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Abstract Introduction Primary health care has regained its importance in global policy making. In 2018, the Government of India initiated the Ayushman Bharat - Comprehensive Primary Health Care (AB-CPHC) programme. It was based on upgrading the existing primary health facilities into Health and Wellness Centers (HWCs). The current study aimed to assess the readiness and performance of HWCs in providing comprehensive primary health care services in India’s Chhattisgarh state. Methods We conducted a cross-sectional health facility assessment with a state-representative sample of 404 HWCs. A standardized health facility survey tool was used to collect information on essential inputs and service outputs of HWCs. The expected population healthcare needs were estimated using secondary sources. The performance of HWCs was assessed by comparing the volume of services provided against the expected population need for outpatient care. Results On an average, 358 outpatients including 128 non-communicable disease (NCD) patients were treated monthly at an HWC. HWCs were able to cover 31% of the total population’s health need for outpatient care, 26% for hypertension, and 21% for diabetes care. In addition to services for reproductive and child health, HWCs provided services for common acute ailments (cold, cough, fever, aches and pains); infections of skin, eye, ear, and reproductive tract, and minor injuries. HWCs were also contributing significantly to national disease control programmes. Acute ailments followed by NCDs and communicable diseases had the largest share among services provided. The key gaps were in coverage of mental illnesses and chronic respiratory diseases. Most of the HWCs showed adequate readiness for the availability of required human resources, supplies, and infrastructure. Conclusion HWCs were able to provide a comprehensive range of primary care services and able to cater to a sizable portion of the rural population’s acute and chronic health care needs. The performance was made possible by the adequate availability of medicines, staff, training programmes and tele-consultation linkages. If HWCs in other states are able to reach a similar level of performance, the initiative will prove to be a game changer for equitable primary care in India.

Abstract Background Defects in the ataxin-2 (ATXN-2) protein and CAG trinucleotide repeat expansion in its coding gene, Atxn-2, cause the neurodegenerative disorder spinocerebellar ataxia type 2 (SCA2). While clinical studies suggest potential benefits of human-derived mesenchymal stem cells (hMSCs) for treating various ataxias, the exact mechanisms underlying their therapeutic effects and interaction with host tissue to stimulate neurotrophin expression remain unclear specifically in the context of SCA2. Methods Human bone marrow-derived MSCs (hMSCs) were injected into the cisterna magna of 26-week-old wild-type and SCA2 mice. Mice were assessed for impaired motor coordination using the accelerating rotarod, open field test, and composite phenotype scoring. At 50 weeks, the cerebellum vermis was harvested for protein assessment and immunohistochemical analysis. Results Significant loss of NeuN and calbindin was observed in 25-week-old SCA2 mice. However, after receiving multiple injections of hMSCs starting at 26 weeks of age, these mice exhibited a significant improvement in abnormal motor performance and a protective effect on Purkinje cells. This beneficial effect persisted until the mice reached 50 weeks of age, at which point they were sacrificed to study further mechanistic events triggered by the administration of hMSCs. Calbindin-positive cells in the Purkinje cell layer expressed bone-derived neurotrophic factor after hMSC administration, contributing to the protection of cerebellar neurons from cell death. Conclusion In conclusion, repeated administration of hMSCs shows promise in alleviating SCA2 symptoms by preserving Purkinje cells, improving neurotrophic support, and reducing inflammation, ultimately leading to the preservation of locomotor function in SCA2 mice.

Abstract Objective To evaluate implementation of a patient decision aid for symptomatic uterine fibroid management to improve shared decision-making at five clinical settings across the United States. Methods We used a type 3 hybrid effectiveness-implementation stepped-wedge design and the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) planning and evaluation framework. We conducted clinician training, monthly reach tracking with feedback to site clinical leads, patient and clinician surveys, and visit audio-recordings. Implementation strategies included assessment of organizational readiness for shared decision-making, synchronous clinician training, audit and feedback of decision aid reach, and access to multiple decision aid formats. Outcomes and analyses included patient-level reach, clinician-level adoption, and associations of patient-reported decision aid exposure (as treated) and setting-level implementation (intention-to-treat) with patient-reported (collaboRATE measure) and observed (OPTION-5 measure) shared decision-making. We also designed and assessed setting-level plans for sustainability and other factors impacting sustained decision aid use. Results The decision aid was adopted by 72 of the 74 eligible gynecologists (97%) and reached 2553 patients across five settings. CollaboRATE scores improved among patients who reported receiving the decision aid (as-treated analysis, 69% vs. 59%; OR 1.6, 95% CI 1.16–2.27). CollaboRATE scores remained consistent before and after setting-level decision aid implementation (intention-to-treat analysis, 64% vs. 63%; OR 0.86, 95% CI 0.61–1.22). Participants would prefer to receive a decision aid at multiple time points (91.9% before the visit, 90.7% during the visit, 86.5% after the visit). Shared decision-making experiences did not improve when comparing pre vs. post-implementation collaboRATE scores across included settings (intention-to-treat, 64% vs. 63%; OR 0.86, 95% CI 0.61–1.22). Conclusion When patients with symptomatic uterine fibroids are given decision aids, they report higher shared decision-making scores. However, the differences we observed between the as-treated and intention-to-treat results suggest that unaddressed implementation challenges continue to limit the extent to which patients receive decision aids and likely hinder their overall impact. Future efforts to implement decision aids should explore enhancing their integration into clinical workflows and standard operating procedures, supported by organizational incentives that prioritize shared decision-making. Trial registration ClinicalTrials.gov NCT03985449; registered 6 June 2019.

Abstract Background Telemedicine holds immense potential to revolutionise healthcare delivery, particularly in resource-limited settings and for patients with chronic diseases. Despite proven benefits and policy reforms, the use of telemedicine remains low due to several patient, technology, and system-level barriers. Assisted telemedicine employs trained health professionals to connect patients with physicians, which can improve access and scope of telemedicine. The study aims to describe the design, service utilisation and chronic disease outcomes following the implementation of an assisted telemedicine initiative. Methods This is an observational implementation study. Barriers and potential solutions to the implementation of telemedicine were identified through interviews with key stakeholders. The assisted telemedicine solution using an interoperable platform integrating electronic health records, point-of-care diagnostics, and electronic clinical decision support systems was designed and piloted at three telemedicine clinics in Tamil Nadu, India. Nurses were trained in platform use and facilitation of tele-consultations. Health records of all patients from March 2021 to June 2023 were included in the analysis. Data were analysed to assess the utilisation of clinic services and improvements in health outcomes in patients with diabetes mellitus and hypertension. Results Over 2.4 years, 11,388 patients with a mean age of 45 (± 20) years and median age of 48 years, predominantly female (59.3%), accessed the clinics. The team completed 15,437 lab investigations and 26,998 consultations. Among 5542 (48.6%) patients that reported chronic conditions, diabetes mellitus (61%) and hypertension (45%) were the most frequent. In patients with diabetes mellitus and hypertension, 43% and 75.3% were newly diagnosed, respectively. Diabetes mellitus and hypertension patients had significant reductions in fasting blood sugar (-33.0 mg/dL (95% CI (-42.4, -23.7, P

Abstract Background The value of co-produced research in health and social care is increasingly recognised, but accounts into the processes and individual experiences of co-producing research are lacking. This paper describes the personal journeys of four researchers (two experts by foster caring experience and two experts by profession) throughout the life course of a co-produced research project exploring the barriers and facilitators to inclusive research in foster caring, the InCLUDE project. Methods Each researcher kept a diary throughout the InCLUDE project of their personal reflections, questions, and learning. These were synthesised and reviewed by the researchers and two colleagues external to the team, and key themes were extracted. Results Narratives constructed from the diaries are presented in relation to distinct aspects of the co-production journey, alongside illustrative quotes. These aspects include: motivations for starting the project; making sense of the project; defining roles and responsibilities; challenges; and reflections on acquired knowledge and skills. From these insights, the researchers present recommendations for others endeavouring to engage in co-produced research. These include: recognising vulnerabilities and challenges during the early stages of a project; creating safe spaces; seeing the value of diversity; harnessing individual strengths; establishing a strong routine; and ensuring equal voice. Conclusions This paper presents a novel perspective on the realities of co-produced research by documenting the lived experiences of researchers within the context of foster care research. It highlights the importance of both measurable, tangible project outcomes, and the personal and skills growth of team members. The consistent use of diaries is encouraged as a valuable practice to capture learning, progress and achievements throughout the co-production process.

Abstract Burn injuries are serious injuries that have a big impact on a person’s health and can even cause death. Incurring severe burns can incite an immune response and inflammation within the body, alongside metabolic changes. It is of utmost importance to grasp the fact that the effects of the burn injury extend beyond the body, affecting the mind and overall well-being. Burn injuries cause long-lasting changes that need to be taken care of in order to improve their quality of life. The intricate process of skin regeneration at the site of a burn wound involves a complex and dynamic interplay among diverse cells, growth factors, nerves, and blood vessels. Exciting opportunities have arisen in the field of stem cells and regenerative medicine, allowing us to explore the development of cell-free-based alternatives that can aid in the treatment of burn injuries. These cell-free-based therapies have emerged as a promising facet within regenerative medicine. Exosomes, also referred to as naturally occurring nanoparticles, are small endosome-derived vesicles that facilitate the delivery of molecular cargo between the cells, thus allowing intercellular communication. The knowledge gained in this field has continued to support their therapeutic potential, particularly in the domains of wound healing and tissue regeneration. Notably, exosomes derived from mesenchymal stem cells (MSCs) can be safely administered in the system, which is then adeptly uptaken and internalized by fibroblasts/epithelial cells, subsequently accelerating essential processes such as migration, proliferation, and collagen synthesis. Furthermore, exosomes released by immune cells, specifically macrophages, possess the capability to modulate inflammation and effectively diminish it in adjacent cells. Exosomes also act as carriers when integrated with a scaffold, leading to scarless healing of cutaneous wounds. This comprehensive review examines the role of exosomes in burn wound healing and their potential utility in regeneration and repair. Graphical Abstract

Abstract Chronic Limb Threatening Ischemia (CLTI) is a challenging clinical problem associated with high morbidity and mortality. Endovascular interventions have been the cornerstone of treatment whenever possible. It is estimated that CLTI represents

Abstract Background Migraine is a severe neurological disorder that is recognized as one of the most common debilitating diseases worldwide. Although the exact cause of migraine is not known, research suggests that inflammation, oxidative stress, mitochondrial dysfunction, and insufficient nutrients may contribute to its development. Studies indicate that nutrition-based approaches are safer and more cost-effective strategies for managing migraine symptoms compared to medication. In this regard, the impact of nutrition, as a complementary medicine, is largely attributed to that of certain nutrients on inflammation and mitochondrial function. It is hypothesized that alpha-linolenic acid and L-carnitine, which possess anti-inflammatory and antioxidant properties, may be synergically beneficial for migraine patients. Therefore, this study will be conducted to assess the efficacy of alpha-linolenic acid and L-carnitine co-supplementation in patients with migraine. Methods This is a parallel, randomized, triple-blind, placebo-controlled clinical trial, in which 80 women aged 20 to 50 years with migraine will be assigned to receive either intervention group (n = 40) receiving both 1000 mg/day flaxseed oil and 500 mg/day L-carnitine simultaneously for 12 weeks, or control group (n = 40) receiving both 1000 mg/day paraffin oil and 500 mg/day maltodextrin as the placebos for the same duration. The primary outcomes include changes in clinical symptoms of migraine, including frequency, severity, and duration of attacks, serum levels of C–reactive protein (CRP), total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), and superoxide dismutase (SOD). Secondary outcomes include mental health, sleep quality, and quality of life (QOL). Discussion In this study, we aim to investigate the potential benefits of combining alpha-linolenic acid and L-carnitine as a treatment option for migraine sufferers. Migraine, characterized by recurrent severe headaches, affects a significant portion of the population and can significantly impact an individual's quality of life. By studying alternative therapies such as alpha-linolenic acid and L-carnitine, researchers hope to expand the range of treatment options available and potentially provide relief to migraine sufferers. Trial registration Iranian Registry of Clinical Trials ( www.irct.ir ) (ID: IRCT20121216011763N57). Registration date: 29 March 2023. Trial status The protocol is version 1.0 dated December 30, 2023. Recruitment began on July 10, 2023, and is expected to be completed by January 22, 2024.

Male infertility is an emerging health problem and there is an urgent need to search for therapeutic options. Altered metabolic states such as obesity and metabolic syndrome have been linked with male infertility. Therefore, searching for metabolic biomarkers is vital. Present work aimed to study metabolic alterations in infertile males. The seminal levels of L-Carnitine (LC), Kisspeptin (Kiss1) and Ghrelin (GHRL) were evaluated in 14 infertile and 10 fertile males. Baseline semen analysis was performed for both cases and controls. The levels of LC and Kiss1 were found to be lower in infertile patients as compared to fertile controls and the difference was found to be statistically significant. There was no significant difference observed in GHRL levels between patients and controls. The study presents a preliminary data where LC and Kiss1 levels could possibly studied further for their association with male infertility. But to confirm their association with pathogenesis of male infertility, future studies need to be conducted in larger cohorts.

Liver transplantation is the most effective treatment for end-stage liver disease. Despite improvements in surgical techniques, transplant rejection remains a significant concern. The liver is considered an immune-privileged organ due to its unique microenvironment and complex interactions among various cell types. Alloimmune responses mediated by T cells and antigen-presenting cells (APCs) play crucial roles in transplant rejection. The liver’s dual blood supply and unique composition of its sinusoidal endothelial cells (LSECs), Kupffer cells (KCs), hepatocytes, and hepatic stellate cells (HSCs) contribute to its immune privilege. Alloantigen recognition by T cells occurs through direct, indirect, and semidirect pathways, leading to acute cellular rejection (ACR) and chronic rejection. ACR is a T cell-mediated process that typically occurs within the first few weeks to months after transplantation. Chronic rejection, on the other hand, is a gradual process characterized by progressive fibrosis and graft dysfunction, often leading to graft loss. Acute antibody-mediated rejection (AMR) is less common following surgery compared to other solid organ transplants due to the liver’s unique anatomy and immune privilege. However, when it does occur, AMR can be aggressive and lead to rapid graft dysfunction. Despite improvements in immunosuppression, rejection remains a challenge, particularly chronic rejection. Understanding the mechanisms of rejection and immune tolerance, including the roles of regulatory T cells (Tregs) and hepatic dendritic cells (DCs), is crucial for improving transplant outcomes. Strategies to induce immune tolerance, such as modulating DC function or promoting Treg activity, hold promise for reducing rejection and improving long-term graft survival. This review focuses on the liver’s unique predisposition to rejection and tolerance, highlighting the roles of individual cell types in these processes. Continued research into the mechanisms of alloimmune responses and immune tolerance in liver transplantation is essential for developing more effective therapies and improving long-term outcomes for patients with end-stage liver disease.

Abstract Background The human endometrium, lining the inner uterus, regenerates over 400 times uniquely during a woman’s reproductive life. Endometrial stem cells (eSCs) enrich the tissue, resulting in a dense vascular network, significant angiogenic potential, and effective regeneration power. Being of natural angiogenic properties and proven effective in the treatment of vascular disorders, eSCs can be considered safe, reliable, and superior to other post-natal stem cells. Cluster of Differentiation 146 (CD146) has emerged as a pivotal marker associated with pericytes and endothelial cells for promoting angiogenesis. Endometrial cells with high CD146 expression could proliferate and differentiate into multiple lineages. This study will explore the role of CD146 in eSCs, focusing on the potential to boost the angiogenic and regenerative functions of the cells. The novelty of this study lies in the investigation of CD146 on eSC function, which may open new possibilities for eSC-based therapy in regenerative medicine and vascular disorders. Methods The study involved obtaining endometrial biopsies from active reproducing women to isolate and cultivate eSCs. eSCs were assessed for growth factor secretion pattern, characterized for their mesenchymal properties. Finally, eSCs were tested for their angiogenic potential by angiogenic gene expression profile and in-ovo chick embryo model. As aimed, to check the role of CD146 in eSC angiogenesis, CD146+ cells were magnetically sorted and cultured. The sorted cells underwent various analyses, including flowcytometry to identify mesenchymal markers and human growth factor panel to analyze growth factor secretion profiles The study evaluated the angiogenic potential of CD146 + cells using functional assays, including ring formation, endothelial differentiation, and wound scratch assays, to evaluate cell migration and healing capabilities. Molecular insights were obtained through chemokine and cytokine investigations In-ovo Chick model assay was conducted to check the angiogenic potential and evaluated through macroscopic as well as through immunohistochemistry. Result Endometrial stem cells (eSCs) were successfully isolated using a combination of mechanical and enzymatic digestion, followed by culturing in complete DMEM media. The secretion profile of eSCs revealed significant production of various angiogenic growth factors, including Granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte colony stimulating factor (G-CSF), Vascular endothelial growth factor (VEGF), Fibroblast growth factors (FGF), and Platelet derived growth factor AA (PDGF-AA). The angiogenic gene profile indicated upregulation of several angiogenic genes in eSCs. The mesenchymal nature of eSCs was demonstrated through surface marker analysis (Cluster of differentiation 73, Cluster of differentiation 90, Cluster of differentiation 105) and trilineage differentiation. The in-ovo chick model confirmed the angiogenic potential of eSCs. CD146+ cells, isolated via magnetic sorting, exhibited enhanced angiogenic potential. These cells secreted significant levels of angiogenic growth factors such as VEGF. In Matrigel assays, CD146+ cells formed endothelial ring structures more rapidly and persistently than unsorted eSCs. Semi-quantitative PCR confirmed their endothelial differentiation. CD146+ cells express various angiogenic chemokines such as CXCL5, CXCL8, CCL3, and CCL20 and cytokines such as GM-CSF, Interleukin-1β (IL-1β), Interleukin-6 (IL-6), PDGF AA/BB, Epidermal growth factor (EGF), Endothelin 1, Angiopoietin. In-ovo chick model assay showed that CD146+ cells had superior angiogenesis, with more nodes, junctions, and segments compared to eSCs and controls. Immunohistochemistry confirmed increased expression of endothelial markers (Cluster of differentiation 31, VEGF, Vascular associated protein (VAP), Von Willebrand factor (vWF) in CD146+ cells. Conclusion The study highlights the angiogenic potential of endometrial stem cells, particularly the CD146+ cell population. These cells promote angiogenesis, secreting growth factors and forming stable blood vessel structures. CD146+ cells have higher expression levels of VEGF and TGF-α, key factors in angiogenesis. This suggests CD146+ eSCs may be promising for therapeutic applications in vascular diseases requiring angiogenesis. Further research is needed.

Background: Periprosthetic Joint Infection (PJI) is a nightmare for both patient and surgeon. Despite advances made in arthroplasty still incidence is 1-2%. Many of our understanding regarding PJI come from registry data. Despite performing large number of joint replacement surgeries there is a lack of optimal registry data from this part of world. We retrospectively analysed PJI data in four NABH accredited hospital of around 5370 patients and tried to identify common risk factors in them and proposed a clinical scoring system for assessing risk of PJI. Materials and Methods: The study population was patients requiring surgical intervention in the form of arthroplasty. PJIs were defined as patients requiring procedure at the operated site within 2 years of index surgery. We retrospectively analysed patients’ data from hospital records and lab investigations done at the time of surgery. Results: We found that statistical significant risk factor in our study were number of joint replacement performed, poor blood glucose and serum albumin, increase duration and complexity of surgeries, Rheumatoid Arthritis (RA), Chronic Kidney Disease (CKD) and chronic liver disease and use of allogenic blood transfusion. Relative risk (RR) of diabetes (RR 2.4), liver disease (RR 1.6), connective tissue and rheumatic diseases (RR 1.5), serum albumin (RR 2.1), allogenic blood transfusion (RR 2.3), Increase duration for surgery (RR2.1), CKD (RR1.3) was there with PJI. Conclusions: Our research consistently identified the most significant risk factors for PJI across all cases. We propose a patient-based scoring system to estimate individual PJI risk. By addressing modifiable risk factors before joint replacement, we can potentially reduce the incidence of PJI.

Introduction: Children with beta thalassemia are on regular blood transfusions, which could result in iron deposition in the liver causing decreased synthesis of Vitamin D-25OH. There are limited publications on the association of Vitamin D deficiency with blood transfusion-dependent thalassemia in the Nepalese population. This study aims to determine the prevalence of Vitamin D deficiency among blood transfusion-dependent beta-thalassemia patients. Methods: This was a descriptive cross-sectional study conducted among beta-thalassemia major patients under 15 years of age, receiving regular blood transfusion, from July 17, 2022, to July 16, 2023, after ethical approval obtained from Ethical Review Committee, Kanti Children’s Hospital (reference number 155). Data were collected using convenience sampling, and descriptive analyses were performed using Microsoft Excel and Statistical Package for Social Sciences (SPSS) 2024. Results: A total of 127 blood transfusion-dependent beta-thalassemia major patients were included in the study, of whom 82 (64.56%) were male. Among these patients, 104 (81.88%) were aged between 5 and 14 year. Almost one-third 41 (32.28%) had Vitamin D insufficiency, and a quarter, 34 (26.77%), had Vitamin D deficiency. Ten percent of the children were underweight, and a quarter were stunted. Conclusions: Children with blood transfusion dependent beta thalassemia major are at a greater risk for Vitamin D deficiency and iron overload

Chat generative pretrained transformer (ChatGPT) is a conversational language model powered by artificial intelligence (AI). It is a sophisticated language model that employs deep learning methods to generate human-like text outputs to inputs in the natural language. This narrative review aims to shed light on ethical concerns about using AI models like ChatGPT in writing assistance in the health care and medical domains. Currently, all the AI models like ChatGPT are in the infancy stage; there is a risk of inaccuracy of the generated content, lack of contextual understanding, dynamic knowledge gaps, limited discernment, lack of responsibility and accountability, issues of privacy, data security, transparency, and bias, lack of nuance, and originality. Other issues such as authorship, unintentional plagiarism, falsified and fabricated content, and the threat of being red-flagged as AI-generated content highlight the need for regulatory compliance, transparency, and disclosure. If the legitimate issues are proactively considered and addressed, the potential applications of AI models as writing assistance could be rewarding.

Abstract Background Infectious keratitis secondary to fungus or acanthamoeba often has a poor outcome despite receiving the best available medical therapy. In vitro rose bengal photodynamic therapy (RB-PDT) appears to be effective against fungal and acanthamoeba isolates (Atalay HT et al., Curr Eye Res 43:1322–5, 2018, Arboleda A et al. Am J Ophthalmol 158:64-70, 2014). In one published series, RB-PDT reduced the need for therapeutic penetrating keratoplasty in severe bacterial, fungal, and acanthamoeba keratitis not responsive to medical therapy. Methods This international, randomized, sham and placebo controlled 2-arm clinical trial randomizes patients with smear positive fungal and acanthamoeba and smear negative corneal ulcers in a 1:1 fashion to one of two treatment arms: 1) topical antimicrobial plus sham RB-PDT or 2) topical antimicrobial plus RB-PDT. Discussion We anticipate that RB-PDT will improve best spectacle-corrected visual acuity and also reduce complications such as corneal perforation and the need for therapeutic penetrating keratoplasty. This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. Our results will be disseminated via ClinicalTrials.gov website, meetings, and journal publications. Our data will also be available upon reasonable request. Trial registration NCT, NCT05110001 , Registered on November 5, 2021.

The integration of artificial intelligence (AI) into healthcare practice has improved patient management and care. Many clinical laboratory specialties have already integrated AI in diagnostic specialties such as radiology and pathology, where it can assist in image analysis, diagnosis, and clinical reporting. As AI technologies continue to advance, it is crucial for biomedical science students to receive comprehensive education and training in AI concepts and applications and to understand the ethical consequences for such development. This review focus on the importance of integrating AI into biomedical science curricula and proposes strategies to enhance curricula for different specialties to prepare future healthcare workers. Improving the curriculum can be achieved by introducing specific subjects related to AI such as informatics, data sciences, and digital health. However, there are many challenges to enhancing the curriculum with AI. In this narrative review, we discuss these challenges and suggest mitigation strategies.

Abstract Background Adolescents and Young Adult (AYA) cancer survivors are at risk for psychological distress due to their unique developmental and medical needs. Healthcare providers can leverage the convenience and appeal of technology to provide supportive care for this vulnerable population. Using evidence-based mindfulness-based mobile interventions as a case example, the goal of this study was to identify key patient-, provider-, and organization-level barriers and facilitators to supportive care and implementing digital health interventions in AYA survivorship care. Methods Twenty semi-structured interviews were conducted with stakeholders including AYA survivors (n = 10; between 18–29 years old) and clinical providers and administrators (n = 10). Interviews were transcribed and deductively mapped using the Consolidated Framework for Implementation Research (CFIR) and Theoretical Domains Framework (TDF) complementary frameworks. Results Results indicated that factors like cost and patients’ needs and resources were prevalent among both survivors and providers. There were key differences between providers and AYA survivors. Providers’ adoption and promotion of digital health interventions were influenced most strongly by contextual factors, including available resources (Inner Setting), culture (Outer Setting), and networks and communications (Outer Setting). On the other hand, survivors emphasized individual and intervention-related factors; they reported that social influence and knowledge influenced their adoption and use of digital health interventions, including meditation apps. Conclusions These results identified barriers and facilitators to the adoption of supportive care digital health interventions from multiple stakeholders. Results can be used to guide the development of implementation strategies to improve the uptake of digital health interventions in survivorship care, ultimately improving the psychosocial well-being of AYA cancer survivors.

Lung cancer is the leading cause of cancer-related deaths worldwide. Many patients tend to have a very poor prognosis due to being diagnosed at an advanced stage especially in densely populated nations. The current study presents a case series of lung tumors. All the lung tumors presented as endobronchial mass; however histopathological diagnoses were different in each of the lung tumors after bronchoscopic guided lung mass biopsies. The first case was small cell lung cancer (SCLC) with endobronchial growth in a 64‑year‑old male. Bronchoscopy was suggestive of Left vocal cord palsy. The tiny nodule was seen over both cords with nodule present over carina. Chest CT scans revealed a well-defined irregularly shaped mass lesion with spiculated margin seen in the left lower lobe. The analysis of a biopsy specimen obtained from the tumor resulted in a diagnosis of SCLC. The second case was of non-small cell lung cancer (NSCLC) with endobronchial growth in a 77-year-old male. CECT reveals a right upper lobe malignant mass lesion with mediastinal invasion with mediastinal metastatic nodes. Bronchoscopy revealed a right upper lobe malignant mass. Histopathological examination revealed features consistent with NSCLC of Squamous cell carcinoma. The third case was a 58-year-old male whose CECT Thorax revealed a malignant pulmonary mass lesion in the left hilar region. Bronchoscopy was suggestive of endobronchial growth present in Left main bronchus around 1.5 cm from the carina. Tissue taken from the Left Hilar mass showed features of NSCLC-Adenocarcinoma carcinoma of the lung.

Abstract Background This update outlines amendments to the CHAMPION2/STRIPES2 cluster randomised trial protocol primarily made due to the COVID-19 pandemic and nationwide lockdown in India in 2020. These amendments were in line with national guidelines for health research during the COVID-19 pandemic. Methods We did not change the original trial design, eligibility, and outcomes. Amendments were introduced to minimise the risk of COVID-19 transmission and ensure safety and wellbeing of trial staff, participants, and other villagers. CHAMPION2 intervention: participatory learning and action (PLA) and fixed day service (FDS) meeting were revised to incorporate social distancing and hygiene precautions. During the COVID-19 pandemic, PLA participation was limited to pregnant women and birthing partners. STRIPES2 intervention: before/after-school classes were halted for a period and then modified temporarily (reducing class sizes, and/or changing meeting places) with hygiene and safe distancing practices introduced. Data collection: The research team gathered as much information as possible from participants by telephone. If the participant had no telephone or could not be contacted by telephone, data were collected in person. COVID-19 precautions: trial teams were trained on COVID-19 precautions and used personal protective equipment whilst in the villages for trial-related activities. After restarting the trial between June and September 2020 in a phased manner, some trial activities were suspended again in all the trial villages from April to June 2021 due to the second wave of COVID-19 cases and lockdown imposed in Satna, Madhya Pradesh. Trial timelines were also revised, with outcomes measured later than originally planned. Trial registration Clinical Trial Registry of India CTRI/2019/05/019296. Registered 23 May 2019. https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MzExOTg=&Enc=&userName=champion2 .

Abstract Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on “sepsis,” the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the “physician diagnosed sepsis.” To align all the three above, the investigators meeting, held on 17th–18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that “physician diagnosed sepsis” is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine “physician diagnosed sepsis”: (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes. Trial registration Clinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

Redoy Ranjan,1 Gie Ken-Dror,1 Pankaj Sharma1,2 On behalf of the BEAST Collaborators1Department of Biological Sciences, Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, Greater London, UK; 2Department of Clinical Neuroscience, Imperial College Healthcare NHS Trust, London, UKCorrespondence: Pankaj Sharma, Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, Greater London, TW20 0EX, UK, Email pankaj.sharma@rhul.ac.ukIntroduction: Risk prediction models are commonly performed with logistic regression analysis but are limited by skewed datasets. We utilised neural networks (NNs) model to identify independent predictors of poor outcomes in cerebral venous thrombosis (CVT) due to the limitations of logistic regression (LR) analysis with complex datasets.Methods: We evaluated 1309 adult CVT patients from the prospective BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. The area under the receiver operating characteristic (AUROC) curve confirmed the goodness-of-fit of prediction models. The normalised importance (NI) of the NNs determines the significance of independent predictors.Results: The stepwise logistic regression model found thrombolysis (OR 32.1; 95% CI 3.6– 287.0; P=0.002), craniotomy (OR 6.9; 95% CI 1.3– 36.8; P=0.02), and cerebral haemorrhage (OR 4.5; 95% CI 1.3– 15.4; P=0.01) as predictors of poor clinical outcome with the AUROC of 0.71. Conversely, the NNs model identified major independent predictors of long-term poor clinical outcomes as cerebral haemorrhage (NI 100%) and thrombolysis (NI 98%), as well as trivial predictors of age (NI 2.8%) and altered mental status (NI 3.5%). The accuracy of the NNs model was 95.1% and 94.1% for self-learned randomly selected training and testing samples with an AUROC of 0.82. Positive and negative predictive values for poor outcomes were 13.2% and 97.1% for the LR model, compared with the NNs model of 18.8% and 98.7%, respectively.Conclusion: Cerebral haemorrhage and thrombolysis was a strong independent predictor, whereas age merely impacts the long-term poor clinical outcome in adult CVT. Integrating unorthodox neural networks risk prediction model can improve decision-making as it outperforms conventional logistic regression with complex datasets.Keywords: cerebral venous thrombosis, neural network, stroke, predictors, outcome

Abstract Despite clinical benefits of tyrosine kinase inhibitors (TKIs) in cancer, most tumors can reactivate proliferation under TKI therapy. Here we present transcriptional profiling of HER2+ breast cancer cells transitioning from dormant drug tolerant cells to re-proliferating cells under continuous HER2 inhibitor (HER2i) therapy. Focusing on phosphatases, expression of dual-specificity phosphatase DUSP6 was found inhibited in dormant cells, but strongly induced upon regrowth. DUSP6 expression also selectively associated with poor patient survival in HER2+ breast cancers. DUSP6 overexpression conferred apoptosis resistance, whereas its pharmacological blockade prevented therapy tolerance development under HER2i therapy. DUSP6 targeting also synergized with clinically used HER2i combination therapies. Mechanistically DUSP6 is a positive regulator of HER3 expression, and its impact on HER2i tolerance was mediated by neuregulin-HER3 axis. In vivo, genetic targeting of DUSP6 reduced tumor growth in brain metastasis model, whereas its pharmacological targeting induced synthetic lethal therapeutic effect in combination with HER2i. Collectively this work demonstrates that DUSP6 drives escape from HER2i-induced dormancy, and that DUSP6 is a druggable target to overcome HER3-driven TKI resistance.

Abstract Background In Kenya, 65% of sexually active unmarried women use modern contraceptives, a population at increased risk of HIV acquisition compared to other populations. Anchoring HIV prevention services, including pre-exposure prophylaxis (PrEP), to trusted contraceptive delivery settings offers opportunities to efficiently reach this important population. In Kenya, almost half (40%) of women accessing contraception services do so outside traditional healthcare facilities, such as retail pharmacies. Thus, integrating PrEP services into retail pharmacies may increase options for reaching adolescent girls and young women (AGYW) who could benefit from PrEP. Efforts are underway to define care pathways for pharmacy-delivered PrEP services in Kenya, including unsupported and supported models with nurse navigators. Methods The AGYW Pharmacy PrEP study is an unblinded 2-arm cluster-randomized controlled trial in Kisumu, Kenya. The objective is to determine the effect that unsupported versus supported pharmacy-delivered PrEP services has on PrEP initiation, persistence, and adherence among AGYW seeking contraception. Twenty retail pharmacies offering pharmacy provider-led PrEP delivery will be randomized 1:1 to either receive or not receive a nurse navigator to support PrEP delivery. Eligible AGYW (n = 1900 total, n = 950/arm) will be ≥ 15 years old, purchasing a method of contraception at the pharmacy. Trained pharmacy provider will offer eligible AGYW either daily oral PrEP or the monthly DPV vaginal ring. The primary trial outcomes are PrEP initiation (use of PrEP at 1 month), persistence (use of PrEP at 10 months), and adherence (quantified by levels of TFV or DPV in hair samples). Additionally, several secondary (STI incidence, PrEP method selection, predictors of PrEP adherence) and exploratory outcomes (HIV incidence, quality of care, contraceptive method mix) will be explored. Discussion We hypothesize pharmacy-delivered PrEP services supported with nurse navigator, versus delivered by pharmacy providers alone, will improve PrEP outcomes among AGYW seeking contraception. Our results will help policy makers better understand how to potentially implement this novel differentiated service model for PrEP and prime pharmacies for the delivery of new PrEP agents in the pipeline (e.g., long-acting injectables and multi-purpose technologies). The study was initiated on May 13, 2023, and is expected to be completed by February 2025. Trial Registration ClinicalTrials.gov (NCT05467306), with registration on July 20, 2022.

Abstract Background Maternal dietary diversity is a key to improving the birth and child health outcomes. Besides socio-economic factors, the nutrition specific program- Social and Behavioural Change Communication (SBCC) interventions aimed to improve maternal dietary diversity has varied levels of impact on the socio-economic groups in poor resource setups. Objective To measure the factors associated with the minimum dietary diversity (MDD) among pregnant women in selected districts of Rajasthan with special emphasis on the SBCC components. Additionally, it measures the socio-economic gaps in the behaviour of consumption of diversified diet during pregnancy. Methods Data from a cross sectional survey of 6848 pregnant women, who have received a continuous SBCC counselling and registered under a state introduced conditional cash transfer program, during May to June, 2023, in five intervention districts -Banswara, Baran, Dunagrpur, Pratapgarh and Udaipur in Rajasthan was used. A 24 h recall based food consumption behaviour has been gathered to measure the MDD of pregnant women. Study has used descriptive statistics, multivariate regressions, and multivariate decomposition analysis to address the research objectives. Results Study finds that only 55.2% of pregnant women are consuming diverse diet in the study duration with mean dietary diversity score is 4.8 (+/- 1.5). Logistic regression finds that SBCC components such as frontline workers (aOR = 1.3, CI: 1.1–1.4), community motivators (aOR = 1.9, CI: 1.7–2.1), and participation in MCHND (aOR = 1.0, CI: 0.9-1.2) have significant and higher likelihood on consumption of MDD food on previous day. A higher education and belonging from richer wealth quintile also show higher association for consumption of MDD. Multivariate decomposition shows, among richest and poorest wealth categories there is 19% point difference (58% difference due to coefficient vs. 42% difference due to composition) in MDD consumption. This is positively contributed by the caste and educational categories of women. Conclusion Despite a predominant vegetarian diet consuming population, better maternal dietary diversity was observed among those exposed to higher dose of SBCC intervention package. Educational status and caste of the respondent were significantly associated with minimum dietary diversity and contributed to the socio-economic inequality highlighting the importance of tailored and sustained SBCC interventions.

Background: Iodine deficiency disorder results in avoidable brain damage, cognitive impairment, and inhibited growth and development among children. The aim of this study was to ascertain pervasiveness of IDD in the Bhuj City of Kutch district of Gujarat by measuring urinary iodine excretion levels(UIE) and iodine intake from salt among school-going children. Material and methods: A cross-sectional investigation was conducted to evaluate iodine deficiency levels in 350 schoolchildren of both genders, 6-12 years of ages, from Bhuj Taluka, a subdivision of the Kachchh district. The evaluation involved estimating urinary iodine levels through the Sandell–Kolthoff reaction and determining the iodine levels in samples of cooking salt using Spot testing kit (STK). Results: With a median iodine levels in urine of 166.93 μg/L, there appears to be no biochemical evidence of iodine deficiency in the region. Approximately 98.57% of salt samples found iodine levels exceeding 15 ppm, while only about 1.42% had iodine levels below 15 ppm, indicating that household salt samples contain adequate iodine levels. Conclusions: The region's median concentration of Iodine content found in urine 166.93μg/L, suggesting the absence of biochemical iodine deficiency. Analysis of salt samples revealed that approximately 98.57% contained iodine levels exceeding 15 ppm, while only about 1.42% had iodine content below this threshold. This indicates that household salt samples possess adequate iodine levels, aligning with criteria for monitoring progress in eradicating iodine deficiency disorders as a public health concern.

Bancroftian filariasis is caused by the filarial parasite Wuchereria Bancrofti and is transmitted by Culexmosquitoes. It is found in tropical and subtropical countries. Traditionally, peripheral blood smears identify this condition by finding microfilaria. Inadvertently found adult worms and microfilaria in fine needle aspiration cytology (FNAC). The disease may be missed in the absence of eosinophilia in a CBC or peripheral blood smear. One must be aware of this possibility. Chronic inflammation and lymphedema lead to lymphatic damage, swelling and elephantiasis of the legs, arms, scrotum, breasts, and vulva. A 29-year-old male patient presented with chief complaints of pain and swelling over the right lower limb for one and a half years. It was reported to be filariasis during laboratory investigations.

Objective: To assess the effect of coronavirus disease 2019 (COVID-19) infection on heart transplant recipients requiring immunotherapy. To investigate the effectiveness of vaccination in immunosuppressed heart transplant recipients during the initial years of the COVID-19 pandemic, and to examine the timing of COVID-19 infections in heart transplant recipients’ posttransplantation. Patients and Methods: International data on COVID-19 infection in immunosuppressed populations is limited. Heart transplant recipients requiring immunotherapy are at risk for increased complications with COVID-19 infection. The availability of vaccination and temporal trends in this population has not been well described. We report outcomes in immunosuppressed patients during the initial years of the COVID-19 pandemic from March 1, 2019, to October 31, 2021, at Mayo Clinic in Florida. Results: A total of 98 patients were reviewed, of which 49 were COVID-19–positive (CP), and 49 were negative (CN). The cohort was well matched, with a median age of 58 years (49–65 years) in both groups. Females consisted of 41% in the CP group and 18.4% in the CN group. Immunosuppression was not significantly different for CP or CN patients. The median time from transplant to CP was 384 days (237–677 days). The CN group’s median follow-up after transplant was 947 days (737–1191 days). The CP hospitalization rate was 24% with only 1 death. More CP patients were vaccinated than the CN group (92% vs 78%, P=.025). Conclusion: Our study sheds light on COVID-19’s effect on heart transplant recipients and vaccination in this population. Our findings suggest a potentially heightened infection risk within the first 1.5 years posttransplant, highlighting the need to optimize management strategies and vaccine efficacy in this vulnerable group.

الملخص: أهداف البحث: يعد السرطان سببا رئيسيا للوفاة على مستوى العالم ويضع عبئا ثقيلا على المرضى ومقدمي الرعاية لهم. غالبا ما يشعر مقدمو الرعاية بالتوتر، مما يؤثر على صحتهم العقلية. تهدف هذه الدراسة إلى تقييم مستويات القلق والاكتئاب بين مقدمي الرعاية غير الرسميين لمرضى السرطان في مستشفيات التعليم العالي المختارة في نيبال. بالإضافة إلى ذلك، سعت الدراسة إلى تحديد العوامل الاجتماعية والديموغرافية المرتبطة بنتائج الصحة العقلية. طريقة البحث: تم إجراء دراسة مقطعية على 383 من مقدمي الرعاية غير الرسميين باستخدام مقياس القلق والاكتئاب في المستشفى. وشملت التحليلات الإحصائية التحليل الوصفي والانحدار اللوجستي الثنائي لاستكشاف الارتباطات مع المتغيرات الاجتماعية والديموغرافية. النتائج: كان متوسط عمر المشاركين 36.1 ± 13.1، وتراوحت أعمار 56.1% منهم بين 12 و36 عاما. وكان معظمهم متزوجين (81.5%)، وعاطلين عن العمل (66.6%)، وحصلوا على التعليم الابتدائي حتى الثانوي (66.6%). كشفت النتائج عن انتشار ملحوظ للقلق المعتدل إلى الشديد (52٪) والاكتئاب (45٪) بين مقدمي الرعاية. مقدمو الرعاية للمرضى الذين يتلقون العلاج من مستشفى غير حكومي لديهم أكثر احتمالا ست مرات للإصابة بالقلق وأكثر احتمالا بخمس مرات للإصابة بالاكتئاب. الاستنتاجات: غالبا ما يشعر الأشخاص الذين يعتنون بمرضى السرطان في نيبال بالكثير من التوتر. إن معرفة أسباب هذه المشاعر يمكن أن يساعد في إنشاء برامج لدعم صحتهم العقلية. من المهم حقا الاهتمام بالصحة العقلية لمقدمي الرعاية من أجل رعاية أفضل لمرضى السرطان وحياة أكثر سعادة بشكل عام. Abstract: Objective: Cancer is a major cause of death globally, and places a substantial burden on both patients and their caregivers. Frequent stress among caregivers often affects their mental well-being. This study was aimed at assessing anxiety and depression levels among informal caregivers of patients with cancer treated at selected tertiary hospitals in Nepal. An additional aim was to identify socio-demographic factors associated with these mental health outcomes. Methods: In this cross-sectional study, 383 informal caregivers were surveyed with the Hospital Anxiety and Depression Scale (HADS). Statistical analyses, including descriptive analysis and binary logistic regression, were conducted to explore associations with socio-demographic variables. Results: The mean age of participants was 36.1 ± 13.1 years, and 56.1% were 12–36 years old. Most participants were married (81.5%), were unemployed (66.6%), and had primary to secondary education (66.6%). The prevalence of moderate to severe anxiety (52%) and depression (45%) among caregivers was notable. Caregivers of patients treated at non-governmental hospitals were six times more likely (OR 6.3, 95% CI: [3.62–10.95], P = 0.001) to have anxiety and five times more likely (OR 5.3, 95% CI: [8.28–19.32], P = 0.001) to have depression. Conclusion: People who take care of patients with cancer in Nepal often feel substantial stress. Determining the causes of these feelings can aid in the creation of programs to support caregivers’ mental health. Caring for mental well-being among caregivers is critical to achieving better cancer care and quality of life.

Introduction: Nodulin-26-like intrinsic proteins (NIPs) are integral membrane proteins belonging to the aquaporin family, that facilitate the transport of neutral solutes across the bilayer. The OsNIP2;1 a member of NIP-III class of aquaporins is permeable to beneficial elements like silicon and hazardous arsenic. However, the atomistic cross-talk of these molecules traversing the OsNIP2;1 channel is not well understood. Objective: Due to the lack of genomic variation but the availability of high confidence crystal structure, this study aims to highlight structural determinants of metalloid permeation through OsNIP2;1. Methods: The molecular simulations, combined with site-directed mutagenesis were used to probe the role of specific residues in the metalloid transport activity of OsNIP2;1. Results: We drew energetic landscape of OsNIP2;1, for silicic and arsenous acid transport. Potential Mean Force (PMF) construction illuminate three prominent energetic barriers for metalloid passage through the pore. One corresponds to the extracellular molecular entry in the channel, the second located on ar/R filter, and the third size constriction in the cytoplasmic half. Comparative PMF for silicic acid and arsenous acid elucidate a higher barrier for silicic acid at the cytoplasmic constrict resulting in longer residence time for silicon. Furthermore, our simulation studies explained the importance of conserved residues in loop-C and loop-D with a direct effect on pore dynamics and metalloid transport. Next we assessed contribution of predicted key residues for arsenic uptake, by functional complementation in yeast. With the aim of reducing arsenic uptake while maintaining beneficial elements uptake, we identified novel OsNIP2;1 mutants with substantial reduction in arsenic uptake in yeast. Conclusion: We provide a comprehensive assessment of pore lining residues of OsNIP2;1 with respect to metalloid uptake. The findings will expand mechanistic understanding of aquaporin’s metalloid selectivity and facilitate variant interpretation to develop novel alleles with preference for beneficial metalloid species and reducing hazardous ones.

Sushmita Negi,1,2,* Nikunj Tandel,3,* Neeraj K Garg,4 Prakriti Sharma,1 Rajinder Kumar,1 Praveen Sharma,1 Reetesh Kumar,5 Sheetal Saini,1 Aman Sharma,6 Rajeev K Tyagi1,2 1Biomedical Parasitology and Translational-Immunology Lab, Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Chandigarh, 160036, India; 2Academy of Scientific and Innovation Research (Acsir), Ghaziabad, 201002, India; 3Institute of Science, Nirma University, Ahmedabad, Gujarat, India; 4University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India; 5Faculty of Agricultural Sciences, Institute of Applied Sciences and Humanities, GLA University, Mathura, Uttar Pradesh, India; 6Clinical Immunology and Rheumatology Wing, Department of Internal Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India*These authors contributed equally to this workCorrespondence: Rajeev K Tyagi, Biomedical Parasitology and Translational-immunology Lab, Division of Cell Biology and Immunology, CSIR-Institute of Microbial Technology (IMTECH), Sec-39a, Chandigarh, 160036, India, Tel +91-172-6665278; +91-172-6665279, Email rajeevtyagi@imtech.res.in; rajeev.gru@gmail.comBackground: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events.Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund’s adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA.Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater “therapeutic index” of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations.Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the “combination drug regimen” to treat RA.Keywords: methotrexate, aceclofenac, lipid polymer hybrid nanoparticles, nanostructured lipid nanocarriers, rheumatoid arthritis, MMP-1

Primary thyroid lymphoma is one of the rare and distinct type of extra nodal lymphomas originating within the thyroid gland. It accounts for less than 5% of all thyroid malignancies and 2% of extra nodal lymphomas. It predominantly affects older adults, with a higher incidence in women. Patients typically present with a rapidly enlarging thyroid mass, accompanied by clinical symptoms of compression such as dysphagia, dyspnea, and hoarseness. Diagnosis is established through a combination of fine-needle aspiration, core needle biopsy, and advanced imaging techniques. Standard treatment involves a multimodal strategy of chemotherapy, often with the addition of radiotherapy and surgical intervention. Herein presented is the first reported case of diffuse large B-cell lymphoma treated with Pola-R-CHP.

Readiness to practice is the state of being prepared and capable of engaging in professional activities in a specific field. Graduates of healthcare professions require a diverse set of skills, knowledge and attitudes to meet the demands of complex healthcare settings. This systematic review provides a comprehensive analysis of readiness for professional practice among graduates of health professions education. It encompasses a wide range of articles published between 2013 and 2024, incorporating various health professions and utilizing a combination of quantitative, qualitative, and mixed methods designs. The review identified 93 studies from 32 diverse countries. The review revealed that factors influencing readiness to practice, include individual capabilities, the workplace context, and educational provision. It also explored strategies to enhance readiness to practice. The findings underscore the significance of addressing challenges such as lack of confidence, stress, communication, time management, job satisfaction, clinical experience, academic workload, teaching quality, mentorship and curriculum design. This comprehensive analysis serves as a valuable resource for healthcare educators, policymakers, and practitioners seeking to optimize the preparedness of graduates for the complexities of contemporary healthcare environments. Future studies should explore the interactions between readiness to practice stakeholders’ perception of the educational curriculum, and the quality of support in the professional practice environment.

Skin cancer is a widespread and perilous disease that necessitates prompt and precise detection for successful treatment. This research introduces a thorough method for identifying skin lesions by utilizing sophisticated deep learning (DL) techniques. The study utilizes three convolutional neural networks (CNNs)—CNN1, CNN2, and CNN3—each assigned to a distinct categorization job. Task 1 involves binary classification to determine whether skin lesions are present or absent. Task 2 involves distinguishing between benign and malignant lesions. Task 3 involves multiclass classification of skin lesion images to identify the precise type of skin lesion from a set of seven categories. The most optimal hyperparameters for the proposed CNN models were determined using the Grid Search Optimization technique. This approach determines optimal values for architectural and fine-tuning hyperparameters, which is essential for learning. Rigorous evaluations of loss, accuracy, and confusion matrix thoroughly assessed the performance of the CNN models. Three datasets from the International Skin Imaging Collaboration (ISIC) Archive were utilized for the classification tasks. The primary objective of this study is to create a robust CNN system that can accurately diagnose skin lesions. Three separate CNN models were developed using the labeled ISIC Archive datasets. These models were designed to accurately detect skin lesions, assess the malignancy of the lesions, and classify the different types of lesions. The results indicate that the proposed CNN models possess robust capabilities in identifying and categorizing skin lesions, aiding healthcare professionals in making prompt and precise diagnostic judgments. This strategy presents an optimistic avenue for enhancing the diagnosis of skin cancer, which could potentially decrease avoidable fatalities and extend the lifespan of people diagnosed with skin cancer. This research enhances the discipline of biomedical image processing for skin lesion identification by utilizing the capabilities of DL algorithms.

Introduction: The dural venous system, composed of various sinuses, plays a crucial role in draining deoxygenated blood from the central nervous system. Understanding its anatomical variations is essential to differentiate it from pathological conditions like cerebral venous sinus thrombosis. This study aims to evaluate the anatomical variations of the dural venous sinuses using Magnetic Resonance Venography. Methods: An observational, cross-section study was performed in the Department of Radiology from September 2023 to March 2024 after the approval by the Institutional Review Committee (Reference number: 149/080/081(6-11)E2). Magnetic Resonance Venography of 109 adult patients was performed using a 1.5 Tesla MRI scanner. Diameters of the superior sagittal sinus, straight sinus, and transverse sinuses were measured. Variations in transverse sinuses, straight sinus, and confluence were categorized and analyzed. Results: The study included 52 (47.70%) male and 57 (52.30%) female, with median age of 42 (IQR: 30.5 - 56) years. The superior sagittal sinus had the diameter of 6.4±1 mm. Symmetric transverse sinus variant seen was in 80 (73.39%) patients, and left transverse sinus hypoplasia was seen in 20 (18.35%) patients. Variations in the straight sinus and confluence were also documented with a true confluence (type III) was seen in 71 (65.10%) patients. Conclusions: Anatomical variations of the dural venous sinuses as observed in 1.5 Tesla MRI was quite common.

Key Clinical Message This report presents a 14‐year‐old male with seizures and facial port‐wine stains, who upon further evaluation was found to have SWS. Early diagnosis and consistent treatment of Sturge–Weber syndrome in children are essential to prevent seizures and improve quality of life. Anti‐seizure medications play a crucial role in preventing and controlling seizures.

Clostridium paraputrificum is a gram-positive anaerobic spore-forming bacillus with a pathological prevalence of

Spermatocytic Seminoma is a rare yet distinct testicular germ cell tumor which represent less than 01% of testicular tumor. Here we presented a case of testicular swelling in young male. On histopathological examination Spermatocytic Seminoma was confirmed. However, Spermatocytic Seminoma is common is elderly age group. Since the prognosis for this tumor type is favourable, accurate diagnosis and differentiation from other malignant testicular neoplasm (classical seminoma) is must for therapeutic management with long term follow up.

Introduction: This study aimed to investigate the pattern of developmental milestones of children born during the COVID-19 pandemic and the impact of caregivers' physical, psychosocial and economic wellbeing on achievement of developmental milestones in children. Methodology: A cross-sectional study was conducted on children (6 to 10 and

Summary: Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p 15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114–285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

Introduction: Most developing regions of the world are undergoing gradual epidemiological transition resulting in high burden of both communicable and noncommunicable diseases. Morbidity and mortality pattern is a reflection of disease burden. Detailed assessment of these parameters tends to aid in formulating pivotal aspects of in-hospital policies, standards of care and so consequently promoting efficient work systems. The aim of this study is to identify the pattern of mortalities in medical wards in a tertiary care hospital. Methods: This retrospective descriptive cross-sectional study was conducted in National Academy of Medical Sciences, Bir hospital focusing on all patients admitted to the medical wards (General Medical, Hepatology, Nephrology, Neurology, Endocrinology, Pulmonology, Cardiology and Gastrology) between January 1 to December 31, 2023 after obtaining ethical approval from Institutional Review Committee (Reference Number: 390/2080/81). Total population sampling was done. Data were analyzed using Microsoft Excel and SPSS. Results: Among 10124 admitted patients in medical wards, mortality was reported in 732 (7.22%). The number of deaths seen in general medical ward was 389 (53.14%) and in liver ward was 85 (11.61%). Systemic cause of death due to respiratory diseases was 157 (21.5%) and liver disease was 143 (19.6%). Conclusions: The respiratory disease is responsible for a higher proportion of deaths among admitted patients. However, the deaths due to liver disease are increasing because of the rise in cirrhosis of the liver in the younger age group.

IntroductionMetabolic dysfunction-associated steatotic liver disease (MASLD) has become a major cause of end-stage hepatic disease worldwide requiring liver transplantation, whereas cardiovascular disease (CVD) remains the leading cause of morbidity and mortality globally. Development of MASLD and CVD among young adults is understudied. This study aimed to assess CVD risk in healthy young medical university students using lipid-based and body mass index (BMI)-based 30-year Framingham risk scores (FS30) and to evaluate disease burden for asymptomatic patients with MASLD by performing FibroScan.MethodsWe included medical university students aged 18–30 years without any known medical conditions. All participants underwent physical and anthropometric measurements, and completed a questionnaire. Blood samples were collected for the analysis of glycosylated haemoglobin levels, renal and liver function, biomarker analysis to calculate liver fibrosis risk, and subclinical atherosclerosis biomarkers. Liver stiffness measurements (LSM) and controlled attenuation parameter (CAP) values were measured using FibroScan 430 mini to calculate liver fibrosis and steatosis, respectively. FS30 based on body mass index (FS30-BMI) and lipid levels (FS30-Lipid) were also calculated.ResultsOverall, 138 medical students participated in this study after providing informed consent. Using FS30-Lipid and FS30-BMI, CVD risk was identified in two (1.5%; n = 138) and 23 (17.6%; n = 132) individuals, respectively. MASLD fibrosis was identified based on FibroScan LSMs >7.0 kPa in 12 medical students (9.4%, n = 128; 95% CI, 4.7–14.8%). Consumption of coffee and sugary soft drinks were predictive of liver fibrosis. In total, 36 students (28.6%; n = 128) were found to have hepatic steatosis based on FibroScan CAP values >236 dB, and the predictive factors included increased body fat percentage, male sex, and lack of physical activity. Levels of inflammatory biomarkers, such as C-reactive protein and lipids were not elevated in participants with MASLD.DiscussionCVD risk was identified in >17% of young medical students. The frequency of liver fibrosis and steatosis was also high among the participants, indicating that liver damage starts at a relatively early age. Early intervention is needed among young adults via health promotion and lifestyle changes.

Key Clinical Message Left‐atrial septal pouch (LASP) is a newly described anatomical variant caused by incomplete fusion of the septa primum and secundum. This case visualizes LASP as a potential nidus for blood stasis and cardiac embolism and highlights the need for consideration of TEE in the work up of cryptogenic stroke.

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Summary: Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D15]octanoate to deuterated water and detection with deuterium magnetic resonance methods. Perfused livers from a mouse model of MASLD reveal dysregulated hepatic β-oxidation, findings that corroborate in vivo imaging. The high-fat-diet-induced MASLD mouse studies indicate that decreased β-oxidative efficiency in the fatty liver could serve as an indicator of MASLD progression. Furthermore, our method provides a clinically translatable imaging approach for determining hepatic β-oxidation efficiency.