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Idiopathic granulomatous mastitis (IGM) is a debilitating, chronic, inflammatory condition of the breast. Several studies have emerged evaluating intralesional steroid (ILS) injection and topical steroid administration as a treatment for IGM. However, there is a dearth of international consensuses with regards to the management of IGM. Therefore, we have systematically reviewed the effectiveness of ILS in the management of IGM. A systematic search was conducted in PubMed and Cochrane Library databases, the Google Scholar website and by citation searching up to June 15th, 2023. Eight articles were selected and analyzed. A total of 397 IGM patients were included in the review. The mean patient age was 35.7 years, ranging from 23–62 years. The mean pre-treatment diameter of lesions was 27.5 mm. A total of 184 patients were treated with ILS. The mean complete clinical response time was 2.6 months. The overall complete response rate was 92.8%. Complications following ILS were minor, with hematoma, skin atrophy and hyperemia being commonly described, while avoiding the systemic side effects of oral steroid use, such as weight gain and hirsutism, which were the most commonly reported side effects with oral steroids. The recurrence rates in the ILS group (6.6%) appear to be lower than in the oral steroid group (25.8%) and surgery group (26.3%). ILS seem to show a favorable outcome in terms of complete response rate, complete clinical response time and has a lower recurrence rate and complication rate when compared to other intervention strategies. However, more comparative studies with standardized protocols are necessary to ascertain the optimum type, dosage and frequency of ILS regimens.

Paradigm shift is a significant modification of the core assumptions and methods of experimentation in a scientific discipline. The field of education, at all levels, has undergone tremendous change recently, precipitated by extraordinary demand for high quality and meaningful sustainable education at all levels across the globe. The national education system is segregated into five main categories: primary, junior secondary, senior secondary, collegiate (higher education) and tertiary. In Sri Lanka, basic and higher education levels are compulsory for students; however tertiary education is an optional level. Recent data show that just 20% of students who pass the GCE Advanced Level Test can be admitted into the government university system, leaving the remaining students with few options for higher education. The framework or for determining students' university choice based on their qualifications, talents, demand and supply characteristics, or their willingness to select an appropriate degree program is somewhat non-existent in Sri Lanka's existing educational system. To determine the steps that can be taken for a paradigm shift in higher education, this study aims to highlight the need for one in Sri Lankan post-secondary education while also proposing a relevant conceptual framework. The Marketing Mix Model for Higher Education, Hossler, Kotler and Fox, and the Integrated Complex Decision Model was the framework used to identify the demand pull and supply push factors affecting the university choice in Sri Lanka. Both qualitative and quantitative techniques were used. The study sample was drawn using stratified sampling technique and clustered into several sub-clusters such as state university, private university, technological campus and vocational Institute. Both descriptive and essential inferential statistics tools were used for the data analysis. This study identified the measures that can be used for a paradigm shift in the tertiary education.

Recently, many researchers have found that education systems in many nations are very comprehensive and competitive. They revealed that the primary goal of many universities is to increase the number of students' enrolment as much as possible. In students' perspective, they also consider different factors when they make their higher education decision. Therefore, this article aims to investigate the factors affecting for students' university choice and satisfaction. Relevant literature reviews explained in terms of four models which link to students' university choice process: economic model, sociological model, combined complex decision model and the marketing mixed model. Then, the study investigated the other main factors that are affecting to the university choice of students from empirical evidence. In terms of students' university satisfaction, this paper has described several models and other factors influencing on students' university satisfaction.

Abstract Background The economic crisis in Sri Lanka worsened food insecurity, with millions facing moderate-to-severe food shortages. This study evaluates the effectiveness of cash transfers combined with mobile health education in enhancing dietary diversity and food security among Sri Lankan households during the crisis. Methods This quasi-experimental single-group pre-post study involved 1040 eligible individuals selected through stratified random sampling from eligible households of Samurdhi beneficiaries and smallholder farmers. The intervention included a cash transfer of LKR 22,500 and weekly nutrition awareness messages via WhatsApp and SMS complemented by a one-time awareness session. Dietary diversity and food security were assessed using standard validated tools such as the Diet Quality Questionnaire and Food Security Questionnaire. Results Food insecurity decreased significantly from 89.3% (n = 681) in the pre-test to 76.9% (n = 533) in the post-test, with a 12.4% reduction (95% CI, 8.57 to 16.24, p

Abstract Gestational Diabetes Mellitus (GDM) is associated with adverse maternal and perinatal outcomes and increased risk of developing diabetes in later life. Sri Lanka adopted universal GDM screening at two time points in pregnancy (before 12 weeks and between 24 and 28 weeks) in 2014 and its utilization has not been assessed. This study assessed the utilization of GDM screening services and associated factors among antenatal mothers in Southern Sri Lanka. A cross-sectional study was carried out in a consecutive sample of 420 postpartum mothers who delivered at three major hospitals in Sri Lanka. Data were collected on socio-demographics, pregnancy, availability and utilization of screening services and logistics using an interviewer-administered questionnaire and a data record sheet. Data was analysed using SPSS software. Chi-square test and binary logistic regression was used to assess the association between variables. The coverage of first and second screening tests were 91.4% and 94.5% and timeliness were 72.4% and 59.5%, respectively. The median period of amenorrhoea at the first and second screening were 10.0 (inter-quartile range: 2.5) weeks and 28.0 (inter-quartile range: 1.5) weeks. A higher utilization was associated with higher income (OR = 3.4, 95% CI: 1.1–10.5) and planned pregnancy (OR = 4.9, 95% CI: 2.2–10.7) for the first screening test. Primiparity (OR = 0.3, 95% CI: 0.1–0.9) and proximity of the nearest laboratory (OR = 3.5, 95% CI: 1.0–12.0) were positively associated with the second screening test. The timeliness of both screening tests was associated with planned pregnancy (OR = 2.1, 95% CI: 1.1-4.0 and OR = 2.3, 95% CI: 1.1–4.5) and being non-employed during the pregnancy (OR = 2.5, 95% CI: 1.4–4.3 and OR = 2.3, 95% CI: 1.3–4.1). A high utilization of GDM screening was observed. Timeliness should be ensured through improved availability and accessibility of screening facilities.

Abstract Background Early Childhood Caries (ECC) is a highly prevalent disease among preschoolers in Sri Lanka, with stagnated prevalence over the decades. Therefore, it is important to determine the socio-behavioural associations of ECC among preschoolers to reduce the country’s ECC burden. Methods A cross-sectional study with a multistage cluster sampling technique was used to select 3 to 4 year-old preschoolers/mothers dyads in Gampaha district in 2019. Preschoolers who completed third birthday and had not completed fifth birthday on the day of data collection were selected. The dependent variable was the presence (dmft ≥ 1) or absence (dmft = 0) of ECC. Independent variables were sex, monthly family income, mother’s educational and occupational status, child’s birth order, family type, frequency of consumption of sweets and sweetened drinks, time of sweet consumption during the last 24 h, toothbrushing frequency, supervision of toothbrushing, dental visit, and maternal dental caries. A pre-tested validated questionnaire was used. Multiple logistic regression analysis was used. Results Total of 1038 preschoolers were selected. There were 529 females (51.0%) and 509 males (49.0%). The prevalence of ECC was 56.3% (95% CI: 53.1–59.3). Consuming sweets between meals had a higher odds ratio than consuming sweets after main meals (OR = 1.72, 95% CI:1.25–2.35), consumption of sweets every day had a higher odds ratio than consumption of sweets several times a week or less (OR = 2.89, 95% CI: 2.02–4.13), consumption of sweetened drinks every day had a higher odds ratio than consumption of sweetened drinks several times a week or less (OR = 1.73, 95% CI: 1.07–2.79), and the presence of maternal caries had a higher odds ratio than the absence of maternal caries (OR = 1.74, 95% CI: 1.12–2.69). The use of adult fluoridated toothpaste than not using adult fluoridated toothpaste (OR = 0.64, 95% CI:0.48–0.85), tooth brushing twice per day than not brushing twice per day (OR = 0.67, 95% CI:0.51–0.89), and supervised toothbrushing than unsupervised toothbrushing (OR = 0.61, 95% CI: 0.41–0.93) was negatively associated with ECC. Conclusions ECC is highly associated with sweet consumption and oral hygiene behaviours among preschoolers in Gampaha District. Interventions should focus on the oral health behaviours of preschoolers to reduce ECC burden.

Abstract Objective This quasi-experimental study aimed to describe the outcome of a social skills intervention for adolescents with depression followed up at an outpatient Child and Adolescent Psychiatry Unit. Twenty adolescents with depression attending a tertiary care facility in Colombo, Sri Lanka were recruited, who participated in two social skills training programmes (6 months apart), in addition to pharmacological treatment. Outcome of the programme was measured by a self-administered questionnaire that assessed perceived changes in social skills, before and after the intervention. Wilcoxon Signed Rank test was used to determine the statistical significance of improvement in social skills. Results The sample consisted of 80% (n = 16) female adolescents. Median scores (inter-quartile range) for social skills before and after the first social skills programme were 31.5 (21.0–36.0) and 33.0 (28.25–40.25) respectively, indicating a significant improvement in social skills following intervention (p = 0.011, r = 0.57). A similar improvement was observed after the second programme (n = 10), reporting higher median scores for social skills after intervention (29.5 vs. 37.5, p = 0.005, r = 0.89). A significant improvement was also observed in perceived ability to cope with depressive thoughts after intervention (p = 0.032), indicating that social skills training can be a useful adjunct to pharmacological interventions, in the management of depression in adolescents.

Abstract Urinary tract infections (UTIs) pose a substantial burden on global healthcare systems. When unraveling the complex pathophysiology of UTIs, bladder models are used to understand complex and multifaceted interactions between different components within the system. This review aimed to bridge the gap between in vitro and in vivo experimental bladder models towards UTI research. We reviewed clinical, animal, and analytical studies and patents from 1959 to the end of 2023. Both in vivo and in vitro models offer unique benefits and drawbacks in understanding UTIs. In vitro models provide controlled environments for studying specific aspects of UTI biology and testing potential treatments, while in vivo models offer insights into how UTIs manifest and progress within living organisms. Thus, both types of models are leading to the development of more effective diagnostic tools and therapeutic interventions against UTIs. Moreover, advanced methodologies involving three-dimensional bladder organoids have also been used to study bladder biology, model bladder-related disorders, and explore new treatments for bladder cancers, UTIs, and urinary incontinence. Narrowing the distance between fundamental scientific research and practical medical applications, these pioneering models hold the key to unlocking new avenues for the development of personalized diagnostics, precision medicine, and ultimately, the alleviation of UTI-related morbidity worldwide.

Abstract Women with a history of Gestational diabetes mellitus (GDM) have a high risk of developing Type 2 diabetes mellitus (T2DM) in their future life. Lifestyle interventions are known to reduce this progression. The success of a lifestyle intervention mainly depends on its feasibility. Therefore, this study aimed to evaluate the feasibility of a lifestyle intervention programme aimed to attenuate the development of T2DM in mothers with a history of GDM. This qualitative phenomenological study was carried out in selected Medical offices of Health (MOH) areas in Sri Lanka. Postpartum mothers with a history of GDM who have undergone a comprehensive, supervised lifestyle intervention program for 1 year, their family members, and public health midwives (PHM) were recruited for this study. Focus group discussions (FGD) were carried out with mothers and PHM while In-depth interviews (IDI) were conducted with family members. Framework analysis was used for the analysis of data. A total of 94 participants (45 mothers, 40 healthcare workers, and 9 family members) participated in FGDs and IDIs to provide feedback regarding the lifestyle intervention. Sixteen sub-themes emerged under the following four domains; (1) Feelings and experiences about the lifestyle intervention programme for postpartum mothers with a history of GDM (2) Facilitating factors (3) Barriers to implementation and (4) Suggestions for improvement. Spouse support and continued follow-up were major facilitating factors. The negative influence of healthcare workers was identified as a major barrier to appropriate implementation. All participants suggested introducing continuing education programmes to healthcare workers to update their knowledge. The spouse’s support and follow-ups played a pivotal role in terms of the success of the programme. Enhancing awareness of the healthcare workers is also essential to enhance the effectiveness of the programme. It is imperative to introduce a formal intervention programme for the postpartum management of mothers with a history of GDM. It is recommended that the GDM mothers should be followed up in the postpartum period and this should be included in the national postpartum care guidelines.

Background: Breast cancer (BC) poses a significant public health concern as it is the most common cancer detected among women worldwide. Early detection and intervention are associated with better prognosis and survival. A primary reason for the rising mortality and morbidity in developing countries is the lack of patient education and practice early detection programs and presentation. Aims and Objectives: The main objective of this study is to evaluate the prevalence of delayed presentation and the factors lead to delay among BC patients in Sri Lanka. Materials and Methods: A descriptive cross-sectional study was conducted from January 01, 2023, to June 30, 2023 among women diagnosed with BC attending two selected state hospitals in Sri Lanka. All women with histological diagnosis of early, locally advanced, or metastatic BC attending for treatment were included and women with recurrent BC and concomitant other cancers were excluded. Presentation delay was defined as ≥3 months. The calculated sample size was 396. Results: About 47.5% of our study population (n=188) had a presentation delay of more than 3 months. The main reasons for the delay in presentation were, being unaware that BC is a major problem in Sri Lanka, difficulty in accessing healthcare, and not being able to find time due to family and social commitments. Women who had not been practicing self-breast examination had a significant association with presentation delay (OR=3.26, 95% CI - 0.090–0.362, P=0.001). The participants who were having a presentation delay were also more likely to be diagnosed with an advanced stage of cancer (OR=2.86, 95% CI - 2.573–3.153, P=0.000). Conclusion: Our study population depicts a good knowledge related to BC symptoms, risk factors, and early detection methods. However, very few are practicing them. There is also a significant delay of presentation due to various factors. Awareness and good practices would lead to early detection and diagnosis and improve overall survival.

Background: The shadowing house officer is an experiential learning activity that usually takes place within the final year clinical rotations of medical undergraduates. An exposure to a surgical intern is especially useful as the work extends to more practical aspects of ward work. Objective: We assessed the impact of the shadowing house officer experience during medical student clinical rotation on the surgical internship and to evaluate the challenges of the shadowing period. Methods: A descriptive cross-sectional survey was carried out among 108 surgical intern doctors in Sri Lanka via electronic media in 2023. Results: Our study population consisted of 108 interns, with a response rate of 43.2%. This study demonstrates that on average a final year medical student undergoes a 4-day shadowing period in surgery which was considered by a majority to help in smooth transition to internship. 56% had a clear understanding about learning outcomes and less than half has had an induction session prior to commencement of shadowing. Official documentation, routine ward work, team work and communication skills were meaningfully experienced during shadowing. The main criticisms were inadequate breaks leading to exhaustion and missing out on important teaching activities. Another major concern was shadowing close to the final examination. Conclusions: Surgical shadowing house officer is an authentic work experience that intern doctors consider as important component in orientating the role of an intern. Introduction of shadowing at an earlier stage would be more beneficial and provide a broader view about the clinical set up to undergraduates.

Abstract Background Unhealthy diet is a key risk factor for Non-Communicable Diseases (NCDs) that contribute to increased morbidity and premature mortality. With increased computer literacy and mobile phone penetration, there is a high opportunity for mobile application-based interventions. The current study was conducted to develop a mobile application to monitor dietary intake and to assess its acceptability and effectiveness in diet control compared to a similar paper-based intervention. A mobile application was developed based on research evidence and opinions of local experts. The mobile application was introduced to a selected group of office workers who were in preparation, action, and maintenance stages of the Trans Theoretical Model (TTM) and a paper-based intervention was used as the comparator. Socio-demographic data were collected through a self-administered questionnaire. Participants were followed up for three months for adherence. The effectiveness of interventions was assessed at the end of three months by comparing the progressive change in the stage of change and the change from unhealthy to healthy dietary intake between two groups as primary and secondary outcomes respectively. Results Among 123 office workers who participated in the study, 19.5% preferred the mobile intervention over the paper-based intervention. Younger, unmarried office workers and those who do not have children, had a higher acceptance for the mobile intervention (p

Introduction: The incidence of endometrial cancer in low-income countries is rising at a rapid rate. This could be due to changes in risk factors and socio-economic transitions occurring in developing countries. The main aim of this study was to assess the changes in endometrial cancer incidence in Sri Lanka. Materials and Methods: Incidence data for uterine corpus cancer and endometrial cancer between 2011 and 2020 were extracted from the National Cancer Register of Sri Lanka. This included the crude rate, age standardised incidence rate, and age-specific incidence. Joinpoint trend analysis software was used to analyse the temporal pattern of incidence. The estimated annual percentage change of incidence (EAPC) was calculated Results: A total of 8332 patients with uterine corpus cancer were reported with the highest incidence in the 60–70-year-old age group. The EAPC of uterine corpus cancer was 9.26%, while it was 8.26% for endometrial cancer. The highest rise of age-specific incidence was observed in the 70 years plus age group (EAPC 13.3968%, 95% confidence interval (CI): 9.6916–17.1994). Conclusion: There is a clear rise in endometrial and uterine cancer incidence in Sri Lanka. While part of this could be due to better reporting of new cases, a true increase in incidence should have occurred due to different rates of EAPC among age categories. Studies to evaluate the factors leading to the rising incidence of endometrial cancer are recommended.

Abstract The classical amyloid cascade hypothesis postulates that the aggregation of amyloid plaques and the accumulation of intracellular hyperphosphorylated Tau tangles, together, lead to profound neuronal death. However, emerging research has demonstrated that soluble amyloid-β oligomers (SAβOs) accumulate early, prior to amyloid plaque formation. SAβOs induce memory impairment and disrupt cognitive function independent of amyloid-β plaques, and even in the absence of plaque formation. This work describes the development and characterization of a novel anti-SAβO (E3) nanobody generated from an alpaca immunized with SAβO. In-vitro assays and in-vivo studies using 5XFAD mice indicate that the fluorescein (FAM)-labeled E3 nanobody recognizes both SAβOs and amyloid-β plaques. The E3 nanobody traverses across the blood–brain barrier and binds to amyloid species in the brain of 5XFAD mice. Imaging of mouse brains reveals that SAβO and amyloid-β plaques are not only different in size, shape, and morphology, but also have a distinct spatial distribution in the brain. SAβOs are associated with neurons, while amyloid plaques reside in the extracellular matrix. The results of this study demonstrate that the SAβO nanobody can serve as a diagnostic agent with potential theragnostic applications in Alzheimer’s disease.

Abstract Background A woman with a history of GDM has a high risk of developing type two diabetes (T2DM) in her future life. Lifestyle modifications are known to attenuate the progression of GDM to T2DM. Therefore, the aim of this study was to assess the impact of a simple, cost effective, culturally acceptable lifestyle intervention programme on the trajectory towards T2DM in women with a history of GDM. Methods This cluster randomized trial was conducted in 100 postpartum women in three selected districts of Sri Lanka. The subjects were divided into intervention (n = 50) and control groups (n = 50) by cluster randomization method. A culturally adapted protocol (comprised of dietary and physical activity modifications) was administered to the intervention group. The glycemic profile was assessed using fasting and 2-hour post-OGTT plasma glucose and HbA1c, and insulin resistance by HOMA-IR at baseline and after one year of intervention. Results The mean age (SD) of the subjects in the intervention and control groups were 33.0 (5.1) and 34.3 (6.5) years respectively. All glycemic and insulin resistance parameters (i.e. Fasting plasma glucose- FPG, 2-hour post-OGTT plasma glucose, HbA1c and HOMA-ir) were comparable (p > 0.05) between the two groups at baseline. FPG, 2 h post OGTT, HbA1c and HOMA-ir values between intervention vs. control (p) at 12 months were 87.3 vs. 123.2 (

Abstract Background Fundamentally defined by an imbalance in energy consumption and energy expenditure, obesity is a significant risk factor of several musculoskeletal conditions including osteoarthritis (OA). High-fat diets and sedentary lifestyle leads to increased adiposity resulting in systemic inflammation due to the endocrine properties of adipose tissue producing inflammatory cytokines and adipokines. We previously showed serum levels of specific adipokines are associated with biomarkers of bone remodelling and cartilage volume loss in knee OA patients. Whilst more recently we find the metabolic consequence of obesity drives the enrichment of pro-inflammatory fibroblast subsets within joint synovial tissues in obese individuals compared to those of BMI defined ‘health weight’. As such this present study identifies obesity-associated genes in OA joint tissues which are conserved across species and conditions. Methods The study utilised 6 publicly available bulk and single-cell transcriptomic datasets from human and mice studies downloaded from Gene Expression Omnibus (GEO). Machine learning models were employed to model and statistically test datasets for conserved gene expression profiles. Identified genes were validated in OA tissues from obese and healthy weight individuals using quantitative PCR method (N = 38). Obese and healthy-weight patients were categorised by BMI > 30 and BMI between 18 and 24.9 respectively. Informed consent was obtained from all study participants who were scheduled to undergo elective arthroplasty. Results Principal component analysis (PCA) was used to investigate the variations between classes of mouse and human data which confirmed variation between obese and healthy populations. Differential gene expression analysis filtered on adjusted p-values of p

Abstract Infrastructure is often a limiting factor in microplastics research impacting the production of scientific outputs and monitoring data. International projects are therefore required to promote collaboration and development of national and regional scientific hubs. The Commonwealth Litter Programme and the Ocean Country Partnership Programme were developed to support Global South countries to take actions on plastics entering the oceans. An international laboratory network was developed to provide the infrastructure and in country capacity to conduct the collection and processing of microplastics in environmental samples. The laboratory network was also extended to include a network developed by the University of East Anglia, UK. All the laboratories were provided with similar equipment for the collection, processing and analysis of microplastics in environmental samples. Harmonised protocols and training were also provided in country during laboratory setup to ensure comparability of quality-controlled outputs between laboratories. Such large networks are needed to produce comparable baseline and monitoring assessments.

Recent research has shown that droughts have intensified in South Asia over the past two decades. As a natural disaster, this has severely impacted people’s livelihoods, especially in the dry zones of Sri Lanka. Thus, to ensure human well-being, security of water resources, and ecosystem health, it is essential to minimize the impacts of droughts using reliable information. Remote sensing (RS) data and techniques help bridge the gap by enabling the analysis of drought phenomena through a diverse array of indices developed in the fields. However, until now, there has been a lack of systematic monitoring and reliable data for accurately characterizing droughts in the study area. As the first comprehensive analysis, we tried to evaluate the spatial–temporal dynamics of drought conditions in two Divisional Secretariat Divisions of the Anuradhapura district, Sri Lanka using eight standardized remote sensing-derived indices over a decade (2013–2023) including the Standardized Precipitation Index (SPI). SPI values indicated that the region has experienced notably below-average precipitation. According to SPI results, a significant portion of the Medawchchiya area experienced arid conditions in 2023. All other indices proved that 2018 was the driest year and 2013 was the wettest year among the three time points, as reflected by their low and high index values. However, according to NVSMI and LST, the wettest year is 2023, with only 1.78 % of areas experiencing severe drought and a maximum LST of 31.4 °C. LULC change detection revealed that 14.3 % of agricultural lands and 5.1 % of forest areas were converted into barren lands over a decade. Overall, this conversion may be another leading factor contributing to increased LST and dryness in the area during the concerned period while increasing the mean LST of barren land by around 4.7 °C per decade. Land surface-related and vegetation-related indices, such as NDWI, NDMI, LST, and NDVI, exhibited a more pronounced impact on short-term drought occurrences. The findings revealed that average precipitation coincides with short-term drought episodes in the area, with 2018 standing out as having the least rainfall and the driest year. The study’s findings may provide additional insights for planning authorities, supporting environmental protection and enhancing agricultural production by mitigating droughts’ impacts through short- and long-term strategies. Although, the study focused on a small area, a similar approach could be extended to other areas by incorporating advanced machine learning techniques and additional drought indices in the future.

Abstract Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, neuro‐acquired HIV (neuroHIV) remains a significant problem and approximately half of people living with HIV will experience HIV‐associated neurocognitive disorders (HAND). Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, neuronal injury and synaptodendritic culling, viral replication, and potentially altering antiretroviral concentrations within the brain. The present study examined the effects of HIV and morphine co‐exposure on the accumulation and spatial distribution of antiretroviral drugs across multiple regions within the brain in an HIV‐1 Tat transgenic mouse model by using infrared‐matrix‐assisted laser desorption electrospray ionization mass spectrometry imaging (IR‐MALDESI MSI). Morphine exposure uniquely decreased antiretroviral concentrations in anterior cerebral (primary motor and somatosensory) cortices, corpus collosum (anterior forceps), caudoputamen, nucleus accumbens, and posterior regions including the hippocampus, corpus callosum (main body), cerebral cortex (somatosensory and auditory cortices), thalamus, and hypothalamus. Interestingly, male mice experienced greater morphine‐associated decreases in antiretroviral concentrations than females. The study also assessed whether changes in antiretroviral concentrations were linked with inflammation in astroglia, assessed through the measurement of astroglial activation using glial fibrillary acidic protein (GFAP) as a marker. Alterations in antiretroviral concentrations co‐registering with areas of astroglial activation exhibited sex‐specific treatment differences. This study highlights the intricate interplay between HIV, opioids, and antiretroviral drugs within the CNS, elucidating distinct regional and sex variations in responsiveness. Our findings emphasize the identification of vulnerabilities within the neural landscape and underscore the necessity of carefully monitoring opioid use to maintain the efficacy of antiretroviral therapies.

Cancer cell invasion relies on an equilibrium between cell deformability and the biophysical constraints imposed by the extracellular matrix (ECM). However, there is little consensus on the nature of the local biomechanical alterations in cancer cell dissemination in the context of three-dimensional (3D) tumor microenvironments (TMEs). While the shortcomings of two-dimensional (2D) models in replicating in situ cell behavior are well known, 3D TME models remain underutilized because contemporary mechanical quantification tools are limited to surface measurements. Here, we overcome this major challenge by quantifying local mechanics of cancer cell spheroids in 3D TMEs. We achieve this using multimodal mechano-microscopy, integrating optical coherence microscopy-based elasticity imaging with confocal fluorescence microscopy. We observe that non-metastatic cancer spheroids show no invasion while showing increased peripheral cell elasticity in both stiff and soft environments. Metastatic cancer spheroids, however, show ECM-mediated softening in a stiff microenvironment and, in a soft environment, initiate cell invasion with peripheral softening associated with early metastatic dissemination. This exemplar of live-cell 3D mechanotyping supports that invasion increases cell deformability in a 3D context, illustrating the power of multimodal mechano-microscopy for quantitative mechanobiology in situ.

Deep venous thrombosis is a common and potentially life-threatening condition that is often associated with various risk factors including underlying malignancy. In this case report, we present a male patient who presented with deep venous thrombosis as the earliest presenting feature of metastatic gallbladder carcinoma. This case report emphasizes the importance of thorough evaluation of patients presenting with unprovoked deep venous thrombosis to early detection of underlying malignancy.

Abstract Novel methods for sampling and characterizing biodiversity hold great promise for re-evaluating patterns of life across the planet. The sampling of airborne spores with a cyclone sampler, and the sequencing of their DNA, have been suggested as an efficient and well-calibrated tool for surveying fungal diversity across various environments. Here we present data originating from the Global Spore Sampling Project, comprising 2,768 samples collected during two years at 47 outdoor locations across the world. Each sample represents fungal DNA extracted from 24 m3 of air. We applied a conservative bioinformatics pipeline that filtered out sequences that did not show strong evidence of representing a fungal species. The pipeline yielded 27,954 species-level operational taxonomic units (OTUs). Each OTU is accompanied by a probabilistic taxonomic classification, validated through comparison with expert evaluations. To examine the potential of the data for ecological analyses, we partitioned the variation in species distributions into spatial and seasonal components, showing a strong effect of the annual mean temperature on community composition.

Abstract Intracellular membranes composing organelles of eukaryotes include membrane proteins playing crucial roles in physiological functions. However, a comprehensive understanding of the cellular responses triggered by intracellular membrane-focused oxidative stress remains elusive. Herein, we report an amphiphilic photocatalyst localised in intracellular membranes to damage membrane proteins oxidatively, resulting in non-canonical pyroptosis. Our developed photocatalysis generates hydroxyl radicals and hydrogen peroxides via water oxidation, which is accelerated under hypoxia. Single-molecule magnetic tweezers reveal that photocatalysis-induced oxidation markedly destabilised membrane protein folding. In cell environment, label-free quantification reveals that oxidative damage occurs primarily in membrane proteins related to protein quality control, thereby aggravating mitochondrial and endoplasmic reticulum stress and inducing lytic cell death. Notably, the photocatalysis activates non-canonical inflammasome caspases, resulting in gasdermin D cleavage to its pore-forming fragment and subsequent pyroptosis. These findings suggest that the oxidation of intracellular membrane proteins triggers non-canonical pyroptosis.

Summary: This Health Policy reviews the preparedness and response of public health laboratories in the WHO South-East Asia Region (SEAR) during the COVID-19 pandemic. Through a scoping review and in-depth interviews with key stakeholders, the study identifies successes, challenges, and lessons learned from available literature and the perspective of senior laboratory leaders. Key themes include human resources, health information systems, diagnostic capacity, public risk communication, biosafety, biosecurity, funding, and laboratory network coordination. The findings provide a comprehensive overview of the adaptive capacities of laboratories, the contextual factors influencing their response, and the implications for future pandemic preparedness. This study demonstrates the resilience and adaptability of diagnostic networks in the face of a pandemic but also emphasises the need for strategic resource allocation, highlighting the importance of flexible and scalable networks in managing public health crises. The success of these deployments highlights the necessity for continual investment and coordination of national, regional, and global resources in diagnostic infrastructure to improve preparedness for future public health crises.

Summary: Tumor cells undergo uncontrolled proliferation driven by enhanced anabolic metabolism including glycolysis and glutaminolysis. Targeting these pathways to inhibit cancer growth is a strategy for cancer treatment. Critically, however, tumor-responsive T cells share metabolic features with cancer cells, making them susceptible to these treatments as well. Here, we assess the impact on anti-tumor T cell immunity and T cell exhaustion by genetic ablation of lactate dehydrogenase A (LDHA) and glutaminase1 (GLS1), key enzymes in aerobic glycolysis and glutaminolysis. Loss of LDHA severely impairs expansion of T cells in response to tumors and chronic infection. In contrast, T cells lacking GLS1 can compensate for impaired glutaminolysis by engaging alternative pathways, including upregulation of asparagine synthetase, and thus efficiently respond to tumor challenge and chronic infection as well as immune checkpoint blockade. Targeting GLS1-dependent glutaminolysis, but not aerobic glycolysis, may therefore be a successful strategy in cancer treatment, particularly in combination with immunotherapy.

Diagnosing neoplastic fever requires excluding identifiable causes, making it a diagnostic challenge. Fever as a primary manifestation of pancreatic adenocarcinoma is uncommon with few cases reported in the literature. Here we present an unusual case of metastatic pancreatic adenocarcinoma primarily manifesting as pyrexia of unknown origin. A 63-year-old Sri Lankan male, a non-smoker who was diagnosed with diabetes, hypertension and dyslipidaemia presented with a history of fever, anorexia and weight loss for 2 months. Despite the completion of treatment for positive serology for paratyphi, his symptoms and inflammatory markers remained elevated while the rest of the infectious screening was negative. On further evaluation, the patient was found to have a hypodense distal pancreas with ring-enhancing multiple liver lesions on imaging. Histology confirmed pancreatic adenocarcinoma with liver metastasis. Atypical liver metastases may present with evidence of ring enhancement in computed tomography imaging; thus, the biopsy is mandatory for diagnosis and decision-making. Usually, tumours of the pancreatic tail are resectable but if they are associated with liver metastatic disease, surgical resection is not recommended because it is not potentially curative. Therefore, in the context of metastatic pancreatic adenocarcinoma, palliative chemotherapy and pharmacological management of fever are required.