Introduction: Primary aldosteronism (PA), most commonly caused by aldosterone-producing adenomas (APAs), represents the leading form of surgically curable secondary hypertension. While genomic studies have elucidated the mutational landscape of APAs, the spatial organisation and functional role of immune populations across APAs, aldosterone-producing micronodules (APMs), and adjacent adrenal cortex remain poorly defined at single-cell resolution. Methodology: Single-cell RNA sequencing (scRNA-seq) was integrated with spatial transcriptomics in APAs and paired adjacent adrenal cortex, complemented by immunohistochemical (IHC) validation. Immune populations were spatially mapped using canonical markers (CD14, CD68, CD163, HLA-DR, CD8A, and CD4) across defined adrenocortical regions. Results: The adrenal microenvironment in PA demonstrates structured immune organisation rather than passive infiltration. CD14+ monocyte-lineage cells localize intraparenchymally within APAs (n = 10), intercalating between CYP11B2+ aldosterone-producing cells and forming a pattern distinct from perivascular immune niches. scRNA-seq further identified a transcriptionally distinct CD14+ population within the zona reticularis (zR) that co-expresses steroidogenic markers (CYB5A, SULT2A1, TSPAN12) while lacking canonical monocyte transcripts. IHC supported this observation, demonstrating CD14 expression within adrenocortical zR parenchymal cells (n = 5). In parallel, CD4 and HLA-DRA exhibited diffuse cytoplasmic staining within zR parenchymal cells in the absence of classical macrophage marker coexpression (CD68), suggesting non-canonical or context-dependent expression within steroidogenic compartments. CD68+ and CD163+ macrophages were sparsely distributed across APA, APM and adjacent cortex, consistent with lowdensity tissue-resident populations, while CD8A+ cytotoxic lymphocytes were enriched in APAs and APMs with diffuse parenchymal cytoplasmic staining of CD8A additionally observed within the zR. Conclusion These findings reveal a previously unrecognized spatially organised immune-steroidogenic interface within the adrenal cortex. The presence of immune-associated transcriptional and protein signatures within zR cells suggests potential functional plasticity of steroidogenic cells, possibly extending to antigen presentation-related pathways, warranting further mechanistic investigation
Hyperaldosteronism ; Humans

Rare Diseases-Malaysia.

Mullerian agenesis or Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) Type-II is a congenital defect in the Mullerian duct that results in the absence of a uterus in women. The aetiology of this syndrome is unknown and has been considered a sporadic genetic disease. MRKH, together with anorectal anomaly, is an extremely rare condition and has only been reported in a few cases without any information on genetic analysis. This study investigated the mutational profile of a girl diagnosed with MRKH and anorectal anomalies with rectovaginal fistula. The whole exome sequencing (WES) trio-genetic analysis of a 5-year-old Malaysian girl diagnosed with MRKH (having anorectal anomaly with rectovaginal fistula) was performed together with her normal parents, using the Ion AmpliSeq Exome RDY kit (ThermoFisher Scientific, USA). Data were analysed using Torrent Suite v.5.0.4 and annotated using ANNOVAR. Single nucleotide polymorphisms (SNPs) with an allele frequency >0.01 were excluded, and the remaining variants were filtered based on de novo mutations, autosomal recessive, and autosomal recessive genetic traits. Related genes were analysed by biological pathway analysis (g:Profiler) and protein-protein interaction (HIPPIE v.2.3, STRING v.11.5, dan GeneMANIA). A total of 36 mutations were identified, and two of them, the LHX5 (p.P358Q), inherited from the father, and CFTR (p.R1158X), inherited from the mother. There were 28 de-novo mutations from 28 genes. All genes were involved in 27 biological processes that connected with 23 interactions, and are likely to cause MRKH syndrome in this patient.

Background:Shared decision-making(SDM)implementation is a priority for Australian health systems,including general practices but it remains complex for specific groups like older rural Australians.We initiated a qualitative study with older rural Australians to explore barriers to and facilitators of SDM in local general practices. Methods:We conducted a patient-oriented research,partnering with older rural Australians,families,and health service providers in research design.Participants who visited general practices were purposively sampled from five small rural towns in South Australia.A semi-structured interview guide was used for interviews and reflexive thematic coding was conducted. Results:Telephone interviews were held with 27 participants.Four themes were identified around older rural adults'involvement in SDM:(1)Understanding of"patient involvement";(2)Positive and negative outcomes;(3)Barriers to SDM;and(4)Facilitators to SDM.Understanding of patient involvement in SDM considerably varied among participants,with some reporting their involvement was contingent on the"opportunity to ask questions"and the"treatment choices"offered to them.Alongside the opportunity for involvement,barriers such as avoidance of cultural care and a lack of continuity of care are new findings.Challenges encountered in SDM implementation also included resource constraints and time limitations in general practices.Rural knowledge of general practitioners and technology integration in consultations were viewed as potential enablers. Conclusion:Adequate resources and well-defined guidelines about the process should accompany the implemen-tation of SDM in rural general practices of South Australia.Innovative strategies by general practitioners pro-moting health literacy and culturally-tailored communication approaches could increase older rural Australians'involvement in general.

Aims: Hypoxia is believed to be one of the key components contributing to the clinical resistance of cancer therapies. Alternative strategies are under investigation to overcome this resistance and the oncolytic virus stands amongst the others. Newcastle disease virus (NDV) has been demonstrated to possess oncolytic activity against cancer cells. The present study investigated the effects of oncolytic NDV strain AF2240 and V4-UPM on osteosarcoma cells (Saos-2) under normoxic and hypoxic conditions. Methodology and results: Results showed that the NDV strain AF2240 and V4-UPM could infect and kill normoxic and hypoxic Saos-2 cells equally well by inducing hypoxia-independent apoptosis, and S-phase cell cycle arrest under the microscopy examination, cell viability assay, Annexin V apoptosis assay and cell cycle analysis experiments. However, the Velogenic NDV strain AF2240 excelled over the lentogenic NDV V4-UPM with increased oncolytic effects in Saos-2 cells. Conclusion, significance and impact of study In a nutshell, normoxia or hypoxia microenvironment has little effect on NDV-induced oncolysis of Saos-2 cancer cells which poses as a potential agent for the treatment of resistant cancer.

Introduction: A popular intervention for paediatric clients, Ayres Sensory Integration® (ASI) must adhere to sensory integration (SI) fidelity. This study describes fidelity adherence in ASI intervention by occupational therapy practitioners in Malaysia. Methods: A questionnaire on ASI fidelity was developed before being tested for its validity by seven experts and for its internal consistency and test-retest reliability by 30 occupational therapists. The questionnaire was then used nationally to collect data on ASI practitioners. Data were collected from 161 occupational therapists working in various settings. Results: The mean of the sub-scales I-CVI was excellent, ranging between 0.97 and 1.00. The total S-CVI/Ave of the form was also reported as excellent, at 0.98, with subscales S-CVI ranging between 0.75 and 1.00. Cronbach’s alpha was 0.80 for the questionnaire’s internal consistency and the ICC for test-retest reliability ranged from 0.80 to 0.95. The survey received 161 responses, indicating that most respondents perceived themselves as having ‘moderate competence’ and showing ‘high interest’ in ASI implementation. Most fidelity aspects were addressed in their practices. Majority of the respondents adhered to the process elements. It was indicated that three aspects of physical space under the structural elements could not be provided by most occupational therapists in the study. Conclusion: To implement evidence-based practice, adherence to fidelity when providing ASI is important to ascertain its effectiveness. Improvements to ensure optimal space, ASI certification, and more related training are the first steps that can be taken by the related agencies to ensure effective ASI intervention could be delivered.

Introduction: Dietary inflammation is a significant risk factor for age-related cognitive impairments among older adults. However, information related to the relationship between Empirical Dietary Inflammatory Index (eDII) score and cognitive frailty (CF) among Malaysian community-dwelling older adults is still limited. The objective of this study is to determine the association between dietary inflammatory risk and CF among community-dwelling older adults. Method: This is a cross sectional study involving community-dwelling older adults in Klang Valley. The Fried’s Criteria and Clinical Dementia Rating (CDR) were used to determine CF status. Subjects were also interviewed using the Dietary History Questionnaire (DHQ) and eDII food checklist to assess the food intake and dietary inflammatory risk. Data collected was analyzed using SPSS version 26.0. Results: A total of 158 older adults (66.7 ± 5.2 years old) residing in Klang Valley were involved. Energy and macronutrients have a weak positive association with pro-inflammatory score (p<0.05). There is no significant mean difference between CF older adults consumed a more pro-inflammatory diet (mean 2.07 ± 1.10) compared to non CF (mean 2.06 ± 1.14). However, white rice food item significantly consumed by CF people (22.4%) than non CF (8.5%) (p<0.05). Conclusion: CF older adults were more likely to consume a pro-inflammatory diet particularly from the rice food group. There is a need to further assess the risk of consuming a pro-inflammatory diet using larger sample size and appropriate biomarkers.

Background:The prevalence of pediatric mental illnesses has been increasing in recent years,with a great potential to impact on individual's functionality and adaptation in adulthood.Objective:This study aims to assess emotional and behavioral problems among schoolchildren in Herat City of Afghanistan.Methods:This cross-sectional study was conducted on schoolchildren(grade 5-10),between September and November 2021.Sociodemographic data was collected using a paper-based 14-item structured questionnaire.Data on emotional and behavioral problems was collected using the Strengths and Difficulties Questionnaire(SDQ)based on teachers'and children's report.Statistical analyses were performed in IBM SPSS Statistics(version 27).Results:A total of 418 students,including 190(45.5％)males and 228(54.5％)females with a mean age of 14.1±1.7(11-＜18)years were included in the study.The prevalence of students'self-reported total difficulties and prosocial problem were 5.7％and 1.2％,respectively.An insignificant difference was observed between mean total difficulties scores between students'self-reported and teachers'reported SDQ.Gender,grade,concern about shortage of food,and concern about losing house were significantly predicting students'self-reported total difficulties scores.Conclusion:This is the first study to report the prevalence of emotional and behavioral problems among schoolchildren in Herat City,Afghanistan.This,together with relevant global literature,highlight the need to address pediatric mental health,and provide services aimed at preventing,and treating children with these prob-lems around the world.

Objective:A study was conducted about the putative links of older rural Australians'health knowledge and preparation with their quality of involvement in patient-general practitioner(GP)communication during health intake visits. Methods:It was a cross-sectional study between January 2021 and April 2022.The 32-item quality of involve-ment in communication scale was designed and incorporated into the Survey Gizmo software.This online survey was administered by sending an email request to the Renmark Rotary Club,which actively promoted this study across five rural towns in South Australia.121 participants completed the surveys.Mean-sum scores were cal-culated based on the questionnaire responses to evaluate outcomes,specifically initiation of information,active participation,and emotional expression.We employed different methods including t-tests,ANOVA,and leaner regressions to analyse data. Results:The demographic profile of participants characterised by a female predominance(58.7％,71/121),a ma-jority falling within the 65-＜70 age bracket(47.1％,57/121),and a high level of educational attainment(58.7％had completed high school or higher,71/121).Additionally,35％of the participants predominantly spoke a lan-guage other than English at home.Regarding the initiation of information with GPs,the mean sum-score was(20.5±3.7),indicating a marginally above-average level of engagement.Contrarily,the active participation was suboptimal,as suggested by a mean sum score of(35.9±6.3).Furthermore,the emotional expression was rela-tively low,with a mean score of(13.9±1.8).Substantial variations were discerned in the quality of patient-GP communication,contingent upon factors such as educational background,language spoken at home,health lit-eracy,and preparatory measures for clinical visits.Participants who predominantly spoke a language other than English at home demonstrated significantly lower levels of information initiation with their GPs(P＜0.001).Higher educational attainment was positively correlated with increased active participation(P＜0.001).En-hanced health literacy and thorough visit preparation were significantly associated with increased levels of active participation(P＜0.001). Conclusion:Meaningful engagement through recognition,empowerment,and support(health literacy pro-grams)for older rural adults is suggested for improving their quality of involvement in communication with GPs.

Objective:Afghanistan has witnessed a long-lasting 4-decade armed conflict,which together with high levels of poverty and interpersonal violence,resulted in high incidence and prevalence of mental disorders in general population,including children and adolescents.Until mid-2018,there was neither mental health care facility nor a child psychiatrist in Afghanistan.Here,we report the establishment of the first children and adolescents'mental health center(CAMHC)in Herat province of Afghanistan. Methods:In July 2018,CAMHC was initiated at Mental Health Training Center-Herat.CAMHC was initially planned by the International Assistance Mission(IAM)and Herat Public Health Directorate;and financially sup-ported by the Tearfund UK,the United Methodist Committee on Relief and Tearfund Australia.The target pop-ulation of CAMHC was children and adolescents in Herat and neighboring provinces,healthcare professionals,staff of government and non-governmental organizations,school teachers and community leaders. Results:A group of eight mental health professionals were trained and made the interdisciplinary board for di-agnosis and management of mental disorders in children and adolescents.During the initial three-year period,2 448 patients,including 1 264(51.6％)boys and 1 184(48.4％)girls,presented with mental disorders to CAMHC.Diagnosis and management of mental disorders were performed according to standard international protocols.Eighteen awareness-raising seminars were held;2 000 leaflets,10 000 posters,and 30 000 brochures were pre-pared and distributed;and two short video clips were produced and broadcast via IAM website,social media and local TV channels.A database was developed to house for project data,assessment of outcomes and reporting to stakeholders. Conclusion:Establishment of CAMHC resulted in significant achievements in diagnosis and management of men-tal disorders among children and adolescents,healthcare staff capacity building,and awareness-raising about mental disorders.Data obtained in CAMHC offers government,mental health professionals and the community the opportunity of improving mental health in the region.