Nevin Manimala

J Clin Endocrinol Metab. 2022 Sep 14:dgac527. doi: 10.1210/clinem/dgac527. Online ahead of print.

ABSTRACT

OBJECTIVE: A hypothesis-free genetic association analysis has not been reported for patients with primary hyperparathyroidism (PHPT). We aimed to investigate genetic associations with PHPT using both genome-wide association study (GWAS) and candidate gene approaches.

METHODS: A cross-sectional study was done among patients of European Caucasian ethnicity recruited in Tayside (Scotland, UK). Electronic medical records were used to identify PHPT cases and controls, and linked to genetic biobank data. Genetic associations were performed by logistic regression models and Odds Ratios (ORs). The combined effect of the genotypes was researched by genetic risk score (GRS) analysis.

RESULTS: We identified 15,622 individuals for the GWAS that yielded 34 top single-nucleotide polymorphisms, and LPAR3-rs147672681 reached genome-wide statistical significance (P=1.2e-08). Using a more restricted PHPT definition 8,722 individuals with data on the GWAS-identified loci were found. Age-sex adjusted ORs for the effect alleles of SOX9-rs11656269, SLITRK5-rs185436526, and BCDIN3D-AS1-rs2045094 showed significant increased risks (P<1.5e-03). GRS analysis of 5482 individuals showed an OR of 2.51 (P=1.6e-04), 3.78 (P=4.0e-08) and 7.71 (P=5.3e-17) for the second, third and fourth quartiles respectively compared to the first, and there was a significant linear trend across quartiles (P<1.0e-04). Results were similar when stratifying by gender.

CONCLUSIONS: Using genetic loci discovered in a GWAS of PHPT carried out in a Scottish population, this study suggests new evidence for the involvement of genetic variants at SOX9, SLITRK5, LPAR3 and BCDIN3D-AS1. It also suggests that both male and female carriers of greater numbers of PHPT-risk alleles have a significant increased risk of PHPT.

PMID:36102151 | DOI:10.1210/clinem/dgac527

World J Biol Psychiatry. 2022 Sep 14:1-11. doi: 10.1080/15622975.2022.2124451. Online ahead of print.

ABSTRACT

OBJECTIVES: Believing that a neurodevelopmental pathology may cause bipolar affective disorder (BAD), we aimed to measure the concentrations of α-N-acetylgalactosaminidase (α-NAGAL), a lysosomal enzyme.

METHODS: The study included 32 patients with BAD and 32 healthy controls. The Young Mania Rating Scale was used to measure the severity of the disease. Serum α-N-acetylgalactosaminidase concentrations were measured in all blood samples using the human α-N-acetylgalactosaminidase ELISA Kit.

RESULTS: A statistically significant difference was found in the α-NAGAL values between the groups. The mean α-NAGAL values of BAD patients are lower than the mean α-NAGAL values of the control group. A strong negative and statistically significant relationship was found between the α-NAGAL values of patients with BAD and their Young Mania Rating Scale scores. And a positive strong correlation was found between the age of onset of the disease and α-NAGAL levels.

CONCLUSIONS: Low α-N-acetylgalactosaminidase concentrations may cause accumulation of some glycoproteins in the lysosomes in the brain during the gestational period, producing the clinical symptoms of BAD. α-N-acetylgalactosaminidase deficiency may not be the only cause of BAD, but it may be an important factor in the etiology of this disease.

PMID:36102137 | DOI:10.1080/15622975.2022.2124451

Endocrinol Diabetes Metab. 2022 Sep;5(5):e363. doi: 10.1002/edm2.363. Epub 2022 Aug 9.

ABSTRACT

INTRODUCTION: Diabetic ketoacidosis (DKA) is a serious acute complication of diabetes mellitus that carries a significant risk of mortality with delayed treatment in low-resource countries. This study aimed to determine the outcome of paediatric DKA patients’ managed with a modified DKA treatment protocol using intermittent bolus subcutaneous insulin administration.

METHODS: A cross-sectional study design with retrospective data collection was conducted among children younger than 14 years of age admitted from January 2013 to February 2017. A modified protocol was prepared based on a reference from the international society for paediatric and adolescent diabetes and other international guidelines. Data were analysed using Statistical package for social science (SPSS) version 22.0. Descriptive statistics were performed. Binary logistic regression was used to identify associations, and significant variables were further considered for multivariate logistic regression to determine the outcome of DKA patients.

RESULT: Among the 190 patients, 55.5% (n = 105) were newly diagnosed. The overall average time required for resolution of DKA was 48 ± 27.8 h. Mental status on presentation (p = .001), shock on presentation (p < .01) and severity of DKA (p < .001) were found to have a significant association with the mean time for clearance of DKA. Hypoglycaemia was the most common treatment-related complication, which occurred in 23.7% of patients (n = 45) followed by hypokalaemia in 4.3% of patients (n = 8), and no patient developed cerebral oedema and death.

CONCLUSION: The time required for clearance of DKA was prolonged, and hypoglyceamia was a common complication for children younger than 5 years of age. The modified protocol of DKA is reasonable management for low-resource settings with further modification.

PMID:36102127 | DOI:10.1002/edm2.363

Endocrinol Diabetes Metab. 2022 Sep;5(5):e365. doi: 10.1002/edm2.365. Epub 2022 Aug 14.

ABSTRACT

INTRODUCTION: Diabetes mellitus itself is a known predictor of physical disability and impairment in activities of daily living (ADL); however, there are existing controversies about the factors explaining the association between diabetes and disability. Therefore, we assessed the possible determinants associated with ADL impairment among people with diabetes in Dhaka city, Bangladesh.

METHODS: We conducted a cross-sectional study among 480 people with diabetes aged between 50 and 70 years, and attended a tertiary level hospital in Dhaka city. For determining the ADL impairment, we used the Katz Index Scoring (6 = no impairment; <6 = impairment). Age, sex, educational attainment, household expenditure, body mass index, the status of diabetes (controlled or uncontrolled), hypertension and medication adherence to anti-diabetic drugs were included in the statistical models, and we defined any ADL impairment (Katz score <6) as an event. Multivariable logistic regression was performed to assess the significance of relevant factors.

RESULTS: The mean age of the participants was 59.0 (standard deviation [SD], 7.0) years. The majority of the participants (76.3%) had at least some sort of physical disability. In multivariable logistic regression analysis after adjusting for all covariates simultaneously, age (odds ratio [95% confidence interval]: 1.35 [1.20 to 1.75] per 1-SD increment), BMI (1.32 [1.08 to 1.21] per 1-SD increment), higher educational attainment (0.34 [0.09-0.90]), multi-morbidity (2.79 [1.48-5.25]) and uncontrolled diabetes (1.35 [1.10-1.45]) were independently associated with ADL impairment.

CONCLUSIONS: Physical disability was common, and ADL impairment was associated with age, educational attainment, BMI, multi-morbidities and uncontrolled diabetes among the people with diabetes in Bangladesh.

PMID:36102126 | DOI:10.1002/edm2.365

World J Mens Health. 2022 Sep 2. doi: 10.5534/wjmh.220069. Online ahead of print.

ABSTRACT

PURPOSE: Overall, male factor infertility (MFI) accounts for up to 50% of etiologies of couple’s infertility, with almost 30% of MFI cases being idiopathic in nature. Idiopathic MFI does not support a tailored treatment work-up in clinical practice. To investigate rates of and characteristics of men presenting for idiopathic versus unexplained primary infertility as compared with same-ethnicity, age-comparable fertile men.

MATERIALS AND METHODS: Demographic, clinical and laboratory data from 3,098 primary infertile men consecutively evaluated were analyzed and compared with those of 103 fertile controls. Idiopathic male infertility (IMI) was defined for abnormality at semen analysis with no previous history of diseases affecting fertility and normal findings on physical examination and genetic and laboratory testing. Unexplained male infertility (UMI) was defined as infertility of unknown origin with completely normal findings at semen analysis. Descriptive statistics and logistic regression models tested the association between clinical variables and idiopathic infertility status.

RESULTS: Overall, 570 (18.5%) and 154 (5.0%) patients depicted criteria suggestive for either IMI or UMI, respectively. Groups were similar in terms of age, BMI, CCI, recreational habits, hormonal milieu, and sperm DNA fragmentation indexes. Conversely, testicular volume was lower in IMI (p<0.001). Vitamin D3 levels were lower in IMI vs. UMI vs. fertile controls (p=0.01). At multivariable logistic regression analysis only vitamin D3 deficiency (OR, 9.67; p=0.03) was associated with IMI. Characteristics suggestive for IMI versus UMI were observed in almost 20% and 5% of men, respectively. Overall, clinical differences between groups were slightly significant and certainly not supportive of a tailored management work-up.

CONCLUSIONS: Current findings further support the urgent need of a more detailed and comprehensive assessment of infertile men to better tailoring their management work-up in the everyday clinical setting.

PMID:36102103 | DOI:10.5534/wjmh.220069

Andrologia. 2022 Sep 14:e14590. doi: 10.1111/and.14590. Online ahead of print.

ABSTRACT

Inability to conceive is one of the health concerns. Chromodomain helicase DNA-binding protein5 (CHD5) gene is a major regulator in the replacement of histone proteins with protamines, the chromatin remodelling in spermatogenesis process. Thus, functional SNPs in this gene can disrupt sperm development. This study aimed to investigate the relationship between CHD5 polymorphism (rs9434741) and male infertility. This case-control study was conducted on 103 infertile and 121 fertile men. CHD5 polymorphism rs9434741 was tested using T-ARMS-PCR to investigate its association with male infertility. The presence of G allele caused 1.52 fold increase (OR = 1.52, 95% CI = 1.09-2.31 and p = 0.019) in infertility susceptibility in the patient group. GG genotype and (AG+GG) were significantly related to the increased risk of infertility (OR = 3.13, 95% CI = 1.26-7.76, p = 0.013; OR = 2.72, 95% CI = 1.35-5.47), respectively. Significant differences were observed between genotypes in NOA and SO groups compared to the control group (p = 0.029). Sperm count and total motility were significantly different among three genotypes in infertile men and the control group (p < 0.001). Analysis of genotypes and alleles frequency indicated statistically significant differences between the patient and control groups (p < 0.05). This study showed that CHD5 polymorphism (rs9434741) could be associated with the risk of male infertility. It is recommended to conduct further studies on different populations.

PMID:36102082 | DOI:10.1111/and.14590

Afr J AIDS Res. 2022 Sep 14:1-7. doi: 10.2989/16085906.2022.2087532. Online ahead of print.

ABSTRACT

Background: People living with HIV or AIDS in resource-limited settings are faced with challenges in their nutrition and micronutrient levels. This study aimed to determine the effect of nutrition education on the nutrition status and serum zinc level of HIV and AIDS clients, and its implication for HIV care in resource-limited settings.Methods: This intervention study was conducted among HIV clients at the University of Nigeria Teaching Hospital and Enugu State University Teaching Hospital, which served as the intervention and control groups respectively. A nutrition education programme was delivered to the intervention group. In both groups, before and after the intervention, the body mass index of participants was calculated using their height (m2) and weight (kg) while their serum zinc levels were analysed using spectrophotometry. Chi-square and McNemar chi-square tests were used in the analysis.Results: A total of 185 respondents was studied in each group, with the majority in the 30-39 and 40-49 age groups, respectively (65.4% of the study group and 64.4% of the control group). Larger proportions of respondents in both groups were females (72.4% vs 75.1% respectively). Three months after the intervention, the proportion of respondents with normal serum zinc levels improved significantly from 20.5% to 51.9% in the intervention group (χ²_McNemar, p < 0.001), whereas the control group had no appreciable improvement (16.8% vs 22.7%) (χ²_McNemar, p < 0.117). Furthermore, the post-intervention serum zinc level difference between the intervention and control groups was statistically significant (χ² = 33.699; p < 0.001). No statistically significant difference existed in the nutritional status between the groups (χ² = 3.469; p = 0.325).Conclusion: Nutrition education had a positive effect on the serum zinc levels of HIV clients. Integrating nutrition education programmes as a key component of HIV care in resource-limited settings will help improve the serum zinc level of people living with HIV, which ultimately improves their immune status and life expectancy.

PMID:36102067 | DOI:10.2989/16085906.2022.2087532

Swiss Med Wkly. 2022 Sep 7;152:w30212. doi: 10.4414/smw.2022.w30212. eCollection 2022 Aug 29.

ABSTRACT

AIMS OF THE STUDY: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together.

METHODS: Retrospective analysis of consecutive SARS-CoV-2 pneumonia patients suffering from acute respiratory failure with moderate to severe hypoxaemia for whom aPP was performed for at least 45 minutes based on the prescription of the clinician in charge according to predefined criteria. Respiratory rate, blood gases and oxygenation parameters (PaO2/FiO2 and Aa-O2), before and after the first aPP were compared between patients who were subsequently intubated or not. Effects of all the aPP sessions together were also analysed.

RESULTS: One hundred and sixty-six patients were admitted for SARS-CoV-2 pneumonia during the study period. Among them, 50 received aPP lasting at least 45 minutes. Because 17 denied consent for data analysis and 2 were excluded because of a “do not intubate order”, 31 patients (for a total of 116 aPP sessions without any severe adverse events reported) were included. Among them, 10 (32.3%) were intubated. Mean age ± standard deviation (SD) was 60 ± 12 years. At ICU admission, respiratory rate was 26 ± 7/minute, median PaO2/FiO2 94 (interquartile range [IQR] 74-116) mm Hg and median Aa-O2 412 (IQR 286-427) mm Hg (markedly increased). Baseline characteristics did not statistically differ between patients who subsequently needed intubation or not. During the first aPP, PaO2/FiO2 increased and Aa-O2 decreased. When comparing patients who later where intubated or not, we observed, in the non intubated group only, a clinically significant decrease in median Aa-O2, from 294 (280-414) to 204 (107-281) mm Hg, corresponding to a 40% (26-56%) reduction, and a PaO2/FiO2 increase, from 103 (84-116) to 162 (138-195), corresponding to an increase of 48% (11-93%). The p value is <0.005 for both. When all the aPP sessions (n = 80) were considered together, aPP was associated with a significant increase in PaO2/FiO2 from 112 (80-132) to 156 (86-183) mm Hg (p <0.001) and Aa-O2 decrease from 304 (244-418) to 224 (148-361) mm Hg (p = 0.001).

CONCLUSIONS: Awake pronation in spontaneously breathing patients is feasible, and improves PaO2/FiO2 and Aa-O2. Response to the first session seems to be associated with lower intubation rate.

PMID:36102065 | DOI:10.4414/smw.2022.w30212

Clin Shoulder Elb. 2022 Sep;25(3):173-181. doi: 10.5397/cise.2022.01046. Epub 2022 Aug 26.

ABSTRACT

BACKGROUND: Healing of the tendon itself is not always related to successful clinical outcomes after rotator cuff repair. It was hypothesized that certain radiologic factors affecting clinical outcomes could exist in case of the retear after arthroscopic rotator cuff repair (ARCR) and the radiologic factors could help predict clinical process. The purpose of this study was to identify the radiologic factors associated with clinical outcomes of the retear after ARCR.

METHODS: Between January 2012 and December 2019, among patients with sufficient footprint coverage for ARCR, 96 patients with Sugaya classification 4 or higher retear on follow-up magnetic resonance imaging were included. The association between clinical outcomes such as American Shoulder and Elbow Surgeons (ASES) score, Constant score and range of motion and radiologic variables such as initial tear dimension, retear dimension, variance of tear dimension, critical shoulder angle, acromial index, and acromiohumeral distance was analyzed.

RESULTS: Preoperatively, the ASES and Constant scores were 59.81±17.02 and 64.30±15.27, respectively. And at the last follow-up, they improved to 81.56±16.29 and 78.62±14.16, respectively (p&lt;0.01 and p&lt;0.01). In multiple linear regression analysis, the variance of the mediolateral dimension of tear had statistically significant association with the ASES and Constant scores (p&lt;0.01 and p=0.01).

CONCLUSIONS: In patients with the retear after ARCR, the variance in the mediolateral dimension of tear had significantly negative association with the clinical outcomes. This could be considered to be reference as relative criteria and needed more sample and mechanical study.

PMID:36102050 | DOI:10.5397/cise.2022.01046

J Intellect Disabil Res. 2022 Sep 13. doi: 10.1111/jir.12979. Online ahead of print.

ABSTRACT

BACKGROUND: Exercise has the potential to reduce cognitive decline in people with Down syndrome by maximising their cognitive function. The aim of the study was to determine the effect of regular exercise on cognitive functioning in young people with Down syndrome.

METHOD: People with Down syndrome were eligible if aged between 13 and 35 years and enrolled to participate in an exercise programme (called FitSkills). The intervention was a 12-week community-based exercise programme completed with a student mentor. Outcomes were assessed before (week 0) and immediately after (week 13) the intervention. Executive functioning (planning, response inhibition, attention shifting) was assessed using Tower of London, Sustained Attention to Response Task, CANTAB Intra-extra Dimensional Set Shift Test, Cognitive Scale for Down Syndrome, and Behaviour Rating Inventory of Executive Function (BRIEF). Working memory was assessed using the CANTAB Paired Associates Learning task, and information processing speed was assessed using the Motor Screening Task. Outcomes were analysed using ANCOVA with the baseline measure as the covariate.

RESULTS: Twenty participants (9 women; mean age 23.6 ± 6.6 years) enrolled. Between-group differences, in favour of the experimental group, were found for the global executive composite score of the BRIEF (mean difference -4.77 units, 95% CI -9.30 to -0.25). There were no between group differences for any other outcome measured.

CONCLUSION: Participation in a 12-week exercise programme was effective in improving everyday executive functions in young people with Down syndrome. These preliminary findings need to be confirmed in future randomised controlled trials of community-based exercise with larger sample sizes.

PMID:36101998 | DOI:10.1111/jir.12979