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Introduction: The escalation of community-acquired pneumonia cases amidst the COVID-19 pandemic has engendered a concerning phenomenon characterized by the unwarranted utilization of antimicrobial agents. Aims: To analyze the utilization trends of antimicrobial agents within the cohort of hospitalized individuals diagnosed with community-acquired pneumonia (CAP). Material and methods: A prospective observational study was conducted for 6 months within the Department of Medicine to investigate patients diagnosed with CAP. Detailed records of drug prescriptions were meticulously recorded, with subsequent computation of both the Daily Defined Dose (DDD) and Antibiotics Consumption Index (ACI). A dataset comprising information from 130 patients was meticulously examined and subsequent analysis conducted. Descriptive statistical analyses were undertaken to utilize both Microsoft Excel and SPSS software version 27. Results: The predominant empirical therapy for antibacterial agents was found to be amoxicillin-clavulanic acid, utilized by 73 (56.2%) patients, succeeded by levofloxacin, administered to 33 (25.4%) patients. Following culture and sensitivity testing, the most frequently employed antibacterial agents for definitive therapy included levofloxacin for 33 (25.4%) patients. Notably, the highest Antibiotics Consumption Index (ACI) value recorded was 14.4 for amoxicillin-clavulanic acid in empirical therapy, while in definitive therapy, levofloxacin exhibited an ACI of 14.8. A significant disparity in ACI values between empirical and definitive therapy was observed (p

Abstract This study aimed to progress the understanding of idiopathic hypersomnia (IH) by assessing the moderating influence of individual characteristics, such as age, sex, and body mass index (BMI) on sleep architecture. In this retrospective study, 76 IH participants (38.1 ± 11.3 years; 40 women) underwent a clinical interview, an in-laboratory polysomnography with a maximal 9-h time in bed and a multiple sleep latency test (MSLT). They were compared to 106 healthy controls (38.1 ± 14.1 years; 60 women). Multiple regressions were used to assess moderating influence of age, sex, and BMI on sleep variables. We used correlations to assess whether sleep variables were associated with Epworth Sleepiness Scale scores and mean sleep onset latency on the MSLT in IH participants. Compared to controls, IH participants had shorter sleep latency (p = 0.002), longer total sleep time (p

Cystic fibrosis (CF) is a life-threatening genetic disorder caused by mutations in the CFTR gene. This leads to a defective protein that impairs chloride transport, resulting in thick mucus buildup and chronic inflammation in the airways. The review discusses current and future therapeutic approaches for CFTR dysfunction and airway dysbiosis in the era of personalized medicine. Personalized medicine has revolutionized CF treatment with the advent of CFTR modulator therapies that target specific genetic mutations. These therapies have significantly improved patient outcomes, slowing disease progression, and enhancing quality of life. It also highlights the growing recognition of the airway microbiome’s role in CF pathogenesis and discusses strategies to modulate the microbiome to further improve patient outcomes. This review discusses various therapeutic approaches for cystic fibrosis (CFTR) mutations, including adenovirus gene treatments, nonviral vectors, CRISPR/cas9 methods, RNA replacement, antisense-oligonucleotide-mediated DNA-based therapies, and cell-based therapies. It also introduces airway dysbiosis with CF and how microbes influence the lungs. The review highlights the importance of understanding the cellular and molecular causes of CF and the development of personalized medicine to improve quality of life and health outcomes.

Key Clinical Message Uterine artery embolization demonstrated significant efficacy in the treatment of utero‐cervical cancer. This minimally invasive procedure holds promise as a valuable adjunct therapy, potentially offering improved outcomes and reduced morbidity in select cases. Further research is warranted to validate its broader clinical utility. Abstract Vaginal bleeding is a common complication of Cervical cancer that can be considered a critical emergency. Conventional hemostatic treatments may occasionally help reduce the bleeding but are not an effective long‐term solution. Uterine Artery Embolization, a minimally invasive intervention, can halt the bleeding, achieving hemostasis, while removing many of the complications that alternative interventions carry. We outline a case study of a patient with extensive vaginal bleeding who had uterocervical malignancy and talk about the benefits of uterine artery embolisation for therapeutic management.

BackgroundThe public health landscape in North-East India is marked by the foundational principle of equitable health care provision, a critical endeavor considering the region’s intricate geography and proximity to international borders. Health care workers grapple with challenges, such as treacherous routes, limited infrastructure, and diverse cultural nuances, when delivering essential medical services. Despite improvements since the National Rural Health Mission in 2005, challenges persist, prompting a study to identify health care workers’ challenges and alternative strategies in Manipur and Nagaland. ObjectiveThis study aims to document the challenges experienced by health care workers during service delivery in the geographically challenging terrains of North-East India. MethodsThis study is part of the i-DRONE (Indian Council of Medical Research’s Drone Response and Outreach for North East) project, which aims to assess the feasibility of drone-mediated vaccine and medical delivery. This study addresses the secondary objective of the i-DRONE project. In-depth interviews of 29 health care workers were conducted using semistructured questionnaires in 5 districts (Mokokchung and Tuensang in Nagaland, and Imphal West, Bishnupur, and Churachandpur in Manipur). Nineteen health facilities, including primary health care centers, community health centers, and district hospitals, were selected. The study considered all levels of health care professionals who were in active employment for the past 6 months without a significant vacation and those who were engaged in ground-level implementation, policy, and maintenance activities. Data were recorded, transcribed, and translated, and subsequently, codes, themes, and subthemes were developed using NVivo 14 (QSR International) for thematic analysis. ResultsFive themes were generated from the data: (1) general challenges (challenges due to being an international borderline district, human resource constraints, logistical challenges for medical supply, infrastructural issues, and transportation challenges); (2) challenges during the COVID-19 pandemic (increased workload, lack of diagnostic centers, mental health challenges and family issues, routine health care facilities affected, stigma and fear of infection, and vaccine hesitancy and misinformation); (3) perception and awareness regarding COVID-19 vaccination; (4) alternative actions or strategies adopted by health care workers to address the challenges; and (5) suggestions provided by health care workers. Health care workers demonstrated adaptability by overcoming these challenges and provided suggestions for addressing these challenges in the future. ConclusionsHealth care workers in Manipur and Nagaland have shown remarkable resilience in the face of numerous challenges exacerbated by the pandemic. Despite infrastructural limitations, communication barriers, and inadequate medical supply distribution in remote areas, they have demonstrated adaptability through innovative solutions like efficient data management, vaccination awareness campaigns, and leveraging technology for improved care delivery. The findings are pertinent for not only health care practitioners and policymakers but also the broader scientific and public health communities. However, the findings may have limited generalizability beyond Manipur and Nagaland.

Introduction: Following abdominal surgery, transversus abdominis plane (TAP) block, a peripheral nerve block, can be a useful supplement to multimodal postoperative analgesia. The aim was assessment of postoperative analgesic effectiveness of 0.25% ropivacaine with 4 mg of dexamethasone on each side and 0.25% ropivacaine alone in the management of postoperative pain following total abdominal hysterectomy (TAH). Materials and Methods: Sixty adult patients planned for elective TAH with ASA Grades I–II under general anesthesia participated in this prospective, randomized, double-blinded study. Patients of Group A were given 20 mL of 0.25% ropivacaine on both the sides and Group B patients were given 20 mL of 0.25% ropivacaine with dexamethasone 4 mg on each side. The primary objective of this study was a comparison of Visual Analog Scale (VAS) scores between the groups and comparison of mean time of first rescue analgesia. The secondary objectives of this study were a comparison of hemodynamic parameters, postoperative analgesic requirement, patient satisfaction, and incidence of side effects. Results: VAS shows no discernible variation in 1 and 4 h after administration of block in Groups A and B. However, a significant difference appeared in VAS 8 h (P = 0.007), VAS 12 h (P = 0.000), and VAS 24 h (P = 0.000) after the administration of block between Groups A and B. The median time for first rescue analgesia was 2.75 h (interquartile range [IQR] = 1 h) and 5.8 h (IQR = 1.6 h) in Groups A and B, respectively, which was highly significant. Conclusion: We concluded that, after abdominal hysterectomy, dexamethasone added to ropivacaine TAP block tends to prolong postoperative analgesia and decrease the need for analgesics.

Abstract In recent years, there has been an increasing interest in the green synthesis of metallic nanoparticles, mostly because of the evident limitations associated with chemical and physical methods. Green synthesis, commonly referred to as "biogenic synthesis," is seen as an alternative approach to produce AgNPs (silver nanoparticles). The current work focuses on the use of Asterarcys sp. (microalga) for biological reduction of AgNO3 to produce AgNPs. The optimal parameters for the reduction of AgNPs were determined as molarity of 3 mM for AgNO3 and an incubation duration of 24 h at pH 9, using a 20:80 ratio of algal extract to AgNO3. The biosynthesized Ast-AgNPs were characterised using ultraviolet–visible spectroscopy (UV–Vis), zeta potential, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), and high-resolution transmission electron microscopy (HR-TEM) with selected area electron diffraction (SAED) patterns. The nanoparticles exhibited their highest absorption in the UV–visible spectra at 425 nm. The X-ray diffraction (XRD) investigation indicated the presence of characteristic peaks at certain angles: 38.30° (1 1 1), 44.40° (2 0 0), 64.64° (2 2 0), and 77.59° (3 1 1) according to the JCPDS file No. 04-0783. Based on SEM and TEM, the Ast-AgNPs had an average size of 35 nm and 52 nm, respectively. The zeta potential was determined to be − 20.8 mV, indicating their stability. The highest antibacterial effectiveness is shown against Staphylococcus aureus, with a zone of inhibition of 25.66 ± 1.52 mm at 250 μL/mL conc. of Ast-AgNPs. Likewise, Ast-AgNPs significantly suppressed the growth of Fusarium sp. and Curvularia sp. by 78.22% and 85.05%, respectively, at 150 μL/mL conc. of Ast-AgNPs. In addition, the Ast-AgNPs exhibited significant photocatalytic activity in degrading methylene blue (MB), achieving an 88.59% degradation in 120 min, revealing multiple downstream applications of Ast-AgNPs.

Introduction: Hip surgery is a common surgical procedure in the elderly population, leading to significant pain. Ultrasound (USG)guided regional nerve blocks are a newer, safe, and effective postoperative pain control modality for elderly patients. Aim: To compare the analgesic efficacy of Fascia Iliaca Compartment Block (FICB) with the three-in-one block for postoperative analgesia in elderly patients after lower limb orthopaedic surgeries. Materials and Methods: It was a randomised double- blinded study performed at Uttar Pradesh University of Medical Sciences, Saifai, Etawah, Uttar Pradesh, India on 60 elderly patients of Americian Soceity of Anaesthesiologists (ASA) class I-II scheduled for elective hip and femur shaft surgery under spinal anaesthesia.All patients were randomly allocated into two groups. Group A received ultrasound-guided FICB with 35-40 mL of 0.25% bupivacaine, and group B received ultrasound-guided three-in-one block with 35-40 mL of 0.25% bupivacaine after completion of surgery. In the postoperative period, pain was assessed using the Visual Analogue Scale (VAS), and inj. diclofenac sodium 1.5 mg/kg intravenous (i.v.) was given as rescue analgesic whenever VAS was ≥4. The primary outcome was changes in VAS scores at rest and during passive leg elevation between the two groups at various time intervals within 24 hours. Secondary outcomes measured were the duration of analgesia and total rescue analgesic required in 24 hours. Qualitative variables were compared between groups using the Chi-square test. A p-value

Background: An adverse drug reaction (ADR) is defined as a harmful or unpleasant reaction due to the use of a drug and may cause different types of effects, such as side effects. The World Health Organization states that adverse drug effects are a response to harmful and unintended medicine and occur at doses normally used in men for the prevention, diagnosis, or therapy of disease or for modifying physiological function. Aims and Objectives: The objective of the study was ADR monitoring of commonly prescribed antimicrobial agents. Materials and Methods: The study was conducted at Rama Hospital and the Research Center Mandhana Kanpur. Data were collected from the patients attending the outpatient and inpatient departments (OPD and IPD) of the medicine departments during the study period at Rama Hospital Mandhana, Kanpur. The sample size was a total of 60 patients. The study duration was conducted for 1 year. Data were collected by analyzing OPDs and IPDs in the Department of Medicine. Results: There are different types of adverse drug effects; we observed only three types of adverse drug effects in this study. The most commonly observed ADR was type A (56.66%). Out of the total ADRs reported in antimicrobial agents, skin ADRs (42.02%) and gastrointestinal tract ADRs (57.97%) are higher. There are also three different types of severity conditions observed in patients prescribed antimicrobial drugs; among them, the most commonly observed severity conditions were mild (58.33%). Conclusion: These study findings suggest that antimicrobial drugs are generally safe for most patients but can cause mild ADRs. It is important to monitor patients for ADRs while taking antimicrobial drugs and to provide appropriate treatment if necessary. Pharmacovigilance programs can help to identify and monitor ADRs, which can lead to improved patient safety.

Background: Opioid overdoses differentially affect demographic groups. Strategies to reduce overdose deaths, specifically overdose education and naloxone distribution (OEND), are not consistently delivered equitably. Methods: The HEALing Communities StudySM (HCS) is a cluster-randomized trial designed to implement evidence-based practices, including OEND, to reduce overdose deaths across communities. Individuals receiving OEND in eight Kentucky counties between January 2020 and June 2022 provided demographics and overdose history. Recipient characteristics were compared to opioid overdose decedent characteristics to evaluate whether OEND was equitably delivered to the target population. Recipient characteristics were also analyzed based on whether OEND was delivered in criminal justice, behavioral health, or health care facilities. Results: A total of 26,273 demographic records were analyzed from 137 partner agencies. Most agencies were in behavioral health (85.6 %) or criminal justice sectors (10.4 %). About half of OEND recipients were male (50.6 %), which was significantly lower than the 70.3 % of overdose decedents who were male, (p

Abstract Hot springs are a valuable source of biologically significant chemicals due to their high microbial diversity. To investigate the possibilities for industrial uses of these bacteria, researchers collected water and sediment samples from variety of hot springs. Our investigation employed both culture-dependent and culture-independent techniques, including 16S-based marker gene analysis of the microbiota from the hot springs of Surajkund, Jharkhand. In addition, we cultivated thermophilic isolates and screened for their ability to produce amylase, xylanase, and cellulase. After the optimized production of amylase the enzyme was partially purified and characterized using UPLC, DLS-ZP, and TGA. The retention time for the amylase was observed to be around 0.5 min. We confirmed the stability of the amylase at higher temperatures through observation of a steady thermo gravimetric profile at 400 °C. One of the thermophilic isolates obtained from the kund, demonstrated the potential to degrade lignocellulosic agricultural waste.

Key Clinical Message Accurate diagnosis of rare neurological conditions like Balo's concentric sclerosis (BCS) is challenging but crucial for tailored treatment. Interdisciplinary collaboration and further research are essential to advance our understanding. Abstract This case report presents a 32‐year‐old female patient with a puzzling neurological condition characterized by feverish feelings, joint pain, unclear speech, and an unsteady gait. Initial management did not lead to improvement, and further examination revealed neurological involvement and joint tenderness without signs of inflammatory arthritis. Laboratory investigations ruled out infectious and autoimmune causes. Magnetic resonance imaging (MRI) showed well‐defined lesions with concentric rings, leading to a diagnosis of Balo' concentric sclerosis. Treatment with intravenous methylprednisolone resulted in limited improvement. This case highlights the importance of thorough evaluation and collaboration in diagnosing rare neurological conditions. Further research is needed to enhance the understanding and treatment of rare neurological disorders.

Abstract Temporal distribution shift negatively impacts the performance of clinical prediction models over time. Pretraining foundation models using self-supervised learning on electronic health records (EHR) may be effective in acquiring informative global patterns that can improve the robustness of task-specific models. The objective was to evaluate the utility of EHR foundation models in improving the in-distribution (ID) and out-of-distribution (OOD) performance of clinical prediction models. Transformer- and gated recurrent unit-based foundation models were pretrained on EHR of up to 1.8 M patients (382 M coded events) collected within pre-determined year groups (e.g., 2009–2012) and were subsequently used to construct patient representations for patients admitted to inpatient units. These representations were used to train logistic regression models to predict hospital mortality, long length of stay, 30-day readmission, and ICU admission. We compared our EHR foundation models with baseline logistic regression models learned on count-based representations (count-LR) in ID and OOD year groups. Performance was measured using area-under-the-receiver-operating-characteristic curve (AUROC), area-under-the-precision-recall curve, and absolute calibration error. Both transformer and recurrent-based foundation models generally showed better ID and OOD discrimination relative to count-LR and often exhibited less decay in tasks where there is observable degradation of discrimination performance (average AUROC decay of 3% for transformer-based foundation model vs. 7% for count-LR after 5–9 years). In addition, the performance and robustness of transformer-based foundation models continued to improve as pretraining set size increased. These results suggest that pretraining EHR foundation models at scale is a useful approach for developing clinical prediction models that perform well in the presence of temporal distribution shift.

Background Large carnivores play a crucial role in maintaining the balance of the ecosystem. Successful conservation initiatives have often led to a huge increase in predators which has often led to negative interactions with humans. Without the knowledge of the carrying capacity of the top predator, such decisions become challenging. Here, we have derived a new equation to estimate the carrying capacity of tigers based on the individual prey species density. Methods We used tiger densities and respective prey densities of different protected areas. Relative prey abundance was used instead of absolute prey density as this could be a better surrogate of the prey preference. We used a regression approach to derive the species-wise equation. We have also scaled these coefficients accordingly to control the variation in the standard error (heteroscedasticity) of the tiger density. Furthermore, we have extended this regression equation for different species to different weight classes for more generalized application of the method. Results The new equations performed considerably better compared to the earlier existing carrying capacity equations. Incorporating the species-wise approach in the equation also reflected the preference of the prey species for the tiger. This is the first carrying capacity equation where the individual prey densities are used to estimate the carnivore population density. The coefficient estimates of the model with the comparison with prey-predator power laws also reflect the differential effect of tigers on different prey species. The carrying capacity estimates will aid in a better understanding of the predator-prey interaction and will advance better management of the top predator.

The organic anion transporter OAT1 (SLC22A6, originally identified as NKT) is a multispecific transporter responsible for the elimination by the kidney of small organic anions that derive from the gut microbiome. Many are uremic toxins associated with chronic kidney disease (CKD). OAT1 is among a group of “drug” transporters that act as hubs in a large homeostatic network regulating interorgan and interorganismal communication via small molecules. The Remote Sensing and Signaling Theory predicts that genetic deletion of such a key hub in the network results in compensatory interorganismal communication (e.g., host-gut microbe dynamics). Recent metabolomics data from Oat1-KO mice indicate that some of the most highly affected metabolites derive from bacterial tyrosine, tryptophan, purine, and fatty acid metabolism. Functional metagenomic analysis of fecal 16S amplicon and whole-genome sequencing revealed that loss of OAT1 was impressively associated with microbial pathways regulating production of urate, gut-derived p-cresol, tryptophan derivatives, and fatty acids. Certain changes, such as alterations in gut microbiome urate metabolism, appear compensatory. Thus, Oat1 in the kidney appears to mediate remote interorganismal communication by regulating the gut microbiome composition and metabolic capability. Since OAT1 function in the proximal tubule is substantially affected in CKD, our results may shed light on the associated alterations in gut-microbiome dynamics.

Background The Kashmir red deer or Hangul (Cervus hanglu hanglu) is the only Tarim red deer species endemic to India. With a current estimated population size of fewer than 200 individuals, this critically endangered species is confined to the greater Dachigam landscape in Jammu and Kashmir. Poaching, habitat loss and fragmentation, resource competition with livestock, and small population size are the major conservation challenges for this species. Methods Blood sampling was conducted from two wild Hangul individuals during radio-collaring operations at Dachigam National Park, Kashmir in 2013 and 2020, respectively. Using next-generation sequencing approach, we sequenced the 16,351 bp long mitogenome of two wild-caught Hangul individuals (1 M:1 F at ~14× and ~10× coverage, respectively) from Dachigam National Park. Results The annotated sequences were identical with an AT-rich composition, including 13 protein-coding genes (11,354 bp), 22 tRNA genes (1,515 bp), two ribosomal genes (2,526 bp) and a non-coding control region (917 bp) in a conserved order like other red deer species. Bayesian phylogenetic reconstruction of the red deer complex revealed two major groups: the elaphoid and the wapitoid clades. Hangul formed a distinct clade with its other subspecies C. hanglu yarkandensis and is sister to the Hungarian red deer (C. elaphus hippelaphus). Divergence time analyses suggested that the Tarim deer species group separated ~1.55 Mya from their common ancestors and Hangul diverged ~0.75 Mya from closely related C. yarkandensis, corroborating with the known paleobiogeographic events related to refugia during glaciations in the Pleistocene era. This study provides baseline information on Hangul mitogenome for further research on phylogeography and other population parameters and helps in developing suitable conservation plans for this species.

Introduction Despite proven programmes, implementing lifestyle interventions for pre-diabetes and type 2 diabetes is challenging. Cardiac rehabilitation, provide a valuable opportunity to promote the adoption of healthy lifestyle behaviours for patients with atherosclerotic cardiovascular disease (ASCVD). However, only a limited number of studies have explored the potential for reversing the underlying causes of ASCVD in this setting.Objectives The DIABEPIC1 study is an ongoing single-arm lifestyle clinical trial to assess the feasibility of an upgraded 6-month intensive cardiac rehabilitation programme combining an innovative diet assignment with exercise training to reverse newly onset pre-diabetes (glycated haemoglobin 5.7%–6.4%) to normal glucose concentrations in patients with coronary heart disease.Methods and analysis 36 patients referred from the Montreal Heart Institute for cardiac rehabilitation, aged ≥40 years with a recent diagnosis of pre-diabetes in the last 6 months, will be offered to participate in the upgraded programme. Interventions will include four sessions of nutritional counselling on ultra-processed foods intake reduction and a moderate-carbohydrate (

Introduction: Misoprostol is widely used in the medical management of missed abortions. However, pretreatment with Mifepristone has shown to be effective but still not recommended to be used in missed abortions. Aims and Objectives: To compare the outcome of medically managed missed abortion or blighted ovum using combination regime (Mifepristone and Misoprostol) vs Misoprostol alone. Materials and Methods: It was a prospective single-centre study performed in the Department of Obstetrics and Gynaecology, HIMSR and HAHC hospital, New Delhi, over, for one year. All the patients with diagnosed missed abortions were randomized into two groups (Group A and Group B). Group A was given Mifepristone 200 mg orally followed by Misoprostol 800 microgram per vaginal. Group B was given Misoprostol 800 microgram per vaginal. All the patients were observed for 24 hours for the expulsion of products of conception following the given regime. Ethical approval was taken from the Institutional Ethical Committee. Results: Both groups were comparable in demographic characteristics. On applying Fisher's exact test, it has been observed that the odds of nonexpulsion of the product of conception, time taken in expulsion, and surgical evacuation because of excessive bleeding were significantly higher in Group B (Misoprostol) compared with Group A (Mifepristone followed by Misoprostol). The cost-effective analysis showed that the cost is higher among Misoprostol Group B compared with combination drugs of Group A (Mifepristone + Misoprostol), but this result is not significant. Conclusion: Mifepristone can be considered before Misoprostol in missed abortions. This regime might decrease the need for surgical evacuation.

Abstract The aryl hydrocarbon receptor (AHR) is a transcription factor with roles in detoxification, development, immune response, chronic kidney disease and other syndromes. It regulates the expression of drug transporters and drug metabolizing enzymes in a proposed Remote Sensing and Signaling Network involved in inter-organ communication via metabolites and signaling molecules. Here, we use integrated omics approaches to analyze its contributions to metabolism across multiple scales from the organ to the organelle. Global metabolomics analysis of Ahr −/− mice revealed the role of AHR in the regulation of 290 metabolites involved in many biochemical pathways affecting fatty acids, bile acids, gut microbiome products, antioxidants, choline derivatives, and uremic toxins. Chemoinformatics analysis suggest that AHR plays a role in determining the hydrophobicity of metabolites and perhaps their transporter-mediated movement into and out of tissues. Of known AHR ligands, indolepropionate was the only significantly altered molecule, and it activated AHR in both human and murine cells. To gain a deeper biological understanding of AHR, we employed genome scale metabolic reconstruction to integrate knockout transcriptomics and metabolomics data, which indicated a role for AHR in regulation of organic acids and redox state. Together, the results indicate a central role of AHR in metabolism and signaling between multiple organs and across multiple scales.

Abstract In vitro and in vivo studies have established the organic anion transporters OAT1 (SLC22A6, NKT) and OAT3 (SLC22A8) among the main multi-specific “drug” transporters. They also transport numerous endogenous metabolites, raising the possibility of drug-metabolite interactions (DMI). To help understand the role of these drug transporters on metabolism across scales ranging from organ systems to organelles, a formal multi-scale analysis was performed. Metabolic network reconstructions of the omics-alterations resulting from Oat1 and Oat3 gene knockouts revealed links between the microbiome and human metabolism including reactions involving small organic molecules such as dihydroxyacetone, alanine, xanthine, and p-cresol—key metabolites in independent pathways. Interestingly, pairwise organ-organ interactions were also disrupted in the two Oat knockouts, with altered liver, intestine, microbiome, and skin-related metabolism. Compared to older models focused on the “one transporter-one organ” concept, these more sophisticated reconstructions, combined with integration of a multi-microbial model and more comprehensive metabolomics data for the two transporters, provide a considerably more complex picture of how renal “drug” transporters regulate metabolism across the organelle (e.g. endoplasmic reticulum, Golgi, peroxisome), cellular, organ, inter-organ, and inter-organismal scales. The results suggest that drugs interacting with OAT1 and OAT3 can have far reaching consequences on metabolism in organs (e.g. skin) beyond the kidney. Consistent with the Remote Sensing and Signaling Theory (RSST), the analysis demonstrates how transporter-dependent metabolic signals mediate organ crosstalk (e.g., gut-liver-kidney) and inter-organismal communication (e.g., gut microbiome-host).

Objective To assess the uptake of second line antihyperglycaemic drugs among patients with type 2 diabetes mellitus who are receiving metformin.Design Federated pharmacoepidemiological evaluation in LEGEND-T2DM.Setting 10 US and seven non-US electronic health record and administrative claims databases in the Observational Health Data Sciences and Informatics network in eight countries from 2011 to the end of 2021.Participants 4.8 million patients (≥18 years) across US and non-US based databases with type 2 diabetes mellitus who had received metformin monotherapy and had initiated second line treatments.Exposure The exposure used to evaluate each database was calendar year trends, with the years in the study that were specific to each cohort.Main outcomes measures The outcome was the incidence of second line antihyperglycaemic drug use (ie, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, and sulfonylureas) among individuals who were already receiving treatment with metformin. The relative drug class level uptake across cardiovascular risk groups was also evaluated.Results 4.6 million patients were identified in US databases, 61 382 from Spain, 32 442 from Germany, 25 173 from the UK, 13 270 from France, 5580 from Scotland, 4614 from Hong Kong, and 2322 from Australia. During 2011-21, the combined proportional initiation of the cardioprotective antihyperglycaemic drugs (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors) increased across all data sources, with the combined initiation of these drugs as second line drugs in 2021 ranging from 35.2% to 68.2% in the US databases, 15.4% in France, 34.7% in Spain, 50.1% in Germany, and 54.8% in Scotland. From 2016 to 2021, in some US and non-US databases, uptake of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors increased more significantly among populations with no cardiovascular disease compared with patients with established cardiovascular disease. No data source provided evidence of a greater increase in the uptake of these two drug classes in populations with cardiovascular disease compared with no cardiovascular disease.Conclusions Despite the increase in overall uptake of cardioprotective antihyperglycaemic drugs as second line treatments for type 2 diabetes mellitus, their uptake was lower in patients with cardiovascular disease than in people with no cardiovascular disease over the past decade. A strategy is needed to ensure that medication use is concordant with guideline recommendations to improve outcomes of patients with type 2 diabetes mellitus.

Endometriosis is a prevalent benign condition arising from the female reproductive system and affects about 7%–10% of females. The association of endometriosis with serous borderline ovarian tumors has been a matter of interest in gynecology. Sampson first described the association between endometriosis and carcinoma. The endometriosis-associated ovarian malignancies are clear cell adenocarcinoma and endometrioid adenocarcinoma, whereas serous and mucinous are rare malignancies associated with endometriosis. Here, we present the case report of a 45-year-old female in which endometriosis was associated with borderline serous tumor, since there is a lack of enough confident criteria for diagnosing endometriosis-associated ovarian tumors.

Abstract Studies on resource utilisation by carnivores are essential as they aid in assessing their role in a community, by unravelling predator–prey relationships. Globally, prey depletion is one of the primary causes of declining Asiatic wild dog (dhole) populations. Therefore, it is essential to examine their diet across their range. Our study presents insights into dhole feeding ecology across multiple sites from the central Indian landscape of Maharashtra, India, for the first time. We conducted scat analysis using a subset of genetically identified scats and collected additional data from kills observed while tracking radio-collared dholes and other known packs from 2 study sites. We analysed 861 scats, and 191 dhole kills to identify species and age class of prey. We estimated the relative contribution of various prey, utilising non-linear biomass models of prey consumption. Overall, wild ungulates like sambar and chital were the principal prey in terms of biomass (sambar 61.08%; chital 19.08%) and number of prey consumed (sambar 39.28%; chital 13.83%). An analysis of kill data also suggested that dholes strongly preferred the two deer species; and differential selection of age classes was observed at the 2 study sites. Our study can potentially help manage and conserve this important population of an endangered carnivore.

Introduction: Osteomyelitis is an inflammatory process that affects bone due to the contiguous infection, direct inoculation, or haematogenous spread of microorganisms. It is an infectious disease that is difficult to diagnose and treatment is complex because of its heterogeneity, pathophysiology, clinical presentation and management. Aim: To determine microbiological profile osteomyelitis and antibiotic resistance pattern of bacterial isolates with special reference to Multidrug Resistance (MDR) strains. Materials and Methods: A cross-sectional study was conducted in the Department of Microbiology and Department of Orthopedics Rama Medical College Hospital and Research Centre Kanpur, Uttar Pradesh, India. A total of 100 samples from osteomyelitis cases were aerobically cultured and isolates from culture positives were identified by standard procedures. Antimicrobial Susceptibility Testing (AST) was done following Clinical and Laboratory Standards Institute (CLSI) guidelines. Staphylococcal isolates were screened for methicillin resistance and Gram negative bacilli were screened for MDR production. Results: Out of 100 samples, 76% were culture positive and 24% were culture negative. Males were more affected than females. Staphylococcal spp. (47.3%) was predominant, E. coli (14.4%) and Klebsiella spp. (11.8%), Pseudomonas spp. (9.2%), Proteus spp. (5.2%), Coagulase-Negative Staphylococci (CoNS) (3.9%). Among the MDR strains, Methicillin Resistant Staphylococcus aureus (MRSA) was 44.4%. All the MDR Staphylococcal isolates were 100% sensitive for linezolid. Among the MDR Gram negative bacilli were Extended Spectrum Beta Lactamases (ESBL) (50%), AmpC (17.6%) and Metallo Beta Lactamase (MBL) (14.7%) and they were 100% sensitive for polymixin B and colistin. Conclusion: The microbiological profile of osteomyelitis in the present study showed high prevalence of MRSA44% as the commonest agent, sensitive only to linezolid. E. coli ESBL (50%) and MBL-14.7% were sensitive only to colistin and polymixin B, therefore proper infection control practices and antibiotic policy has to be followed to reduce the incidence of MDR strains.

Lymphangiomas are developmental malformations that present as benign hamartomas of lymphatic channels. They present at birth or before two years of age, with 50-70% predilection for the head and neck region and less frequently reported in the oral cavity. However, affected sites in the oral cavity include the tongue, palate, gingiva, buccal mucosa, lips and alveolar ridge. Lymphangioma of the buccal mucosa is rare, only 27 cases of lymphangioma of buccal mucosa have been reported till date, out of which seven were in children. The prognosis is good for most patients, but recurrence has also been reported in some cases. This present case is of Lymphangioma Circumscriptum in a 13-year-old child involving right buccal mucosa and lip since birth. This lesion was surgically removed under general anaesthesia and there was a recurrence of the lesion after one year of follow-up. In the literature there was no reported case of Lymphangioma Circumscriptum involving the lip of a child, so this present case was the first reported case of Lymphangioma Circumscripta involving the lip in a child with recurrence.

Abstract In recent years, deep learning techniques have shown impressive performance in the field of identification of diseases of crops using digital images. In this work, a deep learning approach for identification of in-field diseased images of maize crop has been proposed. The images were captured from experimental fields of ICAR-IIMR, Ludhiana, India, targeted to three important diseases viz. Maydis Leaf Blight, Turcicum Leaf Blight and Banded Leaf and Sheath Blight in a non-destructive manner with varied backgrounds using digital cameras and smartphones. In order to solve the problem of class imbalance, artificial images were generated by rotation enhancement and brightness enhancement methods. In this study, three different architectures based on the framework of ‘Inception-v3’ network were trained with the collected diseased images of maize using baseline training approach. The best-performed model achieved an overall classification accuracy of 95.99% with average recall of 95.96% on the separate test dataset. Furthermore, we compared the performance of the best-performing model with some pre-trained state-of-the-art models and presented the comparative results in this manuscript. The results reported that best-performing model performed quite better than the pre-trained models. This demonstrates the applicability of baseline training approach of the proposed model for better feature extraction and learning. Overall performance analysis suggested that the best-performed model is efficient in recognizing diseases of maize from in-field images even with varied backgrounds.

The global re-emergence of monkeypox (Mpox) in non-endemic regions in 2022 has highlighted the critical importance of timely virus detection and robust public health surveillance in assessing outbreaks and their impact. Despite significant Mpox research being conducted worldwide, there is an urgent need to identify knowledge gaps and prioritize key research areas in order to create a roadmap that maximizes the utilization of available resources. The present research article provides a comprehensive mapping of health research priorities aimed at advancing our understanding of Mpox and developing effective interventions for managing its outbreaks, and, as evidenced by the fact that achieving this objective requires close interdisciplinary collaboration. The key research priorities observed were identifying variants responsible for outbreaks; discovering novel biomarkers for diagnostics; establishing suitable animal models; investigating reservoirs and transmission routes; promoting the One Health approach; identifying targets for vaccination; gaining insight into the attitudes, experiences, and practices of key communities, including stigma; and ensuring equity during public health emergencies. The findings of this study hold significant implications for decision making by multilateral partners, including research funders, public health practitioners, policy makers, clinicians, and civil society, which will facilitate the development of a comprehensive plan not only for Mpox but also for other similar life-threatening viral infections.

Introduction: Government runs teaching hospitals to impart a high-quality medical education to budding medicos and paramedical students in training. The experiences these trainees at various tenure positions get then and there shape their worldview for rest of the life and have an indelible impression. The Covid-19 pandemic disrupted all the routines at the hospitals around the world—including ours—and we make an attempt to measure it in one dimension in this study. Materials and Methods: We obtained attendance data of patients at out patient department and in patient department of our hospital. During the pandemic for a certain duration offline (physical) registrations were closed and they were attended only by online ones. Hence that data (actually a part of it) got captured electronically and we analyzed it to get an idea of the traversed course of the scourge. Results: When the pandemic surged during the spring and summer of 2021, our hospital was turned into a Covid facility. Hence average routine attendance of patients got reduced to a significant extent, elective surgeries/interventions and procedures were postponed and this data is reflected in an electronic system, perhaps making a long-lasting effect on the budding trainees. This fact needs to be realized so as to take appropriate action. Conclusion: We need to realize that the effects of the viral communicable disease may be enduring, not only for the infected patients and their families but also for those who learn on those patients. Therefore, the transmissible diseases disabled not only our society, economy, and health care services when they ascended but pedagogy too. Online learning came to rescue but only up to a certain extent and with several caveats and limitations.

Organic anion transporter 1 (OAT1/SLC22A6, NKT) is a multispecific drug transporter in the kidney with numerous substrates, including pharmaceuticals, endogenous metabolites, natural products, and uremic toxins. Here, we show that OAT1 regulates levels of gut microbiome–derived metabolites. We depleted the gut microbiome of Oat1-KO and WT mice and performed metabolomics to analyze the effects of genotype (KO versus WT) and microbiome depletion. OAT1 is an in vivo intermediary between the host and the microbes, with 40 of the 162 metabolites dependent on the gut microbiome also impacted by loss of Oat1. Chemoinformatic analysis revealed that the altered metabolites (e.g., indoxyl sulfate, p-cresol sulfate, deoxycholate) had more ring structures and sulfate groups. This indicates a pathway from gut microbes to liver phase II metabolism, to renal OAT1–mediated transport. The idea that multiple gut-derived metabolites directly interact with OAT1 was confirmed by in vitro transport and magnetic bead binding assays. We show that gut microbiome–derived metabolites dependent on OAT1 are impacted in a chronic kidney disease (CKD) model and human drug-metabolite interactions. Consistent with the Remote Sensing and Signaling Theory, our results support the view that drug transporters (e.g., OAT1, OAT3, OATP1B1, OATP1B3, MRP2, MRP4, ABCG2) play a central role in regulating gut microbe–dependent metabolism, as well as interorganismal communication between the host and microbiome.

Background: Characterization studies of COVID-19 patients with chronic obstructive pulmonary disease (COPD) are limited in size and scope. The aim of the study is to provide a large-scale characterization of COVID-19 patients with COPD. Methods: We included thirteen databases contributing data from January-June 2020 from North America (US), Europe and Asia. We defined two cohorts of patients with COVID-19 namely a ‘diagnosed’ and ‘hospitalized’ cohort. We followed patients from COVID-19 index date to 30 days or death. We performed descriptive analysis and reported the frequency of characteristics and outcomes among COPD patients with COVID-19. Results: The study included 934,778 patients in the diagnosed COVID-19 cohort and 177,201 in the hospitalized COVID-19 cohort. Observed COPD prevalence in the diagnosed cohort ranged from 3.8% (95%CI 3.5-4.1%) in French data to 22.7% (95%CI 22.4-23.0) in US data, and from 1.9% (95%CI 1.6-2.2) in South Korean to 44.0% (95%CI 43.1-45.0) in US data, in the hospitalized cohorts. COPD patients in the hospitalized cohort had greater comorbidity than those in the diagnosed cohort, including hypertension, heart disease, diabetes and obesity. Mortality was higher in COPD patients in the hospitalized cohort and ranged from 7.6% (95%CI 6.9-8.4) to 32.2% (95%CI 28.0-36.7) across databases. ARDS, acute renal failure, cardiac arrhythmia and sepsis were the most common outcomes among hospitalized COPD patients. Conclusion: COPD patients with COVID-19 have high levels of COVID-19-associated comorbidities and poor COVID-19 outcomes. Further research is required to identify patients with COPD at high risk of worse outcomes.

Honey is a natural substance that has existed alongside humanity since the time of antiquity, acting then as a source of nutrition, as well as a source of medicinal aid for people. Ancient civilizations from multiple nations of the world, from ancient China to ancient Greece and Egypt, utilized the supposed healing properties of honey to treat lacerations and wounds, as well as for internal pathologies such as intestinal disease. At present, honey has entered the modern scientific research program in search of novel antibiotics. In recent research, honey has demonstrated its potential use for static and/or cidal effects on microbial strains which are becoming resistant to chemical antibiotics. Additionally, the use of honey as an agent of treatment for more severe infections, namely blood infections pertaining to septicemia, HIV, and SARS-CoV-2, as well as parasitic infections such as malaria, have also been investigated in recent years. In this article, the literature has been reviewed on some of the therapeutic properties of natural nutraceutical honey, where it has been observed to act as a potential ameliorating agent; reducing the severity of such conditions that may amplify a disease, as well as reducing the progression of the disease and its symptoms.

Introduction: Rhino-cerebral Mucormycosis (RCM), in the pre-Coronavirus Disease-2019 (COVID-19) era, was thought to be solely associated with an immunocompromised state. However, an unforeseen outbreak in the number of mucormycosis cases was seen with the increase in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Aim: To study and investigate the clinical characteristics, imaging findings, associated risk factors, and clinical outcomes in COVID-19 associated mucormycosis. Materials and Methods: A retrospective cohort study was conducted comprising 480 cases of COVID-19 associated mucormycosis who presented to the institution between April 2020 and September 2020. The clinical and radiological data were studied and analysed. Results: Out of a total of 480 cases, 443 (92.29%) were found to suffering from diabetes mellitus and 392 patients (81.66%) had a history of steroids intake in the studied population. Facial or per orbital swelling followed by pain were the most frequent presenting complaints found in 188 (39.16%) and 162 (33.75%) patients, respectively. Nasal septum and middle turbinate were the most common sites of disease involvement on nasal endoscopic examination. On radiological imaging, maxillary (438; 91.25%) was the most commonly involved sinus followed by ethmoids (395; 82.29%). Premaxillary/retroantral fat and orbits were the most common sites of extra sinonasal spread of infection found in 278 (57.91%) and 244 (50.83%) patients, respectively. About 238 (49.58%) patients showed bony erosion and dehiscence. Intracranial complications were seen in 73 (15.21%) patients. Glycated Haemoglobin (HbA1c) levels showed significant value with higher disease staging. Oxygen supplementation was frequently associated with extrasinus spread of infection. A total of 44 (9.17%) patients succumbed to death despite aggressive antifungal treatment. Conclusion: COVID-19 associated RCM shows frequent and extensive spread to extrasinus regions, especially with uncontrolled diabetes mellitus, steroid administration, and oxygen supplementation. High clinical suspicion, early imaging, and prompt institution of antifungal therapy can aid in reducing mortality rate.

Abstract Background Primary urethral carcinoma (PUC) is rare and accounts for

Introduction: Pioglitazone has been a cornerstone of oral hypoglycemic therapy. Concerns have been raised about its association with urinary bladder cancer. Considering the wide usage of this drug, concrete and multiple population-based studies are needed to establish the safety of this drug. The present retrospective study is aimed to assess the association of pioglitazone with urinary bladder cancer. Materials and Methods: Clinical records of 4170 patients (2085 pioglitazone users and similar number of nonpioglitazone users) attending the diabetes clinic at a tertiary level teaching hospital were accessed, and the patients were subjected to symptom-directed questionnaire, urine examination, and cystoscopy and bladder biopsy (whenever clinically indicated). The risk of bladder cancer was also assessed with respect to cumulative dose and duration of pioglitazone. Results: We did not observe any increased risk of bladder malignancy with pioglitazone exposure; furthermore, there was no association with cumulative dose and duration of pioglitazone therapy. Pioglitazone was found to be effective and safe in managing glycemic control in diabetic patients.

Purpose: To compare the macular and peripapillary RNFL thicknesses of the amblyopic and normal eye in patients with anisometropic amblyopia. Methods: This is a hospital based cross-sectional study for which we studied 36 amblyopic subjects aged between 5 to 16 years in which the amblyopic eye was taken as the case and the unaffected eye was taken as control eye. The inclusion criteria included children having unilateral strabismic or anisometropic amblyopia who underwent macular and RNFL thickness assessment by SD-OCT. Results: Central Macular thickness as well as the thickness of the other macular segments was significantly greater in the affected eye (p

Aim: To know the prevalence of sexual activity, their sexual behaviour and attitude towards sex among unmarried adolescent females. Materials and Methods: It was a hospital-based prospective observational study. The study duration was 1 year. The study participants were unmarried girls between the age group of 10–19 years who gave written informed consent. In the case of a minor, consent was obtained from parents also. Pre-designed, pre-structured and pre-tested questionnaire was used to evaluate the sexual behaviour. Results: Out of the 320 adolescents presented to the OPD, only 165 consented to participate in the study. Prevalence of sexual activity was 16.9% (28/165) in the study. Eight (8/165) adolescent girls have not attained menarche and all were not having any knowledge of sex. Three girls were the victims of sexual exploitation. Around 64% of these girls were sexually active with their classmates. All the sexually active females were having intercourse through the vaginal route, however non-vaginal route was also practiced by 6 girls. Home (11, 39%) was the preferred place followed by the hotel (10, 35.7%) for sexual activity. Conclusion: Prevalence of sexual activity is low among Indians as compared to the western world but it may be a tip of iceberg as it is a hospital-based study. This is the first study that assessed the route of intercourse, frequency of sexual activity, and place preferred by these adolescents to evaluate the sexual health behaviour.

Thrombotic microangiopathy (TMA) is devastating for renal transplantation (RT) causing graft/ patient loss. We present 5-year experience of TMA in RT in retrospective study of indicated renal allograft biopsies with TMA. Patient–donor demographics and associated histological findings with respect to transplants under tolerance induction protocol (Group 1) were compared with patients transplanted under triple immunosuppression (Group 2). Statistical analysis was performed using IBM SPSS Statistics version 20. Sixty-one (4.1%) of 1520 biopsies [Group 1:17 (1.9%)/882, Group 2:44 (6.9%)/638] revealed TMA. Tacrolimus trough levels were normal. There was no evidence of systemic involvement in any patient. Mean age was 36.8 years with 70.6% males, HLA-match, 2.6/6, and the most common original disease unknown (41.2%) in Group 1, and 35.9 years with 86.4% males, HLA-match, 2.1/6, and the most common original disease unknown (50%) in Group 2. Biopsies were performed at mean 5.1-year posttransplant in Group 1 and 2.3 years in Group 2. Acute TMA constituted 47% Group 1 and 43.2% Group 2 biopsies; of these, antibody-mediated rejections were observed in 58.8%, T-cell mediated rejections in 11.8%, tacrolimus toxicity in 76.5%, and other findings in 35.3% Group 1; and 61.4%, 25%, 50%, and 18.2%, respectively, in Group 2 biopsies. Higher rejection activity scores were more in Group 2. Postbiopsy 1- and 5- year patient survival was 94.1%, 86.9% in Group 1 and 92.1%, 88.3% in Group 2; 1- and 4-year graft survival was 52.9%, 15.9% in Group 1 and 20.3%, 5.4% in Group 2. TMA was poor prognosticator for RT, especially under triple immunosuppression. Antibody- mediated rejection and tacrolimus toxicity were more prone to TMA.

Scrub typhus is a zoonotic disease caused by the bite of a mite Orientia tsutsugamushi, a bacterium from the Rickettsiaceae family, which is transmitted to humans by bite of trombiculid mite. Scrub typhus is widely spread all across India, and despite its vast occurrence, it remains underdiagnosed. The probable reasons could be the lack of specific symptoms, poor access to the diagnostic facilities, and low index of suspicion by the clinicians. It is a common trend to rule out the common causes of infection such as malaria, typhoid, and leptospirosis, and then, a good number of cases are ultimately diagnosed as scrub typhus. The common presentation is high-grade fever (98%), tender regional/generalized lymphadenopathy (40%–97%), hepatosplenomegaly, cough, and a characteristic eschar that is found in nearly 50% of cases, which represents the site of bite by the mite. Here, we present with a series of cases from Indore of scrub typhus with pulmonary complications which too were underdiagnosed. Immunoglobulin M typhus (enzyme-linked immunosorbent assay) confirmed the diagnosis, and all three were efficiently managed with doxycycline.

Increasing evidence associates apathy with worsening in cognitive performance and greater risk of dementia, in both clinical and healthy older populations. In older adults with neurocognitive disorders, apathy has also been related to specific fronto-subcortical structural abnormalities, thus differentiating apathy and major depressive disorder. Yet, the neural mechanisms associated with apathy in healthy older adults are still unclear. In the present study, we investigated the frontal cortical response during a dual-task walking paradigm in forty-one healthy older adults with and without apathy symptoms, controlling for depressive symptoms. The dual-task walking paradigm included a single cognitive task (2-back), a single motor task (walking), and a dual-task condition (2-back whilst walking). The cortical response was measured by means of functional Near-Infrared Spectroscopy (fNIRS). The results revealed that participants with apathy symptoms showed greater activation of subregions of the prefrontal cortex and of the premotor cortex compared to healthy controls during the single cognitive component of the dual-task paradigm, whilst cognitive performance was equivalent between groups. Moreover, increased cortical response during the cognitive task was associated with higher odds of exhibiting apathy symptoms, independently of depressive symptoms. These findings suggest that apathy may be related to differential brain activation patterns in healthy older individuals and are in line with previous evidence of the distinctiveness between apathy and depression. Future research may explore the long-term effects of apathy on the cortical response in healthy older adults.

Background: Malignant gliomas are deadly tumours with few therapeutic options. Although immunotherapy may be a promising therapeutic strategy for treating gliomas, a significant barrier is the CD11b+ tumour-associated myeloid cells (TAMCs), a heterogeneous glioma infiltrate comprising up to 40% of a glioma's cellular mass that inhibits anti-tumour T-cell function and promotes tumour progression. A theranostic approach uses a single molecule for targeted radiopharmaceutical therapy (TRT) and diagnostic imaging; however, there are few reports of theranostics targeting the tumour microenvironment. Methods: Utilizing a newly developed bifunctional chelator, Lumi804, an anti-CD11b antibody (αCD11b) was readily labelled with either Zr-89 or Lu-177, yielding functional radiolabelled conjugates for PET, SPECT, and TRT. Findings: 89Zr/177Lu-labeled Lumi804-αCD11b enabled non-invasive imaging of TAMCs in murine gliomas. Additionally, 177Lu-Lumi804-αCD11b treatment reduced TAMC populations in the spleen and tumour and improved the efficacy of checkpoint immunotherapy. Interpretation: 89Zr- and 177Lu-labeled Lumi804-αCD11b may be a promising theranostic pair for monitoring and reducing TAMCs in gliomas to improve immunotherapy responses. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Glomus tumor (GT) is a benign mesenchymal tumor with an estimated incidence of 1.5 to 2% of soft tissue tumors. The majority of glomus tumors are benign and are mostly seen in the superficial skin & soft tissue of upper and lower distal extremity. The malignant variant of the glomus tumor is scarce. We report a case of a recurrent glomus tumor diagnosed in a 28-year-old male patient, who complained of painful swelling in the proximal phalanx of the right index finger. The magnetic resonance imaging of the hand revealed a well-defined multilobulated soft tissue mass at the palmar aspect of the 2nd digit along the shaft of the proximal phalanx. Histopathology revealed a well-circumscribed tumor arranged in solid sheets, nests and cords interconnect by vessels of varying size. The tumor cells were round to oval, showed moderate nuclear pleomorphism, eosinophilic cytoplasm, atypical mitoses (>5/10HPF), and necrosis. Immunohistochemically tumor cells reveal diffuse and strong cytoplasmic positivity with smooth muscle actin (SMA). Based on histomorphology and immunohistochemistry, a final diagnosis of malignant glomus tumor was made. We report this case due to its rarity, and it to be included among the differential if the lesion is painful and recurrent.

Background Drug-resistant tuberculosis (DR-TB) continues to be a major public health threat posing a critical challenge to TB treatment and control worldwide. The present study was conducted among patients with DR-TB of the Saharia tribe residing in Madhya Pradesh state of Central India to document their experiences and needs, and to identify gaps for treatment adherence as this population is known to be poor because of migration and other factors.Methods We conducted 16 in-depth interviews on purposively selected patients with DR-TB among the Saharia tribe using a predesigned open-ended in-depth interview guide, which included questions on domains like general physical health, diagnosis, treatment adherence, side-effects of drugs and experience related to the health facility. Out of these interviews, various subthemes were extracted. The obtained qualitative data were subjected to thematic analysis.Results The study helped to understand the experiences and needs of the patients with DR-TB in various stages from diagnosis to treatment. Also, there was the impact of factors like lack of education and awareness, poor living conditions and lack of healthcare facilities on predominance of the disease in the community. Poor access to a healthcare facility, high pill burden and related side-effects, longer duration of treatment, financial burden, misbeliefs and misconceptions were prominent issues posing a challenge to treatment adherence. The narratives pointed out their struggle at every stage be it with diagnosis, treatment initiation or treatment adherence.Conclusion It is paramount to address the needs and experiences of patients with DR-TB to develop a patient-centric and context-specific approach conducive to the sociocultural set-up of tribal people. This will scale down the attrition rate of tribal patients while adhering to the complete treatment process and reducing the high burden of TB among the Saharia community. In addition, tribal patients should be counselled at regular intervals to increase their confidence in the treatment.

Microbial fibrinolytic proteases are therapeutic enzymes responsible to ameliorate thrombosis, a fatal cardiac-disorder which effectuates due to excessive fibrin accumulation in blood vessels. Inadequacies such as low fibrin specificity, lethal after-effects and short life-span of available fibrinolytic enzymes stimulates an intensive hunt for novel, efficient and safe substitutes. Therefore, we herewith suggest a novel and potent fibrinolytic enzyme RFEA1 from Bacillus cereus RSA1 (MK288105). Although, attributes such as in-vitro purification, characterization and thrombolytic potential of RFEA1 were successfully accomplished in our previous study. However, it is known that structure-function traits and mode of action significantly aid to commercialization of an enzyme. Also, predicting structural model of a protein from its amino acid sequence is challenging in computational biology owing to intricacy of energy functions and inspection of vast conformational space. Our present study thus reports In-silico structural-functional analysis of RFEA1. Sequence based modelling approaches such as—Iterative threading ASSEmbly Refinement (I-TASSER), SWISS-MODEL, RaptorX and Protein Homology/analogY Recognition Engine V 2.0 (Phyre2) were employed to model three-dimensional structure of RFEA1 and the modelled RFEA1 was validated by structural analysis and verification server (SAVES v6.0). The modelled crystal structure revealed the presence of high affinity Ca1 binding site, associated with hydrogen bonds at Asp147, Leu181, Ile185 and Val187residues. RFEA1 is structurally analogous to Subtilisin E from Bacillus subtilis 168. Molecular docking analysis using PATCH DOCK and FIRE DOCK servers was performed to understand the interaction of RFEA1 with substrate fibrin. Strong RFEA1-fibrin interaction was observed with high binding affinity (−21.36 kcal/mol), indicating significant fibrinolytic activity and specificity of enzyme RFEA1. Overall, the computational research suggests that RFEA1 is a subtilisin-like serine endopeptidase with proteolytic potential, involved in thrombus hydrolysis.