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Abstract Objective There is conflicting evidence whether decreased clerkship duration is associated with reduced NBME shelf examination performance. We hypothesized that scores would remain stable for students in a shortened 2-week flipped classroom-based virtual rotation as compared to the traditional 4-week Neurology clerkship. Background There is conflicting evidence whether decreased clerkship duration is associated with reduced NBME shelf examination performance. We hypothesized that Neurology shelf exam scores would remain stable for students in a shortened 2-week flipped classroom-based virtual rotation as compared to the traditional 4-week Neurology clerkship with direct patient care supplemented by didactics. Methods This is a retrospective observational cohort study. In April 2020, the neurology clerkship at Rutgers Robert Wood Johnson Medical School switched from a traditional 4-week in-person clinical rotation supplemented by didactics to a 2-week flipped classroom-based virtual-only curriculum decoupled from a supplementary 2-week in-person clinical rotation to be completed later. Students were offered the opportunity to test after the 2-week virtual curriculum. NBME shelf scores for these “exam before clinical rotation” (EBC) students over the final quarter of the academic year 2019–2020 were compared to those of the “exam after clinical” (EAC) students undergoing the 4-week traditional rotation from July 2018 to March 2020. Results 321 students completed the shelf exam between July 2018 and June 2020, of which 284 students comprised the EAC cohort and 37 students, the EBC cohort. Mean scores did not differ between the EBC and EAC cohorts (81.8 ± 6.7 versus 81.8 ± 6.5, p = 0.96). Additional analyses showed no significant differences in the performance of EBC students as compared to the EAC students that tested within the same academic year 2019–2020 or within the matched quarter of the prior academic year 2018–2019, and students completing the virtual rotation who delayed testing after the clinical experience. Conclusions Testing after a 2-week flipped classroom-based virtual curriculum in Neurology without additional clinical training did not negatively affect neurology NBME shelf scores. Decoupling clinical experiences from knowledge acquisition and the evaluation of that knowledge base by means of NBME shelf examination is not likely to disadvantage learners with respect to shelf examination performance.

Abstract CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.

Background: T2DM is a common metabolic disease with enormous effects on health worldwide; moreover, the use of phytochemicals as therapeutic compounds has drawn increasing attention. Therefore, the objective of this study was to assess the effectiveness of these phytochemicals in combating diabetes through a comprehensive evaluation of their interactions with biological networks through network pharmacology, molecular docking, and molecular dynamics simulations. Objectives: The first goal of this study was to search and screen potential phytochemicals for binding with key proteins involved in T2DM, with special emphasis on AKT1 kinase, an integral component of the insulin signaling pathway. Methods: Network pharmacology analysis was carried out, and the interaction network of targets associated with T2DM was generated using KEGG, STRING and Cytoscape 3.9.1 software's. To determine the specific metabolic processes, cellular compartments, and molecular functions involved in T2DM, we performed Gene Ontology and KEGG analyses. An initial and short molecular docking study was conducted to analyze the binding modes, while the molecular dynamics simulations provided insights into the binding energy and stability of phytochemicals at target sites, with emphasis on rutin engaged with AKT1. Results: In total, 10 hub genes were proposed to be involved in T2DM and can be considered candidate therapeutic targets, namely MTOR, CASP3, CCND1, TNF, MMP9, ALB, MDM2, AKT1, and HSP90AA1. Rutin was found to have the highest binding score for AKT1 in docking studies, while MD simulations identified the structural stability and persistence of the compound's activity at the target enzyme loci. Conclusions: This study identified rutin and flavonoids as potential anti-diabetes phytochemicals. Based on these observations, an opportunity for other in vitro experiments and additional in vivo studies to confirm these buildings as multi-target drugs in T2DM patients is provided.

The field experiments were conducted during kharif (July-October) seasons of 2014-15 and 2015-16 at KVK, Rajsamand, Rajasthan and farmers' field with objective to explore and test other alternative and economical methods of weed control. On-farm Trial, technology option Oxadiargyl applied 50 g a.i. ha-1 applied as early post emergence at 20 DAS proved the best over farmers' practice as well over recommended practice of 1.0 kg a.i. ha-1 pendimethalin pre-emergence in terms of growth and yield attributing characters viz., plant height, primary and secondary branches, number of umbels, number of umbellets umbel-1, number of seeds umbel-1 and remained statistically at par with weed free treatment. Weed indices namely weed count, weed dry weight, weed index and weed control efficiency were statistically significant by oxadiargyl applied 50 g a.i. ha-1 as early post emergence at 20 DAS and pre-emergence application of pendimethalin 1.00 kg a.i. ha-1 pendimethalin over farmer's practice. Lower WI and higher WCE was observed by oxadiargyl applied 50 g a.i. ha-1 followed by pendimethalin 1.00 kg a.i ha-1. Grain and starw yield recorded in weed free plot was statistically at par with yield obtained by application of oxadiargyl 50 g a.i. ha-1. Net returns and B:C were also high in refined technology option i.e. of 50 g a.i. ha-1 oxazdiargyl (₹127570 ha-1 and 4.77) over recommended practice of 1.0 kg a.i ha-1 pendimethalin pre-emergence (₹107930 ha-1 and 4.19) and farmers' practice (₹75930 ha-1 and 3.49). [ABSTRACT FROM AUTHOR]

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses. [ABSTRACT FROM AUTHOR]

Background: Pleurotus giganteus (Berk. Karunarathna and K.D. Hyde), has been used as a culinary mushroom and is known to have medicinal properties but its potential as an anti-inflammatory agent to mitigate inflammation triggered diseases is untapped. In this study, the molecular mechanism underlying the protective effect of ethanol extract of P. giganteus (EPG) against lipopolysaccharide (LPS) and combination of LPS and hydrogen peroxide (H2O2)-induced inflammation on RAW 264.7 macrophages was investigated. Method: The effect of EPG on nitric oxide (NO) production as an indicator of inflammation in RAW 264.7 macrophages was estimated based on Griess reaction that measures nitrite level. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NF-κB activating protein (NKAP), signal transducer and activator of transcription 3 protein (STAT 3) and glutathione peroxidase (GPx) genes were assessed using real time reverse transcription polymerase chain reaction (RT-PCR) approach. Results: EPG (10 µg/ml) showed the highest reduction in the LPS-induced NO production in RAW 264.7 macrophages and significantly suppressed (p < 0.05) the expression iNOS, STAT 3 and COX-2. There was a significant increase (p < 0.05) in combination of LPS and H2O2-induced iNOS production when compared to the LPS-induced iNOS production in RAW 264.7 macrophages and this concurred with the NO production which was attenuated by EPG at 10 µg/ml. A significant (p < 0.05) down regulation was observed in the combination of LPS and H2O2-induced iNOS and GPx expression by EPG. Conclusions: Our data suggest that the anti-inflammatory activity of EPG is mediated via the suppression of the STAT 3 and COX-2 pathways and can serve as potential endogenous antioxidant stimulant. [ABSTRACT FROM AUTHOR]

field experiment was conducted during winter (rabi) season of 2013-14 at Agronomy Research Farm of N. D. University of Agriculture & Technology, Kumarganj, Faizabad (U.P.) to study the "Effect of integrated nutrient management on the growth, yield and quality of wheat (Triticum aestivum L.)". Treatments consist of 12 levels of fertility were evaluated in a randomized block design. The plant height, dry matter accumulation, no. of effective tillers m-2 and grain yields were significantly higher under incorporation of 125% recommended dose of fertilizer + 25% N through vermicompost, however, test weight, nitrogen and protein content were shows no significant differences. [ABSTRACT FROM AUTHOR]

AbstractBackgroundPurposeMethodResultIntranasal drug delivery shows potential for brain access via olfactory and trigeminal routes.This work aimed to ensure brain availability of nalbuphine via the nasal route.Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised.SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management. [ABSTRACT FROM AUTHOR]

Renewable lignocellulosic biomass is a favorable energy resource since its co-pyrolysis with hydrogen-rich plastics can produce high-yield and high-quality biofuel. In contrast to earlier co-pyrolysis research that concentrated on increasing product yield, this study comprehends the synergistic effects of two distinct feedstocks that were not considered earlier. This work focuses on co-pyrolyzing wheat straw (WS) with non-reusable polyethylene terephthalate (PET) for the production of pyrolysis oil. WS and PET were blended in different ratios (100/0, 80/20, 60/40, 40/60, 20/80, and 0/100), and pyrolysis experiments were conducted in a fixed-bed reactor under different temperatures to assess their synergistic effect on oil yield. Synergy rates of up to 7.78 % were achieved on yield for the blends of plastic and biomass at a temperature of 500 °C. In comparison to individual biomass or plastics, co-pyrolyzing PET-biomass blends demonstrated good process interaction and promoted the yields of value-added products. The heating value of the pyrolysis oils was in the range of 16.45–28.64 MJ/kg, which depends on the amount of plastic present in the feedstock. The physical analysis of the oils shows that they can be used for heat production by direct combustion in boilers or furnaces. The correlation between WS and PET was validated with the aid of Fourier transform infrared spectroscopy (FT-IR) and gas chromatography-mass spectrometry (GC-MS) analysis. The GC-MS result demonstrated the presence of different compounds such as O-H compounds, esters, carbonyl group elements, acids, hydrocarbons, aromatics, and nitrogenated compounds in the pyrolysis oil, which differed based on the proportions of PET in the feedstock. The increased hydrocarbon and reduced oxygen percentages in the pyrolysis oil were implicitly caused by enhanced hydrocarbon pool mechanisms, in which the breakdown of PET may be supplied as a hydrogen donor. Overall, waste lignocellulosic biomass and plastics can be used to produce biofuels, which helps reduce the amount of solid waste that ends up in landfills. This study also revealed that future research should be focused on the reaction mechanisms of WS and PET co-pyrolysis in order to examine the synergistic interactions.

This case report describes the precursor lesion of uterine papillary serous carcinoma (UPSC). A 65-year-old post-menopausal female presented with prolapse and vaginal discharge and underwent a hysterectomy revealing an atrophic endometrium, highly atypical endometrial glands, the lining cells of which showed pseudostratification, hobnailing, a high nuclear to cytoplasmic ratio, and prominent nucleoli. A p53 immunoreactivity score of 8 and a MIB-1 index of 80% was obtained leading to a diagnosis of endometrial intraepithelial carcinoma (EIC). Since serous EIC is commonly associated with extra-uterine serous carcinoma, it is a uniquely aggressive precursor lesion. Molecular studies support the hypothesis that EIC is a precursor of both uterine and extra-uterine invasive serous carcinomas. This is why the treatment protocol for EIC cases is total abdominal hysterectomy (TAH), accompanied by a staging procedure. In our patient, EIC was limited to the endometrium; associated with an excellent clinical outcome.

The novel coronavirus disease 2019 (COVID-19) pandemic outbreak caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has garnered unprecedented global attention. It caused over 2.47 million deaths through various syndromes such as acute respiratory distress, hypercoagulability, and multiple organ failure. The viral invasion proceeds through the ACE2 receptor, expressed in multiple cell types, and in some patients caused serious damage to tissues, organs, immune cells, and the microbes that colonize the gastrointestinal tract (GIT). Some patients who survived the SARS-CoV-2 infection have developed months of persistent long-COVID-19 symptoms or post-acute sequelae of COVID-19 (PASC). Diagnosis of these patients has revealed multiple biological effects, none of which are mutually exclusive. However, the severity of COVID-19 also depends on numerous comorbidities such as obesity, age, diabetes, and hypertension and care must be taken with respect to other multiple morbidities, such as host immunity. Gut microbiota in relation to SARS-CoV-2 immunopathology is considered to evolve COVID-19 progression via mechanisms of biochemical metabolism, exacerbation of inflammation, intestinal mucosal secretion, cytokine storm, and immunity regulation. Therefore, modulation of gut microbiome equilibrium through food supplements and probiotics remains a hot topic of current research and debate. In this review, we discuss the biological complications of the physio-pathological effects of COVID-19 infection, GIT immune response, and therapeutic pharmacological strategies. We also summarize the therapeutic targets of probiotics, their limitations, and the efficacy of preclinical and clinical drugs to effectively inhibit the spread of SARS-CoV-2.

Abstract Background There has been a recent growth in the use of whole body Computerised Tomography (CT) scans in the private sector as a screening test for asymptomatic disease. This is despite scant evidence to show any positive effect on morbidity or mortality. There has been concern raised over the possible harms of the test in terms of radiation exposure as well as the risk and anxiety of further investigation and treatment for the large numbers of benign lesions identified. Case Presentation A healthy 64 year old lady received a privately funded whole body CT scan for her birthday which revealed an incidental mass in the right iliac fossa. This was investigated with further imaging and colonoscopy and as confident diagnosis could not be made, eventually excised. Histology demonstrated this to be a benign ancient schwannoma and we believe this to be the first reported case of an abdominal wall schwannoma in the English literature Conclusions Ancient schwannomas are rare tumours of the peripheral nerve sheaths more usually found in the head, neck and flexor surfaces of extremities. They are a subtype of classical schwannomas with a predominance of degenerative changes. Our case highlights the pitfalls of such screening tests in demonstrating benign disease and subjecting patients to what turns out to be unnecessary invasive investigation and treatment. It provides evidence as to the consequences of the large number of false positive results that are created by blind CT scanning of asymptomatic patients i.e. its tendency to detect pseudodiesease rather than affect survival rates. Should the number of scans increase there may be an unnecessary burden on NHS resources due to the large numbers of benign lesions picked up, that are then referred for further investigation.

Colorectal cancer (CRC) is one of the most deaths causing diseases worldwide. Several risk factors including hormones like insulin and insulin like growth factors (e.g., IGF-1) have been considered responsible for growth and progression of colon cancer. Though there is a huge advancement in the available screening as well as treatment techniques for CRC. There is no significant decrease in the mortality of cancer patients. Moreover, the current treatment approaches for CRC are associated with serious challenges like drug resistance and cancer re-growth. Given the severity of the disease, there is an urgent need for novel therapeutic agents with ideal characteristics. Several pieces of evidence suggested that natural products, specifically medicinal plants, and derived phytochemicals may serve as potential sources for novel drug discovery for various diseases including cancer. On the other hand, cancer cells like colon cancer require a high basal level of reactive oxygen species (ROS) to maintain its own cellular functions. However, excess production of intracellular ROS leads to cancer cell death via disturbing cellular redox homeostasis. Therefore, medicinal plants and derived phytocompounds that can enhance the intracellular ROS and induce apoptotic cell death in cancer cells via modulating various molecular targets including IGF-1 could be potential therapeutic agents. Alkaloids form a major class of such phytoconstituents that can play a key role in cancer prevention. Moreover, several preclinical and clinical studies have also evidenced that these compounds show potent anti-colon cancer effects and exhibit negligible toxicity towards the normal cells. Hence, the present evidence-based study aimed to provide an update on various alkaloids that have been reported to induce ROS-mediated apoptosis in colon cancer cells via targeting various cellular components including hormones and growth factors, which play a role in metastasis, angiogenesis, proliferation, and invasion. This study also provides an individual account on each such alkaloid that underwent clinical trials either alone or in combination with other clinical drugs. In addition, various classes of phytochemicals that induce ROS-mediated cell death in different kinds of cancers including colon cancer are discussed.

Objective: In recent years, an overwhelming association between Pediatric Type 1 Diabetes Mellitus (T1DM) and autoimmune diseases has been largely reported. The current study was designed to determine a possible association between autoimmune thyroiditis (AIT), celiac disease (CD) - associated autoantibodies, and Parvovirus B19 infection among pediatric T1DM cases in the southwestern region of Saudi Arabia., Patients and Methods: Blood samples from age groups 1-18 years attending the Diabetic Clinic were collected over a period of 12 months. Serum anti-thyroid peroxidase (TPO), anti-thyroglobulin (TG), anti-tissue transglutaminase immunoglobulin A (TG-IgA), endomysial IgA (EMA-IgA), Parvovirus B19-IgG and IgM antibodies were detected by standard methods., Results: The results showed the prevalence of autoantibodies against thyroid and CD among pediatric T1DM patients to be 44 (25%) and 25 (14.4%), respectively. The prevalence of antibodies against B19 was 70 (40%). Further determination of the prevalence of Parvovirus B19-IgG antibodies and thyroid antibodies among T1DM pediatric patients revealed that there was a significant association between them with a p<0.0491., Conclusions: The prevalence of autoantibodies against the thyroid was higher among the seropositive Parvovirus B19 children with T1DM. A positive association between the prevalence of autoantibodies against thyroid disease and the increase in the duration of diabetes was also noted. Hence, periodic screening of T1DM patients for B19 antibodies and autoantibodies for thyroid is crucial.

Prostate cancer is the most commonly diagnosed and frequently occurred cancer in the males globally. The current treatment strategies available to treat prostate cancer are not much effective and express various adverse effects. Hence, there is an urgent need to identify novel treatment that can improve patient outcome. From times immemorial, natural products are highly recognized for novel drug development for various diseases including cancer. Cancer cells generally maintain higher basal levels of reactive oxygen species (ROS) when compared to normal cells due to its high metabolic rate. However, initiation of excess intracellular ROS production can not be tolerated by the cancer cells and induce several cell death signals which are in contrast to normal cells. Therefore, small molecules of natural origin that induce ROS can potentially kill cancer cells in specific and provide a better opportunity to develop a novel drug therapy. In this review, we elaborated various classes of medicinal compounds and their mechanism of killing prostate cancer cells through direct or indirect ROS generation. This can generate a novel thought to develop promising drug candidate to treat prostate cancer patients., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Pleurotus giganteus (Berk. Karunarathna and K.D. Hyde), has been used as a culinary mushroom and is known to have medicinal properties but its potential as an anti-inflammatory agent to mitigate inflammation triggered diseases is untapped. In this study, the molecular mechanism underlying the protective effect of ethanol extract of P. giganteus (EPG) against lipopolysaccharide (LPS) and combination of LPS and hydrogen peroxide (H 2 O 2 )-induced inflammation on RAW 264.7 macrophages was investigated., Method: The effect of EPG on nitric oxide (NO) production as an indicator of inflammation in RAW 264.7 macrophages was estimated based on Griess reaction that measures nitrite level. The expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), NF-kB activating protein (NKAP), signal transducer and activator of transcription 3 protein (STAT 3) and glutathione peroxidase (GPx) genes were assessed using real time reverse transcription polymerase chain reaction (RT-PCR) approach., Results: EPG (10 μg/ml) showed the highest reduction in the LPS-induced NO production in RAW 264.7 macrophages and significantly suppressed (p < 0.05) the expression iNOS, STAT 3 and COX-2. There was a significant increase (p < 0.05) in combination of LPS and H 2 O 2 - induced iNOS production when compared to the LPS-induced iNOS production in RAW 264.7 macrophages and this concurred with the NO production which was attenuated by EPG at 10 μg/ml. A significant (p < 0.05) down regulation was observed in the combination of LPS and H 2 O 2 -induced iNOS and GPx expression by EPG., Conclusions: Our data suggest that the anti-inflammatory activity of EPG is mediated via the suppression of the STAT 3 and COX-2 pathways and can serve as potential endogenous antioxidant stimulant.