The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

Neuropathy 10-15 years after Roux-en-Y gastric bypass for severe obesity: A community-controlled nerve conduction study.

Objective: We searched for long-term peripheral nerve complications 10-15 years after Roux-en-Y gastric bypass surgery (RYGB), using a comprehensive nerve conduction study (NCS) protocol. Methods: Patients (n = 175, mean age 52.0, BMI 35.2) and 86 community-controls (mean age 56.8, BMI 27.2) had NCS of one upper and lower limb. New abnormality scores from 27 polyneuropathy-relevant (PNP27s) and four carpal tunnel syndrome-relevant NCS-measures (CTS4s) were compared between groups with non-parametric statistics. Estimated prevalences were compared by 95 % confidence limits. The clinical neurophysiologist's diagnosis was retrieved from hospital records (PNP-ncs, CTS-ncs, other). Results: Abnormality score did not differ between RYGB and control groups (PNP27s: 1.9 vs 1.7, CTS4s: 0.7 vs 0.6, p > 0.29). BMI correlated weakly with CTS4s in patients (rho = 0.19, p = 0.01), and less with PNP27s (rho = 0.12, p = 0.12). Polyneuropathy (PNP-ncs) prevalence was 12 % in patients and 8 % in controls. CTS-ncs prevalence was 21 % in patients and 10 % in controls (p = 0.04). Conclusions: NCS-based abnormality scores did not differ between patients 10-15 years after RYGB and community-recruited controls, neither for PNP nor CTS. Significance: Long-term polyneuropathic complications from RYGB have probably been avoided by modern treatment guidelines. NCS-diagnosed CTS is common in overweight RYGB patients. RYGB-patients with significant neuropathic symptoms need clinical evaluation.

A Somatic-Type Delusional Disorder Resulted in Severe Weight Loss With a Body Mass Index of 10.2: A Case Report.

Weight loss is not uncommon in the field of psychiatry; however, when severe cases arise, it necessitates attention and thorough evaluation for accurate diagnosis and appropriate treatment. This report highlights the case of a 32-year-old man referred to psychiatry due to significant weight loss. The patient mentioned consuming small food portions, attributing it to an undetected stomach illness despite repeated investigations by previous treating doctors. His current weight stood at 31 kg, with a body mass index (BMI) of 10.2 kg/m². Physical examinations and laboratory investigations were otherwise within normal parameters. A somatic delusion was confirmed, and the patient has been diagnosed with a delusional disorder after excluding other possibilities. This report highlights the importance of considering delusional disorder (somatic type) as a potential diagnosis for substantial weight loss, and it records an unexpected degree of physical well-being despite a notably low BMI.

Association between pathological positivity rate of endometriosis, demographics, and concomitant gynecological conditions.

Background: To date, there remains a paucity of present-day literature on the topic of demographics and the biopsy-proven pathological positivity rate of endometriosis. Objective: The goal of this study was to explore the association between patients' demographics and other concomitant gynecological conditions or procedures and the pathological positivity rate of excision of endometriosis. Design: Retrospective cohort study. Methods: All women >18 years old who underwent laparoscopic surgery for endometriosis at a tertiary care hospital from October 2011 to October 2020. Women were classified into two groups: (1) Study group: women with >80% pathological positivity rate of endometriosis and (2) Control group: women with <80% pathological positivity rate. Results: A total of 401 women were included in the analysis. No difference was noted in the 80% pathological positivity rate based on body mass index [BMI; 68.7% in normal BMI versus 80% in underweight, versus 74.5% in overweight, and 74.1% in obese patients (p = 0.72)]. The percentage of patients reaching 80% pathological positivity of endometriosis was lower in women who had undergone previous laparoscopy for endometriosis compared to surgery naïve women (66.5% versus 76.5%, p = 0.03). In addition, a higher percentage of women who underwent concomitant hysterectomy (83.5% versus 68.8% for non-hysterectomy, p = 0.005) or bilateral oophorectomy (92.7% versus 70.0% for non-oophorectomy, p = 0.002) reached 80% pathological positivity. Women with an associated diagnosis of fibroids (79.7% versus 70.5%) or adenomyosis (76.4% versus 71.7%) were more likely to reach 80% pathological positivity compared to women without any other coexisting pathology; however, the observed differences were not statistically significant. After applying a log-binomial regression model, compared to White non-Hispanics, Hispanic patients were 30% less likely to reach 80% positivity (RR: 0.70, 95% CI: 0.49-1.02), although not statistically significant. Conclusion: No significant racial difference was found when comparing the rates of 80% pathological positivity of suspected endometriosis lesions among groups. Endometriosis pathological positivity rate was unaffected by patients' BMI and the presence of concomitant pathologies. In addition, prior laparoscopic surgery for endometriosis might cause tissue changes that result in a decrease in the observed pathological positivity rate of endometriosis lesions during subsequent surgeries.

Child eating behavior predicts body mass index after 1 year: results from the Swiss Preschooler's Health Study (SPLASHY).

Child obesity is a growing global issue. Preventing early development of overweight and obesity requires identifying reliable risk factors for high body mass index (BMI) in children. Child eating behavior might be an important and malleable risk factor that can be reliably assessed with the parent-report Child Eating Behavior Questionnaire (CEBQ). Using a hierarchical dataset (children nested within child care centers) from a representative cohort of Swiss preschool children, we tested whether eating behavior, assessed with a 7-factor solution of the CEBQ, and BMI at baseline predicted the outcome BMI after 1 year, controlling for socioeconomic status (n = 555; 47% female; mean age = 3.9 years, range: 2.2-6.6; mean BMI = 16 kg/m2, range: 11.2-23; mean age- and sex-corrected z-transformed BMI, zBMI = 0.4, range -4 to +4.7). The statistical model explained 65.2% of zBMI at follow-up. Baseline zBMI was a strong positive predictor, uniquely explaining 48.8% of outcome variance. A linear combination of all CEBQ scales, taken together, explained 10.7% of outcome variance. Due to their intercorrelations, uniquely explained variance by any individual scale was of negligible clinical relevance. Only food responsiveness was a significant predictor, when accounting for all other predictors and covariates in the model, and uniquely explained only 0.4% of outcome variance. Altogether, our results confirm, extend, and refine previous research on eating behavior and zBMI in preschool children, by adjusting for covariates, accounting for intercorrelations between predictors, partitioning explained outcome variance, and providing standardized beta estimates. Our findings show the importance of carefully examining the contribution of predictors in multiple regression models for clinically relevant outcomes.

Prevalence of metabolic disorders among women in reproductive age group in hilly rural area of North India.

Background: Metabolic syndrome consists of cardiometabolic risk factors that promote the development of atherosclerotic cardiovascular disease, type 2 'DM' and obesity. These are associated with increased cardiovascular mortality and morbidity. Metabolic disorders (MD) are becoming more prevalent both in developing countries and developed countries and are now considered as lifestyle diseases. In women of reproductive age group, especially pregnancy, the blood glucose level is increasing which adversely affects the health of mother and child. Similarly, high blood pressure also precipitates the problems. This study was carried out to find the prevalence of hypertension, diabetes mellitus, obesity and 'MD' among the women living in remote rural set-up. Materials and Methods: This cross-sectional study was done among women of reproductive age group in 15 villages from 5 panchayats of field practice area of Maharishi Markandeshwar Medical College and Hospital, Kumarhatti, Solan. They were screened for 'MD' through investigative procedures (weight, height, BMR, abdominal girth, blood pressure through sphygmomanometer, blood glucose through the glucometer method), serum HDL and triglycerides. Respondents from the family were asked about the common/general information of house. The tool used for collecting general and relevant information from the respondent was a questionnaire, which was pretested for validity before being used in the field. Results: Four-hundred and sixty-seven women of reproductive age group participated in the study. Half of the participants were with qualification of matriculate and 9.2% participants were illiterate. Three-fourths of the participants were married women and 89% were vegetarian. Sixty-four per cent of participants were housewives. Half of the participants had a normal BMI, whereas 28.9% were overweight and 10% were obese. The prevalence of hypertension and diabetes among the participants were 12.5% and 9.8%, respectively. Forty-seven per cent participants had a waist circumference above 80 cm. Conclusion: The level of non-communicable diseases is related with the MD which has the adverse effect on the various systems and organs of the subjects. The MD can be controlled with the certain changes in the life style pattern. The GOI is also concerned with such scenarios in the country. It is recommended that women of reproductive age group undergo regular blood pressure and blood sugar screenings to detect hypertension and diabetes early and take appropriate measures to manage them.

Effect of a two-only-meals-a-day and exercise lifestyle on HbA1c and anti-diabetic medication in a follow-up study of subjects with type 2 diabetes attending a free clinic in a north Maharashtra city.

Background: Type 2 Diabetes (T2D) is a global challenge with rising prevalence, inadequate compliance, and poor outcomes. Aims: Assess the effect of a 2-only-daily-meals with exercise lifestyle (2-OMEX) on (a) HbA1c, (b) anti-diabetic medication count (ADMC), (c) Kcal intakes, body weight, fasting insulin, and subjective well-being. Materials and Methods: This is a single-arm follow-up study conducted in a free 2-OMEX clinic in 2019-2020. Information for two meals and exercise compliance was obtained during the clinic visit. HbA1c was tested by HPLC and fasting insulin by the CLIA/CMIA method in private laboratories. Results: Eligible subjects (f = 49, m = 116) completing two or more visits and 60 days of follow-up had a mean age of 55.92 (10.43) years, a T2D duration of 8.20 (6.28) years, and a median observation period of 140 days. Statistically significant changes included HbA1c decline from 7.69 (1.70) to 7.00 (1.20) gm% (equivalent by the LogNormal method to 1.088 gm%), average weight loss at 5%(m), and 2%(f). ADMC declined from 2.32 to 2.14, the difference being significant with the WSR test (z = 2.0087, P = 0.0223). Subjects attaining anti-diabetic medication-free and normoglycemic status (HbA1c < 6.5 gm%) were 20 (12%). The number attaining HbA1c ≤ 7 gm%) significantly rose from 73 (44%) to 101 (61%) with an ADMC of 1.9 (chi-square = 9.531, df1, P = 0.0020203). Participants reported 'feeling energetic' (79%), feeling lighter (50%), and better sleep (35%). Average energy intakes dropped by 120 Kcal to 1580/day. Fasting insulin remained unchanged, from 12.61 (11.06) to 12.34 (11.78) mlU/L. The dropout rate was 35%. Conclusions: The 2-OMEX lifestyle showed a sizeable, favorable, and significant change in HbA1c, body weight, ADMC use in five months, and subjective benefits. Studies are necessary for remission impact and pathways.

Multipronged effects of increased screen time on the nutritional imbalance: A cross-sectional study of students of Amritsar aged 6-16 years.

Background: Intense marketing of fast-food items impacts the eating habits among children and adolescents. Various studies suggest that increased screen time leads to increased fast-food consumption and decreased sleep duration, both of which are linked to obesity in growing age. Objectives: To assess screen time and dietary habits among the study group and to estimate their effect on sleep deprivation and obesity. Methods: This cross-sectional study was conducted from January 2019 to December 2019 in three schools in Amritsar selected by lottery method of simple random sampling. Out of 4,226 students, 355 overweight and obese students were interviewed regarding their dietary habits. An informed written assent was taken from the mothers. The information was collected on a semi-structured, pre-designed questionnaire by interviewing the mothers of students between 6 and 11 years of age and the students of 12-16 years. Results: 94.4% of students preferred fast foods to regular meals and 58.3% were in the habit of skipping breakfast. 59.4% had a history of daily intake of fast foods while 76.1% had a habit of consuming fast foods while watching television. Only 31.7% had an adequate sleeping pattern of 9-11 hours and 79.7% of the students had a screen time of over 3 hours. Conclusions: More the screen time, the more the chances of missing meals. Being awake for a long odd time leads to increased consumption of foods/snacks furthermore. Regarding the harmful effects of fast foods, the source of information was from schools, but only 41.4% were aware about these effects.

Body composition parameters as predictors of low back pain in rural homemakers of North India.

Background: Homemakers are the backbones of families, but in rural India, females suffer from many musculoskeletal problems due to excessive workload in their houses. The objective of the present study is to compare body composition parameters as predictors of low back pain (LBP) in nonworking rural homemakers of North India. Materials and Methods: The study was conducted among 296 homemakers from rural areas of Lucknow district in Uttar Pradesh. Details of LBP and body composition parameters (body mass index, body fat, visceral fat) were taken. Results: The prevalence of LBP among homemakers was found to be 15.54%. BMI was found to be a better predictor of LBP than body fat and visceral fat. The risk of LBP is 7.24 times higher in BMI ≥23 than in women with BMI <23. The risk of LBP is 3.67 times more in visceral fat % ≥10% than in women with visceral fat % <10%. Conclusion: Age, type of family, socioeconomic status income was identified as risk factors in this population. Maintaining an adequate BMI is essential for the prevention of LBP.

Assessment of Generalized Joint Hypermobility and Its Association With Osteoarthritis, BMI, and Age: A Study in Southern Lahore.

BACKGROUND AND OBJECTIVE: Joint hypermobility is a physiological variation in the joint range of motion that allows individuals to move their joints beyond the normal limit. Generalized joint hypermobility (GJH) refers to an increased flexibility observed throughout various joints in the body. In younger individuals, joint hypermobility is often more pronounced, serving as a double-edged sword by providing enhanced flexibility for certain activities while simultaneously increasing the susceptibility to musculoskeletal issues. Weight gain and overactivity of joints (joint hypermobility) are associated with the onset of osteoarthritis (OA), and data for the local populace is lacking. This study aims to assess GJH and OA in young and middle-aged women in southern Lahore. METHODOLOGY: A cross-sectional study recruited 116 diagnosed OA patients through a random convenient sampling method. These patients were assessed for GJH using the Beighton criterion. For the assessment of GJH, the Beighton criterion was used, and for OA, radiographs of knee joints were taken. The Beighton criterion consists of nine movements, and each maneuver is assigned a score of either 0 or 1, resulting in a range from 0 to 9. A chi-square test was used for the group comparison of study variables. RESULTS: A total of 116 adult females participated, with a mean age of 38.34 ± 9.761 and an age range of 20 to 55 years. GJH was assessed and correlated with age using the chi-square correlation and test. Results indicated that 78 (67.24%) exhibited hypermobility at various joint levels, with a likelihood ratio of 43.336 and a P-value of <0.001. GJH and BMI were correlated by employing Pearson chi-square correlation, with Pearson chi-square of 2.51 and P-value of 0.112 suggestive of no significant association between BMI and GJH. CONCLUSIONS: The dynamic nature of joint hypermobility emphasizes the need to consider age-related changes when assessing its impact on musculoskeletal health. Assessment and management of hypermobility in patients of OA, especially in females, should be made part of routine practices.

Association of Waist Circumference and Body Mass Index Deciles Ratio with All-Cause Mortality: Findings from the National Health and Nutrition Examination Survey.

Given the importance and continued interest in finding a simple, accessible, and universal measure which reflects both general and abdominal adiposity, this study tested for an association of the ratio of WC decile to BMI decile (WC-d/BMI-d) with all-cause mortality. Individuals aged 18-79 years who had participated in the National Health and Nutrition Examination Survey (NHANES) during the years 2007 to 2018 were included in the analysis. WC and BMI deciles were defined separately for males and females, while WC-d/BMI-d was calculated for each individual. The association of WC-d/BMI-d with mortality was assessed using logistic models for the total study population, and then again after stratification by sex, ethnicity, morbidity level, and BMI categories. Positive associations between WC-d/BMI-d and mortality were demonstrated for the total study population (adjusted OR = 1.545, 95%CI: 1.369-1.722) and within different sub-groups, including the population with a normal BMI level (adjusted OR = 1.32, 95%CI: 1.13-1.50). WC-d/BMI-d increased with age, with ~40 years representing a critical time point when WC-d surpasses BMI-d, with a sharper incline for males as compared to females. WC-d/BMI-d was significantly associated with all-cause mortality amongst NHANES American adults; thus, measurements of WC and its integration with BMI in this metric should be considered in clinical practice.

Association of air temperature exposure during pregnancy with risk of preeclampsia in Guangzhou, China.

Environmental exposures during pregnancy have been associated with adverse obstetric outcomes. However, limited and inconsistent evidence exists regarding the association between air temperature exposure and the risk of preeclampsia (PE). This study aimed to evaluate the correlation between ambient temperature exposure during pregnancy and PE risk, as well as identify the specific time window of temperature exposure that increases PE risk. A population-based cohort study was conducted from January 2012 to April 2022 in Guangzhou, China. Pregnant women were recruited in early pregnancy and followed until delivery. A total of 3,314 PE patients and 114,201 normal pregnancies were included. Ambient temperature exposures at different gestational weeks were recorded for each participant. Logistic regression models were used to evaluate the correlation between ambient temperature exposure and PE risk. Stratified analyses were conducted based on maternal age and pre-pregnancy BMI. Distributed lag models were employed to identify the time window of temperature exposure related to PE. Exposure to extreme high temperature (aOR = 1.24, 95 % CI 1.12-1.38) and moderate high temperature (aOR = 1.22, 95 % CI 1.10-1.35) during early pregnancy was associated with an increased risk of PE. Furthermore, women with higher pre-pregnancy BMI had a higher risk of developing PE when exposed to high temperature during early pregnancy compared to normal-weight women. The time window of temperature exposure related to PE was identified as pregnancy weeks 1 to 8. This study provides evidence for the association of high temperature exposure during early pregnancy with the risk of PE, as well as identifies the specific time window of temperature exposure related to PE. These findings have implications for developing potential strategies to protect pregnant women, particularly those with higher pre-pregnancy BMI, from the adverse effects of extreme temperatures during early pregnancy.

Velocity-selective arterial spin labeling perfusion measurements in 2nd trimester human placenta with varying BMI.

INTRODUCTION: Proper placental development is crucial to fetal health but is challenging to functionally assess non-invasively and is thus poorly characterized in populations. Body mass index (BMI) has been linked with adverse outcomes, but the causative mechanism is uncertain. Velocity-selective arterial spin labeling (VS-ASL) MRI provides a method to non-invasively measure placental perfusion with robustness to confounding transit time delays. In this study, we report on the measurement of perfusion in the human placenta in early pregnancy using velocity-selective arterial spin labeling (VS-ASL) MRI, comparing non-obese and obese participants. METHODS: Participants (N = 97) undergoing routine prenatal care were recruited and imaged with structural and VS-ASL perfusion MRI at 15 and 21 weeks gestation. Resulting perfusion images were analyzed with respect to obesity based on BMI, gestational age, and the presence of adverse outcomes. RESULTS: At 15 weeks gestation BMI was not associated with placental perfusion or perfusion heterogeneity. However, at 21 weeks gestation BMI was associated with higher placental perfusion (p < 0.01) and a decrease in perfusion heterogeneity (p < 0.05). In alignment with past studies, perfusion values were also higher at 21 weeks compared to 15 weeks gestation. In a small cohort of participants with adverse outcomes, at 21 weeks lower perfusion was observed compared to participants with uncomplicated pregnancies. DISCUSSION: These results suggest low placental perfusion in the early second trimester may not be the culpable factor driving associations of obesity with adverse outcomes.

Successful therapy with tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) does not guarantee amelioration of liver damage assessing by transient elastography. A retrospective - prospective multicenter study.

BACKGROUND: Preventing disease progression and viral suppression are the main goals of antiviral therapy in chronic hepatitis B (CHB). Liver stiffness measurement (LSM) by transient elastography is a reliable non-invasive method to assess liver fibrosis in patients with CHB. Our aim was to explore factors that may affect changes in LSMs during long term tenofovir (TDF) monotherapy in a well characterized cohort of patients with compensated CHB. METHODS: We analyzed serial LSMs in 103 adult patients with CHB who were on TDF monotherapy and had at least three LSMs over a period of 90 months. RESULTS: Twenty-five (24%) patients had advanced fibrosis at baseline. A significant decline in mean LSM between baseline and last visit (8.7 ± 6.2 kPa vs. 6.7 ± 3.3, p = 10- 3) was observed. Twenty-four (23%) patients had progression of liver fibrosis with mean increase in liver stiffness of 2.8 kPa (range: 0.2-10.2 kPa). Multivariate analysis showed that BMI ≥ 25 (OR, 0.014; 95% CI, 0.001-0.157; p = 0.001) and advanced fibrosis (OR, 5.169; 95% CI, 1.240-21.540; p = 0.024) were independently associated with a fibrosis regression of > 30% of liver stiffness compared to baseline value. CONCLUSIONS: In CHB patients TDF monotherapy resulted in liver fibrosis regression, especially in patients with advanced fibrosis. Despite the successful antiviral effect of TDF, 1 out of 4 patients had liver fibrosis progression. Obesity and advanced fibrosis at baseline were independently associated with significant liver fibrosis regression.

FTO rs9939609: T>A Variant and Physical Inactivity as Important Risk Factors for Class III Obesity: A Cross-Sectional Study.

BACKGROUND: The prevalence of obesity has been increasing worldwide. It has been reported that physiological and environmental factors such as diet, culture, physical activity, and genetics are the principal factors related to obesity. The fat mass and obesity-associated (FTO) gen variant (rs9939609: T>A) has been associated with class III obesity. The A variant has been correlated with anthropometric and metabolic alterations. Therefore, the purpose of this study was to analyze the association of the FTO rs9939609: T>A variant and environmental factors with clinical, anthropometric, and biochemical variables in subjects with class III obesity. RESULTS: The A variant frequency was higher in the class III obesity group compared with the normal weight group (44% vs. 25%, p < 0.001). Subjects with the AA genotype had a higher body mass index (BMI) than those with the AT genotype (35.46 kg/m2 (31-39.8) vs. 26.91 kg/m2 (23.7-30), p = 0.005). Women with the AA genotype showed higher waist circumferences than the AT group (101.07 cm (90.9-111.1) vs. 85.45 cm (77-93.8) p = 0.047). The FTO A variant increases the risk by 3.54 times and physical inactivity increases the risk by 6.37 times for class III obesity. CONCLUSIONS: Our results suggest that among the studied variables, those most related to class III obesity were the FTO risk genotype (A allele) and physical inactivity.

Exploring Physical Activity Levels in Patients with Cardiovascular Disease-A Preliminary Study.

Increased physical activity may prevent disease onset and severity in individuals with cardiovascular disease. However, studies evaluating physical activity in people with cardiovascular disease are limited. This prospective observational study aimed to objectively assess the level of physical activity in patients with cardiovascular disease and determine the actual extent of physical activity in their daily lives. Participants aged 20 years or older with cardiovascular disease at a cardiology clinic were included. Physical activity was measured using an activity meter with a three-axis acceleration sensor. Overall, 58 patients were included in the study. Household activities were found to be more frequent sources of physical activity. The step count was related to age and housework, while total physical activity and household activity were related to age and work. Locomotive activity was related to sex and housework. Total physical and household activities tended to decrease with age. These findings indicate the influence of work and household chores on physical activity and suggest that physical activity may be underestimated if household activity is not also assessed. These fundamental findings may provide clinical evidence to underpin physical activity for patients with cardiovascular disease.

Development of gemcitabine-modified miRNA mimics as cancer therapeutics for pancreatic ductal adenocarcinoma.

Despite the recent advancement in diagnosis and therapy, pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is still the most lethal cancer with a low five-year survival rate. There is an urgent need to develop new therapies to address this issue. In this study, we developed a treatment strategy by modifying tumor suppressor miRNAs, miR-15a and miR-194, with the chemotherapeutic gemcitabine (Gem) to create Gem-modified mimics, Gem-miR-15a and Gem-miR-194, respectively. In a panel of PDAC cell lines, we found that Gem-miR-15a and Gem-miR-194 induce cell-cycle arrest and apoptosis, and these mimics are potent inhibitors with IC50 values up to several hundred fold less than their native counterparts or Gem alone. Furthermore, we found that Gem-miR-15a and Gem-miR-194 retained miRNA function by downregulating the expression of several key targets including WEE1, CHK1, BMI1, and YAP1 for Gem-miR-15a, and FOXA1 for Gem-miR-194. We also found that our Gem-modified miRNA mimics exhibit an enhanced efficacy compared to Gem in patient-derived PDAC organoids. Furthermore, we observed that Gem-miR-15a significantly inhibits PDAC tumor growth in vivo without observing any noticeable signs of toxicity. Overall, our results demonstrate the therapeutic potential of Gem-modified miRNAs as a treatment strategy for PDAC.

The Relationship of Pathological Response and Visceral Muscle and Fat Volume in Women With Breast Cancer Who Received Neoadjuvant Chemotherapy.

Objective: Differences in individual muscle/fat volumes may change the effectiveness of chemotherapy. In this study, the relationship between trunkal muscle and fat volume and body mass index (BMI) obtained before receiving neoadjuvant chemotherapy (NCT) in patients with breast cancer and complete pathological response (pCR) was investigated. Materials and Methods: The volumes of psoas, abdominal and paraspinal muscles, and trunkal subcutaneous and visceral fat were calculated using CoreSlicer AI 2.0 opensource program from the F-18 fluorodeoxyglucose positron emission tomography/computed tomography (CT) and CT images before NCT and postoperative pCR rates to NCT were recorded. Muscle/fat volumes and BMI prior to NCT were compared in terms of pathological pCR rates. Patients were followed up regularly for recurrence and survival. Results: Ninety-three patients were included with median (range) values for age, BMI, and body weights of 48 (28-72) years, 27 (16.8-51.6) kg/m2, and 71.94 (43-137) kg, respectively. The median follow-up time was 18.6 (6.7-59.6) months. No significant correlation was found between total muscle or fat volumes of patients with and without pCR. BMI [26.2 (16.8-51.6) kg/m2 vs. 24.6 (20.3-34.3) kg/m2, p = 0.03] and pCR rates in patients with low right-psoas muscle volume [11.74 (7.03-18.51) vs. 10.2 (6.71-13.36), p = 0.025] were significantly greater. A significant relationship was found between right psoas muscle volume and disease-free survival (DFS) (11.74 cm3 (7.03-18.51) vs. 10.2 cm3 (6.71-13.36), p = 0.025). However, no significant relationship was detected between total muscle-fat volume, BMI and overall survival and DFS (p>0.05). Conclusion: This is the first published study investigating the relationship between the pCR ratio and body muscle and fat volume measured by CoreSlicer AI 2.0 in patients with breast cancer who received NCT. No correlation was found between the pCR ratio and total muscle plus fat volume. However, these results need to be validated with larger patient series.

Prevalence of Metabolic Syndrome and Its Risk Factors Influence on Microvascular Complications in Patients With Type 1 and Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) long-term macrovascular and microvascular complications pose significant health risks and increase mortality. In DM patients, metabolic syndrome (MetSy) either precedes or coexists with the condition. Central obesity, poor glycemic control, hypertension, elevated triglycerides (TG), and low high-density lipoproteins (HDL-C) are the components of MetSy. The purpose of this study is to investigate related diabetic microvascular complications in type 1 DM (T1DM) by comparing them with type 2 DM (T2DM), determine potential risk factors, and estimate prevalence based on the diagnosis of MetSy. METHODOLOGY: This study included 160 T1DM and 160 T2DM patients, totaling 320 DM patients. It was carried out from April 20, 2022, to September 31, 2023, at the Sheikh Zayed Hospital, Rahim Yar Khan, in the Outdoor Diabetic Clinic and Medicine Department. A unique questionnaire was utilized to gather socio-demographic, general, clinical, and laboratory data for the MetSy criteria set forth by the International Diabetes Federation (IDF). The blood pressure, BMI, and waist circumference (WC) were measured, while venous fasting blood was used to assess biochemical markers such as HDL-C, TG, and fasting blood sugar. The microvascular diabetes complications were identified using abdominal ultrasound, fundus ophthalmoscopy, and routine laboratory tests. We quantified and analyzed these variables individually for T1DM and T2DM patients with or without MetSy and compared them in the presence or absence of diabetes microvascular complications. RESULTS: MetSy prevalence was 25.62% (41, n=160) for T1DM and 60.62% (97, n=160) for T2DM, totaling 43.12%. Among T1DM patients with MetSy, the majority were married males, aged 36-49 years, with a BMI of 26.69±2.20 kg/m2 and a WC of 85.12±4.23, and 67.5% (108) patients had diabetes microvascular complications. Comparatively, in T2DM with MetSy, the majority were married females aged 50-59 years with a BMI of 29.79 ± 4.65 kg/m² and a large WC of 93.43±4.49, and 75% (123) patients had diabetes microvascular complications. Overall, this study noted significant p-values for hypertension, elevated TG, low HDL-c, high WC, obesity, female gender in T2DM, and above 36 years of age in both groups with MetSy. Diabetic retinopathy (DR) at 32.4% (p<0.001) was the most prevalent T1DM microvascular complication, followed by nephropathy (30.6%), neuropathy (DN) at 28.1%, and gastroparesis (DG) at 22.3%. Whereas in T2DM, the prevalence of DN was 36.3% (p<0.001), followed by DKD (29.3%), DG (28.9%), and DR (24.9%). CONCLUSION: Nearly a quarter of T1DM patients had MetSy, with increasing percentages of overweight and obese patients who are more likely to have DR, DKD, or DN. MetSy affects two-thirds of T2DM patients, with married obese females aged 50-59 being more susceptible than males, who are more likely to suffer DN, DKD, or DG. Risk factors that contribute to the MetSy burden in T1DM and T2DM include hypertension, poor glycemic management, low HDL-C, high TG, and a higher BMI or WC. Increasing age, female gender in T2DM, longer diabetes duration, and co-morbid hypertension were independent predictors of microvascular complications. DR, DN, DKD, and gastroparesis are the most prevalent diabetic microvascular sequelae. The clinical management of diabetic patients with healthy lifestyle adaptations, good glycemic control, antihypertensives, and statins will contribute greatly to MetSy prevention.

An examination of the predictors of change in BMI among 38 026 school students in Makkah, Saudi Arabia.

BACKGROUND: The prevalence of childhood obesity has substantially increased in the Gulf Cooperation Council countries, including Saudi Arabia. The Rashaka initiative is a Saudi national school-based multicomponent intervention that was introduced in the school year 2016-2017 to address childhood overweight and obesity. This study aims to examine the effect of the Rashaka initiative on students' body mass index (BMI) for two academic years (2016-2017 and 2018-2019) and to analyse predictors of BMI change. METHODS: Secondary data for this pre-post study was provided by the Ministry of Health for 38 026 students from 89 intermediate and secondary schools that implemented the initiative in Makkah City, Saudi Arabia. It was analysed using non-parametric tests and multiple regressions at a 5% level of significance. RESULTS: Over 2 y of implementation, BMI was reduced significantly across the schools (p < 0.001). Based on the regression modelling, school gender and education stage were found to be the only significant predictors of BMI change. Girls and intermediate schools had greater BMI reductions than boys and secondary schools (p < 0.001 and p = 0.031). CONCLUSIONS: This study provides tentative evidence for the effectiveness of the Rashaka intervention in Makkah City. In addition, our study has identified that the Rashaka initiative may require modification to improve its effect on boys and students in secondary schools.