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This study was undertaken to evaluate the complication rates and visual outcomes of outreach cataract surgeries done in makeshift operating rooms.In this retrospective study, surgical outcomes of consecutive Manual Small Incision Cataract Surgeries (MSICS) done in 11 rural camps in Nepal were compared with the results of consecutive hospital surgeries (MSICS and phacoemulsification) done by the same surgeon. Surgeries were done from September 2018 to March 2020.Out of 1034 study population in each group, a significantly higher number (Makeshift operating rooms can be used for cataract surgeries in rural areas where no standard operating rooms are available. If appropriate patient selection criteria and standard surgical protocols are followed, good surgical outcomes can be achieved in camps by an experienced surgical team.

Alzheimer’s disease is a result of unexpected mix of epigenetic, hereditary, and certain ecological elements. It is one of the most complex neurodegenerative problems in human being. The restorative methodologies to overcome the symptoms still a long way from satisfactory. There is subsequently an utmost need to investigate elective speculations during beginning of this neurodegenerative problem. The current review designed to work out endogenous and exogenous sources of formaldehyde and its correlation to Alzheimer’s disease. The current manuscript work encompassed utilization of various open web databases including Sci-Hub as search tools for unique and audit reviews from proficient social orders. In cerebrum tissues, rise of formaldehyde may lead to significant progress in Alzheimer’s disease development, including diverse systems. An increase in degree of intracranial formaldehyde was found in single infusion of methanol and demonstrates oxidation of formaldehyde to methanol in brains of non-human primates. It reveals connections of methanol’s harmfulness in terms of its produce as formaldehyde and noticed as profound corrosives in brain. The causal connections and interconnected pathways including formaldehyde to epigenetics, microRNA and hereditary molecules along β-amyloid, tau protein, changes in histone, assembly of chromatin, misfortune, and methylation of histone. Consistent investigation during current review leads advancement and progress of Alzheimer’s disease correlates to epigenetics and cerebral formaldehyde may furnish a new understanding in management of Alzheimer’s disease and possible restorative targets. Taking this into account, zeroing inhibitors could be one of the most encouraging methodologies for planning and creating drugs against AD.

OBJECTIVE Immune checkpoint inhibitors such as anti–programmed cell death protein 1 (anti-PD-1) have shown promise for the treatment of cancers such as melanoma, but results for glioblastoma (GBM) have been disappointing thus far. It has been suggested that GBM has multiple mechanisms of immunosuppression, indicating a need for combinatorial treatment strategies. It is well understood that GBM increases glutamate in the tumor microenvironment (TME); however, the significance of this is not well understood. The authors posit that glutamate upregulation in the GBM TME is immunosuppressive. The authors utilized a novel glutamate modulator, BHV-4157, to determine synergy between glutamate modulation and the well-established anti-PD-1 immunotherapy for GBM. METHODS C57BL/6J mice were intracranially implanted with luciferase-tagged GL261 glioma cells. Mice were randomly assigned to the control, anti-PD-1, BHV-4157, or combination anti-PD-1 plus BHV-4157 treatment arms, and median overall survival was assessed. In vivo microdialysis was performed at the tumor site with administration of BHV-4157. Intratumoral immune cell populations were characterized with immunofluorescence and flow cytometry. RESULTS The BHV-4157 treatment arm demonstrated improved survival compared with the control arm (p < 0.0001). Microdialysis demonstrated that glutamate concentration in TME significantly decreased after BHV-4157 administration. Immunofluorescence and flow cytometry demonstrated increased CD4+ T cells and decreased Foxp3+ T cells in mice that received BHV-4157 treatment. No survival benefit was observed when CD4+ or CD8+ T cells were depleted in mice prior to BHV-4157 administration (p < 0.05). CONCLUSIONS In this study, the authors showed synergy between anti-PD-1 immunotherapy and glutamate modulation. The authors provide a possible mechanism for this synergistic benefit by showing that BHV-4157 relies on CD4+ and CD8+ T cells. This study sheds light on the role of excess glutamate in GBM and provides a basis for further exploring combinatorial approaches for the treatment of this disease.

Introduction Enrolling patients with metastatic urothelial carcinoma (mUC) in phase I trials provides an opportunity to identify biological drug activity. Developing prognostic scores may aid in patient selection for phase 1 trials. Patients and Methods :We analyzed records of patients with mUC who participated in targeted therapy and immunotherapy phase I clinical trials at MD Anderson Cancer Center (MDACC). The Bellmunt and Bajorin scores were calculated as bladder cancer-specific prognostic scores. The Royal Marsden Hospital (RMH) and MDACC scores were calculated as phase I prognostic scores. Hazard ratios (HR) were calculated using the Cox proportional hazard model. The prognostic value of the Bellmunt, Bajorin, RMH, and MDACC scores were assessed using the Likelihood ratio (LR) χ2 test and the c-index. Results Between 2015 and 2019, 43 patients were enrolled in phase I trials and 12 were enrolled in >I trial leading to a total of 57 trial participants (TPs). Ninty-seven percent of TPs received prior platinum therapy and 60% received a prior checkpoint inhibitor. Median overall survival (OS) and progression-free survival (PFS) were significantly shorter with increasing Bajorin, RMH, or MDACC scores, but not with increasing Bellmunt score. The RMH (c-index=0.658, LR χ2=11.8, P=.008) and MDACC scores (c-index =0.66, LR χ2=12.76, P=.01) outperformed the Bajorin score (c-index=0.522, LR χ2=1.22, P=.5) and the Bellmunt score (c-index=0.537, LR χ2=0.36, P=.9) in predicting overall survivalover. The Bajorin, RMH, and MDACC scores, but not the Bellmunt score, were also predictive of progression-free survival (PFS)prog. The RMH and MDACC scores again outperformed the Bajorin scoreand the Bellmunt score for predicting PFS. Conclusion The RMH and MDACC phase I prognostic scores accurately predicted survival in patients with mUC and outperformed the bladder cancer-specific scores at time of enrollment on phase 1 clinical trials. The RMH and MDACC scores could optimize selection of patients with mUC for phase I clinical trials.

Highlights • Iron folic acid consumption can reduce anemia, but compliance remains low. • Interventions can promote interpersonal communication for behavior change. • Topic-specific and general interpersonal communication modalities appear effective. • Interpersonal communication mediated the intervention effect on iron supplement use., Objective More than half of Indian women of reproductive age are anemic. Regular iron folic acid uptake can prevent and treat anemia. This study investigated the effect of interpersonal communication on improving IFA use among women of reproductive age. Methods The Reduction in Anemia through Normative Innovations (RANI) Project is a cluster randomized trial that collected longitudinal data from control (n = 1896) and intervention (n = 1898) communities in Odisha, India at Time 1 and six months later at Time 2. Structural equation models assessed the effect of the intervention on iron folic acid use via multiple interpersonal communication pathways. Results Compared to the control arm, iron folic acid use significantly increased in the intervention arm. Both, general health interpersonal communication and anemia-specific interpersonal communication were augmented in the intervention communities. The impact of the intervention on iron folic acid use was mediated through anemia-specific interpersonal communication. Conclusion The RANI Project increased interpersonal communication among participants, resulting in increased iron folic acid use for anemia reduction. Practice implications Strategic use of targeted interpersonal communication to promote behavior change appears to be a viable strategy to increase iron folic acid use to reduce anemia.

OBJECTIVE Atypical teratoid rhabdoid tumors (ATRTs) are aggressive pediatric brain tumors with no current standard of care and an estimated median patient survival of 12 to 18 months. Previous genetic analyses have implicated cyclin D1 and enhancer of zeste homolog 2 (EZH2), a histone methyltransferase that is implicated in many cancers, as key drivers of tumorigenicity in ATRTs. Since the effects of EZH2 and cyclin D1 are facilitated by a host of cyclin-dependent kinases (CDKs), the authors sought to investigate the potential therapeutic effects of targeting CDKs in ATRTs with the multi–CDK inhibitor, TG02. METHODS Human ATRT cell lines BT12, BT37, CHLA05, and CHLA06 were selected for investigation. The effects of TG02 on cell viability, proliferation, clonogenicity, and apoptosis were assessed via Cell Counting Kit-8 assays, cell counting, clonogenic assays, and flow cytometry, respectively. Similar methods were used to determine the effects of TG02 combined with radiation therapy (RT) or cisplatin. Synergism indices for TG02-cisplatin combination therapy were calculated using CompuSyn software. RESULTS TG02 was observed to significantly impair ATRT cell growth in vitro by limiting cell proliferation and clonogenicity, and by inducing apoptosis. TG02 inhibited ATRT cell proliferation and decreased cell viability in a dose-dependent manner with nanomolar half maximal effective concentration (EC50) values (BT12, 207.0 nM; BT37, 127.8 nM; CHLA05, 29.7 nM; CHLA06, 18.7 nM). TG02 (150 nM) dramatically increased the proportion of apoptotic ATRT cells 72 hours posttreatment (TG02 8.50% vs control 1.52% apoptotic cells in BT12, p < 0.0001; TG02 70.07% vs control 15.36%, p < 0.0001). Combination therapy studies revealed that TG02 acted as a potent radiosensitizer in ATRT cells (BT12 surviving fraction, RT 51.2% vs RT + TG02 21.7%). Finally, CompuSyn analysis demonstrated that TG02 acted synergistically with cisplatin against ATRT cells at virtually all therapeutic doses. These findings were consistent in cell lines that cover all three molecular subgroups of ATRTs. CONCLUSIONS The results of this investigation have established that TG02 is an effective therapeutic against ATRTs in vitro. Given the lack of standard therapy for ATRTs, these findings help fill an unmet need and support further study of TG02 as a potential therapeutic option for patients with this deadly disease.

BackgroundCommunication skills (CS) are important and teachable, however, many Asian medical schools’ curricula do not incorporate them. Patan Academy of Health Sciences in Nepal identifies CS within its’ aims and curriculum. CS are taught from commencement of medical school and re-emphasised throughout preclinical learning (first 2 years). There is no explicit CS teaching in clinical years but placements allow students to learn through observation. These ‘role-modelling’ interactions form part of CS learning and development.MethodsThis study is a qualitative evaluation of CS learning in PAHS, through participants’ experiences. Through purposive sampling, twenty medical students from 2nd, 4th and Intern years were selected for inclusion. Data were collected via audio recorded, semi-structured interviews, employing a piloted schedule. Transcripts were manually coded and analysed thematically. Codes were organised into themes and subthemes. This paper discusses themes related to role-modelling.ResultsThe majority of participants described role-modelling in CS learning, recounting both positive and negative incidents, reflected in the themes of; Positive and Negative experiences. Subthemes of Personal Qualities and Inspiring, emerged from positive experiences, describing students’ desire to imitate or aspire to be like their role models. Learners reported predominantly negative experiences and interns exclusively so. From these emerged subthemes of; Good doctors but.., Contradictory messages, How not to behave, Unprofessional behaviour and Affect-Emotional Distress. Learners received conflicting messages from observing behaviour contradictory to explicit CS teaching. Many identified learning “how not to behave” from such incidents, however, several described feeling distressed.DiscussionRole-modelling is a powerful and important CS learning tool, seen as positively reinforcing or negatively contradicting explicit CS teaching. Negative modelling created internal conflict, confusion and distress amongst learners, despite its’ potential for positive learning. The worldwide problem of negative role-modelling is also prevalent in Nepal.Medical educators need to ensure the explicit curriculum aligns with implicit learning. Clinical tutors must be alerted to their powerful role-model position and supported in developing intentional modelling skills. Learners’ reflections upon their experiences should be facilitated, enabling them to critically evaluate observations and hence consciously adopt or reject role-modelled behaviour and attitudes.

Context: Whether the alcohol-based mouth rinses are as good as nonalcoholic mouth rinses as far as oral mucosal safety is concerned? Aims: The aim of the study was to investigate the oral mucosal safety of widely used alcohol- and nonalcohol-based mouth rinses at their recommended doses. Settings and Design: The clinical and cytological investigations were carried out by enrolling 120 systemically healthy volunteers fulfilling the inclusion criteria. The volunteers were subjected to a repeated mouth rinse for 60 days to either alcohol-based or alcohol-free mouth rinses at their recommended dosages. A comparative analysis for any clinical adverse response on the oral mucosa and efficacy, i.e., reduction of plaque and gingival index was done at the terminal of the exposure. The studies were also carried out to investigate the cytotoxicity and genotoxicity potential of alcohol-based and alcohol-free mouth rinses in the exposed mucosal cells. Subjects and Methods: The data have been presented in comparative account between alcohol-based and alcohol-free mouth rinses in the volunteers at day 0 and day 60. The cytotoxicity and genotoxicity potential of prescribed doses of alcohol- and alcohol-free mouth rinses have also been evaluated using tetrazolium bromide salt 3-(4, 5-dimethylthiazol-2-yl)-2,-diphenyl tetrazolium bromide, neutral red uptake, and trypan blue dye, micronucleus and chromosomal aberrations. Results: The study findings reveal no statistically as well as biologically significant adverse responses of both alcohol-based and alcohol-free mouth rinses at clinical and cytological level. Conclusions: Under cytological observation, repeated dose exposure up to 60 days of the mouth rinses (alcohol-based and alcohol-free) used in the study was found to be effective and safe at their prescribed dosages.

Objectives: To study the prescription pattern of psychotropic drugs in different psychiatric disorder. Methodology: The prospective observational study was conducted in 100 psychiatric in-patients at a tertiary care hospital in Bangalore. Study was conducted on gaining approval from the institutional human ethical committee. All patients who meet the study criteria were enrolled in to the study after taking the informed consent from the patients or their legal representatives. The demographic, clinical and medications data were documented into a specially designed case report form. All the data was analyzed using descriptive statistics. Results and Discussion: In 100 study subjects 194 different psychotropic drugs were prescribed. Among 194 psychotropic drugs 38.14% were sedatives and hypnotics, 36.08% were antipsychotics, 18.55% were antidepressants and 7.21% were mood stabilizer. Conclusion: This study found that schizophrenia was the most common illness in psychiatric patients. Male patients were more prone to psychiatric disorders than female. Most of the study populations were non-alcoholic and non-smokers. Sedatives and hypnotics of benzodiazepine class were found to be the most commonly used drugs followed by antipsychotics, anti-depressants and mood stabilizers in the studied population. Future studies to evaluate the drug utilization evaluation of psychotropic drugs in large patient populations are much needed to promote patient safety and increase the quality of psychiatric patients.

Parkinson's disease is a chronic and progressive neurodegenerative disease, induced by slow and progressive death of the dopaminergic (DA) neurons from the midbrain region called substantia nigra (SNc) leading to difficulty in locomotion. At present, very few potential therapeutic drugs are available for treatment, necessitating an urgent need for development. In the current study, the parkin transgenic Drosophila melanogaster model that induces selective loss in dopaminergic neurons and impairment of locomotory functions has been used to see the effect of the aza-flavanone molecule. D. melanogaster serves as an amazing in vivo model making valuable contribution in the development of promising treatment strategies. Our in-silico study showed spontaneous binding of this molecule to the D2 receptor making it a potential dopamine agonist. PARKIN protein is well conserved, and it has been reported that Drosophila PARKIN is 42% identical to human PARKIN. Interestingly, this molecule enhances the motor coordination and survivability rate of the transgenic flies along with an increase in expression of the master regulator of Dopamine synthesis, that is, tyrosine hydroxylase (TH), in the substantia nigra region of the fly brain. Moreover, it plays a significant effect on mitochondrial health and biogenesis via modulation of a conserved mitochondrial protein PHB2. Therefore, this molecule could lead to the development of an effective therapeutic approach for the treatment of PD.

Introduction: Non-invasive ventilation (NIV) is a method of ventilator support or delivery of positive pressure into the lungs usually through a face mask, mostly initiated before severe acidosis occurs. NIV failure requiring invasive mechanical ventilation in decompensated chronic obstructive pulmonary disease (COPD) patients is low, but, in critical patients, it is as high as 60%. Acute respiratory failure (ARF) is the common reason for admission to the intensive care unit. This study assesses the outcome of NIV among patients with acute respiratory failure, the duration of use, stay in ICU, and failure rate of NIV. Such type of study result is scarce in our country. Methods: Arterial blood gases were assessed prior, after, and at discontinuation of NIV. NIV was delivered by ventilator via face mask. All patients above age 15 years who presented to the hospital, diagnosed to have ARF by ABG were included and admitted to Medical Intensive Care Unit (MICU). . Appropriate statistical tests (Chi-square) were performed and the statistical significance of the results was assessed. Results: 35 patients with the median age of 73 years (range: 39- 89 years), of 60.0 % females among which 74.3 % were current smokers. Arterial blood pH prior to admission ranged from 7.11-7.39 and 7.06-7.41 among NIV success and failure, respectively. Similarly, PCo2 ranged from 54.0-127.5 and 29.5-105.9 among them, respectively. Two hours after ventilation pH ranged from 7.12-7.43 and 7.05-7.30 respectively in the success and failure group. The most common disease condition requiring NIV was 77.1% COPD. Out of NIV failure group (n=19) ,57.8 % were intubated and 42.1% patients left the intervention. Conclusions: Usage of NIV among ARF patients was associated with lower intubation and ICU mortality rate. COPD patients showed the most benefit with NIV, whereas patients suffering from interstitial lung disease, lung cancer had less benefit.

ST-elevation myocardial infarction (STEMI) is a cardiac emergency. However, multiple clinical disorders can cause ST-elevation ECG changes, one of which is pericarditis. Regional pericarditis is a less known clinical phenomenon that can mimic STEMI. We report a case of poorly differentiated lung carcinoma associated reactive regional pericarditis mimicking inferior STEMI.

Breast cancer is one of the most challenging health problems in women worldwide. Early detection and regular breast cancer screening can considerably improve the survival rate. Many advanced imaging technologies are currently being used in the detection of breast malignancy. However, these methods are costly, uncomfortable, and time-consuming. Therefore, in this work, a simple and noninvasive thermographic technique, based on a Fiber Bragg Grating (FBG) thermal sensor array, has been developed to detect breast cancer. Breast tissue is simulated using agar gel phantom, and the heaters are embedded inside the phantom in different locations to mimic the tumors. FBG thermal sensor array is employed to acquire the surface temperature distribution of the simulated breast phantom. Also, modeling of the tissue-mimicking phantom and tumor in COMSOL Multiphysics software is carried out to provide a detailed 3D thermal view of the proposed prototype. Both experimental and simulated results are found to be in agreement and display the same trend as expected. Experimental results show that a temperature variation of ≥0.3°C is detected at the location of the tumor’s presence, which can be easily picked up by FBG interrogators which have sensitivity of ~1 pm, indicating the efficacy of the proposed sensing prototype as a potential screening tool for the diagnosis of breast cancer.

To assess whether improvements in social norms related to iron and folic acid consumption are associated with increased iron and folic acid consumption.In a cluster randomized trial in Odisha, India, we implemented an intervention to improve descriptive norms (people's perceptions about how many other people take iron and folic acid), injunctive norms (social pressures people feel to take iron and folic acid) and collective norms (actual levels of iron and folic acid consumption). We assessed changes in these norms and self-reported iron and folic acid consumption in control and intervention arms after 6 months (September 2019-February 2020). We collected data from control (At follow-up, mean scores in self-reported iron and folic acid consumption in the control arm had decreased from 0.39 to 0.31 (21% decrease; not significant). In the intervention arm, mean scores increased from 0.39 to 1.62 (315% increase;Our results show that social norms can be improved and that these improvements are associated with positive behavioural changes. A social norms-based approach may help promote iron and folic acid consumption in India.Déterminer si l'évolution des normes sociales en matière de consommation de fer et d'acide folique a permis d'accroître cette consommation.Dans le cadre d'un essai randomisé en grappes dans l'Odisha, en Inde, nous avons mené une intervention visant à améliorer les normes descriptives (perception des gens vis-à-vis du nombre de personnes prenant du fer et de l'acide folique), injonctives (pression sociale ressentie par les gens, les incitant à prendre du fer et de l'acide folique) et collectives (niveaux de consommation réels pour le fer et l'acide folique). Nous avons évalué les changements affectant ces normes, ainsi que la consommation déclarée de fer et d'acide folique dans les groupes d'intervention et de contrôle après 6 mois (septembre 2019 – février 2020). Nous avons récolté des données dans les groupes de contrôle (Lors du suivi, les scores moyens en termes de consommation déclarée de fer et d'acide folique au sein du groupe de contrôle ont diminué de 0,39 à 0,31 (baisse de 21%; non significative). Au sein du groupe d'intervention, les scores moyens sont passés de 0,39 à 1,62 (hausse de 315%;Nos résultats montrent que les normes sociales peuvent évoluer, et qu'une telle évolution est liée à des modifications comportementales positives. L'adoption d'une approche fondée sur ces normes pourrait contribuer à promouvoir la consommation de fer et d'acide folique en Inde.Evaluar si las mejoras en las normas sociales relacionadas con el consumo de hierro y ácido fólico se asocian a un mayor consumo de hierro y ácido fólico.En un ensayo aleatorizado por grupos en Odisha, India, se implementó una intervención para mejorar las normas descriptivas (las percepciones de las personas sobre cuántas otras personas consumen hierro y ácido fólico), las normas por mandato (las presiones sociales que las personas sienten para que tomen hierro y ácido fólico) y las normas colectivas (los niveles reales de consumo de hierro y ácido fólico). Se evaluaron los cambios en estas normas y el consumo de hierro y ácido fólico informado por los participantes en los grupos de control y de intervención después de 6 meses (septiembre de 2019 a febrero de 2020). Se recopilaron datos de los grupos de control (En el seguimiento, las puntuaciones medias en el consumo de hierro y ácido fólico informado por los participantes en el grupo de control disminuyeron de 0,39 a 0,31 (disminución del 21 %; no significativa). En el grupo de intervención, las puntuaciones medias aumentaron de 0,39 a 1,62 (315 % de aumento;Los resultados de este ensayo demuestran que las normas sociales se pueden mejorar y que estas mejoras se asocian a cambios positivos del comportamiento. Un enfoque basado en las normas sociales puede ayudar a promover el consumo de hierro y de ácido fólico en la India.تقييم ما إذا كانت التحسينات في الثوابت الاجتماعية المتعلقة باستهلاك الحديد وحمض الفوليك مرتبطة بزيادة استهلاك الحديد وحمض الفوليك. اأثناء المتابعة، انخفض متوسط الدرجات في استهلاك الحديد وحمض الفوليك الذي أبلغ عنه الأشخاص ذاتيًا في ذراع التحكم من 0.39 إلى 0.31 (انخفاض بنسبة 21%؛ ليس ملموسًا). في ذراع التدخل، زاد متوسط الدرجات من 0.39 إلى 1.62 (زيادة بنسبة 315%؛ نسبة الاحتمال أقل من 0.001). كان الفرق بين الذراعين ذي دلالة إحصائية (نسبة الاحتمال أقل من 0.001). تحسن كل من الثوابت الثلاثة أيضًا بمعدلات أعلى بشكل ملموس في ذراع التدخل عنه في ذراع التحكم (نسبة الاحتمال أقل من 0.001 لكل من الثوابت). ارتبطت التغييرات في الثوابت الوصفية والجماعية (ولكن ليس الثوابت التحذيرية) بالتغيرات في استهلاك الحديد وحمض الفوليك الذي أبلغ عنه الأشخاص ذاتيًا (نسبة الاحتمال أقل من 0.001 لكلا الثابتين).تظهر نتائجنا أنه يمكن تحسين الثوابت الاجتماعية، وأن هذه التحسينات مرتبطة بالتغيرات السلوكية الإيجابية. قد يساعد الأسلوب القائم على الثوابت الاجتماعية في الارتقاء باستهلاك الحديد وحمض الفوليك في الهند.旨在评估与铁和叶酸消耗相关的社会规范的改善是否与铁和叶酸消耗量的增加有关。.在印度奥里萨邦的一项集群随机试验中，我们实施了一项干预措施以改善描述性规范（人们对有多少人服用铁和叶酸的看法）、指令性规范（人们对服用铁和叶酸感受到的社会压力）和群体性规范（铁和叶酸消耗的实际水平）。我们对这些规范的变化进行了评估，并对 6 个月后（2019 年 9 月至 2020 年 2 月）对照组和干预组中铁和叶酸的消耗量进行了自我报告。我们从对照组（n = 2048）和干预组（n = 2060）收集了基线数据和后续数据（分别为 n = 1966 和 n = 1987）。.在后续跟踪中，自我报告显示对照组中铁和叶酸消耗量的平均分值从 0.39 下降到 0.31（下降了 21%；不显著）。干预组中的平均分值从 0.39 增加到 1.63（增加了 315%；我们的结果表明社会规范可以得到改善，并且这些改善与积极的行为改变有关。基于社会规范采取的方法可能有助于促进印度地区铁和叶酸的消耗量。.Оценить, связаны ли улучшения социальных норм, относящихся к потреблению железа и фолиевой кислоты, с увеличением потребления железа и фолиевой кислоты.В кластерном рандомизированном исследовании, проводимом в штате Одиша, Индия, авторы осуществили мероприятие, направленное на улучшение дескриптивных норм (представления людей о том, какое количество человек принимают железо и фолиевую кислоту), предписательных норм (социальное давление, которое люди испытывают, чтобы принимать железо и фолиевую кислоту) и коллективных норм (фактические уровни потребления железа и фолиевой кислоты). Была проведена оценка изменения этих норм и самоотчетности о потреблении железа и фолиевой кислоты в группе контроля и экспериментальной группе после 6 месяцев (сентябрь 2019 г. — февраль 2020 г.). Авторы собрали данные группы контроля (В период последующего наблюдения средний балл по самоотчетности о потреблении железа и фолиевой кислоты в группе контроля снизился с 0,39 до 0,31 (снижение на 21%; несущественное). В экспериментальной группе средний балл увеличился с 0,39 до 1,62 (увеличение на 315%;Наши результаты показывают, что социальные нормы можно улучшить и что эти улучшения связаны с положительными изменениями поведения. Подход, основанный на социальных нормах, может способствовать увеличению потребления железа и фолиевой кислоты в Индии.

According to the World Health Organisation, as of 2019, globally around 50 million people suffer from dementia, with approximately another 10 million getting added to the list every year, wherein Alzheimer’s disease (AD) stands responsible for almost a whopping 60–70% for the existing number of cases. Alzheimer’s disease is one of the progressive, cognitive-declining, age-dependent, neurodegenerative diseases which is distinguished by histopathological symptoms, such as formation of amyloid plaque, senile plaque, neurofibrillary tangles, etc. Majorly four vital transcripts are identified in the AD complications which include Amyloid precursor protein (APP), Apolipoprotein E (ApoE), and two multi-pass transmembrane domain proteins—Presenilin 1 and 2. In addition, the formation of the abnormal filaments such as amyloid beta (Aβ) and tau and their tangling with some necessary factors contributing to the formation of plaques, neuroinflammation, and apoptosis which in turn leads to the emergence of AD. Although multiple molecular mechanisms have been elucidated so far, they are still counted as hypotheses ending with neuronal death on the basal forebrain and hippocampal area which results in AD. This review article is aimed at addressing the overview of the molecular mechanisms surrounding AD and the functional forms of the genes associated with it.

PURPOSE KRAS p.G12C mutations occur in approximately 3% of metastatic colorectal cancers (mCRC). Recently, two allosteric inhibitors of KRAS p.G12C have demonstrated activity in early phase clinical trials. There are no robust studies examining the behavior of this newly targetable population. METHODS We queried the MD Anderson Cancer Center data set for patients with colorectal cancer who harbored KRAS p.G12C mutations between January 2003 and September 2019. Patients were analyzed for clinical characteristics, overall survival (OS), and progression-free survival (PFS) and compared against KRAS nonG12C. Next, we analyzed several internal and external data sets to assess immune signatures, gene expression profiles, hypermethylation, co-occurring mutations, and proteomics. RESULTS Among the 4,632 patients with comprehensive molecular profiling, 134 (2.9%) were found to have KRAS p.G12C mutations. An additional 53 patients with single gene sequencing were included in clinical data but excluded from prevalence analysis allowing for 187 total patients. Sixty-five patients had de novo metastatic disease and received a median of two lines of chemotherapy without surgical intervention. For the first three lines of chemotherapy, the median PFS was 6.4 months (n = 65; 95% CI, 5.0 to 7.4 months), 3.9 months (n = 47; 95% CI, 2.9 to 5.9 months), and 3.0 months (n = 21; 95% CI, 2.0 to 3.4 months), respectively. KRAS p.G12C demonstrated higher rates of basal EGFR activation compared with KRAS nonG12C. When compared with an internal cohort of KRAS nonG12C, KRAS p.G12C patients had worse OS. CONCLUSION PFS is poor for patients with KRAS p.G12C metastatic colorectal cancer. OS was worse in KRAS p.G12C compared with KRAS nonG12C patients. Our data highlight the innate resistance to chemotherapy for KRAS p.G12C patients and serve as a historical comparator for future clinical trials.

The present work is a significant contribution to the production of 5-hydroxymethylfurfural (5-HMF) from carbohydrates-based feedstocks using environmentally benign choline chloride (ChCl)-based deep eutectic solvents (DESs) as catalyst in the presence of an inexpensive acetone/water solvent system. Under microwave irradiations, the acidity of organic acids in DESs can be a key criterion in screening out different eutectic mixtures. Among others, the ChCl: Lactic acid (LA) mixture was found to be the most efficient DES giving a 5-HMF yield of 30.12% on fructose dehydration. Optimization of different reaction parameters resulted in an enhanced 5-HMF yield of 87.2% in 30 min at 140 °C using ChCl: LA DES. The synergistic effect between LA and ChCl is also highlighted in boosting the 5-HMF yield. As compared to conventional oil bath heating, microwave heating resulted in significantly higher 5-HMF yield at a lower reaction time. The catalytic system ChCl: LA showed an appreciable yield of 5-HMF ranging from 83.1 to 71.2% for 5 recycle runs. Overall, we have developed a low cost, easy, energy-effective, green, and sustainable process ensuring high 5-HMF production.

Following photopigment bleaching, the rhodopsin and cone-opsins show a characteristic exponential regeneration in the dark with a photocycle dependent on the retinal pigment epithelium. Melanopsin pigment regeneration in animal models requires different pathways to rods and cones. To quantify melanopsin-mediated light adaptation in humans, we first estimated its photopigment regeneration kinetics through the photo-bleach recovery of the intrinsic melanopsin pupil light response (PLR). An intense broadband light (~120,000 Td) bleached 43% of melanopsin compared to 86% of the cone-opsins. Recovery from a 43% bleach was 3.4X slower for the melanopsin than cone-opsin. Post-bleach melanopsin regeneration followed an exponential growth with a 2.5 min time-constant (τ) that required 11.2 min for complete recovery; the half-bleaching level (Ip) was ~ 4.47 log melanopic Td (16.10 log melanopsin effective photons.cm−2.s−1; 8.25 log photoisomerisations.photoreceptor−1.s−1). The effect on the cone-directed PLR of the level of the melanopsin excitation during continuous light adaptation was then determined. We observed that cone-directed pupil constriction amplitudes increased by ~ 10% when adapting lights had a higher melanopic excitation but the same mean photometric luminance. Our findings suggest that melanopsin light adaptation enhances cone signalling along the non-visual retina-brain axis. Parameters τ and Ip will allow estimation of the level of melanopsin bleaching in any light units; the data have implications for quantifying the relative contributions of putative melanopsin pathways to regulate the post-bleach photopigment regeneration and adaptation.

Mesenchymal stem cells (MSCs) are multipotent, adult stem cells which are found in numerous tissues like the umbilical cord, Wharton's jelly, bone marrow, and adipose tissue. They possess the capacity of self-renewal by dividing and differentiating into various cellular lineages. Their characteristic therapeutic potential exploited so far has made them a desirable candidate in regenerative medicine. Neurodegenerative diseases (NDs) like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and ischemic stroke have been treated with MSCs and MSC-derived products. Over the past few decades, we have witnessed significant contributions in discovering the etiology of various NDs and their possible therapeutic solutions. One of the MSC-based therapeutics is extracellular vesicles (EVs), which contain multiple biologically active molecules like nucleic acids and proteins. The contents of EVs are ferried between cells for intercellular communication which then leads to regulation of the homeostasis of recipient cells. EVs serve as a considerable means of cell-free therapies like for tissue repair or regeneration as EVs can maintain therapeutically effective cargo of parent cells and are free of various ethical issues in cell-based therapies. Due to paucity of standard protocols in extraction procedures of EVs and their pharmacological properties and mechanisms, the development of new EV dependent therapies is challenging. With this review, an attempt has been made to annotate these mechanisms, which can help advance the novel therapeutic approaches towards the treat and define a more narrowed down approach for each ND to devise effective MSC-based therapies to cure and avert these diseases.

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.

Attachment of a nitric oxide (NO) donor to an electrospun polymer has the potential to improve its proliferative and antimicrobial capabilities. This study presents the novel, covalent attachment of S-nitroso-N-acetylpenicillamine (SNAP) to polyacrylonitrile (PAN) fibers. By attaching the NO donor to the polymer, rather than blending it, leaching is reduced to maintain a NO flux within the physiologically relevant range for a longer duration, while limiting any cytotoxic effects. The synthesized fibers were characterized using a variety of techniques such as scanning electron microscopy, 1H NMR, and drop shape analysis. Due to the antimicrobial activity of NO, the SNAP-PAN fibers demonstrated a 2-log reduction of S. aureus adhesion. Furthermore, the extended zone of inhibition of S. aureus by SNAP-PAN demonstrates the ability of NO to impact the environment surrounding the material, in addition to the environment in direct contact with it. The combination of NO release, hydrophilicity of PAN, and the fibrous network led to increased fibroblast proliferation and attachment, potentially expanding the fibers as an improved cell scaffolding platform. The results from this study demonstrate a novel preparation and design of NO-releasing fibers to provide multiple benefits for a variety of biomedical applications.

To design novel antimicrobial peptides by utilizing the sequence of the human host defense protein, chemerin, a seven-residue amphipathic stretch located in the amino acid region, 109-115, was identified, which possesses the highest density of hydrophobic and positively charged residues. Although this 7-mer peptide was inactive toward microorganisms, its 14-mer tandem repeat (Chem-KVL) was highly active against different bacteria including methicillin-resistant Staphylococcus aureus, a multidrug-resistant Staphylococcus aureus strain, and slow- and fast-growing mycobacterial species. The selective enantiomeric substitutions of its two l-lysine residues were attempted to confer cell selectivity and proteolytic stability to Chem-KVL. Chem-8dK with a d-lysine replacement in its middle (eighth position) showed the lowest hemolytic activity against human red blood cells among Chem-KVL analogues and maintained high antimicrobial properties. Chem-8dK showed in vivo efficacy against Pseudomonas aeruginosa infection in BALB/c mice and inhibited the development of resistance in this microorganism up to 30 serial passages and growth of intracellular mycobacteria in THP-1 cells.

BACKGROUND Mucormycosis is a potentially lethal angioinvasive fungal infection. Increasing incidence of rhino-orbital-cerebral mucormycosis in setting of corona virus disease-19 (COVID-19) during second wave in India and elsewhere has become a matter of immediate concern. This study was done to assess the clinical findings and treatment outcomes of rhino-orbital-cerebral-mucormycosis presenting to a tertiary care center in central India. METHODS This is a longitudinal study. We observed 38 COVID-19 associated mucormycosis cases. Their demographic data, clinical manifestations, underlying systemic conditions, microbiological and radiological reports, medical treatments and surgical interventions were recorded and analysed. RESULTS Common ocular presenting features were ophthalmoplegia (68 %), proptosis (44 %), periorbital swelling (13 %), diminution of vision (37 %), central retinal arterial occlusion (2.5 %), optic atrophy (2.5 %). Visual acuity at 1 month after surgery was compared with that at presentation and was found unchanged in 27 patients, improved in 3 patients and deteriorated in 6 patients. Functional outcome was evaluated in terms of ocular movements, and it was found that ocular movements were same as presentation in 30 patients, improved in 3 patients and deteriorated in 3 patients at follow up one month after surgery. Radiological outcome was evaluated, and it was found that residual disease was present in 4 patients and absent in 32 patients. Mortality was found in 2 patients at 1 month follow-up period. CONCLUSIONS Early diagnosis, blood sugar levels control, urgent systemic antifungal therapy and sinus debridement surgery are lifesaving in cases of COVID-19 associated mucormycosis. KEYWORDS Mucormycosis, COVID-19, Diabetes Mellitus, Ophthalmoplegia, Orbital Apex Syndrome, Orbital Cellulitis, Proptosis

Background The purpose of the study was to evaluate survival outcomes in post-operative oral tongue cancer patients undergoing adjuvant radiotherapy (RT) at a tertiary cancer care center and to critically review the impact of various clinical-pathological factors on recurrence and survival. Demographic factors, stage of all the histology proven oral tongue cancer, and treatment details were documented. Overall survival (OS) and recurrence-free survival (RFS) were analyzed along with the potential prognostic factors affecting outcome. Results One hundred forty-four post-operative oral tongue cancer patients referred to our department for adjuvant treatment were evaluated. Median age at presentation was 45 years. Forty-seven patients had pathological early stage disease (stages I and II) and 95 had locally advanced (stages III and IV) disease while post-op details were not present in 2 patients. At a median follow-up of 87 months (60–124) of alive patients, the median RFS for entire cohort was 62 months while median OS was 74 months respectively. Age, perineural invasion (PNI), and grade of the tumor emerged as independent prognostic factors for OS and RFS. Among patients with early stage disease, depth of invasion (DOI), age, and PNI were found as independent prognostic factors for RFS and OS. In locally advanced disease, higher grade, age, and PNI independently impacted the respective survival end points. Conclusions Age (> 45 years), higher grade, and presence of PNI showed inferior survival outcomes across the sub-groups (early versus locally advanced disease). This may warrant adjuvant treatment intensification. DOI > 10 mm was particularly found to worsen survival in early node negative SCC oral tongue patients.

Background & Objective: Ayurveda, the “Mother of all healing”, has existed for over 5,000 years and hence is considered to be the oldest healing science. Ayurveda states that the mind can heal and transform a person's whole being as the mind and body are associated. Herbs are the heart of Ayurvedic belief. They are used to boost defense against diseases and viruses and keep the brain, body, and soul in complete balance. Although ayurvedic medicines and herbs have natural components, they should still be used with certain precautions under the supervision of a medical practitioner. This study aims to manually curate information for the various ayurvedic medicinal herbs that have antiviral activity against harmful viruses. Methods: Detailed information is collected from the literature regarding the following (a) types of viruses (b) which particular category they belong to(c) the respective components of herbs that are responsible for curing viruses. We developed a web interface with the help of php and mysql to get the desired output. Results: The database consists of 104 viruses and 704 natural components. The web server is available at: http://ayurvir.com. Interpretation & Conclusion: We believe that AyurVirDB database will be extremely beneficial for the research community. It not only aids in investigations of Ayurvedic medicinal plants and their components. On the emergence or re-emergence of a virus, one could be able to predict the ayurvedic plants/herbs used for viral treatment based on virus similarity or disease symptoms.

Staphylococcus aureus is the leading cause of hospital-acquired infections. The enzyme sortase A, present on the cell surface of S. aureus, plays a key role in bacterial virulence without affecting the bacterial viability. Inhibition of sortase A activity offers a powerful but clinically less explored therapeutic strategy, as it offers the possibility of not inducing any selective pressure on the bacteria to evolve drug-resistant strains. In this Perspective, we offer a chemical space narrative for the design of sortase A inhibitors, as delineated into three broad domains: peptidomimetics, natural products, and synthetic small molecules. This provides immense opportunities for medicinal chemists to alleviate the ever-growing crisis of antibiotic resistance.

BACKGROUND Cardiac remodeling and diastolic dysfunction may occur, in women with early-onset preeclampsia, following raised total vascular resistance in response to the impaired placentation. These changes can increase the risk of premature cardiac morbidity and mortality later in life. According to updated guidelines by the American and European Societies of Echocardiography (ASE/ESE) to diagnose diastolic dysfunction, using a simpler criterion is not yet used in pregnant women. OBJECTIVE To compare the maternal cardiovascular changes and the variation in the diastolic dysfunction using the 2009 and 2016 criteria by ASE/ESE among women with early onset preeclampsia and gestational age-matched normotensive controls. METHODS A prospective matched cross-sectional study conducted in a tertiary hospital in South India, involving 40 women with early and 40 women with gestational age-matched normotensive controls. Cardiac function and remodeling were assessed by conventional 2D, M-mode, and Doppler echocardiography. RESULTS Compared to the controls, women with early-onset preeclampsia had significantly higher. Total vascular resistance index (2867.6 vs. 2277.2 dynes/s/cm5/m2, p = .035) and median end-systolic stress index (5.2 vs. 9.2 dyne/cm2/m2), suggesting a higher afterload. Cases had a significant rate of left ventricular diastolic dysfunction using the 2009 criteria (grade II/III: 21 (52%) vs. 0 (0%), p

Bone remodeling is a complex physiological process that spans across multiple spatial and temporal scales and is regulated by both mechanical and hormonal cues. An imbalance between bone resorption and bone formation in the process of bone remodeling may lead to various bone pathologies. One powerful and non-invasive approach to gain new insights into mechano-adaptive bone remodeling is computer modeling and simulation. Recent findings in bone physiology and advances in computer modeling have provided a unique opportunity to study the integration of mechanics and biology in bone remodeling. Our objective in this review is to critically appraise recent advances and developments and discuss future research opportunities in computational bone remodeling approaches that enable integration of mechanics and cellular and molecular pathways. Based on the critical appraisal of the relevant recent published literature, we conclude that multiscale in silico integration of personalized bone mechanics and mechanobiology combined with data science and analytics techniques offer the potential to deepen our knowledge of bone remodeling and provide ample opportunities for future research.