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Background Accurate prediction of reference ranges of renal lengths facilitates clinical decision making. Currently a single renal-length-reference chart is used for both kidneys, which is solely based on the age of the child without adjusting for anthropometrics. Objective of the study is to assess the length of morphologically-normal kidneys ultrasonically and to build models to predict the renal lengths of children presenting at the Radiology Department of Lady Ridgeway Hospital for Children. Methods A descriptive cross sectional study was done among 424 children with 233 males and 191 females at the study setting. Study population included children undergoing abdominal ultrasound scans for indications not related to renal disease. Children with a family history of renal diseases or with morphologically-abnormal kidneys were excluded. Bipolar-lengths of kidneys, gender and anthropometrics were documented. Having tested for assumptions, Wilcoxon-signed rank test, Mann-Whitney U test and multiple linear regression were used. Results The mean (SD) bipor-length of right and left kidneys were 6.83 (1.43) and 7.05 (1.36) respectively ( p  < 0.001). Age, height and weight were significantly correlated with the renal lengths ( p  < 0.05). Until 16 months, there was a significant difference between the renal lengths between males and females ( P  < 0.05). Yet the association with gender was not significant from 17 months and in overall. Until 16 months, the best linear-regression equation ( p  < 0.001) for the left kidney was; 3.827 +  0.019(length in centimeters) +  0.141(weight in kilograms) - 0.023(age in months) - 0.347(for male sex). For the right kidney, it was; 3.888 + 0.020(length or height) + 0.121(weight) - 0.037(age) - 0.372 (for male sex). The respective R squares were 59.2 and 53.5% with VIF (Variance-Inflation-Factor) ranging from 1.06 to 2.08. From 17 months, best equation for left kidney (p < 0.001) was; 5.651+ 0.022(age) + 0.01(BMI). For right kidney it was; 5.336 + 0.022(age) + 0.012(BMI). The R squares were 62.5 and 66.1% with VIF being 1. Conclusions The established models explain more variability for children above 17 months. Both renal lengths are affected significant by the body’s’ anthropometric parameters. For each kidney, separate normograms of renal lengths which are local-context-specific must be prepared. Further research must be promoted.

IntroductionDespite the improvement in medical management, many patients with transfusion-dependent β-thalassaemia die prematurely due to transfusion-related iron overload. As per the current guidelines, the optimal chelation of iron cannot be achieved in many patients, even with two iron chelators at their maximum therapeutic doses. Here, we evaluate the efficacy and safety of triple combination treatment with deferoxamine, deferasirox and deferiprone over dual combination of deferoxamine and deferasirox on iron chelation in patients with transfusion-dependent β-thalassaemia with very high iron overload.Methods and analysisThis is a single-centre, open-label, randomised, controlled clinical trial conducted at the Adult and Adolescent Thalassaemia Centre of Colombo North Teaching Hospital, Ragama, Sri Lanka. Patients with haematologically and genetically confirmed transfusion-dependent β-thalassaemia are enrolled and randomised into intervention or control groups. The intervention arm will receive a combination of oral deferasirox, oral deferiprone and subcutaneous deferoxamine for 6 months. The control arm will receive the combination of oral deferasirox and subcutaneous deferoxamine for 6 months. Reduction in iron overload, as measured by a reduction in the serum ferritin after completion of the treatment, will be the primary outcome measure. Reduction in liver and cardiac iron content as measured by T2* MRI and the side effect profile of trial medications are the secondary outcome measures.Ethics and disseminationEthical approval for the study has been obtained from the Ethics Committee of the Faculty of Medicine, University of Kelaniya (Ref. P/06/02/2023). The trial results will be disseminated in scientific publications in reputed journals.Trial registration numberThe trial is registered in the Sri Lanka Clinical Trials Registry (Ref: SLCTR/2023/010).

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. In this multicentre, open-label, randomised controlled trial, 80 women older than 18 years, with a diagnosis of PCOS based on the 2018 international evidence-based guidelines for assessing and managing PCOS, and a BMI of 35 kg/m2 or higher, were recruited from two specialist obesity management centres and via social media. Participants were randomly assigned at a 1:1 ratio to either vertical sleeve gastrectomy or behavioural interventions and medical therapy using a computer-generated random sequence (PLAN procedure in SAS) by an independent researcher not involved with any other aspect of the clinical trial. The median age of the entire cohort was 31 years and 79% of participants were White. The primary outcome was the number of biochemically confirmed ovulatory events over 52 weeks, and was assessed using weekly serum progesterone measurements. The primary endpoint included the intention-to-treat population and safety analyses were per-protocol population. This study is registered with the ISRCTN registry (ISRCTN16668711). Participants were recruited from Feb 20, 2020 to Feb 1, 2021. 40 participants were assigned to each group and there were seven dropouts in the medical group and ten dropouts in the surgical group. The median number of ovulations was 6 (IQR 3·5–10·0) in the surgical group and 2 (0·0–4·0) in the medical group. Women in the surgical group had 2.5 times more spontaneous ovulations compared with the medical group (incidence rate ratio 2·5 [95% CI 1·5–4·2], p<0·0007). There were more complications in the surgical group than the medical group, although without long-term sequelae. There were 24 (66·7%) adverse events in the surgical group and 12 (30·0%) in the medical group. There were no treatment-related deaths. Bariatric surgery was more effective than medical care for the induction of spontaneous ovulation in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea. Bariatric surgery could, therefore, enhance the prospects of spontaneous fertility in this group of women. The Jon Moulton Charity Trust.

This study explores climate change's symmetric and asymmetric impacts on rice production in Sri Lanka, a crucial sector for food security in the country. The analysis utilized Autoregressive Distributed Lag (ARDL) and Non-linear Autoregressive Distributed Lag (NARDL) models. This study analyses annual data from 1952 to 2022 to capture relationships among the study variables. The ARDL findings reveal that temperature and cultivated land area have a significant long-term effect on rice production. The NARDL model reveals that positive and negative changes in climate variables have asymmetrical long-term impacts. Positive changes in temperature and rainfall lead to a notable decline in rice yields in the long term. Negative rainfall changes create a significant beneficial effect on rice production in the long term. Cultivated land area shows a significant positive impact on rice yield in the long term. The results of symmetric and asymmetric climate change impact are essential for formulating agricultural climate adaptation policies, such as promoting climate resilience rice varieties, improving irrigation and water management, developing early warning systems that promote sustainability and enhance climate adaptation strategies, ensuring food security in Sri Lanka.

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P =0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P =0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P =0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P =0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.

Purpose Substance use disorder (SUD) is a serious public health concern that requires continuum care with effective treatment modalities such as residential rehabilitation. Improvement in health-related quality of life (HRQoL) is one of the determinants of treatment and rehabilitation effectiveness. Therefore, a retrospective cross-sectional study was carried out in seven residential rehabilitation centres in Sri Lanka to determine the HRQoL of the rehabilitees with SUD. Method The HRQoL of 464 individuals at their enrolment and during the rehabilitation period was assessed using EuroQol five-level five-dimensional questionnaire (EQ-5D-5L). Data were analysed using IBM SPSS version 26. Results The majority of the participants were Sinhala ( n  = 419, 90.3%) and Buddhist ( n  = 368, 79.3%) males ( n  = 461, 99.4%). Most were unmarried ( n  = 302, 65.1%), young adults ( n  = 385, 83.0%) who have pursued secondary or higher education ( n  = 276, 59.5%) and 87.3% were employed ( n  = 405). Most of the selected centres use biopsychosocial model ( n  = 4, 57.1%) as the rehabilitation approach while rest practice therapeutic community ( n  = 3, 42.9%). The average EQ-5D-5L index [range =( − 0.45)–1.00] of the rehabilitees at their enrolment was 0.52 ± 0.28 and the EQ-5D-5L Visual Analogue Scale (EQ-5D-5L VAS) score (range = 0–100%) was 47.17% ± 23.48%. The values were increased up to 0.83 ± 0.18 (EQ-5D-5L index) and 84.25% ± 16.79% (EQ-5D-5L VAS) during the rehabilitation period. Only 19.4% of the rehabilitees had a normal or upper normal HRQoL (≥ 0.75 EQ-5D-5L Index) at their enrolment and 72.2% of rehabilitees reported normal or upper normal HRQoL during the rehabilitation period. Conclusion A significant improvement in the HRQoL of the participants was observed during the residential treatment in comparison to the enrolment, despite the differences in the rehabilitation programs.

Background: Heat shock protein 90 (HSP90) has a key role in the maintenance of the cellular proteostasis. However, HSP90 is also involved in stabilisation of oncogenic client proteins and facilitates oncogene addiction and cancer cell survival. The development of HSP90 inhibitors for cancer treatment is an area of growing interest as such agents can affect multiple pathways that are linked to all hallmarks of cancer. This study aimed to test the hypothesis that targeting cysteine residues of HSP90 will lead to degradation of client proteins and inhibition of cancer cell proliferation. Methods: Combining chemical synthesis, biological evaluation, and structure–activity relationship analysis, we identified a new class of HSP90 inhibitors. Click chemistry and protease-mass spectrometry established the sites of modification of the chaperone. Results: The mildly electrophilic sulphoxythiocarbamate alkyne (STCA) selectively targets cysteine residues of HSP90, forming stable thiocarbamate adducts. Without interfering with the ATP-binding ability of the chaperone, STCA destabilises the client proteins RAF1, HER2, CDK1, CHK1, and mutant p53, and decreases proliferation of breast cancer cells. Addition of a phenyl or a tert -butyl group in tandem with the benzyl substituent at nitrogen increased the potency. A new compound, S-4, was identified as the most robust HSP90 inhibitor within a series of 19 derivatives. Conclusion: By virtue of their cysteine reactivity, sulphoxythiocarbamates target HSP90, causing destabilisation of its client oncoproteins and inhibiting cell proliferation.

Cholinesterase inhibitors produce small improvements in cognitive and global assessments in Alzheimer's disease. We aimed to determine whether donepezil produces worthwhile improvements in disability, dependency, behavioural and psychological symptoms, carers' psychological wellbeing, or delay in institutionalisation. If so, which patients benefit, from what dose, and for how long? 565 community-resident patients with mild to moderate Alzheimer's disease entered a 12-week run-in period in which they were randomly allocated donepezil (5 mg/day) or placebo. 486 who completed this period were rerandomised to either donepezil (5 or 10 mg/day) or placebo, with double-blind treatment continuing as long as judged appropriate. Primary endpoints were entry to institutional care and progression of disability, defined by loss of either two of four basic, or six of 11 instrumental, activities on the Bristol activities of daily living scale (BADLS). Outcome assessments were sought for all patients and analysed by logrank and multilevel models. Cognition averaged 0·8 MMSE (mini-mental state examination) points better (95% Cl 0·5–1·2; p<0·0001) and functionality 1·0 BADLS points better (0·5–1·6; p<0·0001) with donepezil over the first 2 years. No significant benefits were seen with donepezil compared with placebo in institutionalisation (42%vs 44% at 3 years; p=0·4) or progression of disability (58%vs 59% at 3 years; p=0·4). The relative risk of entering institutional care in the donepezil group compared with placebo was 0·97 (95% Cl 0·72–1·30; p=0·8); the relative risk of progression of disability or entering institutional care was 0·96 (95% Cl 0·74–1·24; p=0·7). Similarly, no significant differences were seen between donepezil and placebo in behavioural and psychological symptoms, carer psychopathology, formal care costs, unpaid caregiver time, adverse events or deaths, or between 5 mg and 10 mg donepezil. Donepezil is not cost effective, with benefits below minimally relevant thresholds. More effective treatments than Cholinesterase inhibitors are needed for Alzheimer's disease.

Around the world there are initiatives for encouraging women to become entrepreneurs. Although these initiatives are minor, the number of businesses by women is unlikely to grow in the long run. The study aims to investigate the key success factors and challenges that contribute to female entrepreneurs' motivation to participate in economic development. This study is conducted among the female entrepreneurs in the confectionery industry in Sri Lanka using the in-depth interviews. The sample of the study consists of eight female entrepreneurs who are actively engaged in business activities in the confectionery industry, with more than three years of successful business operations and active presence in social media platforms, Facebook and Instagram. The qualitative data gathered was analyzed using thematic analysis. The findings of the study show that the most significant factors contributing to the success of female entrepreneurs in the confectionery industry are the personality traits, psychological characteristics, and external support. The challenges faced by women entrepreneurs are the cultural barriers and the work-life balancing issues. It is expected that policymakers and support organizations will be able to make effective use of these findings to reduce the economically inactive population in Sri Lanka and thereby improve the economy in general.

Introduction: Substance use becomes censorious when it leads to harmful effects on individuals, their families, and the community. The nature of substance use in Sri Lankan context is poorly understood and empirical evidences are sparse. The study aimed to describe patterns of substance use and characteristics of the individuals enrolled in residential treatment at selected rehabilitation centers in Sri Lanka. Material and methods: A descriptive cross-sectional study was conducted among 205 individuals enrolled in selected rehabilitation centers. Pretested interviewer-administered questionnaire was used to collect data. Data were analyzed using descriptive statistics. Results: Most of the individuals who enrolled in residential treatment at selected rehabilitation centers were unmarried (n = 124, 60.5%), Sinhala (n = 186, 90.7%), Buddhist (n = 166, 81.0%), males (n = 202, 98.5%) and belonged to the young adult age (18-35 years) category (n = 178, 86.8%). All the participants were poly-drug users and cannabis was the most commonly used (n = 183, 89.3%) illicit drug followed by heroin (n = 172, 83.9%), methamphetamine (n = 150, 73.2%) and cocaine (n = 78, 38%). The most (n = 152, 74.1%) problematic substance for life was heroin. Most of the participants (n = 149, 72.7%) had used drugs several times per day. The mean duration of substance use was 7 ± 5 years. Participants (n = 177, 86.3%) reported that the substances were available in their residential areas and their friends (n = 197, 96.1%) were also using the substances. Conclusions: Pattern of substance use and characteristics of the individuals were unique in Sri Lanka and need to be considered when implementing and strengthening the programs for drug prevention and rehabilitation.