Nevin Manimala

Genet Med. 2025 Feb 12:101375. doi: 10.1016/j.gim.2025.101375. Online ahead of print.

ABSTRACT

PURPOSE: AUTS2-related syndrome is a condition characterized by developmental delay, autism spectrum disorder, and intellectual disability. From alternative promoters AUTS2 encodes two distinct long and short isoforms encoding a putative transcriptional activator.

METHODS: Through a European collaborative study, we collected clinical and genotype data on the largest AUTS2- related syndrome cohort of 58 patients harboring genomic rearrangements or single nucleotide variants (SNVs).

RESULTS: Pathogenic SNVs were recurrently found in individuals from different countries, suggesting mutational hotspots. Independent from the underlying defect at the AUTS2 locus, we observed that autistic behavior, hyperactivity, learning difficulties and speech delay are common features of AUTS2- related syndrome. Among patients with SNVs, individuals carrying pathogenic variants affecting both the longer and the shorter AUTS2 transcripts showed a recognizable phenotype with microcephaly, brachycephaly, micro-retrognathia, broad nasal base and anteverted nares. Behavioral disorders were statistically more common in patients with variants affecting only the longer isoform. Arthrogryposis and stiff movements were only noticed in patients with SNVs.

CONCLUSION: This study provides a comprehensive clinical characterization of AUTS2- related syndrome, unravels few genotype-phenotype correlations and it suggests that disruption of the two distinct AUTS2 transcripts has a different impact on clinical phenotype.

PMID:39953909 | DOI:10.1016/j.gim.2025.101375

Natl Med J India. 2024 Sep-Oct;37(5):248-252. doi: 10.25259/NMJI_264_2022.

ABSTRACT

Background Overweight/obesity is an important risk factor for liver disease, affecting changes in liver function-related parameters. The fat mass and obesity associated (FTO) gene has been reported to have a link between overweight/obesity and liver fat metabolism. We studied the association of FTO rs9939609 variants with liver function-related parameters and overweight/obesity in Chinese adolescents aged 16 to 26 as freshmen. Methods We examined rs9939609 polymorphisms in 198 control and 173 overweight/obese people, and the genotypes of the samples were analyzed by Sanger sequencing. We investigated the effects of FTO gene polymorphism on overweight/obesity and liver function-related parameters. Results The values of aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in overweight/obesity group were significantly higher than those in control group. The rs9939609 AA genotype increased the risk of overweight/obesity by 3.45 times independent of body mass index (BMI) compared with TT genotype, the rs9939609 (AA) genotype was significantly associated with AST and ALT. Conclusion FTO rs9939609 variants were associated with overweight/obesity and overweight/obesity has a significant influence on the increased liver function-related parameters. The rs9939609 (AA) positively correlated with AST and ALT levels. Overweight/obese patients should pay more attention to liver function-related parameters.

PMID:39953885 | DOI:10.25259/NMJI_264_2022

Natl Med J India. 2024 Sep-Oct;37(5):241-247. doi: 10.25259/NMJI_374_2022.

ABSTRACT

Background Several risk factors have been associated with early childhood caries (ECC). However, conclusive data are not available about the socio-demographic and behavioural factors which are associated with severe ECC (S-ECC). We assessed the severity and pattern of ECC in young children. We also looked for association of S-ECC with various sociobehavioural risk factors in a hospital-based setting. Methods We included 200 children, 1-6 years old, who reported with dental caries to a paediatric dental outpatient in a tertiary care hospital. Information about socio-demographics and various behavioural factors was recorded in a structured proforma using an interview method. The American Academy of Paediatric Dentistry (AAPD) criteria were used for categorizing children into ECC and severe ECC groups (S-ECC). Qualitative variables were analysed by chi-square test. Multiple logistic regression analysis was done to find the predictors of severe S-ECC. All statistical tests were done at a significance level of p<0.05. Results The majority of children (85%) had S-ECC and anterior-posterior (AP) caries pattern (77%). A significant association was found between the age of the child (p<0.001), absence of siblings (p=0.009), continuation of bottle feed or mother’s milk till the age of reporting to the hospital (p=0.007), frequency of night-time feed (p=0.048) and S-ECC. Conclusions A continued habit of milk feed from bottle/mother till the time of dental visit seeking treatment and night time-feeds more than twice had a significant association with S-ECC.

PMID:39953883 | DOI:10.25259/NMJI_374_2022

Natl Med J India. 2024 Sep-Oct;37(5):267-269. doi: 10.25259/NMJI_618_2022.

ABSTRACT

Background Didactic lectures form a large part of the teaching-learning process in medical education. To impart competency-based medical education (CBME) in the Covid-19 pandemic there was a shift to online learning. This pedagogical change would likely impact the efficacy of student learning outcomes. Several studies have shown that learning outcomes and knowledge retention increase considerably when lectures are interactive. However, the efficacy of online teaching with active learning strategies has not been studied. Methods At the Department of Biochemistry, Osmania Medical College, Hyderabad, we did this study with 203 first year MBBS students. Five sessions were conducted on the topic of ‘Enzymology’ with appropriate active learning methods. Each lecture session was preceded and followed by a test, which included multiple-choice questions (MCQs) and brief note questions (BNQs). Feedback of students, was recorded on the 5-point Likert scale from strongly agree to strongly disagree. Results The majority of students felt that answering questions in the pre-test required substantial effort compared to the post-test. The case scenarios included in the pre-test had a positive impact on the curiosity of students. The activities as part of self-directed learning were interesting, and enhanced understanding and retention. They felt lectures without pre-and post-tests were less efficacious and thus should be continued in all the classes. Conclusion Online lectures without pre-and post-test model were less efficacious. Online teaching, coupled with active learning increased interest and the understanding capacity of students.

PMID:39953874 | DOI:10.25259/NMJI_618_2022

Am J Mens Health. 2025 Jan-Feb;19(1):15579883251317095. doi: 10.1177/15579883251317095.

ABSTRACT

High allostatic load (AL), a measure of physiological dysregulation, has been linked with premature morbidity and mortality. There is a paucity of research assessing AL among non-Hispanic Black (NHB) and non-Hispanic White (NHW) American men of various age groups. This study investigated racial differences in AL among NHB and NHW adult men and assessed whether racial differences in AL varied by age. Data were drawn from NHB (n = 232) and NHW (n = 246) men in the Nashville Stress and Health Study. AL was based on the sum of 10 biomarkers that was dichotomized as high AL (four or more high-risk biomarkers) or low AL (fewer than four high-risk biomarkers). Modified Poisson regression models were estimated to assess race differences in AL, adjusting for age, socioeconomic status (SES), and health behaviors. Interactions assessed whether racial differences in AL varied between young (22-49 years) and older (50-69) men. NHB men had a higher prevalence of being in the high AL group (prevalence ratio [PR] = 1.54, confidence interval [CI] = [1.09, 2.18]), relative to NHW men in the total sample. Among young men ages 22 to 49 years, NHB men had a higher prevalence of being in the high AL group (PR = 2.09, CI = [1.25, 3.49]), relative to NHW men. Among older men ages 50 to 69 years, there were no racial differences in AL. Findings underscore the importance of identifying factors that are associated with high AL, which is critical to mitigate premature morbidity and mortality, among NHB men.

PMID:39953836 | DOI:10.1177/15579883251317095

J Man Manip Ther. 2025 Feb 15:1-8. doi: 10.1080/10669817.2025.2465729. Online ahead of print.

ABSTRACT

OBJECTIVES: Tactile sensitivity is one of the most important skills for developing competence in manual palpation. There is a lack of studies aimed at analyzing the development of tactile sensitivity during different levels of physiotherapy education. The present study aims to compare manual tactile sensitivity in two groups of physiotherapy students.

METHODS: Twenty first-year physiotherapy students (mean age 19.4 yrs ± 0.6) and twenty final-year physiotherapy students (mean age 23.7 yrs ± 3.7) participated in the study. For the tactile sensitivity test, 3 wooden tables were used, in which different geometric structures were engraved. Subjects were instructed to perform a tactile examination of the geometric structures and then reproduce them by drawing on a sheet of paper. The tactile time, drawing time, accuracy, and difficulty of the geometric structures were scored. A two-sample t-test was used for the between-groups comparison if more time in an educational program should result in differences in tactile time, drawing time, accuracy, and difficulty. Linear regression was used to compare the difficulty with the accuracy of all geometric structures. Wilcoxon test was used to test the intra-rater agreement.

RESULTS: The accuracy of the reproduction of geometric structures 1, 2 and 3 were 77.5%, 27.5% and 45%, for all physiotherapy students respectively. Final-year physiotherapy students spent more time exploring geometric structure 2 (p = 0.014) and geometric structure 3 (p = 0.0018) compared to first-year physiotherapy students. No statistically significant differences were found between groups in drawing time, accuracy, and difficulty of geometric structures. The examiner showed a high intra-rater agreement in the assessment (over 96%).

DISCUSSION/CONCLUSION: The study showed that the level of education and gained experience during laboratory teaching may be important in improving the palpation skills of physiotherapy students. Tactile sensitivity exercises should be included in physiotherapy education programs.

PMID:39953824 | DOI:10.1080/10669817.2025.2465729

J Viral Hepat. 2025 Mar;32(3):e70010. doi: 10.1111/jvh.70010.

ABSTRACT

Medication nonadherence among patients with chronic hepatitis B (CHB) can lead to severe liver disease progression, including liver cirrhosis and hepatocellular carcinoma (HCC). Yet the factors that influence adherence in high-risk groups, like Korean Americans, remain unclear. Thus, this study explored the psychosocial and clinical factors affecting medication adherence in CHB patients. A cohort of 365 Korean American patients with CHB from two clinics in Philadelphia and Los Angeles was studied. The 8-item Morisky Medication Adherence Scale (MMAS-8) gauged their adherence to antiviral medication. Using descriptive and multivariable logistic regression analyses, we identified factors associated with MMAS-8 scores. Of the participants, 78% were undergoing antiviral therapy, with over two-thirds (69%) reporting medium to high adherence levels. The multivariable logistic regression analysis revealed that age, knowledge of sequalae of CHB, perceived HBV stigma and possession of pharmacy plan were associated with medication adherence. Older participants had higher medication adherence than younger. High knowledge of sequalae of CHB and low perceived HBV stigma were associated with higher medication adherence. Having pharmacy plans was also associated with higher medication adherence to antiviral therapy. These findings highlight the critical role of person-related factors (e.g., knowledge and stigma) and healthcare factors in medication adherence. Future research should focus on developing targeted educational interventions focusing on personal factors to improve medication adherence among Korean American patients with CHB.

PMID:39953814 | DOI:10.1111/jvh.70010

Pharmacoepidemiol Drug Saf. 2025 Feb;34(2):e70109. doi: 10.1002/pds.70109.

ABSTRACT

PURPOSE: Many post-authorization safety studies focus on congenital malformations and rely on diagnosis codes found in US data sources. However, no authoritative standards exist for identifying and classifying malformations in these data. To address this, we translated an existing public health surveillance guide, the European Concerted Action on Congenital Anomalies and Twins (EUROCAT), into an ICD-10-CM code list for use in studies using US administrative healthcare data. The EUROCAT guide was selected for its decisive major or minor classification of each code. However, translation was required for use in US data sources since EUROCAT utilizes ICD-10-BPA which differs from ICD-10-CM (the coding system commonly encountered in US data sources).

METHODS: We mapped EUROCAT to ICD-10-CM. For each code, manual review was conducted by two or more researchers, and major/minor classification was based on code descriptions since some codes differed between coding systems.

RESULTS: A final code list was created, containing 916 ICD-10-CM codes for 744 major and 172 minor malformations. The code list contains ICD-10-CM codes, their corresponding descriptions, their major or minor classification and disease category according to EUROCAT, and variables indicating anomalies caused by genetic or infectious diseases unlikely attributable to a medication.

CONCLUSIONS: We adapted the EUROCAT Guide 1.5 into an ICD-10-CM code list for use in pregnancy studies using US data sources. This list includes new ICD-10-CM codes available in 2024. As new ICD-10-CM codes become available, or as the EUROCAT Guide is updated, further updates to this list will be needed.

PMID:39953813 | DOI:10.1002/pds.70109

Cancer Med. 2025 Feb;14(4):e70693. doi: 10.1002/cam4.70693.

ABSTRACT

INTRODUCTION: Sleep disturbance (SD) and sleep-related impairment (SRI) significantly impact the lives of primary brain tumor (PBT) patients. We aimed to describe the prevalence of SD and SRI in this population, determine the reliability of the PROMIS-SD and PROMIS-SRI instruments, and identify predictive factors to support the development of targeted interventions for at-risk individuals.

METHODS: This cross-sectional study evaluated SD and SRI in PBT patients enrolled in a Natural History Study who completed 1-year follow-up questionnaires (N = 229). Demographic, clinical, and socioeconomic data were analyzed to identify factors associated with SD and SRI. Descriptive statistics were used to report the prevalence of sleep problems, and linear regression analysis was conducted to identify predictive factors. The reliability of sleep-related instruments was calculated using Cronbach’s alpha.

RESULTS: Fifteen percent of PBT participants reported clinically significant SD and 20% reported clinically significant SRI, which were associated with financial toxicity (p < 0.001), being unemployed (p ≤ 0.02), and taking psychotropic medication (p ≤ 0.002). Good internal consistency was demonstrated by the SD (0.923) and SRI (0.925) questionnaires in this population.

CONCLUSIONS: In this study, social factors such as financial toxicity and employment status were associated with SD and SRI. Psychotropic medications also impacted SD and SRI in PTB survivors, but less so than financial toxicity. Social factors and other medications may impact sleep more strongly in PBT survivors than their previous treatment courses.

IMPLICATIONS FOR CANCER SURVIVORS: SD and SRI can be impacted by multiple factors, including those not related to PBT treatment, which should be considered by their providers.

PMID:39953810 | DOI:10.1002/cam4.70693

Cancer Med. 2025 Feb;14(4):e70680. doi: 10.1002/cam4.70680.

ABSTRACT

BACKGROUND: Germline genomic sequencing (GS) is increasingly offered to children with cancer. To optimize integration into routine care, assessment of implementation barriers and a better understanding of healthcare professionals’ perspectives and experiences are needed.

METHODS: Healthcare professionals delivered trio germline GS to newly diagnosed pediatric and adolescent patients with cancer via the PREDICT completed questionnaires with qualitative and quantitative items. Each study site recorded reasons for eligible families’ nonenrolment in PREDICT to identify barriers to recruitment. Quantitative data were analyzed via descriptive statistics, whereas qualitative data underwent inductive content analysis, with results integrated for interpretation.

RESULTS: Thirty-three healthcare professionals participated, including 23 oncology professionals and 10 genetic professionals. Healthcare professionals perceived PREDICT as beneficial to participating and future families, and that perceptions of personal benefit and altruism were drivers of family uptake. Concerns included workforce capacity and potential family distress given the trio design and high-stress diagnosis setting. Barriers to recruitment related to clinical decision-making, family factors, and logistics. Although most rated their genetics/genomics knowledge as “good,” regarding germline results, few were “very confident” interpreting (29%), explaining (32%), making treatment recommendations (9.7%), and providing psychosocial support to families (29%). They acknowledged a need for further training in these areas for trainees; yet, fewer were interested in training for themselves.

CONCLUSION: Successful implementation of routine germline GS will require targeted strategies to address logistical issues and alleviate potential negative psychosocial impacts for families. Recognizing the escalating demand on genetics experts, upskilling of the current workforce and involvement of a broader spectrum of healthcare professionals are warranted.

PMID:39953756 | DOI:10.1002/cam4.70680