of continuous processing as a method to improve manufacturability of PEGylated therapeutic proteins.

Chikungunya has re-emerged as an epidemic with global distribution and high morbidity, necessitating the need for effective therapeutics. We utilized already approved drugs with a good safety profile used in other diseases for their new property of anti-chikungunya activity. It provides a base for a fast and efficient approach to bring a novel therapy from bench to bedside by the process of drug-repositioning. We utilized an in-silico drug screening with FDA approved molecule library to identify inhibitors of the chikungunya nsP2 protease, a multifunctional and essential non-structural protein required for virus replication. Telmisartan, an anti-hypertension drug, and the antibiotic novobiocin emerged among top hits on the screen. Further, SPR experiments revealed strong in-vitro binding of telmisartan and novobiocin to nsP2 protein. Additionally, small angle x-ray scattering suggested binding of molecules to nsP2 and post-binding compaction and retention of monomeric state in the protein-inhibitor complex. Protease activity measurement revealed that both compounds inhibited nsP2 protease activity with IC50 values in the low micromolar range. More importantly, plaque formation assays could show the effectiveness of these drugs in suppressing virus propagation in host cells. We propose novobiocin and telmisartan as potential inhibitors of chikungunya replication. Further research is required to establish the molecules as antivirals of clinical relevance against chikungunya.

Objectives Human exposure to heavy metals and pesticides is a worldwide major health problem. These environmental pollutants have been considered as the most neurotoxic agents and responsible to causing neurological toxicity. Plant-based therapeutic supplement may be used in the event of toxicity. Citrus limon contains several useful bioactive ingredients including flavonoids, dietary fiber, carotenoids, vitamins, pectin, minerals, and essential oils, which are responsible for its therapeutic potential. In the present investigation, we have studied the toxicity of heavy metals such as lead (Pb) and a carbamate pesticide such as cartap (Cp) on rat brain acetylcholinesterase (AChE). Methods The chemical characterization of C. limon involved determination of total antioxidants and 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical scavenging activity using known methods. The AChE activity and its kinetic characterization were performed by assaying the enzyme activity at varying substrate concentrations, pH, temperature, and time of reaction. Its different kinetic parameters such as K i , V max, K m , K cat, and K cat/K m were determined by using standard procedures. The amelioration potential of the extract was evaluated on the neurotransmission system of rat brain AChE treated with Pb, Cp, and their combination (Pb–Cp), considering their 50% inhibitory concentration (IC50) values. Results The optimal activity of rat brain AChE was recorded at 25 µg of protein, pH of 7.4, substrate concentration [S] of 0.5 mM, and temperature of 37.4–40°C. The enzyme was stable for 10 min when incubated at 37.4 °C in vitro. The enzyme displayed 70% of its activity remaining even after 160 min of incubation in this condition. It may be stable up to 1 month when stored at −20°C. The IC50 values for Pb, Cp, and Pb–Cp were found to be 75, 2.9, and 5 mM, respectively. Pb, Cp, and Pb–Cp inhibited the activity of rat brain AChE in the noncompetitive, mixed, and uncompetitive manners, respectively, with their respective K i values to be 675, 2.37, and 22.72 mM. Conclusions The results indicated that the Pb and Cp were able to cause significant alterations in the level and properties of AChE. However, the introduction of lemon juice on Pb- and Cp-treated AChE indicated protection of its activity from their adverse effects. The results may be useful in prospective therapeutic applications of lemon juice or as a food supplement to protect mammalian systems from adverse effects of these toxicants.

Summary Rice is a staple food for half of the world's population. Changing climatic conditions, water and labour scarcity are the major challenges that shall limit future rice production. Dry direct‐seeded rice (DDSR) is emerging as an efficient, resources conserving, mechanized, climate smart and economically viable strategy to be adopted as an alternative to puddled transplanted rice (TPR) with the potential to address the problem of labour‐water shortages and ensure sustainable rice cultivation. Despite these benefits, several constraints obstruct the adoption of DDSR. In principle, the plant type for DDSR should be different from one for TPR, which could be achieved by developing rice varieties that combine the traits of upland and lowland varieties. In this context, recent advances in precise phenotyping and NGS‐based trait mapping led to identification of promising donors and QTLs/genes for DDSR favourable traits to be employed in genomic breeding. This review discusses the important traits influencing DDSR, research studies to clarify the need for breeding DDSR‐specific varieties to achieve enhanced grain yield, climate resilience and nutrition demand. We anticipate that in the coming years, genomic breeding for developing DDSR‐specific varieties would be a regular practice and might be further strengthened by combining superior haplotypes regulating important DDSR traits by haplotype‐based breeding.

Novel diagnostic technologies, including nanotechnology, microfluidics, -omics science, next-generation sequencing, genomics big data, and machine learning, could contribute to meeting the UNAIDS 95-95-95 targets to end the HIV epidemic by 2030. Novel technologies include multiplexed technologies (including biomarker-based point-of-care tests and molecular platform technologies), biomarker-based combination antibody and antigen technologies, dried-blood-spot testing, and self-testing. Although biomarker-based rapid tests, in particular antibody-based tests, have dominated HIV diagnostics since the development of the first HIV test in the mid-1980s, targets such as nucleic acids and genes are now used in nanomedicine, biosensors, microfluidics, and -omics to enable early diagnosis of HIV. These novel technologies show promise as they are associated with ease of use, high diagnostic accuracy, rapid detection, and the ability to detect HIV-specific markers. Additional clinical and implementation research is needed to generate evidence for use of novel technologies and a public health approach will be required to address clinical and operational challenges to optimise their global deployment.

Plant diseases caused by pathogens and pests are a constant threat to global food security. Direct crop losses and the measures used to control disease (e.g. application of pesticides) have significant agricultural, economic, and societal impacts. Therefore, it is essential that we understand the molecular mechanisms of the plant immune system, a system that allows plants to resist attack from a wide variety of organisms ranging from viruses to insects. Here, we provide a roadmap to plant immunity, with a focus on cell-surface and intracellular immune receptors. We describe how these receptors perceive signatures of pathogens and pests and initiate immune pathways. We merge existing concepts with new insights gained from recent breakthroughs on the structure and function of plant immune receptors, which have generated a shift in our understanding of cell-surface and intracellular immunity and the interplay between the two. Finally, we use our current understanding of plant immunity as context to discuss the potential of engineering the plant immune system with the aim of bolstering plant defenses against disease.

Pumpkin (Cucurbita moschata) is an important tropical vegetable found all around the world. In the present study, herbal enriched pumpkin wines were prepared using 1% pectinase, 0.50% acidulant and honey as sugar source along with the different concentration of dried herbs such as ginger (Zingiber officinale), basil leaves (Ocimum sanctum), licorice (Glycyrrhiza glabra) and their combinations. The herbal enriched pumpkin musts were fermented at a temperature of 28 °C. Further, on the basis of physicochemical and sensory characteristics, the treatment with Ocimum sanctum (basil leaves) 1% (T1) was adjudged as best. The wine had many desirable quality attributes such as a higher concentration of esters, phenols and low level of volatile acidity. The sensory scores also revealed that the herbal wine with basil leaves had high acceptability, with a moderate level of DPPH radical’s scavenging activity value. The wine prepared using Zingiber officinale and G. glabra (GM4) had the highest DPPH radical’s scavenging activity value (84%) and hence will scavenge more free radicals and is beneficial for health. It can be concluded that pumpkin as a base wine holds promise for the preparation of quality herbal enriched pumpkin table wine.

This study aimed to examine the effect of repeated anodal cerebellar transcranial direct current stimulation (ctDCS) on learning a split-belt treadmill task. Thirty healthy individuals randomly received three consecutive sessions of active or sham anodal ctDCS during split-belt treadmill training. Motor performance and strides to steady-state performance were evaluated before (baseline), during (adaptation), and after (de-adaptation) the intervention. The outcomes were measured one week later to assess absolute learning and during the intervention to evaluate cumulative, consecutive, and session-specific effects. Data were analysed using linear mixed-effects regression models. During adaptation, there was no significant difference in absolute learning between the groups (p > 0.05). During de-adaptation, a significant difference in absolute learning between the groups (p = 0.03) indicated slower de-adaptation with anodal ctDCS. Pre-planned secondary analysis revealed that anodal ctDCS significantly reduced the cumulative (p = 0.01) and consecutive-session effect (p = 0.01) on immediate adaptation. There were significant cumulative (p = 0.02) and session-specific effects (p = 0.003) on immediate de-adaptation. Repeated anodal ctDCS does not enhance motor learning measured during adaptation to a split-belt treadmill task. However, it influences the maintenance of learnt walking patterns, suggesting that it may be beneficial in maintaining therapeutic effects.

Development of drug delivery systems has emerged out as significant field in medicinal chemistry because of their localized action, low frequency of drug administration and sustained release of drug at the site of action for a prolonged time. Out of various reported methods, in the present work, we report use of five different polysaccharides for the development of sustained release systems for curcumin, utilizing a surfactant, cetyltrimethylammonium bromide (CTAB). Four of these were novel systems and were first optimized. Sustained release of optimized supports was studied by anti-oxidant, serum protein binding and anti-cathepsin activities. Particle size, FT-IR and SEM were used to characterize the modified supports. CTAB-modified-NCCS, -pectin-15 and Alg-5 were found to be the best supports as they released appreciable amount of curcumin for a longer time. The results have also been interpreted using chemical modeling studies.

Introduction. Psoriasis is a chronic inflammatory skin disease with hyperproliferation, abnormal differentiation and inflammatory infiltration in epidermis and dermis. Sometimes it is clinically and histopathologically challenging to distinguish psoriasis from other non-psoriatic psoriasiform dermatoses (NPPD) like eczema, pityriasis rosea, pityriasis rubra pilaris, and lichen simplex chronicus. Ki-67 is a non-histone nuclear protein complex that regulates the cell cycle and is the most widely used proliferation immunohistochemistry (IHC) marker. Its levels have been shown to be raised in psoriasis compared to normal skin. Aim. To elucidate and compare expression of IHC Ki-67 in psoriasis and NPPD, correlate these levels with clinical variants and disease severity in psoriasis and to observe change in levels with demographic and psoriasis-related variables. Material and Methods. Thirty patients, each with clinically diagnosed psoriasis (cases), and NPPD (controls) were enrolled. Biopsy was taken for histopathology and IHC Ki-67 immunohistochemistry. Statistical analysis was performed. Results. We found a significantly higher expression of IHC Ki-67 in psoriasis as compared to all types of NPPD. The higher level of Ki-67 in pustular and erythrodermic psoriasis compared to plaque-type emphasizes the greater severity and activity of these forms. The Ki-67 expression was found to increase with increasing body surface area involvement and disease severity (PASI) in chronic plaque type. Pityriasis rubra pilaris had the highest Ki67 expression among NPPD group. Conclusion. Ki-67 is a promising tool with diagnostic and prognostic utility in psoriasis, particularly when it comes to its differentiation from nonpsoriasis psoriasiform disorders.

The present study was conducted with an intent to document the reduced morbidity in terms of postoperative hypocalcemia, injury to recurrent laryngeal and external branch of superior laryngeal nerve, in patients undergoing microscope assisted thyroidectomy. The present study enrolled a total of 878 patrients who underwent hemi, total and completion thyroidectomies, over a period of 3 years at Jain ENT Hospital, Jaipur. In the present study, out of 1118 RL nerves dissected temporary paresis was found in 1.52% and permanent palsy in only 0.36%. Temporary hypocalcemia was seen in 8.12% while permanent hypocalcemia in 0.6% patients. EBSLN could be identified in 1082 of the 1118 nerves dissected. We recommend the use microscope routinely for all thyroid surgeries, starting from the very first step in view of the reduced morbidity that it offers.

The use of model organisms for recombinant protein production results in the addition of model-specific post-translational modifications (PTMs) that can affect the structure, charge, and function of the protein. The 70-kDa heat shock proteins (Hsp70) were originally described as intracellular chaperones, with ATPase and foldase activity. More recently, new extracellular activities of Hsp70 proteins (e.g., as immunomodulators) have been identified. While some studies indicate an inflammatory potential for extracellular Hsp70 proteins, others suggest an immunosuppressive activity. We hypothesized that the production of recombinant Hsp70 in different expression systems would result in the addition of different PTMs, perhaps explaining at least some of these opposing immunological outcomes. We produced and purified Mycobacterium tuberculosis DnaK from two different systems, Escherichia coli and Pichia pastoris, and analyzed by mass spectrometry of the protein preparations, investigating the impact of PTMs in an in silico and in vitro perspective. The comparisons of DnaK structures in silico highlighted that electrostatic and topographical differences exist that are dependent upon the expression system. Production of DnaK in the eukaryotic system dramatically affected its ATPase activity and significantly altered its ability to downregulate MHC II and CD86 expression on murine dendritic cells (DCs). Phosphatase treatment of DnaK indicated that some of these differences related specifically to phosphorylation. Altogether, our data indicate that PTMs are an important characteristic of the expression system, with differences that impact interactions of Hsps with their ligands and subsequent functional activities. DATABASE: Mass spectrometry proteomic data are available in the PRIDE database under the accession number PXD011583.

The purpose of current investigation was to explore the role of brassinosteroids (BRs) in Zea mays L. var. DKC 9106 seedlings subjected to salt stress. The seedlings were raised under controlled laboratory conditions and subjected to different concentrations of NaCl (0, 40, 60, 80, 100 mM) for 10 days. The impact of pre-sowing treatment of both 28-homobrassionolide (HBL) and 24-epibrassinolide (EBL) on defense system of Z. mays L. under salt stress was studied by analyzing Na+ and K+ ions, malondialdehyde content (MDA), antioxidative enzymes activities (peroxidase, POD; catalase, CAT; dehydroascorbate reductase, DHAR; monodehydroascorbate reductase, MDHAR), osmoprotectants (proline, glycine betaine, mannitol, and total osmolytes content), total phenolic content, total flavonoid content, and 1,1-diphenylpicrylhydrazyl (DPPH) free radical scavenging activity. The results of our finding showed that treatment of both HBL and EBL under high salt stress balanced the ionic status by decreasing the Na+ ions content by 21.23% and 38.94%, respectively, and enhancing the K+ ions content by 51.94% and 26.66%, respectively. Treatment of both BRs also overcome the oxidative damage induced due to salinity stress by reducing the MDA accumulation 19.50% and 45.0%, respectively, and enhancing the activities of antioxidative enzymes. The osmoprotectants: proline (50.08% and 17.03%), glycine betaine (35.57% and 28.16%), and mannitol content (2.80% and 20.98%) were markedly increased by the treatment of both HBL and EBL, respectively. Further, treatment of both HBL and EBL also increased the total phenolic content by 11.68% and 5.80%, total flavonoid content by 31.56 and 31.09% and DPPH free radical scavenging activity by 37.99% and 77.41%, respectively. Overall the treatment of BRs before seed sowing considerably conquer the salinity-induced damage by stimulating functional components of antioxidative defense system and ultimately reduced oxidative damage.

Background:Citrus limon(lemon) belongs to the Rutaceae family and has great therapeutic applications. The chemical ingredients ofC. limonhave been used in the formulation of several ethnic herbal medicines. The application of antibiotics has shown the development of drug resistance in antibacterial drugs. Due to the drug-resistant nature of microorganisms, there is an urgent need to develop a novel drug active against wildtype and MDR resistant strains of pathogens.Aim:The present study is an endeavor to characterize the juice ofC. limontowards its total antioxidants potential activity (FRAP), DPPH and antibacterial efficacy.Methods and Materials:The antimicrobial activity was evaluated using different bacterial species such asSalmonella typhi, Neisseria gonorrhoeae, Citrobacter species, Shigella flexneriandStaphylococcus epidermidis.Results:The results of the present study indicated the antibacterial potential ofC. limonfruit juice. Among the tested bacterial species,Shigella flexneridisplayed maximum inhibition followed by the other microbes such asStaphylococcus epidermidis, Citrobacter speciesandSalmonella typhi.Conclusion:These findings may be utilized in the development of cost effective, safe and efficient novel drugs active against several pathogenic multi drug-resistant microorganisms.

Summary Background Marked variation exists in the use of genomic data in tumour diagnosis, and optimal integration with conventional diagnostic technology remains uncertain despite several studies reporting improved diagnostic accuracy, selection for targeted treatments, and stratification for trials. Our aim was to assess the added value of molecular profiling in routine clinical practice and the impact on conventional and experimental treatments. Methods This population-based study assessed the diagnostic and clinical use of DNA methylation-based profiling in childhood CNS tumours using two large national cohorts in the UK. In the diagnostic cohort—which included routinely diagnosed CNS tumours between Sept 1, 2016, and Sept 1, 2018—we assessed how the methylation profile altered or refined diagnosis in routine clinical practice and estimated how this would affect standard patient management. For the archival cohort of diagnostically difficult cases, we established how many cases could be solved using modern standard pathology, how many could only be solved using the methylation profile, and how many remained unsolvable. Findings Of 484 patients younger than 20 years with CNS tumours, 306 had DNA methylation arrays requested by the neuropathologist and were included in the diagnostic cohort. Molecular profiling added a unique contribution to clinical diagnosis in 107 (35%; 95% CI 30–40) of 306 cases in routine diagnostic practice—providing additional molecular subtyping data in 99 cases, amended the final diagnosis in five cases, and making potentially significant predictions in three cases. We estimated that it could change conventional management in 11 (4%; 95% CI 2–6) of 306 patients. Among 195 historically difficult-to-diagnose tumours in the archival cohort, 99 (51%) could be diagnosed using standard methods, with the addition of methylation profiling solving a further 34 (17%) cases. The remaining 62 (32%) cases were unresolved despite specialist pathology and methylation profiling. Interpretation Together, these data provide estimates of the impact that could be expected from routine implementation of genomic profiling into clinical practice, and indicate limitations where additional techniques will be required. We conclude that DNA methylation arrays are a useful diagnostic adjunct for childhood CNS tumours. Funding The Brain Tumour Charity, Children with Cancer UK, Great Ormond Street Hospital Children's Charity, Olivia Hodson Cancer Fund, Cancer Research UK, and the National Institute of Health Research.

Diabetes and other lifestyle disorders have been recognized as the leading cause of morbidity and mortality globally. Nuclear factor kappa B (NF-κB) is a major factor involved in the early pathobiology of diabetes and studies reveal that hyperglycemic conditions in body leads to NF-κB mediated activation of several cytokines, chemokines and inflammatory molecules. NF-κB family comprises of certain DNA-binding protein factors that elicit the transcription of pro-inflammatory molecules. Various studies have identified NF-κB as a promising target for diabetic management. Probiotics have been proposed as bio-therapeutic agents for treatment of inflammatory disorders and many other chronic clinical stages. The precise mechanisms by which probiotics acts is yet to be fully understood, however research findings have indicated their role in NF-κB modulation. The current review highlights NF-κB as a bio-therapeutic target for probable management of type 2 diabetes through probiotic intervention.

Pneumococcal capsular polysaccharide (PCP) is the major virulence determinant of Streptococcus pneumoniae (pneumococcus). Strains devoid of the capsule are avirulent or highly attenuated. PCP is present in soluble form and on pneumococci in infected individuals. The present study was undertaken to study the interaction of PCP from serotype 1 (PCP1) with immune cells, and its proinflammatory, immunomodulatory and antigenic properties. Binding of PCP1 to the surface of immune cells led to proinflammatory cytokine production which was not cell line or cytokine restricted. HEK293T transfectants expressing TLR1 and TLR2 produced IL-8 upon stimulation with PCP1, untransfected cells did not do so. PCP1 failed to induce TNF-α production from RAW264.7 cells when pre-incubated with a TLR2 blocking antibody. The surface binding of PCP1 was abrogated in the presence of TLR2 blocking antibody. PCP1 failed to bind TLR2 deficient RAW264.7 cells and induce TNF-α production. Unlike PCP1, alkali-treated PCP1 failed to stimulate RAW264.7 cells to produce TNF-α indicating the importance of alkali-sensitive moieties like O-acetyl groups. Alkali-treated PCP1 elicited lower anti-PCP1 antibody response. Mice experiments suggested that alkali-sensitive groups are significant target of protective antibodies in PCP1 immunized mice. Our findings demonstrate that PCP1 is an important modulator of immune response against pneumococci.

Background: Improvement in short-term outcomes after kidney transplant has been achieved by using different induction and maintenance therapeutic approaches. Long-term outcomes have not matched the expectations of the transplant stakeholders. Our study aimed to address the early impact of induction agents on long-term outcome of kidney transplant when measured by iothalamate clearance. Methods: All adult kidney transplant recipients between January of 2012 and December of 2016 were reviewed. Six hundred forty-nine patients were divided into three groups based on the induction agent (basiliximab, alemtuzumab, and thymoglobulin). Protocoled 4 months and 48 months kidney allograft function evaluations with iothalamate clearance test were compared among the three groups. Results: Patients who received basiliximab were significantly older with no difference among African American and Caucasians. The 48 months assessment showed significant decline in median iothalamate clearance in basiliximab group at 49 mL/min vs. alemtuzumab group 64.8 mL/min and thymoglobulin 60 mL/min with P = 0.007. The basiliximab group developed a significant higher proteinuria measured by spot urine to creatinine ratio at 48 months. Conclusions: The use of basiliximab as an induction agent for kidney transplant is associated with significant decline in kidney function 4 years post transplantation when measured by iothalamate clearance. J Clin Med Res. 2020;12(12):787-793 doi: https://doi.org/10.14740/jocmr4369

Background Familial hypercholesterolemia (FH), an autosomal codominant disorder characterized by very high low-density lipoprotein cholesterol, is strongly associated with premature coronary artery disease. Objectives Molecular landscape of FH in Asian Indians is not well studied, although this ethnic group comprises a large proportion of the world population. Knowledge of mutations in these groups is useful for identifying persons affected with FH, saving their lives, and cascade screening in their relatives. Methods Potential cases of FH (n = 100) were identified by criteria adapted for the Indian population from Dutch Lipid Clinic Network criteria. Pathogenic variants were analyzed in LDLR, APOB 100 (exons 26 and 29), PCSK9, and APOE genes using Sanger sequencing and multiplex ligation-dependent probe amplification technique. Cases in whom there were no pathogenic variants were tested by next-generation sequencing using a targeted panel of genes. Results Thirty-eight pathogenic variants were identified in 47 of 100 unrelated probands. Of these variants, 33 were identified in LDLR, 3 in APOB, and 2 in PCSK9 genes. Ten pathogenic variants were novel. Mutations were detected in 91.4% of those subjects classified as definite, 40% as probable, and in 18.8% as possible FH cases based on modified Dutch Lipid Clinic Network criteria. A likely founder mutation in intron 10 (c.1587-1G>A) of LDLR gene was observed in 6 North Indian families. The conventional pathogenic variants in APOB and PCSK9 genes and those previously reported in LDLR gene among Asian Indians were not detected in this cohort. Conclusion This study demonstrates genetic heterogeneity of FH in India. The variants observed were different from those described in Western populations. Next-generation sequencing technology helped identify new mutations in APOB gene, suggesting that in less-studied populations, it is better to sequence the whole gene rather than test for specific mutations.

Tomato, a widely consumed vegetable crop, offers a real potential to combat human nutritional deficiencies. Tomatoes are rich in micronutrients and other bioactive compounds (including vitamins, carotenoids, and minerals) that are known to be essential or beneficial for human health. This review highlights the current state of the art in the molecular understanding of the nutritional aspects, conventional and molecular breeding efforts, and biofortification studies undertaken to improve the nutritional content and quality of tomato. Transcriptomics and metabolomics studies, which offer a deeper understanding of the molecular regulation of the tomato's nutrients, are discussed. The potential uses of the wastes from the tomato processing industry (i.e., the peels and seed extracts) that are particularly rich in oils and proteins are also discussed. Recent advancements with CRISPR/Cas mediated gene-editing technology provide enormous opportunities to enhance the nutritional content of agricultural produces, including tomatoes. In this regard, genome editing efforts with respect to biofortification in the tomato plant are also discussed. The recent technological advancements and knowledge gaps described herein aim to help explore the unexplored nutritional potential of the tomato.

Aegilops tauschii, the diploid wild progenitor of the D subgenome of bread wheat, is a reservoir of genetic diversity for improving bread wheat performance and environmental resilience. Here we sequenced 242 Ae. tauschii accessions and compared them to the wheat D subgenome to characterize genomic diversity. We found that a rare lineage of Ae. tauschii geographically restricted to present-day Georgia contributed to the wheat D subgenome in the independent hybridizations that gave rise to modern bread wheat. Through k-mer-based association mapping, we identified discrete genomic regions with candidate genes for disease and pest resistance and demonstrated their functional transfer into wheat by transgenesis and wide crossing, including the generation of a library of hexaploids incorporating diverse Ae. tauschii genomes. Exploiting the genomic diversity of the Ae. tauschii ancestral diploid genome permits rapid trait discovery and functional genetic validation in a hexaploid background amenable to breeding.

Background and Aims: Disease progression in children with primary sclerosing cholangitis (PSC) is variable. Prognostic and risk-stratification tools exist for adult-onset PSC, but not for children. We aimed to create a tool that accounts for the biochemical and phenotypic features and early disease stage of pediatric PSC. Approach and Results: We used retrospective data from the Pediatric PSC Consortium. The training cohort contained 1,012 patients from 40 centers. We generated a multivariate risk index (Sclerosing Cholangitis Outcomes in Pediatrics [SCOPE] index) that contained total bilirubin, albumin, platelet count, gamma glutamyltransferase, and cholangiography to predict a primary outcome of liver transplantation or death (TD) and a broader secondary outcome that included portal hypertensive, biliary, and cancer complications termed hepatobiliary complications (HBCs). The model stratified patients as low, medium, or high risk based on progression to TD at rates of