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Background: Tuberculosis (TB) treatment interruption poses risks of antimicrobial resistance, potentially leading to treatment failure and mortality. Addressing the risk of early treatment interruption is crucial in tuberculosis care and management to improve treatment outcomes and curb disease transmission., Objectives: This study aimed to identify risk factors of TB treatment interruption and construct a predictive scoring model that enables objective risk stratification for better prediction of treatment interruption., Methods: A multicentre retrospective cohort study was conducted at public health clinics in Sarawak, Malaysia over 11 months from March 2022 to January 2023, involving adult patients aged ≥18 years with drug-susceptible TB diagnosed between 2018 and 2021. Cumulative missed doses or discontinuation of TB medications for ≥2 weeks, either consecutive or non-consecutive, was considered as treatment interruption. The model was developed and internally validated using the split-sample method. Multiple logistic regression analysed 18 pre-defined variables to identify the predictors of TB treatment interruption. The Hosmer-Lemeshow test and area under the receiver operating characteristic curve (AUC) were employed to evaluate model performance., Results: Of 2953 cases, two-thirds (1969) were assigned to the derivation cohort, and one-third (984) formed the validation cohort. Positive predictors included smoking, previously treated cases, and adverse drug reactions, while concurrent diabetes was protective. Based on the validation dataset, the model demonstrated good calibration (P = 0.143) with acceptable discriminative ability (AUC = 0.775). A cutoff score of 2.5 out of 11 achieved a sensitivity of 81 % and a specificity of 64.4 %. Risk stratification into low (0-2), medium (3-5), and high-risk (≥6) categories showed ascending interruption rates of 5.3 %, 18.1 %, and 41.3 %, respectively (P < 0.001)., Conclusion: The predictive scoring model aids in risk assessment for TB treatment interruption, enabling focused monitoring and personalized intervention plans for higher-risk groups in the early treatment phase., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: This study aimed to investigate the level of family caregivers' (FC) burden and the extent to which patient- and caregiver-related factors influence the caregiving burden among FCs of urologic cancer (UC) patients., Method: A cross-sectional survey was conducted on caregivers of UC patients who sought cancer care. The modified caregiver strain index (MCSI) was used to assess FC burden., Results: Just over half (54.3%) of FCs had moderate/high MCSI scores (score 9-26). By demographics, FCs who were unemployed (OR = 5.55, 95%CI 1.50-20.60) and perceived their current health condition as moderate/poor (OR = 6.05, 95%CI 1.95-18.78) reported higher odds of increased FC burden. Patient performance status played a pivotal role in exacerbating FC burden, whereby the odds of higher FC burden was 13 times higher in caregivers of UC patients having an Eastern Cooperative Oncology Group (ECOG) performance rating score of 3-4 (OR = 13.06, 95%CI 1.44-111.26) than those with a score of 0. Perceived lower levels of confidence in care provision were significantly associated with a higher level of strain (OR = 6.76, 985%CI 1.02-44.90)., Conclusion: Care recipient performance status was a strong patient-related factor associated with higher FC burden regardless of duration of caregiving and other caregiver-related factors after adjusting for caregiver demographics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment. We reported the generation and characterization of an iPS cell line, IBMS-iPSC-063-06, from a patient carrying the BBS2 homologous c534 + 1G > T mutation. The generated iPS cell line retains the mutation and exhibits pluripotency and differentiation ability both in vivo and in vitro condition., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: A pharmacist-led structured group-based intervention (MEDIHEALTH) was formulated to improve medication adherence among Malay type 2 diabetes mellitus (T2DM) patients in the Malaysian state of Sarawak., Objectives: The objective of this study was to examine the effectiveness of MEDIHEALTH and its mechanism of impact for improving medication adherence and the glycated haemoglobin (HbA1c) level., Methods: A two group and parallel randomised controlled trial with a twelve months follow-up period was conducted at two primary health clinics in Malaysia that were surrounded by Malay communities. Malay T2DM patients whose HbA1c was >7% and total score on the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) was <26 were recruited and parallelly randomised to the MEDIHEALTH or usual care (control) groups. The extended theory of planned behaviour was employed to test the mechanism of impact. Repeated measure analysis of variance was used to assess the difference in the estimated marginal mean of the SEAMS scores and HbA1c level between the intervention and control groups at different times., Results: A total of 142 participants were recruited and randomised; three from the intervention group and eight from the control group withdrew before receiving any treatment. Hence, 68 participants in the intervention group and 63 in the control group were included for analyses. The MEDIHEALTH group had a significantly greater increase in the SEAMS score compared to the control group (p < 0.001) at one, three, six and twelve months post-intervention. There was also a significantly greater reduction in HbA1c in the MEDIHEALTH compared to the control group at one, three, six and twelve months post-intervention (p < 0.001). These improvements were mediated by enhancements in perceived behavioural control and knowledge about medications., Conclusions: The MEDIHEALTH may improve medication adherence and glycaemic control among Malay T2DM patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: This study compared the condom failure rate, safety and acceptability of two new synthetic adhesive male condoms, Wondaleaf-Cap® (WLC) and Wondaleaf-On-Man® (WLM), with a marketed latex external condom Durex®-Together (DT)., Study Design: We enrolled healthy married, monogamous, heterosexual condom users in a randomized controlled, cross-over, pilot trial in Malaysia. We randomized participants to six groups with different condom use-orders of the experimental WLC and WLM and control latex condom for four episodes for vaginal sex over 1 month for each condom type. We summarized the clinical and non-clinical failure rate, safety and acceptability of each condom type using descriptive statistics. We tested differences in condom failure and acceptability using generalized estimating equations and repeated measure ANOVA respectively., Results: We screened 75 couples and randomized 50 eligible couples. Two couples withdrew before receiving any condom. The remaining used 576 condoms with 192 uses for each condom variant. Clinical failure rates of WLC, WLM and DT were 1.04%, 0% and 0.52%, respectively. Non-clinical failure rates of WLC, WLM and DT were 2.08%, 3.12% and 1.04%, respectively. Removal was found more painful with Wondaleaf products than the DT. Preferences of participants for WLC, WLM and DT were 33.3%, 29.2% and 25%, respectively. Overall, WLC and DT had greater acceptances among male participants than WLM., Conclusion: Results of this pilot study support that use of synthetic adhesive male condoms is associated with failure rates similar to those seen with existing latex, and with greater acceptability. A larger study to ascertain non-inferiority is underway., Implications: The availability of synthetic adhesive male condoms may increase the acceptability of condom use. However, removal pain and clinical performance requires further study., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Focused ultrasound (FUS) with microbubbles has been used to achieve local blood-brain barrier opening (BBB opening) and increase the penetration of therapeutic drugs into brain tumors. However, inertial cavitation of microbubbles during FUS-induced BBB opening causes intracerebral hemorrhaging (ICH), leading to acute and chronic brain injury and limiting the efficiency of drug delivery. Here we investigated whether induction of drug (1,3-bis(2-chloroethyl)-1-nitrosourea, BCNU)-loaded bubbles (BCNU bubbles) to oscillate at their resonant frequency would reduce inertial cavitation during BBB opening, thereby eliminating ICH and enhancing drug delivery in a rat brain model. FUS was tested at 1 and 10 MHz, over a wide range of pressure (mechanical index ranging from 0.16 to 1.42) in the presence of BCNU bubbles. Excitation of BCNU bubbles by resonance frequency-matched FUS (10 MHz) resulted in predominantly stable cavitation and significantly reduced the occurrence of potential hazards of exposure to biological tissues during the BBB opening process. In addition, the drug release process could be monitored by acoustic emission obtained from ultrasound imaging. In tumor-bearing animals, BCNU bubbles with FUS showed significant control of tumor progression and improved maximum survival from 26 to 35 days. This study provides useful advancements toward the goal of successfully translating FUS theranostic bubble-enhanced brain drug delivery into clinical use., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Drosophila N-cadherin (CadN) is an evolutionarily conserved, atypical classical cadherin, which has a large complex extracellular domain and a catenin-binding cytoplasmic domain. We have previously shown that CadN regulates target selection of R7 photoreceptor axons. To determine the functional domains of CadN, we conducted a structure-function analysis focusing on its in vitro adhesive activity and in vivo function in R7 growth cones. We found that the cytoplasmic domain of CadN is largely dispensable for the targeting of R7 growth cones, and it is not essential for mediating homophilic interaction in cultured cells. Instead, the cytoplasmic domain of CadN is required for maintaining proper growth cone morphology. Domain swapping with the extracellular domain of CadN2, a related but non-adhesive cadherin, revealed that the CadN extracellular domain is required for both adhesive activity and R7 targeting. Using a target-mosaic system, we generated CadN mutant clones in the optic lobe and examined the target-selection of genetically wild-type R7 growth cones to CadN mutant target neurons. We found that CadN, but neither LAR nor Liprin-alpha, is required in the medulla neurons for R7 growth cones to select the correct medulla layer. Together, these data suggest that CadN mediates homophilic adhesive interactions between R7 growth cones and medulla neurons to regulate layer-specific target selection.

The aim of this study is to assess the association linking employment experience with alcohol, tobacco, and betel nut involvement among youth in Taiwan. In 2004, an outreach program was conducted during weekdays to recruit youth sample in seven major geographic regions. A total of 5886 youth aged 12-18 years drawn from 26 cities or towns were assessed by a two-page anonymous self-administered questionnaire, including sociodemographic characteristics, employment-, development-, and drug-related experiences. In Taiwan, youthful experience of alcohol, tobacco, and polydrug use varies by employment status, work intensity, and job type. Holding a full-time job and working in certain settings (e.g., grocery, restaurants) were found associated with an excess of drug-using behaviors. With taking age, male gender, family context, disposable allowance, and school attendance into account, working youths were two to four times as likely to have recent drug involvement than their non-working counterparts, especially for tobacco and polydrug (OR=3.32, 95% CI: 2.58-4.27, p<0.001; OR=3.76, 95% CI: 2.76-5.13, p<0.001). Youths in the labor force emerge as a subgroup experiencing greater use of alcohol, tobacco, betel nut, and polydrug. Future prevention programs may target this high-risk group to reduce possible drug-related negative consequences in developmental and health domains in Taiwan.

Purpose: To evaluate, using a randomized trial, whether a web-based self-administered questionnaire (web SAQ) can improve the reporting rate of substance use in adolescents compared with a paper-and-pencil self-administered questionnaire (paper SAQ)., Methods: Students of junior high, senior high, and vocational high schools in Taipei City and County were selected by a stratified, two-stage, probability proportional to size, random sampling. For each class selected, half of the students were randomly assigned to paper SAQ (n = 990) and the other half to web SAQ (n = 928). The inverse of the sampling probability for each individual was then used as sampling weight in the estimation of prevalence and logistic regression analysis., Results: For readily available substances, the lifetime prevalence in the web SAQ group was significantly higher for alcohol use and borderline higher for tobacco and betel nut use compared to those of the paper SAQ group. For illicit drug use, the lifetime prevalence for the web SAQ group was significantly higher for the use of amphetamines, and borderline higher for ketamine. In multiple logistic regression analysis, the differences between the two groups in the use of alcohol, tobacco, and amphetamines remained significant. Boys, as well as both junior-high and vocational high school students who responded using the web SAQ, were more likely to report alcohol or tobacco use than those using the paper SAQ., Conclusions: Web SAQ leads to higher reporting rates of commonly used substances in adolescents compared with those of paper SAQ.