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Introduction: Tinospora cordifolia (TC) possesses antioxidative properties and has been shown to improve cognition. In this study, the effects of TC were investigated on prenatal vibratory stress, maternal separation-induced amygdala plasticity, and memory retention in pregnant rats and their neonates. Methods: Four experimental animal groups of pregnant Wistar rats were employed in this research, including normal & vehicle controls, the stressed group, which received 3 hours of vibratory stress/day, and the TC-treated group, which received 6 mg/kg TC before vibratory stress. The neonates born to these mothers were then subjected to maternal separation, followed by postnatal TC treatment. After 6 weeks, the animals were assessed to evaluate memory retention, serum cortisol levels, and neuronal structural changes in the amygdala. Results: Neonates exposed to prenatal vibratory stress and maternal separation entered the dark compartment more quickly during the retention test (P

Abstract Background Mesenchymal stem cells (MSCs) have emerged as promising candidates for immune modulation in various diseases that are associated with dysregulated immune responses like Graft-versus-Host-Disease (GVHD). MSCs are pleiotropic and the fate of MSCs following administration is a major determinant of their therapeutic efficacy. Methods Human MSCs were derived from bone marrow (BM) and Wharton’s Jelly (WJ) and preconditioned through exposure to hypoxia and induction of apoptosis, either sequentially or simultaneously. The immune programming potential of preconditioned MSCs was evaluated by assessing their effects on T cell proliferation, induction of Tregs, programming of effector T-cell towards Th2 phenotype, macrophage polarization in the direct co-culture of MSCs and aGVHD patients-derived PBMNCs. Additionally, efferocytosis of MSCs and relative change in the expression of immunomodulatory soluble factors were examined. Results Our study demonstrated that hypoxia preconditioned apoptotic MSCs (BM-MSCs, WJ-MSCs) bear more immune programming ability in a cellular model of acute Graft-versus-Host-Disease (aGVHD). Our findings revealed that WJ-MSCsHYP+APO were superior to BM-MSCsHYP+APO for immune regulation. These induced the differentiation of CD4+T-cell into Tregs, enhanced Th2 effector responses, and simultaneously mitigated Th1- and Th17 responses. Additionally, this approach led to the polarization of M1 macrophages toward an M2 phenotype. Conclusion Our study highlights the potential of WJ-MSCs conditioned with hypoxia and apoptosis concurrently, as a promising therapeutic strategy for aGVHD. It underscores the importance of considering MSC apoptosis in optimizing MSCs-based cellular therapy protocols for enhanced therapeutic efficacy in aGvHD. Graphical Abstract

Abstract Background Mitochondrial DNA variants are significant contributors to cancer progression, as evidenced by numerous findings. This study focuses on characterizing mitochondrial DNA mutations in colorectal cancer progression and their potential as biomarkers. Methodology Next generation sequencing technology was employed to analyze mitochondrial DNA variants in tumor and adjacent normal tissues from 25 patients with colon/rectal cancer. In silico prediction tools (SIFT, Polyphen2, Mutation Assessor, and SNP&GO) were utilized to assess the pathogenicity of these variants. Additionally, homology modeling of mutated protein structures was conducted, and molecular dynamic simulations were performed to assess the impact of mutation on protein function. Results Eighteen variants were identified across most tumor tissue samples, located in genes from Complex I, IV, and V. Among the identified variants, the V302M and S461 mutations in the MT-ND5 gene and L137F and L220P mutations in the ATP6 gene were predicted to be deleterious, potentially affecting protein function. 3D structural analysis of both wild-type and mutant proteins of MT-ND5 revealed changes in flexibility for the V302M and S461G mutations. The MT-ATP6 mutations L135F and L220P disrupt the interactions with surrounding residues and affect the overall function of protein. Further changes in protein dynamics of the mutated proteins by molecular dynamic simulations also indicate the effects; the mutations have on protein function. Conclusion MT-ND5 and MT-ATP6 variants could serve as potential biomarkers and drug targets in colorectal cancer. This study underscores the significance of mitochondrial DNA variants in cancer progression.

Abstract Background Obstetric Bleeding Study UK (OBS UK) (award ID: 152057) is a National Institute for Health and Care Research (NIHR)-funded stepped wedge cluster randomised controlled trial of a complex intervention for postpartum haemorrhage. This was developed in Wales and evaluated in a feasibility study, with improvements in maternal outcomes observed. Generalisability of the findings is limited by lack of control data and limited ethnic diversity in the Welsh obstetric patient population compared to the United Kingdom (UK): 94% of the Welsh population identifies as White, versus 82% in the UK. Non-White ethnicity and socioeconomic deprivation are linked to increased risk of adverse maternal outcomes. Traditionally, decisions regarding site selection are based on desire to complete trials on target in ‘tried and tested’ research active institutions. To ensure widespread applicability of the results and investigate the impact of ethnicity and social deprivation on trial outcomes, maternity units were recruited that represent the ethnic diversity and social deprivation profiles of the UK. Method Using routinely collected, publicly available data, an interactive dashboard was developed that demonstrates the demographics of the population served by each maternity unit in the UK, to inform site recruitment. Data on births per year, ethnic and socioeconomic group of the population for each maternity unit, across the UK, were integrated into the dashboard. Results The dashboard demonstrates that OBS UK trial sites reflect the ethnic and socioeconomic diversity of the UK (study vs UK population ethnicity: White 79.2% vs 81.7%, Asian 10.5% vs 9.3%, Black 4.7% vs 4.0%, Mixed 2.5% vs 2.9%, Other 3.0% vs 2.1%) with variation in site demography, size and location. Missing data varied across sites and nations and is presented. Conclusion The NIHR equality, diversity and inclusion strategy states studies must widen participation, facilitating individuals from all backgrounds to engage. The development of this novel interactive dashboard demonstrates an innovative way of achieving this. National Health Service (NHS) maternity researchers should consider using this tool to enhance diversity in research, address health disparities and improve generalisability of findings. This approach could be applied to healthcare settings beyond maternity care and across different global populations. Trial registration ISRCTN 17679951. Registered on August 30, 2023.

Background: Ranked as the fourth most prevalent cancer among women globally, cervical cancer presents a significant concentration of 90% of cases in low- and middle-income countries. The potential for preventing cervical cancer through vaccination is substantial. However, the implementation of the human papillomavirus (HPV) vaccine encounters challenges, including acceptance barriers, lack of awareness, and high vaccine costs. Overcoming these obstacles is crucial, especially in regions like India, where cervical cancer screening is a significant concern. The objective is to assess the comprehension, viewpoints, and utilization of the HPV vaccine among medical students enrolled in a medical college. Material and Methods: A descriptive cross-sectional study was conducted among 384 study subjects using a pre-tested, semi-structured questionnaire. Results: Perspectives on HPV vaccine administration ranged, with 55% advocating its use in the 10-30 age range. Opinions diverged on vaccine eligibility for boys, administration to sexually active girls, and the necessity of HPV screening before vaccination. Concerns about vaccine safety, administration to HPV-infected women, and cervical cancer screening post-vaccination exhibited considerable diversity. Conclusion: Provides critical insights into medical students' attitudes and awareness regarding HPV and vaccine, highlighting the significance of tailored health education initiatives to address knowledge gaps and misconceptions. Recognizing these diverse perspectives can guide the development of targeted strategies to enhance public acceptance and utilization of the HPV vaccine. This research contributes to shaping informed decision-making among future healthcare professionals, laying the groundwork for improved public health outcomes.

Background: The current definition of obesity implies a rise in total body fat, which may only be evaluated through an examination of body composition. Body Mass Index (BMI) cannot detect percent body fat (BF%) effectively, prompting the need for novel, simple, affordable, and resource-constrained methods of body fat assessment and measurement. Objective: To determine the correlation of BMI and BF% estimated by BIA in children of Karachi Methods: This cross-sectional study was performed in a school located in Karachi. The study was conducted from January to April 2023. The permission to conduct this study was taken from the National Institute of Child Health and School Administration. Healthy children of age 6-15 years of either gender were enrolled in this study. Results: Total 132 children were studied with a mean age of 10.8 ± 2.5 years. The age range was 6-15 years. There was almost equal representation of both gender with 50.8% males and 49.2% females. Median weight, height, BMI, and BF% of study subjects were 30.5 (IQR=23.4-42.4) Kg, 139.5 (IQR=128-153) cm, 15.4 (IQR=13.8-17.6) Kg/m2 and 10.2 (IQR=6.1-16.7) % respectively. A significant strong positive correlation was seen for overall data (rs=0.645, p

Endovascular neurointervention is typically performed with iodinated contrast medium (ICM) under fluoroscopy. However, some patients may be contraindicated to such procedures based on their sensitivity to ICM. In this report, we describe a case of successful coil embolization of a direct carotid cavernous fistula using angiography with gadolinium-based contrast agents in a patient with severe allergic reaction to ICM. The clinical decision-making for this patient was further complicated by comorbidities of renal impairment, drug allergies, and previously severe gastrointestinal bleeding.

D-bifunctional protein (DBP) deficiency, a fatal peroxisomal enzyme disorder, typically manifests with life-threatening symptoms in the first two years of childhood. We present the case of an infant with elevated lysophosphatidylcholine C26:0 (C26:0-LPC) levels identified during X-linked adrenoleukodystrophy (ALD) screening, leading to a diagnosis of DBP deficiency due to a homozygous HSD17B4 c.1041T>A, p.(Tyr347Ter) variant. Starting at two months of age, the infant experienced seizures, hypotonia, and developmental delays, prompting the initiation of experimental treatment with the readthrough agent PTC124 (ataluren) at six months. The treatment led to a decrease in C26:0-LPC levels from 0.65 μM to 0.53 μM; concomitant fish oil supplementation transiently increased C26:0-LPC to 0.74 μM before returning to 0.53 μM after cessation of supplementation. The patient demonstrated improved swallowing and progressive motor and speech development during a two-year treatment period, with no further seizures. This case report highlights the potential of nonsense readthrough therapy for peroxisomal disorders, a group of metabolic diseases that currently lack targeted treatments.

ABSTRACT Introduction Organised by the ‘Qualitative Long Covid Network’, a workshop for qualitative Long COVID (LC) researchers, LC charity representatives and people with LC took place in June 2023, where research on the intersectional inequalities affecting LC prevalence, recognition and care was shared and discussed. Methods Five key themes were drawn up from presentations, discussions and reflections during the workshop, which are presented in this study. Results The following five themes are discussed: the unfairness of LC, difficulties in accessing care, mistrust of the healthcare system, a lack of understanding of LC and experiences of stigma and discrimination. Factors that widen or narrow inequalities related to LC were identified. Conclusion A call to action is proposed to investigate and address inequalities through a robust LC research agenda that speaks with conviction to policy and decision‐makers. We argue that there needs to be a strong investment in research and evidence‐based policy and practice to mitigate the worst effects of the condition and address the inequalities in experience, treatment and support, which are experienced more often and more acutely by some of society's most vulnerable and disadvantaged individuals. Patient and Public (PPI) Contribution Projects included in this article had PPI ongoing activity to inform their research. A member of the CONVALESCENCE PPI group presented at the QLC Network ‘Long Covid and Health Inequalities’ workshop, as did members of Long COVID Kids, Long COVID Support and Long COVID SOS charities. They were all invited to be co‐authors of this article.

With significant advancements in the study of DNA Damage Response (DDR) and Fanconi Anemia (FA) signaling, we previously introduced the term “FA signaling” to encompass “all signaling transductions involving one or more FA proteins.” This network has now evolved into the largest cellular defense network, integrating over 30 key players, including ATM, ATR, BLM, HRR6, RAD18, FANCA, FANCB, FANCC, BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, BRIP1, FANCL, FANCM, PALB2, RAD51C, SLX4, ERCC4, RAD51, BRCA1, UBE2T, XRCC2, MAD2L2, RFWD3, FAAP20, FAAP24, FAAP100, and CENPX. This system responds to both endogenous and exogenous cellular insults. However, the mutational signatures associated with this defense mechanism in non-FA human cancers have not been extensively explored. In this study, we report that different types of human cancers are characterized by distinct somatically mutated genes related to DDR/FA signaling, each accompanied by a unique spectrum of potential driver mutations. For example, in pan-cancer samples, ATM emerges as the most frequently mutated gene (5%) among the 31 genes analyzed, with the highest number of potential driver mutations (1714), followed by BRCA2 (4% with 970 putative driver mutations). However, this pattern is not universal across specific cancer types. For example, FANCT is the most frequently mutated gene in breast (14%) and liver (4%) cancers. In addition, the alteration frequency of DDR/FA signaling due to these mutations exceeds 70% in a subtype of prostate cancer, with each subtype of brain, breast, lung, and prostate cancers displaying distinct patterns of gene alteration frequency. Furthermore, these gene alteration patterns significantly impact patient survival and disease-free periods. Collectively, our findings not only enhance our understanding of cancer development and progression but also have significant implications for cancer patient care and prognosis, particularly in the development of effective therapeutic strategies.

Abstract Introduction India has the largest cohort of community health workers with one million Accredited Social Health Activists (ASHAs). ASHAs play vital role in providing health education and promoting accessible health care services in the community. Despite their potential to improve the health status of people, they remain largely underutilized because of their limited knowledge and skills. Considering this gap, Extension for Community Healthcare Outcomes (ECHO)® India, in collaboration with the National Health System Resource Centre (NHSRC), implemented a 15-h (over 6 months) refresher training for ASHAs using a telementoring interface. The present study intends to assess the impact of the training program for improving the knowledge and skills of ASHA workers. Methods We conducted a pre–post quasi-experimental study using a convergent parallel mixed-method approach. The quantitative survey (n = 490) assessed learning competence, performance, and satisfaction of the ASHAs. In addition to the above, in-depth interviews with ASHAs (n = 12) and key informant interviews with other stakeholders (n = 9) examined the experience and practical applications of the training. Inferences from the quantitative and qualitative approaches were integrated during the reporting stage and presented using an adapted Moore’s Expanded Outcomes Framework. Results There was a statistically significant improvement in learning (p = 0.038) and competence (p = 0.01) after attending the training. Participants were satisfied with the opportunity provided by the teleECHO™ sessions to upgrade their knowledge. However, internet connectivity, duration and number of participants in the sessions were identified as areas that needed improvement for future training programs. An improvement in confidence to communicate more effectively with the community was reported. Positive changes in the attitudes of ASHAs towards patient and community members were also reported after attending the training. The peer-to-peer learning through case-based discussion approach helped ensure that the training was relevant to the needs and work of the ASHAs. Conclusions The ECHO Model ™ was found effective in improving and updating the knowledge and skills of ASHAs across different geographies in India. Efforts directed towards knowledge upgradation of ASHAs are crucial for strengthening the health system at the community level. The findings of this study can be used to guide future training programs. Trial registration The study has been registered at the Clinical Trials Registry, India (CTRI/2021/10/037189) dated 08/10/2021.

Background: Treatment in all forms of Congenital Adrenal Hyperplasia (CAH) includes lifelong replacement of steroids. Steroids have an impact on bone health in multiple ways and are known to cause osteoporosis when given in high doses or for a longer duration. Objective: To evaluate bone mineral density (BMD), using dual-energy X-ray absorptiometry (DEXA) scan in children with CAH taking long-term steroids presenting in the pediatric endocrinology ward of National Institute of Child Health, (NICH) Karachi, Pakistan. Materials and Methods: This cross-sectional study was performed at the Department of Pediatric Endocrinology, National Institute of Child Health, Karachi from October 2021 to July 2022. A total of 47 diagnosed cases of CAH taking steroids for more than 5 years were enrolled. Assessment of BMD was done using a DEXA scan. Lumbar spine BMD was done and Z-score was modified for height for age z-score. The dose of steroids and duration was calculated. Results: Out of 47 patients, low BMD was observed in 8 (17.02%) patients. Individuals with low BMD had significantly higher median duration, (p=0.017), dose (p=0.003), and median alkaline phosphate level (p=0.036),) but low median BMD value (p=0.009) and z score (p

Introduction: Early childhood caries is highly prevalent worldwide. The International Caries Detection and Assessment System incorporates both the non-cavitated and cavitated carious lesions with acceptable reliability. The objective of the present study was to assess the severity and pattern of early childhood caries among children visiting outpatient department of a dental college in Nepal. The study also aimed to compare the severity and pattern based on individual tooth type. Methods: A cross-sectional study was conducted among children of age group 24-71 months in primary dentition stage. The International Caries Detection and Assessment System II criteria was used to detect dental caries, and its severity and pattern. The ethical approval was taken from the institutional ethical committee (IRC Ref. No.: 1, 36, 2079/2080 IRC PDCH 2022 21). Results: The dental cries in children of age group 48-60 months was 1338 (33.46%) and dentinal caries (Code 5) was observed in 112 (8.37%). Multi-surface caries was 644 (16.15%), and occlusal surface caries was 481 (12.06%). Among the study population, 227 (5.69%) of the teeth assessed were associated with restoration and sealants. Enamel caries among the maxillary second molars (55/65) (Code 3) was in 94 (23.5%), and the dentinal caries (Code 5) in maxillary central incisors (51/61)was in 90 (22.78%). Conclusions: Majority of the children enrolled in the study had multiple cavitated and non-cavitated carious teeth involving different surfaces. Severity and pattern of caries also varied among individual tooth type.

Introduction: Hypertension manifests in the eyes as retinopathy, choroidopathy, and optic neuropathy of which retinopathy can be used as a predictor for systemic morbidities and mortalities. The study aims to determine the prevalence of hypertensive retinopathy among hypertensive patients visiting the outpatient Department of Ophthalmology in a tertiary care center. Methods: A descriptive cross-sectional study was conducted among hypertensive patients from 4th April to 19th November 2023 after obtaining ethical approval from the Institutional Review Committee (Reference number: 2079/80/96). A Convenience sampling method was used. The Point estimate was calculated at a 95% Confidence Interval. Results: Among 161 hypertensive patients, hypertensive retinopathy was present in 70 (43.48%) (35.82-51.14, 95% Confidence Interval). Grade I hypertensive retinopathy accounted for 35 (50%) followed by Grade II HR in 17 (24.29%), Grade III HR in 14 (20%) and Grade IV HR in 4 (5.71%) in the study participants. Conclusions: The prevalence of hypertensive retinopathy was found to be higher than other studies done in similar settings.

Background Staff sickness absenteeism and presenteeism (attending work while unwell) incur high costs to the NHS, are associated with adverse patient outcomes and have been exacerbated by the COVID-19 pandemic. The main causes are mental and musculoskeletal ill health with cardiovascular risk factors common. Objectives To undertake a feasibility study to inform the design of a definitive randomised controlled trial of the effectiveness and cost effectiveness of a health screening clinic in reducing absenteeism and presenteeism amongst the National Health Service staff. Design Individually randomised controlled pilot trial of the staff health screening clinic compared with usual care, including qualitative process evaluation. Setting Four United Kingdom National Health Service hospitals from two urban and one rural Trust. Participants Hospital employees who had not previously attended a pilot health screening clinic at Queen Elizabeth Hospital Birmingham. Interventions Nurse-led staff health screening clinic with assessment for musculoskeletal health (STarT musculoskeletal; STarT Back), mental health (patient health questionnaire-9; generalised anxiety disorder questionnaire-7) and cardiovascular health (NHS health check if aged ≥ 40, lifestyle check if < 40 years). Screen positives were given advice and/or referral to services according to UK guidelines. Main outcome measures The three coprimary outcomes were recruitment, referrals and attendance at referred services. These formed stop/go criteria when considered together. If any of these values fell into the ‘amber’ zone, then the trial would require modifications to proceed to full trial. If all were ‘red’, then the trial would be considered unfeasible. Secondary outcomes collected to inform the design of the definitive randomised controlled trial included: generalisability, screening results, individual referrals required/attended, health behaviours, acceptability/feasibility of processes, indication of contamination and costs. Outcomes related to the definitive trial included self-reported and employee records of absenteeism with reasons. Process evaluation included interviews with participants, intervention delivery staff and service providers. Descriptive statistics were presented and framework analysis conducted for qualitative data. Due to the COVID-19 pandemic, outcomes were captured up to 6 months only. Results Three hundred and fourteen participants were consented (236 randomised), the majority within 4 months. The recruitment rate of 314/3788 (8.3%) invited was lower than anticipated (meeting red for this criteria), but screening identified that 57/118 (48.3%) randomised were eligible for referral to either general practitioner (81%), mental health (18%) and/or physiotherapy services (30%) (green). Early trial closure precluded determination of attendance at referrals, but 31.6% of those eligible reported intending to attend (amber). Fifty-one of the 80 (63.75%) planned qualitative interviews were conducted. Quantitative and qualitative data from the process evaluation indicated that the electronic database-driven screening intervention and data collection were efficient, promoting good fidelity, although needing more personalisation at times. Recruitment and delivery of the full trial would benefit from a longer development period to better understand local context, develop effective strategies for engaging with underserved groups, provide longer training and better integration with referral services. Delivery of the pilot was limited by the impact of COVID-19 with staff redeployment, COVID-research prioritisation and reduced availability of community and in-house referral services. While recruitment was rapid, it did not fully represent ethnic minority groups and truncated follow-up due to funding limitations prevented full assessment of attendance at recommended services and secondary outcomes. Conclusions There is both a clinical need (evidenced by 48% screened eligible for a referral) and perceived benefit (data from the qualitative interviews) for this National Health Service staff health screening clinic. The three stop/go criteria were red, green and amber; therefore, the Trial Oversight Committee recommended that a full-scale trial should proceed, but with modifications to adapt to local context and adopt processes to engage better with underserved communities. Trial registration This trial is registered as ISRCTN10237475. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/42/42) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 23. See the NIHR Funding and Awards website for further award information. Plain language summary Sickness absenteeism and presenteeism (attendance at work while ill, with poor work performance) are major problems in the NHS and associated with worse patient health care. The most common causes of NHS staff sickness absenteeism and presenteeism are muscular complaints and mental ill health. Poor lifestyle and illnesses associated with heart disease are also important factors. Staff health checks might improve the health of NHS staff, but no studies have included screening tests to address the most common causes of poor staff health. This pilot study tested whether it would be possible to deliver a randomised controlled trial of an NHS staff health screening clinic, where some people get the screening check and others do not (chosen at random, like flipping a coin). We used an electronic database to capture all data. Participants completed initial questionnaires either at home or at work, then attended a face-to-face screening clinic using recognised screening questionnaires and tests to detect problems with muscular, mental or heart health. We considered how NHS staff and healthcare organisations would want the screening clinic and trial to run, how a diverse range of NHS staff could best be approached, how many staff might need to be invited and what their healthcare needs would be. The study ran in four UK NHS hospitals during the COVID-19 pandemic. Two hundred and thirty-six NHS staff participated, but early trial closure due to the pandemic meant that some results were unavailable. For the primary feasibility outcomes, although recruitment rates of around 8% were lower than anticipated, half of staff screened needed referral for further health care and one-third reported intending to attend. Staff felt that the clinic addressed an important health need. The Trial Oversight Committee recommended proceeding to a full-scale trial but with modifications to address findings from the process evaluation, including ways to encourage a wider group of NHS staff to take part. Scientific summary Background Staff sickness absenteeism and presenteeism (attending work while unwell) incur high costs to the NHS, are associated with adverse patient outcomes and have been exacerbated by the COVID-19 pandemic. The main causes are mental and musculoskeletal ill health with cardiovascular risk factors also common. Objectives The aim of this pilot trial was to assess the feasibility of a definitive randomised controlled trial (RCT) evaluating the clinical and cost effectiveness of a health screening clinic compared to usual care, in reducing sickness absenteeism and presenteeism amongst NHS staff. The key objectives were to: describe recruitment rates describe participant characteristics and assess generalisability compared to the hospital workforce describe intervention screening assessment results describe recommended referrals and their uptake assess the feasibility of measuring the outcomes relating to the definitive trial, and obtain an estimate of the standard deviation of the proposed primary outcomes for a full RCT assess levels of contamination between intervention and usual care arms to inform RCT design (individual vs. cluster RCT) describe and explain the fidelity to the intervention and evaluate the barriers and enablers to participation describe the views, experiences and satisfaction of participants and those delivering the health checks quantify the costs of undertaking the screening service and its consequences. Design A multicentre, two-arm, parallel group, open-label, 1 : 1 individually randomised pilot RCT of a complex intervention comparing a staff health screening clinic with usual care. Setting Three large urban hospitals and one rural district general hospital in the West Midlands. Participants All employees in the participating hospitals were eligible to participate except those who had previously attended a pilot health screening clinic at Queen Elizabeth Hospital Birmingham (QEHB) or who were currently taking part in another non-COVID drug trial or similar health and well-being trial. Participants were informed of the trial through staff meetings, noticeboards, posters and ward champions, and invited (with up to three reminders) through multiple approaches including e-mail and personal invitation. Wards were chosen to reflect the characteristics of the hospital. Data collection Potential participants joined the trial via weblink to a custom-designed electronic trial data collection platform hosted by the Birmingham Clinical Trials Unit. Eligibility questions, consent and a baseline questionnaire were completed prior to randomisation. Randomisation and blinding Participants were randomised to intervention or usual care (1 : 1 ratio) using an integrated randomisation module on the trial database, using a minimisation algorithm (with random element) to ensure balance on key characteristics. Interventions Intervention Staff health screening clinic with two stages: screening assessment for three components: mental health, musculoskeletal health and cardiovascular health, followed by appropriate advice and/or referral, according to level of risk, to appropriate services for management according to NHS/National Institute for Health and Care Excellence (NICE) recommendations. The screening assessment was delivered by trained research nurses using a standardised protocol. All data were captured by a customised database with prompts to guide the research nurses. Local pathways were used for referrals to lifestyle, physiotherapy, psychological and primary care services. Participants reporting relevant conditions already being treated did not receive the referral element of that component. A results letter detailing findings and recommendations was sent to participants and their general practitioners (GPs) for appropriate action. Usual care Standard access to medical services for management of any presenting condition. Main outcome measures This pilot trial was originally planned to have a 52-week follow-up period to fully test the processes for a definitive trial, but this was reduced to 26 weeks due to the pandemic delays and funding restrictions. Primary outcomes and stop/go criteria Three coprimary outcomes were originally planned to inform progression to the definitive trial: Recruitment (consented) as a proportion of those invited. Referral to any recommended services as a result of the three screening components (usually GP, local physiotherapy/community psychological services) – intervention arm only. Attendance at any recommended services at 26 weeks (self-report) – intervention arm only. We defined ‘referral’ as anyone who was eligible for a referral, that is they recorded a suitable risk value and were not already being treated for that condition. Due to the pandemic, only a small number of participants completed the 26-week follow-up assessment. Therefore, acceptance of the referral (signifying intention), which was collected during the screening assessment, was used as a proxy for attendance. The three coprimary outcomes formed stop/go criteria when considered together. If any of these values fell into the ‘amber’ zone, then the trial would require modifications to proceed to full trial. If all were ‘red’, then the trial would be considered unfeasible. Secondary outcomes were collected to inform the design of the definitive RCT and any modifications required. Secondary outcomes Comparison of baseline characteristics of included participants and hospital population. Description of intervention screening assessments results. Number/type of referrals to recommended services (intervention arm only). Attendance at each individual recommended service (intervention arm only). Lifestyle relevant to screening intervention advice and referrals (self-report at 26 weeks compared with baseline). Acceptability of intervention to participants and health screening clinic staff (interviews). Feasibility of trial processes (completeness of relevant data items, interviews). Indication of contamination (comparing pre/post data for health behaviours and health care/other service utilisation in control arm). Outcomes related to the definitive trial Absenteeism at 26 weeks with reasons, measured by days and spells. Self-reported absolute absenteeism, relative absenteeism and relative hours of work – for last 7 days and last 28 days [World Health Organization Health and Work Performance Questionnaire (WHO-HPQ)]. Self-reported absenteeism (6-month recall period). Employee records of absenteeism, the proposed primary outcome of the definitive trial. Routinely collected linked data from the NHS Electronic Staff Record Programme. Presenteeism at 26 weeks [self-reported absolute presenteeism and relative presenteeism for last 28 days (WHO-HPQ)]. Attendance at occupational health service at 26 weeks (self-report). Healthcare utilisation at 26 weeks (self-report) including GP consultations and hospital admissions. EuroQol-5 Dimensions, five-level version (EQ-5D-5L) index value measuring health-related quality of life (HRQoL) (EuroQol EQ-5D 5-level) at 26 weeks. Resource use and costs collected by self-report questionnaire to participants on health service utilisation and information from the screening assessment regarding duration and resources used. Sample size We aimed to recruit 480 participants (20 per week) in 24 weeks. With this sample size, the 95% confidence interval (CI) for the proportion of staff recruited could be estimated to be 4% either side of the estimate. Statistical methods Analyses were mainly descriptive. No statistical modelling was undertaken, and no p-values are reported. No subgroup analyses were planned. Process evaluation A mixed-methods process evaluation explored programme reach, fidelity of screening delivery, attendance at referrals and participants’ views of the intervention to support any modifications required for the design of the definitive trial. Quantitative data to support the process evaluation were obtained as above. Semistructured qualitative interviews/focus groups were conducted (choice of Zoom, telephone, face-to-face) to obtain views of relevant stakeholders [trial participants, enhancing the Health of NHS Staff (eTHOS) nurses, referral providers, outside agencies] on the feasibility and acceptability of the staff health screening intervention and trial and inform any protocol adaptations needed for a full trial. Due to the COVID-19 delays, a pragmatic approach was taken to sampling; all eligible participants in the intervention arm were invited to participate, and invitations were sent to all controls until the target number of participants had been reached. Data were recorded either on Zoom or an encrypted recorder and transferred via secure file transfer to an external company for transcription. Interviews were transcribed intelligent/clean verbatim and anonymised. A thematic analysis of content was informed by the framework analytical approach. Data collection and analysis ran concurrently so that the emergent analytical themes could inform further data collection. Health economic analysis A descriptive analysis was presented with average costs of screening per participant and quality of life obtained in the baseline questionnaire. Information was obtained from participating centres on estimated time taken for each screening clinic task, grade of the member of staff responsible and cost of individual blood tests. Staff time required for each task was then multiplied by the relevant unit costs obtained from standard source. The total cost of blood tests per participant was weighted according to the proportion who received each type of blood test. Quality of life of all participants was estimated using the EQ-5D-5L. Patient and public involvement Four to six clinical, administrative and retired NHS staff met on a regular basis throughout the project to provide advice. One hospital healthcare worker was included on the Trial Oversight Committee (TOC). Similarly, we consulted a stakeholder advisory group representing a wider body of professionals relevant to the trial, for example, GPs. Impact of COVID-19 pandemic on trial delivery It was not possible to commence the trial in March 2020 due to the COVID-19 pandemic. Two hospital sites commenced the trial in December 2020, but after 3–4 weeks, recruitment was paused. The trial recommenced in May 2021 in all four sites. The original trial was planned to include a 52-week follow-up; however, due to the delays, a 26-week follow-up was agreed with the funder, but only a few people reached this time point before trial closure. Results Three thousand seven hundred and eighty-eight of the 24,344 NHS staff across the four sites were invited to take part. Of the 353 eligible respondents, 314 consented (8.3% of those invited and 65.4% of our planned target of n = 480). Two hundred and thirty-six were randomised into the study; n = 118 to the intervention screening arm and 118 to usual care. One hundred and one (85.6%) attended and completed the screening clinic. Only 26/236 (11.0%) participants reached the 26-week follow-up. Primary outcomes and stop/go criteria Three hundred and fourteen of the 3788 [8.3% (95% CI 7.4% to 9.2%)] invited staff gave their consent to participate, which meets the red stop/go criterion for recruitment. Fifty-seven of the 118 [48.3% (95% CI 39.0% to 57.7%)] participants randomised to the intervention arm were eligible for referral to at least one service, which meets the green stop/go criterion for referral. Eighteen of the 57 [31.6% (95% CI 19.9% to 45.2%)] participants eligible for a referral accepted a referral to at least one service, which meets the amber stop–go progression criterion for attendance, although the CIs were wide. Secondary outcomes Assessing generalisability (programme reach) The invited population was similar to the hospital population, although those who participated in the trial were more likely to be white British (78.0% compared to 59.7%), allied health professionals (14.0% compared to 6.9%) and healthcare scientists (11.9% compared to 5.0%), and less likely to be from estates/ancillary, medical/dental and nursing/midwifery registered staff groups. Results of intervention screening assessments Most reported minimal/mild anxiety, but 11 (10.9%) were classified as having moderate and 5 (5.0%) severe anxiety. Most people reported minimal/mild depression, but 13 (12.9%) reported moderate/moderately severe depression and 4 (4.0%) severe depression. Most participants had no significant back pain, although eight (7.9%) were at medium risk and two (2.0%) at high risk on the StarT Back tool. Twenty-seven (27.0%) scored with medium risk for other types of pain and five (5.0%) high risk. Thirty-eight (38.0%) participants were classified as overweight and 32 (32.0%) obese. Forty-six (46.0%) were self-reported as physically active. Twelve (11.9%) reported increasing/higher risk of alcohol dependence and 10 (9.9%) were current smokers. Of those eligible for the cardiovascular risk score (QRISK2), nine (14.5%) had medium risk (10–19.9%) and two (3.2%) had a high risk of developing cardiovascular disease (CVD) in the next 10 years. Completeness of data items and attendance at screening clinic (fidelity) Sixty-six of the 314 (21.0%) consented participants did not complete the baseline questionnaire. One hundred and one of the 118 (86%) participants randomised to the intervention arm attended and completed the screening clinic. Individual data items were generally well completed and deoxyribonucleic acid (DNA) rates low. Costs and quality of life The maximum screening cost per participant (including blood tests) was £107.48 if the highest band staff were used and £99.98 if the lowest band staff ran the clinic. Complete EQ-5D-5L data were available for 233/236 randomised participants [mean score 0.793 (SD 0.168)]. Process evaluation We conducted 51 (63.8%) out of the 80 originally planned interviews. Four different hospital sites utilised a nurse-led screening intervention with prompts and electronic data collection, which was efficient and promoted good fidelity, although this was viewed as impersonal at times. Participants appreciated the convenience of the onsite service and valued time to focus on their own needs. However, some felt that it did not reflect or address their stress levels appropriately or meet their expectations in providing faster access to additional services. There were also concerns that it would not address the wider determinants of ill health and problems in the workplace, that it was just a ‘sticking plaster’. The eTHOS staff delivering the intervention generally found the delivery of the study feasible, although there were a number of suggestions from staff both delivering and receiving the intervention to adapt the approach for a full trial. Conclusions Despite significant delays, truncation and amendments required due to the COVID-19 pandemic, we were able to assess the most important aspects of the feasibility of a RCT to evaluate the clinical and cost effectiveness of a novel hospital-based staff health screening clinic in reducing absenteeism and presenteeism. Recruitment was feasible in a short space of time, and delivery of the intervention feasible, efficient and acceptable. Although a lower proportion of staff were recruited than anticipated, this was offset by the findings of the screening assessments which revealed significant health needs of those attending with 48% requiring referral to additional services. The three stop/go criteria were red, green and amber; therefore, the TOC recommended that a full-scale trial should proceed, but with modifications (see below) to adapt to local context and adopt processes to engage better with underserved communities, to improve both reach and effectiveness. Implications/modifications for full trial design There was no evidence of contamination; therefore, an individual RCT would remain the design of choice. Wait-list controls might also be a potential option to encourage people to participate. While our approach to recruitment was successful for many (most people responded to an e-mail), additional strategies would be needed to recruit the underserved groups, and specific minority staff network groups and leaders should be engaged in order to do so. Messaging to potential participants needs to be clearer in order to reduce concerns about confidentiality, optimise recruitment and manage expectations. More flexible clinic times/alternative options could be explored to improve inclusion. Electronic data capture was considered convenient, but extra training and practice should be provided to ensure sufficient familiarity and personalisation. Consideration (on a site-by-site basis) of clearer referral pathways is important for the full trial, in order to optimise attendance at referrals and realise health outcomes. Further consideration should also be given to the mental health screening tools used, as qualitative interviews with staff revealed their concerns that occupational stress and burnout may not be adequately identified and treated. There was no evidence from this study that self-reported absenteeism data should replace human resources (HR) data as the potential primary outcome as correlation between the two was poor. Acknowledging the 25% dropout between consent and randomisation, the amount of data collected and length of questionnaires should be reviewed prior to a full trial. Resource use and cost data were relatively straightforward to collect, although it was evident that more detailed site-by-site data collection would be required in a full trial, to reflect the full range of clinic organisation scenarios. Trial registration This trial is registered as ISRCTN10237475. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/42/42) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 23. See the NIHR Funding and Awards website for further award information.

Pentalogy of Fallot is a rare form of congenital cyanotic heart disease with a prevalence of 3/10,000 live births characterized by an association of Tetralogy of Fallot with Atrial Septal Defect. Pentalogy of Fallot with anorectal malformation is also a rare combination. Here we describe one of the rare case reports of a full-term, 38 weeks, female baby diagnosed with pentalogy of Fallot with imperforate anus and rectovaginal fistula at a tertiary care hospital. Pentalogy of Fallot combined with an imperforate anus and rectovaginal fistula is an exceptionally rare and complex congenital condition. The co- existence of these anomalies emphasizes the need for thorough prenatal and postnatal evaluation for early detection and management.

Abstract Background Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed to manage anxiety in adults with an autism diagnosis. However, their effectiveness and adverse effect profile in the autistic population are not well known. This trial aims to determine the effectiveness and cost-effectiveness of the SSRI sertraline in reducing symptoms of anxiety and improving quality of life in adults with a diagnosis of autism compared with placebo and to quantify any adverse effects. Methods STRATA is a two-parallel group, multi-centre, pragmatic, double-blind, randomised placebo-controlled trial with allocation at the level of the individual. It will be delivered through recruiting sites with autism services in 4 regional centres in the United Kingdom (UK) and 1 in Australia. Adults with an autism diagnosis and a Generalised Anxiety Disorder Assessment (GAD-7) score ≥ 10 at screening will be randomised 1:1 to either 25 mg sertraline or placebo, with subsequent flexible dose titration up to 200 mg. The primary outcome is GAD-7 scores at 16 weeks post-randomisation. Secondary outcomes include adverse effects, proportionate change in GAD-7 scores including 50% reduction, social anxiety, obsessive-compulsive symptoms, panic attacks, repetitive behaviours, meltdowns, depressive symptoms, composite depression and anxiety, functioning and disability and quality of life. Carer burden will be assessed in a linked carer sub-study. Outcome data will be collected using online/paper methods via video call, face-to-face or telephone according to participant preference at 16, 24 and 52 weeks post-randomisation, with brief safety checks and data collection at 1–2, 4, 8, 12 and 36 weeks. An economic evaluation to study the cost-effectiveness of sertraline vs placebo and a QuinteT Recruitment Intervention (QRI) to optimise recruitment and informed consent are embedded within the trial. Qualitative interviews at various times during the study will explore experiences of participating and taking the trial medication. Discussion Results from this study should help autistic adults and their clinicians make evidence-based decisions on the use of sertraline for managing anxiety in this population. Trial registration ISRCTN, ISRCTN15984604 . Registered on 08 February 2021. EudraCT 2019-004312-66. ANZCTR ACTRN12621000801819. Registered on 07 April 2021.

The international authorities, such as the Food and Agriculture Organization of the United Nations, World Health Organization, World Organization for Animal Health, United Nations Environment Programme, and World Bank, have endorsed the One Health concept as an effective approach to optimize the health of people, animals, and the environment. The One Health concept is considered as an integrated and unifying approach with the objective of sustainably balancing and optimizing the health of people, animals, and ecosystems. Despite variations in its definitions, the underlying principle remains consistent – recognizing the interconnected and interdependent health of humans, animals, and the environment, necessitating interdisciplinary collaboration to optimize health outcomes. The One Health approach has been applied in numerous countries for detecting, managing, and controlling diseases. Moreover, the concept has found application in various areas, including antimicrobial resistance, food safety, and ecotoxicology, with a growing demand. There is a growing consensus that the One Health concept and the United Nations Sustainable Development Goals mutually reinforce each other. The World Bank has recommended five domains as foundational building blocks for operationalising the One Health approach, which includes: i) One Health stakeholders, roles, and responsibilities; ii) financial and personal resources; iii) communication and information; iv) technical infrastructure; and v) governance. The domains provide a generalised overview of the One Health concept and guide to its application. We conducted a scoping review following the five-staged Arksey and O’Malley's framework. The objective of the review was to map and synthesise available evidence of application of the One Health approach to five major zoonotic diseases using the World Bank domains. Publications from the year 2004, marking the inception of the term ‘One Health,’ to 2022 were included. Information was charted and categorised against the World Bank domains identified as a priori. We included 1132 records obtained from three databases: Embase, Medline, and Global Health; as well as other sources. After excluding duplicates, screening for titles and abstracts, and full text screening, 20 articles that contained descriptions of 29 studies that implemented the One Health approach were selected for the review. We found that included studies varied in the extent to which the five domains were utilised. Less than half the total studies (45%) used all the five domains and none of the studies used all the sub-domains. The environmental sector showed an underrepresentation in the application of the One Health approach to zoonotic diseases as 14 (48%) studies in 10 articles did not mention it as a stakeholder. Sixty two percent of the studies mentioned receiving support from international partners in implementing the One Health approach and 76% of the studies were supported by international donors to conduct the studies. The review identified disparate funding mechanisms employed in the implementation of the One Health approach. However, there were limited discussions on plans for continuity and viability of these funding mechanisms in the future.

Summary: Background: People living with HIV (PLWH) with multidrug-resistant (MDR) viruses have limited therapeutic options and present challenges regarding clinical management. Recent studies have shown that passive transfer of combination broadly neutralizing antibodies (bNAbs) against HIV and anti-domain 1 CD4 antibody UB-421 can sustain virologic suppression in PLWH in the absence of antiretroviral therapy (ART). Yet studies addressing the therapeutic potential of these antibodies and/or detailed characterization of immunologic and virologic parameters in PLWH with MDR HIV are lacking. Methods: We examined levels of immune activation and exhaustion markers on CD8+ T cells and the intact HIV proviral DNA burden in 11 PLWH with MDR viruses. For comparison purposes, we included a control group consisting of 27 ART-naïve viremic PLWH. In addition, we determined the sensitivity of infectious viral isolates obtained from the participants against eight bNAbs (3BNC117, 10-1074, VRC01, VRC07, N6, 10E8, PGDM1400, and PGT121) and two anti-CD4 antibodies (ibalizumab and UB-421) using a TZM-bl-based neutralization/suppression assay. Findings: The level of intact HIV proviral DNA was comparable between the two groups (P = 0.29). The levels of activation and exhaustion markers PD-1 (P = 0.0019), TIGIT (P = 0.0222), 2B4 (P = 0.0015), CD160 (P = 0.0015), and CD38+/HLA-DR+ (P = 0.0138) were significantly lower in the MDR group. The infectious viral isolates from each study participant with MDR HIV were resistant to at least 2 bNAbs; however, they were sensitive to at least one of the CD4-binding and non-CD4-binding site antibodies. The majority of participants had ibalizumab-sensitive viruses although the isolates from some participants showed reduced sensitivity to ibalizumab. Notably, none of the 93 viral isolates obtained from the participants were resistant to UB-421. Interpretation: Our data suggest that combination therapy with HIV-specific bNAbs and/or UB-421 in the presence of optimized background therapy could potentially provide sustained virologic suppression in PLWH with MDR HIV. However, this therapeutic strategy needs to be evaluated in human clinical trials. Funding: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

Key Clinical Message Lindane induces severe side effects, including fatality, while Cetrimide causes esophageal damage. With no antidotes available, our patient ingested both, requiring prompt gastric lavage and comprehensive treatment.

The burden of chronic diseases in Nepal is increasing due to demographic and epidemiological transitions; alongside the persistent impact of communicable, maternal, newborn, and child health diseases, this critical situation acts as the precursor to rising healthcare costs. Nepal struggles to sustain its healthcare system amidst political instability, pandemics, natural disasters, and slow economic growth, particularly when healthcare funding is mainly dependent on out-of-pocket payments. Nepal requires lower-cost alternative healthcare delivery arrangements to provide high-value care while relieving economic sustainability pressures. Alternative healthcare delivery arrangements have a broad potential scope; they can involve strategic changes in how care is delivered and by whom, or they can also involve the application of information and communication technologies, e.g., telemedicine. This paper highlights the specific challenges to healthcare system sustainability in Nepal and the potential for high-value, lower-cost alternative healthcare delivery models to improve system performance in the longer term.

Key Clinical Message Osteoblastoma of the frontal sinus, although rare, can manifest with seizures and pneumocephalus, underscoring the importance of thorough evaluation and complete surgical excision to prevent serious complications and ensure optimal patient outcomes. Abstract Osteoblastoma is an infrequent bone tumor, with origins typically in the vertebrae and long bones. While craniofacial involvement is rare, it may occur in regions such as the paranasal sinuses. We present a case of osteoblastoma located in the frontal sinus, an exceptionally uncommon site, resulting in seizures secondary to pneumocephalus. A 21‐year‐old male presented with a generalized tonic–clonic seizure and postictal confusion. Imaging studies revealed a well‐defined lesion in the left frontal sinus causing cortical breach, destruction of the posterior wall, and pneumocephalus. A total surgical excision was performed through bifrontal craniotomy. Histopathological analysis confirmed the diagnosis of osteoblastoma. Postoperative recovery was uneventful, with a follow‐up CT scan showing complete lesion excision. Osteoblastomas, especially in the cranial sinuses, are rare entities that may present asymptomatically but can lead to severe complications. The risk of recurrence underscores the importance of complete surgical resection for optimal patient outcomes.

Abstract Background The COVID-19 pandemic has made devastating impacts on public health and global economy. While most people experience mild symptoms, it is highly transmissible and deadly in at-risk populations. Telemedicine has the potential to prevent hospitalization and provide remote care. Methods This retrospective study included 336 people with COVID-19, among which 141 (42%) and 195 (58%) were in Delta and Omicron dominant groups, respectively. Patients were confirmed to have COVID-19 by PCR or rapid test and were cared for via telemedicine. Severe cases were hospitalized for more intensive treatment. Results The majority of individuals recovered at home (97.02%), while 2.98% required hospitalization. All hospital admissions were in Delta dominant group. No deaths were reported. Delta dominant group was more likely to develop loss of taste and smell, decreased appetite and need longer treatment time than those in Omicron dominant group. Conclusions Telemedicine is a safe measure to provide at-home care for people with COVID-19 infections caused by both Delta and Omicron variants. Trial registration This study was approved by the Institutional Review Board Committee of University of Medicine and Pharmacy at Ho Chi Minh City (IRB No: 22115–DHYD).

Abstract Background Chronic myeloid leukaemia (CML) is a haematopoietic stem cell disorder, caused by a balanced reciprocal translocation (t(9;22) (q34;q11)) that leads to the formation of BCR (Breakpoint Cluster Region)-ABL (Abelson) fusion transcripts known as Philadelphia (Ph) chromosome. The prevalence of BCR-ABL fusion transcripts in Indian CML population is poorly understood, and few studies have been reported from India. The aim of the present study was to determine the frequencies as well as prognostic effects of the three fusion transcripts, i.e. b2a2, b3a2 and e1a2 in an Indian population. Methods RNA was isolated from total 123 samples, 27 bone marrow (BM) samples and 96 peripheral blood (PB) samples, of CML patient followed by cDNA synthesis. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed using TaqMan® assay (ABI, CA, USA) to monitor BCR-ABL transcript. Results Ph' chromosome was observed in 103 patients whereas it was not detected in 20 cases. qRT-PCR revealed that the b3a2 fusion transcripts were the most common transcript in CML patients (63.41%) while b2a2 fusion transcript was present in 16.26% cases. Co-expression of b3a2 + b2a2 fusion transcript was observed in 0.81% cases whereas co-expression of b3a2 + e1a2 fusion transcript was found in 1.63% cases. There was no correlation observed between b3a2 fusion transcript and platelet count. The fusion transcript b2a2 was observed in relatively younger patients compared to b3a2 fusion transcript. Although this correlation was not statistically significant. Conclusion The co-expression of BCR-ABL fusion transcripts was higher (63.41% aggregate of b3a2) in the present population in contrast with other populations reported. This finding was consistent with the frequency data reported from Sudan.

Abstract Background Mankind have suffered several unexpected disasters, heinous crimes, and brutalities, resulting into large number of unknown skeletal remains to be identified and repatriated to their relatives. Case presentation One such incident of mass killing of 282 Indian-origin soldiers by the colonial rulers in 1857 was reported from Ajnala (India) in early 2014. The damaged cranial fragments belonging to two individuals were retrieved from the vicinity of Ajnala mass-burial site later in 2014. In present study, the retrieved cranial elements were examined forensic anthropologically to assess whether their affinity is akin to the slain Ajnala sepoys or to the deceased who were buried prior to or later than it. The morphological and molecular analyses of these remains affirmed their affiliation to the mutiny sepoys of 1857 killed at Ajnala. Conclusions The forensic anthropological and molecular examinations of cranial fragments found that these remains belonged to the individuals killed in the Ajnala incident. The multidisciplinary approach applied for identification of the badly damaged, fragmented, and commingled human remains helped in their presumptive identification.

Pakistan is facing a grave and often overlooked crisis in its nutrition landscape. Hidden hunger, a form of malnutrition resulting from inadequate intake of essential vitamins and minerals, poses a significant threat to the health and well-being of millions of Pakistanis [1]. This editorial sheds light on the prevalence and consequences of hidden hunger in Pakistan, explores its underlying causes, and emphasizes the urgent need for comprehensive interventions to address this silent crisis. The Prevalence and Consequences: Hidden hunger affects individuals across all age groups and socioeconomic backgrounds in Pakistan. Despite an abundance of food, a large proportion of the population suffers from deficiencies in vital nutrients such as iron, vitamin A, iodine, and zinc [2, 3]. These deficiencies have severe consequences, leading to impaired cognitive development, weakened immune systems, increased susceptibility to diseases, and even higher mortality rates, particularly among women and children. Hidden hunger in Pakistan can be attributed to various factors. Inadequate dietary diversity, especially among marginalized populations, is a significant contributor [3]. Dependence on staple foods, such as rice and wheat, often leads to imbalanced nutrient intake. Additionally, poor sanitation and hygiene practices, limited access to safe drinking water, and inadequate healthcare services further exacerbate the problem [4]. Socioeconomic disparities and lack of awareness about proper nutrition also play a role in perpetuating hidden hunger [5]. The impact of xenobiotic contamination in a developing country like Pakistan is another concern. Pakistan may be exposed to xenobiotic contamination present in food, air, and water, which can affect overall health and nutrition [6]. Addressing hidden hunger requires a multi-faceted and comprehensive approach. Firstly, promoting dietary diversity is essential to ensure a well-rounded intake of essential nutrients [5]. This can be achieved through education programs that emphasize the importance of incorporating fruits, vegetables, legumes, and animalsource foods into daily diets. Efforts should also be made to improve agricultural practices, enhance crop diversity, and support small-scale farmers to increase the availability of nutritious food options. The implementation of dietary interventions in the face of xenobiotic contamination may require the use of dietary activators of anti-aging genes, which are critical for preventing programmed cell death and promoting overall health [6]. Public health initiatives should focus on providing targeted interventions to vulnerable populations, such as pregnant women and young children. Supplementation programs, fortified food interventions, and nutrition education campaigns can significantly improve the nutritional status of these high-risk groups [2, 7]. Collaborations with international organizations, NGOs, and the private sector can further strengthen these interventions and ensure their sustainability. Investing in infrastructure, particularly in rural areas, is crucial for addressing hidden hunger effectively. Improving access to clean water, sanitation facilities, and healthcare services will not only reduce the risk of infectious diseases but also enhance the absorption and utilization of essential nutrients [4]. Empowering communities through awareness campaigns and behavior change communication can foster longterm changes in nutritional practices and help sustain improvements in dietary habits. To combat hidden hunger, research and monitoring efforts must be strengthened. Conducting national surveys and studies to assess the prevalence and impact of hidden hunger can provide valuable insights for evidence-based interventions [2, 8]. Monitoring the nutritional status of vulnerable groups and tracking progress over time will aid in evaluating the effectiveness of interventions and identifying areas for improvement. Hidden hunger poses a significant threat to the health and well-being of the Pakistani population, with longlasting consequences for individuals, communities, and the nation as a whole. Addressing this crisis requires a collective effort from government bodies, civil society, healthcare professionals, researchers, and communities *Corresponding author: Versha Rani Rai, Department of Pediatric Medicine, National Institute of Child Health (NICH), Karachi, Pakistan, Email: versharai.sg@gmail.com Received: May 24, 2023; Revised: October 08, 2023; Accepted: October 17, 2023 DOI: https://doi.org/10.37184/lnjpc.2707-3521.6.17 2 Liaquat National Journal of Primary Care 2024; 6(1): 1-2 Versha Rani Rai and Berkha Rani themselves. By implementing comprehensive interventions that prioritize dietary diversity, improve access to essential services, and empower individuals with knowledge, Pakistan can combat hidden hunger and pave the way for a healthier and more prosperous future.

Biotransformation refers to the metabolic conversion of endogenous and xenobiotic chemicals into more hydrophilic substances. Xenobiotic biotransformation is accomplished by a restricted number of enzymes with broad substrate specificities. The biotransformation of xenobiotics is catalyzed by various enzyme systems that can be divided into four categories based on the reaction they catalyze. The primary concentration is in cytochrome P450, while the CYP enzymes responsible for xenobiotic biotransformation are located within the hepatic endoplasmic reticulum (microsomes). Cytochrome P450 (CYP450) enzymes are also present in extrahepatic tissues. Enzymes catalyzing biotransformation reactions often determine the intensity and duration of the action of drugs and play a key role in chemical toxicity and chemical tumorigenesis. The structure of a given biotransforming enzyme may differ among individuals, which can cause differences in the rates of xenobiotic biotransformation. The study of the molecular mechanisms underlying chemical liver injury is fundamental for preventing or devising new modalities of treatment for liver injury using chemicals. Active metabolites arise from the biotransformation of a parent drug compound using one or more xenobiotic-processing enzymes to generate metabolites with different pharmacological or toxicological properties. Understanding how exogenous chemicals (xenobiotics) are metabolized, distributed, and eliminated is critical to determining the impact of these compounds on human health. Computational tools such as Biotransformer have been developed to predict all the possible metabolites of xenobiotic and enzymatic profiles that are linked to the production of metabolites. The construction of xenobiotic metabolism maps can predict enzymes catalyzing metabolites capable of binding to DNA.

ObjectivesAn increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old.MethodsRA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected.ResultsA total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p

Background: Galactosemia was introduced into Taiwan's routine newborn screening (NBS) program in 1985. This study presents a 12-year experience, emphasizing disease diagnosis and screening performance. Method: NBS for galactosemia utilized dried blood spot samples taken 48–72 h post-delivery, with total galactose (TGal) level as the primary marker. Newborns with critical TGal levels were referred immediately, while those with borderline TGal underwent a recall test. GALT activity measurement was applied simultaneously as the second-tier marker. Further confirmatory tests, such as whole exome sequencing (WES), were conducted upon referral. Results: From January 1st, 2011, to December 31st, 2022, 51 cases were identified from 817,906 newborns. Of these, nine individuals had persistently elevated TGal. Diagnoses included one case of GALT deficiency, one of GALM deficiency, and seven of GALE deficiencies. Notably, the classic galactosemia patient (GALT deficiency) presented with extreme high TGal and was referred to the hospital for diet management immediately. All affected patients were instructed to adopt a galactose-restricted diet. By the median age of 2.5 years, all exhibited normal development and liver function. Conclusion: The incidence of classical galactosemia and its variants is extremely low in Taiwan. Incorporating WES into NBS has improved our ability to detect various galactosemia forms, enriching our understanding of the genetic underpinnings. While these newly discovered forms often present with milder initial elevations in TGal, specific biochemical investigations and regular monitoring are essential to understanding the long-term implications and outcomes.

Introduction: Induction of labour, a medical intervention before spontaneous onset, is employed when the risk of continuing pregnancy is elevated. Common indications include intrauterine growth restriction, preeclampsia, gestational diabetes, placental abnormalities, prelabor rupture of membranes, post-term pregnancy, and intrauterine foetal demise. The objective of this study was to find out the prevalence of induction of labour in a rural setting in Nepal. Methods: We conducted a descriptive cross-sectional study in the District Hospital Tehrathum using patients’ record files from 14 January 2021 to 14 January 2023. Ethical approval was obtained from Nepal Health Research Council. Demographic variables were collected along with maternal outcomes which include indication of induction of labour, mode of delivery, indication of lower segment caesarean section and foetal outcomes include APGAR score at one and five minutes, birthweight and liquor colour. A total population sampling method was used in the study and 95% confidence Interval was used to calculate the point estimate. Results: Among 640 deliveries during the study period 118 (18.43%) (15.43- 21.43, 95% Confidence Interval) underwent induction of labour. Sixty-three (53.4%) of the 118 patients who underwent induction of labour were primigravida. Conclusions: The prevalence of induction of labour was comparable with previous studies. Neonatal outcome, rate of vaginal and lower segment C-section deliveries after induction of labour using misoprostol is comparable with other studies.

Key Clinical Message Replantation should be attempted in any case of avulsion, be it immediate or delayed. Retention of the replanted tooth helps in preservation of adjacent alveolar bone. Despite the occurrence of replacement resorption, the tooth can stay healthy and functional in the arch for a longer duration.

Abstract Introduction The importance of including people affected by research (e.g., community members, citizens or patient partners) is increasingly recognized across the breadth of institutions involved in connecting research with action. Yet, the increasing rhetoric of inclusion remains situated in research systems that tend to reward traditional dissemination and uphold power dynamics in ways that centre particular (privileged) voices over others. In research explicitly interested in doing research with those most affected by the issue or outcomes, research teams need to know how to advance meaningful inclusion. This study focused on listening to voices often excluded from research processes to understand what meaningful inclusion looks and feels like, and asked what contributes to being or feeling tokenized. Methods In this deliberative dialogue study, 16 participants with experience of navigating social exclusions and contributing to research activities reflected on what makes for meaningful experiences of inclusion. Using a co‐production approach, with a diversely representative research team of 15 that included patient and community partners, we used critically reflective dialogue to guide an inclusive process to study design and implementation, from conceptualization of research questions through to writing. Results We heard that: research practices, partnerships and systems all contribute to experiences of inclusion or exclusion; the insufficiency or absence of standards for accountability amplifies the experience of exclusion; and inclusive practices require intention, planning, reflection and resources. Conclusions We offer evidence‐informed recommendations for the deeply relational work and practices for inclusivity, focused on promising practices for cultivating welcoming systems, spaces and relationships. Patient or Public Contribution This work reflects a co‐production approach, where people who use and are affected by research results actively partnered in the research process, including study design, data‐generating activities, analysis and interpretation, and writing. Several of these partners are authors of this manuscript.

Introduction: Suicide is a global public health problem. Sensible media reporting on suicide could be useful in suicide prevention. This study aimed to evaluate the knowledge, attitude, and practice regarding media reporting on suicide among media persons of a province. Methods: A qualitative study was done among media persons of the province after obtaining ethical approval from the Institutional Review Committee. Data was collected through online platform using Google form from 15 April 2022 and 15 January 2023. A convenience sampling method was used. Descriptive statistics were used for the data analysis. Results: Among 165 media persons, 54 (32%) of the participants either agreed to or were neutral about prominently reporting suicide news, and 47 (28.48%) were undecided or agreed about mentioning the details of the event. Only 50 (30.30%) thought that it is always possible to help a person with suicidal thoughts. A total of 48 (29.09%) always reported providing information about where to seek help in case one is suicidal. Conclusions: Media personnel were found to possess better knowledge about suicide reporting but exhibited inadequate practice in terms of providing method and site details and promoting support services, alongside maintaining an unfavorable attitude towards suicide. There is an urgent need to focus on coordination, standardisation, evidence generation and capacity building of media persons on suicide.

Background: The present study was aimed to study alterations in lipid levels and its corelation with ferritin in Thalassemia patients. Methods: 50 patients of diagnosed Thalassemia in age group of 9 to 12 years were included in the study and results were compared with controls. Lipid profile and serum ferritin levels were estimated. Results: Significant (

Key Clinical Message Dengue fever can also have various neurological complications but involvement of the spinal cord is often unusual. This is a case where the patient had transverse myelitis as a complication of dengue fever. Abstract Dengue fever can have various neurological complications but involvement of the spinal cord is often unusual. We report a case of a 49‐year‐old female, a known case of dengue fever, who presented with urine retention, inability to stand and walk with tingling sensation of bilateral lower limbs. Her vibration and joint position sensation was reduced below T2 level along with altered reflexes but MRI could not explain the examination findings. She was diagnosed clinically as transverse myelitis (TM) in the background of dengue fever. She showed drastic improvement with treatment of steroids. As TM as a complication in a patient with dengue fever is rare, and due to the paucity of similar case reports in Nepal, this case report is of value for the scientific community.

Introduction The changes in the “uterocervical angle (UCA)” have been reported to play a crucial role in “spontaneous preterm birth (sPTB)”. Purpose The study aimed “to determine whether the UCA correlates with the risk of early 28-34 weeks and late 34-37 weeks preterm birth and assess the interobserver reproducibility of this measurement and evaluate its sensitivity as a predictor of sPTB”. Methods The prospective observational study was conducted on n=50 women with singleton pregnancies of gestational age 16 to 24 weeks. In all the patients, transvaginal sonography (TVS) was performed, and UCA was noted. The ultrasound machine software was utilized for sample size determination, with a set power of 90% and α-error at 0.05 and considering findings from prior studies. To discern the variation in predictive efficacy between these two measures, a minimum sample size of 75 patients was required. Results The mean age of study subjects was 28.16±2.90 years, ranging from 23 to 34 years. Obtuse UCA >95º was seen in 47 cases, out of which 46 had PTBs. A significant difference was found between UCA when compared between the preterm and term group (102.40±4.36 vs 97.67±4.87, P0.05). A significant association was found between UCA >95º and the sPTB (P95º in women who delivered at

Introduction: Overweight is defined as a condition in which abnormal accumulation of fat directly affects an individual personality and health leading to a marked increase in morbidity and mortality. It has a direct impact on both the psychological aspects of an individual's personality and their overall health. The objective of this study was to find out the prevalence of overweight among medical students in a medical college. Methods: A descriptive cross-sectional study was done among first and second-year medical students in a medical college between 20 February 2023 to 3 March 2023 after receiving ethical approval from the Institutional Review Committee. Students studying Bachelor of Medicine, Bachelor of Surgery and Bachelor of Dental Surgery during the study period who gave consent were included and those students with a recent medical history of fever, typhoid, diarrhoea, thyroid disorder, metabolic disorders, or any other relevant medical condition within the preceding 1 month, potentially influencing body weight, were excluded. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 164 students, the prevalence of overweight was 43 (26.22%) (19.49-32.95, 95% Confidence Interval). The mean age was 20.65±1.08 years. Conclusions: The prevalence of overweight among medical students was higher than in other studies done in similar settings.

Shailendra Kumar Singh,1 Rina Singh,1 Santosh Kumar Singh,2 Mir Asif Iquebal,3 Sarika Jaiswal,3 Pradeep Kumar Rai4 1Department of Endocrine, Endocrine Clinic, Varanasi, Uttar Pradesh, India; 2Department of Endocrinology, Endocrine Center, Patna, Bihar, India; 3Division of Agriculture Bioinformatics, ICAR-IASRI, New Delhi, India; 4Department of Nephrology, Opal Hospital, Varanasi, Uttar Pradesh, IndiaCorrespondence: Shailendra Kumar Singh, Department of Endocrine, Endocrine Clinic, Varanasi, Uttar Pradesh, India, Email reenavns@gmail.comIntroduction: Prevalence of obesity is high in diabetes mellitus (DM) and is associated with hyperuricemia (HU), hypertension, metabolic syndrome, cardiovascular disease and dyslipidemia. In obesity, elevated serum uric acid (SUA) has been shown to be associated in many studies from different countries, but data from India are lacking. The aim of the present study is to know the prevalence of obesity and to know the relationship between obesity and SUA in newly onset DM.Methods: In this cross-sectional study from India, 402 consecutive newly onset diabetic patients (male: 284; female: 118) were enrolled. All patients were grouped into four based on BMI (body mass index): underweight (< 18.5 kg/m2), normal weight (18.5– 23 kg/m2), overweight (> 23-27.5 kg/m2), and obese (> 27.5 kg/m2). All participants were grouped into four quartiles based on SUA (Q1: < 4.23; Q2: ≥ 4.24– 5.19; Q3: ≥ 5.20– 6.16; Q4: > 6.16).Results: The mean age, BMI and SUA of the participants were 46.20± 0.52 years, 26.35± 0.21 kg/m2 and 5.24± 0.007 mg/dl, respectively. Overall prevalence of generalized obesity, central obesity and hyperuricemia (HU) were 35.07%, 85.82% and 13.43%, respectively. The prevalence of generalized obesity increased across the SUA quartile. A multinomial logistic regression analysis showed that serum uric acid level was independently associated with generalized obesity (p< 0.001).Conclusion: This first report from India shows a significant positive association between SUA and generalized obesity among newly onset DM. Therefore, routine estimation of SUA is recommended in newly onset DM to prevent and treat HU and its related complications.Keywords: newly onset, diabetes mellitus, hyperuricemia, obesity, association

Pretreatment CT Perfusion (CTP) parameter rCBV < 42% lesion volume has recently been shown to predict 90-day mRS. In this study, we aim to assess the relationship between rCBV < 42% and a radiographic follow-up infarct volume delineated on FLAIR images. In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 9 January 2017 and 10 January 2023. Follow-up FLAIR imaging was used to determine the final infarct volume. Student t, Mann-Whitney-U, and Chi-Square tests were used to assess differences. Spearman’s rank correlation and linear regression analysis were used to assess associations between rCBV < 42% and follow-up infarct volume on FLAIR. In total, 158 patients (median age: 68 years, 52.5% female) met our inclusion criteria. rCBV < 42% (ρ = 0.56, p < 0.001) significantly correlated with follow-up-FLAIR infarct volume. On multivariable linear regression analysis, rCBV < 42% lesion volume (beta = 0.60, p < 0.001), ASPECTS (beta = −0.214, p < 0.01), mTICI (beta = −0.277, p < 0.001), and diabetes (beta = 0.16, p < 0.05) were independently associated with follow-up infarct volume. The rCBV < 42% lesion volume is independently associated with FLAIR follow-up infarct volume.

Background: Health science students, since long time, have been using digital technology mainly for the research purposes only. Due to global spread of corona virus disease (COVID-19), education system has changed and adopted online education which was a solution for the continuity of teaching and learning process during COVID-19 pandemic. The main objective of this study was to assess the attitude towards online education among bachelor level health science students. Methods: A descriptive cross-sectional study was carried out at Karnali Academy of Health Sciences, Jumla. Complete enumeration was done. Total 68 bachelor level students were taken for the study. A pretested self administered questionnaire was used for data collection. Data were entered and analyzed by using SPSS version 16. Frequency and percentage were also computed for demographics variables. Chi-square test was applied to assess the association between socio-demographic variables and attitude level. Results: The study illustrated that, among the 68 bachelor level students, nearly two third (63.2%) students had negative attitude towards online education during COVID-19 pandemic. There was statistically significant association of attitude level with ethnicity, type of program and strength of internet connection (p≤0.05). Conclusion: Majority of students of Karnali Academy had negative attitude towards online education; and they had faced many difficulties like internet and electricity problem etc. Administration and faculty members should take necessary measures for improving online education.

Nasopharyngeal cancer (NPC) cases are often diagnosed in advanced stages. The complexity of clinical management for advanced-stage NPC requires thorough communication and shared decisions between medical professionals and allied teams. Incorporating a multidisciplinary team meeting (MDTM) for newly diagnosed NPC patients was chosen to facilitate collaboration and communication between physicians. This retrospective study aimed to compare the quality of care, clinical responses and survival between NPC patients treated with and without MDTM. Data on clinical responses, assessment visits, date of progression and death with progression-free survival (PFS), overall survival (OS), and hazard ratio (HR) were collected and analyzed with 95% confidence interval (CI) and significance set as P

Abstract Background The primary objective of this study was to explore the feasibility of a virtual study protocol for a future longitudinal study, including recruitment, study measures, and procedures. The secondary objective was to examine preliminary hypotheses of associations, including 1) the correlations between total duration and patterns of screen time and cognitive development, and 2) the differences in quality of parent–child interactions for two screen-based tasks and a storybook reading task. Methods Participants included 44 children aged 3 years and their parents from Edmonton, Alberta and surrounding areas. Children’s screen time patterns (i.e., type, device, content, context) were parental-reported using a 2-week online daily diary design. Children’s cognitive development (i.e., working memory, inhibitory control, self-control, and language) was measured virtually through a recorded Zoom session. Parent–child interactions during three separate tasks (i.e., video, electronic game, and storybook reading) were also measured virtually through a separate recorded Zoom session (n = 42). The quality of the interactions was determined by the Parent–Child Interaction System (PARCHISY). Descriptive statistics, Intra-class correlations (ICC), Spearman’s Rho correlations, and a one-way repeated measures ANOVA with a post-hoc Bonferroni test were conducted. Results All virtual protocol procedures ran smoothly. Most (70%) participants were recruited from four 1-week directly targeted Facebook ads. High completion rates and high inter-rater reliability in a random sample (Diary: 95% for 13/14 days; Cognitive development: 98% 3/4 tests, ICC > 0.93; Parent–child interactions: 100% for 3 tasks, Weighted Kappa ≥ 0.84) were observed for measures. Across cognitive development outcomes, medium effect sizes were observed for five correlations, with positive correlations observed with certain content (i.e., educational screen time) and negative associations observed for total screen time and certain types (show/movie/video viewing) and contexts (i.e., co-use). Medium and large effect sizes were observed for the differences in parent–child interaction quality between the three tasks. Conclusions The virtual study protocol appeared feasible. Preliminary findings suggest it may be important to go beyond total duration and consider type, content, and context when examining the association between screen time and cognitive development. A future longitudinal study using this virtual protocol will be conducted with a larger and more generalizable sample.

Abstract Background Child feeding practices during the first two years of life are crucial to ensure good health and nutrition status. This study aimed to assess the factors influencing inappropriate child feeding practices in children aged 6 − 23 months in families receiving nutrition allowance in the remote Mugu district, Nepal. Methods A community-based cross-sectional study was conducted among 318 mothers who had children aged 6 − 23 months of age in the seven randomly selected wards. Systematic random sampling technique was used to select the desired number of respondents. Data were collected using pre-tested semi-structured questionnaire. Bivariate and multivariable binary logistic regression was used to estimate crude odds ratio (cOR), and adjusted odds ratio (aOR), and 95% confidence intervals (CIs) to understand factor associated with child feeding practices. Results Almost half of the children aged 6 − 23 months were not consuming a diverse diet (47.2%; 95% CI: 41.7%, 52.7%), did not meet the recommended minimum meal frequency (46.9%; 95% CI: 41.4%, 52.4%) and did not consume minimum acceptable diet (51.7%; 95% CI: 46.1%, 57.1%). Only 27.4% (95% CI: 22.7%, 32.5%) of children met the recommended complementary feeding practices. Multivariable analysis showed maternal characteristics such as mothers who gave birth at home (aOR = 4.70; 95% CI: 1.03, 21.31) and mothers in unpaid employment (aOR = 2.56; 95% CI: 1.06, 6.19) were associated with increased odds of inappropriate child feeding practices. Household economy (i.e. family with

Abstract Researchers have paid a lot of attention to complex networks in recent decades. Due to their rapid evolution, they turn into a major scientific and innovative field. Several studies on complex networks are carried out, and other subjects are evolving every day such as the challenge of detecting influential nodes. In this study, we provide a brief overview of complex networks, as well as several concepts key related to measurements, the structure of complex network and social influence, an important state of the art on complex networks including basic metrics on complex networks, the evolution of their topology over the years as well as the dynamic of networks. A detailed literature about influential finding approaches is also provided to indicate their strength and shortcomings. We aim that our contribution of literature can be an interesting base of information for beginners’ scientists in this field. At the end of this paper, some conclusions are drawn and some future perspectives are mentioned to be studied as new directions in the future. More detailed references are provided to go further and deep in this area.

Objective: The objective of this study was to assess the test–retest reliability and inter-rater agreement between the traditional Chinese medicine (TCM) pulse diagnosis between two Indian TCM practitioners. Methods: A total of 300 participants were evaluated for their bilateral pulse based on TCM independently by two investigators with similar years of experience but who graduated from different medical schools. The investigators who were blinded diagnosed the participants as per TCM based on the depth, rate, and strength of their pulse. Cronbach α and weighted kappa were used for assessing the reliability and repeatability. Results: The data of all the 300 participants were included in the analysis. The test–retest reliability computed using Cronbach's alpha indicated high reliability between the investigators (α =0.963). There were a total of 37 different types of diagnoses identified by both investigators. The investigators diagnoses matched for 116 participants out of 300 participants; whereas 184 cases were not matched between the investigators. The inter-rater agreement for the TCM diagnosis tested by weighted Kappa did not returned any significant agreement (Kappa = 0.370). Discussion: The present study shows higher reliability between the pulse diagnoses between the investigators. However, the inter-rater agreement for TCM diagnosis based on pulse diagnosis was not significant probably due to the variation in subjective assessments. This calls for the standardization of training in TCM diagnostic methods among practitioners. Future studies should include the differences in training, medical education, and experience among the practitioners while determining the reliability of pulse diagnosis.

Abstract Background Optimising blood pressure (BP) control is one of the most important modifiable risk factors in preventing subsequent stroke where the risk increases by one-third for every 10 mmHg rise in systolic BP. This study evaluated the feasibility and potential effectiveness of blood pressure self-monitoring with planned medication titration, to inform a definitive trial of the intervention, in patients with a previous stroke or transient ischaemic attack (TIA). Methods Patients with a history of stroke/TIA and sub-optimal BP control were invited to take part in a mixed methods feasibility study for a randomised controlled trial. Those meeting the inclusion criteria with systolic BP >130 mmHg were randomised to a self-monitoring intervention group or usual care group. The intervention involved self-monitoring BP twice a day for 3 days within a 7-day period, every month, following text message reminders. Treatment escalation, based on a pre-agreed plan by the general practitioner (GP) and patient, was initiated according to the results of these readings. Semi-structured interviews were carried out with patients and clinicians and analysed thematically. Results Of those identified, 47% (32/68) attended for assessment. Of those assessed, 15 were eligible for recruitment and were consented and randomised to the intervention or control group on a 2:1 basis. Of those randomised, 93% (14/15) completed the study and there were no adverse events. Systolic BP was lower in the intervention group at 3 months. Participants found the intervention acceptable and easy to use. GPs found it easy to incorporate into their practice activity without increasing workload. Conclusions TASMIN5S, an integrated blood pressure self-monitoring intervention in patients with a previous stroke/TIA, is feasible and safe to deliver in primary care. A pre-agreed three-step medication titration plan was easily implemented, increased patient involvement in their care, and had no adverse effects. This feasibility study provides important information to inform a definitive trial to determine the potential effectiveness of the intervention in patients post-stroke or TIA. Trial registration ISRCTN57946500 . Registered on 12/08/2019.

Covid-19 has been declared a global pandemic Anxiety is a problem that often arises in patients treated at healthcare centers or hospitals. The purpose of this study was to determine the factors related to anxiety in facing societal stigma in Covid-19 patients in the Covid-19 Isolation Room of RSD Mangusada. This research method is a quantitative study with a cross-sectional design conducted in the Covid-19 Isolation Room of RSD Mangusada in March-May 2021. The sampling technique was determined using consecutive sampling with a sample of 256 respondents. The Ordinary Logistic Regression test was used to determine the relationship between the dependent variable and the independent variable and to determine the most influential variable. The results showed that the age variable was the most influential on anxiety with a p-value of 0.049, OR=2.25, which means respondents aged 17-25 years can increase the risk of anxiety by 2.25 times compared to respondents who are adults and the elderly. Age, comorbid status, coping responses, disease-related information, and family support are factors related to patient anxiety in dealing with community stigma in Covid-19 patients at Mangusada Hospital. The involvement of all parties is absolutely necessary for dealing with the Covid-19 pandemic.