Increased Body Weight Research Articles

Aerobic exercise capacity improvement of patients with human immunodeficiency virus one year post-treatment initiation by integrase inhibitors

Abstract Background Infection by Human Immunodeficiency Virus (HIV) leads to chronic inflammation and subsequently to the early development of cardiovascular (CV) disease in young adults. Initiation of antiretroviral therapy (ART) usually leads to patient’s body weight and blood pressure increase. Cardiopulmonary exercise test (CPET) evaluates aerobic exercise capacity and subsequently cardiovascular and respiratory function. Aim of this study is the investigation of any treatment-induced changes in aerobic exercise capacity in treatment naïve young HIV patients’ at 1-year post HIV treatment initiation by different ART agents. Methods We studied 46 recently diagnosed and treatment naïve young HIV patients (37+10 years, 87% males, 62% smokers) at baseline and 1-year post ART initiation (integrase or protease inhibitors). Twenty-six (26) patients were randomly treated by the newer integrase inhibitor Dolutegravir (Group A, mean age=36+9 years, 100% males, 77% smokers) while 19 patients by the older protease inhibitor Darunavir/Cobicistat (Group B, mean age=37+10 years, 90% males, 47% smokers). All patients were submitted in CPET at baseline and 1-year post ART initiation. We estimated any changes in body mass index (BMI), systolic blood pressure (SBP) and CPET parameters (peak VO2, Oxygen pulse, WorkLoad, VE/VCO2) at 1-year post ART initiation. Results At baseline and 1-year re-evaluation, we found no differences between groups regarding age, BMI and CPET parameters. In the whole HIV population, we found an increase in body weight (76+12 vs. 82+15kg, p<0.001), SΒΡ (124+12 vs. 132+14mmHg, p<0.001), WorkLoad (176+35 vs. 186+35watt, p<0.001) and peak VO2 (2171+437 vs. 2299+491ml/min, p=0.03) at 1-year re-evaluation. In Group A, body weight (p<0.001), SBP (p=0.07), WorkLoad (p=0.006) and peak VO2 (p=0.01) were increased while in Group B, body weight (p<0.001), SBP (p=0.001) και WorkLoad (p=0.01) were also increased. Conclusions Aerobic exercise capacity is improved 1-year post-treatment initiation by the newer integrase inhibitor Dolutegravir in treatment-naïve HIV patients despite the adverse BMI and SBP increase. The newer Dolutegravir probably exhibits a more favorable CV profile in HIV patients compared to the older Darunavir/Cobicistat.Re-evaluation 1-year post ART initiation

Inhibition of ketohexokinase prevents fructose-induced insulin resistance and endothelial dysfunction in high fat and sucrose-fed mice via enhancing energy expenditure

Abstract Introduction Cardiovascular disease linked to fatty liver poses a significant threat to health. Consumption of high-fat diets (HFD) is known to trigger a cascade of health issues including obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). These conditions are exacerbated, with the addition of dietary sugar to high-fat diets (HFSD), resulting in non-alcoholic steatohepatitis (NASH). Studies have shown that fructokinase (ketohexokinase or KHK) knockdown protects mice from HFSD-induced NASH. Purpose This study focused on examining the temporal changes of metabolic perturbations, triggered by sugar consumption, particularly in the transition from fatty liver to cardiovascular disease. Methods C57/BL6 wild type (WT) and KHK-knockout mice were fed with HFD or HFSD for different durations between 6 to 20 weeks, to induce NAFLD and NASH. Western blotting and quantitative-PCR were carried out on tissues and isolated endothelial cells for protein and mRNA expressions, respectively. Glucose and insulin tolerance tests and whole-body energy measurements were performed at different time-points. Combined Laboratory Animal Monitoring System was used to monitor various parameters of energy expenditure. Functional interactions between endothelial cells and adipose tissues were carried out using an in-house Organ-On-a-chip technology. Endothelial function was studied by measuring isometric tensions in organ bath. Results KHK-deficient mice had significantly lower weight compared to WT littermates. Wild-type mice fed HFD and HFSD exhibited significant glucose intolerance, insulin resistance, and endothelial dysfunction compared to KHK-knockout mice. However, HFSD led to more severe outcomes compared to HFD, demonstrating differing temporal effects on glucose intolerance and insulin resistance. Interestingly, KHK-knockout mice were significantly protected from the effects induced by HFSD, as well as, such as increased body weight, fasting hyperglycemia, hyperinsulinemia and endothelial function. KHK-knockout mice exhibited significant increase in oxygen consumption and energy expenditure, both in HFD and HFSD-fed conditions. These data suggest that high energy-expenditure is one of the primary mechanisms, in reducing adiposity and body weight in HFSD-fed knockout mice. Notably, KHK-deficient mice were protected against sugar-induced fat accumulation, random hyperinsulinemia and significant impairment of endothelial function. Conclusions A novel finding in this study is that KHK ablation protects not only against HFSD-induced, but also HFD-induced pathologies via significantly enhancing energy expenditure. The results suggest that targeting KHK could potentially mitigate the development of fatty liver and cardiovascular diseases, induced by high calorie diets.

KardioNet Digital - a structured care model involving digital tools for intersectoral communication and a patient-focused strategy for treatment of heart failure

Abstract Introduction Inefficiencies and discontinuities in care at the interfaces within Germany's healthcare system, especially between acute and outpatient care, present significant challenges in managing patients with heart failure (HF). The management complexity of HF has increased with the advent of new digital tools, though patient acceptance of these tools remains contentious. The prevention of loss of diagnostic and therapeutic information for this complex disease is crucial for cross-sectoral communication (hospital - office-based cardiologist - general practitioner) and quality of care. Purpose Our goal was to examine the impact of digital app-supported coordination of HF management across different healthcare providers from hospital discharge to the ambulatory sector and to assess patients' acceptance of a structured care program. A patient-focused digital strategy, supported by a Heart Failure Nurse (HFN), aimed to facilitate structured follow-up and patient empowerment, focusing on patient-reported outcomes and experiences (refer to Table 1). Results Out of 401 patients screened during their hospital stay for HF, only 57 (14.9% male, 12.6% female) participated in the KardioNet Digital (KND) program. NYHA classifications were I (3.5%), II (49.1%), III (40.4%), and IV (7.1%); Diagnoses included CMP (26, 45.6%), CAD (19, 33.3%), valvular HF (8, 14.0%), and others (4, 7.0%). The mean age was 55.03 years, with a notable difference in participation based on age (≥70 years: 9.5% male, 33.3% female; <70 years: 90.5% male, 66.7% female). Age was a significant determinant of program participation. Patients who regularly used the app benefited from several features: A total of 35 alerts (17 patients) were triggered for reasons such as bodyweight increase (2kg or more) and device-induced alerts (i.e. false shock delivery, 3x slow-VT, Syncope), leading the HFN to contact the patients. This early intervention prevented rehospitalization due to decompensation of heart failure in 11 patients (64.7%) and addressed device-related alarms for organizing an emergency hospital visit by HFN. Despite substantial incentives, such as support from an HFN and expedited appointments with specialists for follow-up therapy, refusal rates were high (refer to Table 2). Conclusion A structured, digitally supported cross-sectoral care model for heart failure patients can potentially improve care coordination and outcomes. However, the success of such programs critically depends on patient willingness and the seamless integration into existing healthcare structures. Despite valuable incentives, we observed low acceptance of the program. Even among motivated participants (14.1%), there is a significant need for substantial support and education on digital literacy for the widespread implementation of digital tools in real-world settings for the treatment of heart failure.Workflow of structured digital supportReasons for Declining Participation

Impact of SGLT2 inhibitor dapagliflozin on myocardial protein profile in rats with long-standing Type 1 diabetes mellitus

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors have beneficial effects on the cardiovascular system in diabetes mellitus (DM) patients. However, as most trials have focused on Type 2 DM, the impact of SGLT2 inhibitors on Type 1 DM remains unclear. Objective To investigate the effects of long-term treatment with SGLT2 inhibitor dapagliflozin on the left ventricular (LV) proteome in Type 1 DM rats. Methods Male Wistar rats were divided into three groups: Control (C, n=7); Diabetes (DM, n=6); and Diabetes treated with Dapagliflozin (DM+DAPA, n=8) for 30 weeks. Diabetes was induced by streptozotocin (40 mg/kg). Dapagliflozin was added to chow at 5 mg/kg/day. Label-free mass spectrometry was used to assess LV proteome using a nanoAcquity UPLC-Xevo QTof MS system and ProteinLynx Global Server (PLGS) software. Cytoscape software, Cluster Marker, and Cluego plugins were used for bioinformatic analysis. Statistical analysis: ANOVA and Tukey or Kruskal-Wallis and Dunn. Results Dapagliflozin increased body weight (C 574±43; DM 339±31*; DM+DAPA 413±30*# g; p<0.05: * vs C; # vs DM) and reduced glycemia [C 108 (101–111); DM 554 (529–562)*; DM+DAPA 343 (237–416)*# mg/dL; p<0.05: * vs C; # vs DM]. One rat died in C and two in DM+DAPA. A total of 252 differentially expressed proteins were identified. Most proteins identified in the networks were downregulated in DM vs C and upregulated in DM+DAPA vs DM. Six proteins related to energy metabolism (Atp5j, P21571; CKm, P00564; Ak1, P39069; Atp5h, P31399; Mdh1, O88989; and Idh2, P56574), four involved in myocyte excitation-contraction (Act1, P68065; Casq2, P51868; SERCA1, Q64578; and SERCA2a, P11507), and two associated with oxidative stress (Sod1, P07632; and Sod2, P07895) were upregulated in DM+DAPA x DM. Comparing DM with C, the KEEG Pathway with the highest percentage of gene associations for upregulated proteins was related to gap junction (25.6%), necroptosis (25.6%), and fatty acid degradation (25.6%), and for downregulated proteins was related to Alzheimer disease (27.3%), cardiac muscle contraction (25%) and glycolysis/gluconeogenesis (13.6%). Comparing DM+DAPA with DM, the KEEG Pathway with the highest percentage of gene associations for upregulated proteins was related to Parkinson disease (18.3%), cardiac muscle contraction (14.2%), citrate acid cycle (9.47%), necroptosis (8.88%), and cGMP-PKG signaling (7.10 %), and for downregulated proteins was related to ketone bodies synthesis and degradation (100%). Conclusion Dapagliflozin is safe and prevents changes in the expression of proteins related to energy metabolism, cardiac muscle contraction, and oxidative stress in Type 1 diabetes mellitus rats. These results offer new insights into the cardioprotective mechanisms of dapagliflozin in Type 1 diabetes mellitus.

Anti-Diabetic and Insulinotropic Effects of p-Anisic Acid in High-Fat Diet and Streptozotocin Induced Type-2 Diabetic Rats.

To evaluate the antidiabetic effect of p-anisic acid (p-AA) against type 2 diabetes mellitus (T2DM). Thirty-six male rats were utilized for the study. The animals were provided with the high-fat diet (HFD) and T2DM was induced through 35 mg/kg streptozotocin (STZ). Subsequently, the animals were allocated to 6 groups and subjected to the treatments for 4 weeks followed by a 2-week observation. Three treatment groups were administered with p-AA (25 mg/kg, 50 mg/kg or 100 mg/kg). Glibenclamide (3 mg/kg) was provided to the standard control group. The normal control and disease control groups were supplied with 0.1 % carboxymethyl cellulose (CMC). Subsequently, the effects of treatment on body weight (BW), blood glucose level (BGL), glycosylated haemoglobin (HbA1c), insulin, and lipid parameters were measured and the pancreas was isolated for histopathology. A statistically significant (P-value<0.001) increase in BW was observed in the p-AA (50 mg/kg and 100 mg/kg) groups. The BGL decreased significantly (P-value<0.001) in p-AA groups. p-AA significantly (P-value<0.001) regulated the levels of HbA1c and serum insulin and lipid parameters. A notable improvement in the morphology of the pancreas was observed. Treatment with p-AA exhibited significant antidiabetic effects against STZ-HFD-induced T2DM.

Thyroid function status in patients with hypothyroidism on thyroxine replacement and associated factors: a retrospective cohort study in primary care

BackgroundLong-term management of patients with hypothyroidism on thyroxine replacement requires thyroid function test (TFT) monitoring once every six–12 months as recommended by clinical practice guidelines. This study determined their thyroid function status during two-year follow-up visits in primary care, and the factors influencing their thyroid status, and assessed the optimal interval for TFTs.MethodsA retrospective cohort study was conducted on adults with a clinical diagnosis code for hypothyroidism in their electronic health records taken from a group of polyclinics in Singapore between July 2017 and June 2020. The follow-up thyroid status was categorized as under-replacement (TSH ≥ 3.70mIU/L), over-replacement (TSH ≤ 0.65mIU/L) or euthyroid (TSH 0.65–3.70mIU/L). The patients’ demographic, clinical and TFT data were analyzed using appropriate statistical tests during the two-year follow-up. Stepwise logistic regression analysis identified the factors associated with suboptimal thyroid control. Kaplan–Meier analysis was used to compare their thyroid function status in association with the interval between TFT monitoring.ResultsData from 5,749 eligible subjects (mean age 62.1 ± 13.29 years; 79% female; 79.7% Chinese) were analyzed. After a two-year follow-up, 61.9% (n = 3558) of all subjects were euthyroid, with 29.5% (n = 1694) being under-replaced and 8.6% (n = 497) over-replaced. However, thyroid status did not differ significantly with the various dose regimen (daily, segmented, or alternate days) (p = 0.193). Stepwise logistic regression showed that thyroxine under-replacement was significantly associated with the male gender (AOR = 1.25,95%CI = 1.03–1.51,p = 0.02) and obesity (AOR = 1.34,95%CI = 1.08–1.66,p = 0.008). Every unit (μg/kg body weight) increase in the mean daily thyroxine dose was associated with 2.72 times greater odds of over-replacement. When comparing thyroid function monitoring at intervals of 13-24 months, monitoring at shorter intervals (≤ 12 months) was less likely to detect thyroxine under-replacement (AOR = 0.57,95%CI = 0.44–0.74,p < 0.001) and over-replacement (AOR = 0.62,95%CI = 0.41–0.97,p = 0.033). Among the 3,312 adults who were euthyroid at baseline, 22.2%, 41.7% and 59.6% had suboptimal thyroid control at 6, 12 and 24 months respectively (Kaplan–Meier analysis).ConclusionAround six in ten patients were euthyroid with thyroxine replacement for hypothyroidism in primary care over two years. Thyroxine under-replacement was associated with male gender and obesity. The proportion of euthyroid patients developing abnormal thyroid function doubled with TFTs at six, 12 and 24-month intervals.

Utilization Ecdysterone Hormone of Krokot (Portulaca oleracea) Extract on Molting Activity in Mud Crabs (Scylla serrate)

The Scylla serrate mangrove crab is one of the leading fisheries commodities in terms of exports, only behind shrimp, tuna and shellfish. Crabs have a fairly high price in foreign markets and most of the mud crabs obtained from wild catches are soft shell crabs. In terms of price, cultivating soft shell crabs is quite profitable, but most cultivators have several problems such as long maintenance periods and inconsistent molting times so that they do not experience business continuity. Applying herbal extracts via injection is an effective method because all the substances that trigger molting directly enter the body. Physiological engineering is needed to speed up the molting phase and get the same molting time. This research aims to identify the ecdysterone content in purslane leaves and determine the optimum dose of purslane leaf extract which can encourage skin molting in mud crabs. This research used a Randomized Block Design (RBD). The in silicons test results show that the compound that has the smallest binding affinity is ecdysone, namely -6.80 kcal/mol. Based on analysis of variance, the best molting percentage occurred in treatment B at 55.50%. The fastest molting period occurred in treatment C, namely on days 4 to 29 after injection. Treatments B and C had the highest survival rate, namely 100%, while in terms of increasing body weight and carapace width, the effect of all treatments was not significantly different. The water quality results for all groups were still within the optimum value, temperature 26.40 – 33.80ºC; pH 6.83 – 7.20; salinity 20.70 – 26.70 ppt and dissolved oxygen 4 – 4.52 ppm

The effect of high levels of Glycyrrhiza glabra powder on performance, carcass characteristics, blood parameters, immunity, intestinal microbial flora, intestinal morphology and breast muscle fatty acid profile in broilers

In order to investigate the effect of licorice medicinal plant on performance, carcass characteristics, fatty acid profile of breast muscle, intestinal microbial flora, blood constitutes and immunity of broiler chickens, an experiment using a completely randomized design with 3 treatments, 4 replications, 10 chicks per repetition and a total of 120 pieces of one-day-old male broiler chickens of commercial strain Ross 308 were performed for 42 days. Experimental treatments included three different levels of licorice (0, 300 and 400 mg/kg feed). Data was analyzed using SAS statistical software and averages were compared at the 5% probability level with Duncan's multiple range test. The results showed that although variation in feed consumption, weight gain and feed conversion ratio was not significant in any of the rearing periods (P≥0.05), the highest feed consumption, weight gain and the best feed conversion ratio was observed in the final period of chickens were fed with Diet containing 400mg/kg licorice. Also, according to the data, the best European index was related to this treatment. In addition, the use of two levels of licorice had no significant effect on carcass characteristics or intestinal microbial flora; however, the highest increase in body weight and the lowest number of Lactobacillus acidophilus bacteria were observed at the higher level of licorice. However, these high levels did not lead to a decrease in abdominal fat. According to the results obtained, different levels of licorice led to a significant reduction of harmful fats such as cholesterol, triglycerides, VLDL and LDL (P&lt;0.05). Furthermore, although the level of HDL was not significant (P≥ 0.05), its highest amount was seen at high levels of licorice. In addition, the lowest amount of total protein, albumin and globulin was observed at the level of 400 mg/kg of licorice. According to these results, although the amount of glucose was lowest its level was not significant (P≥0.05), Also, the use of this same level of licorice had no significant effect on the function of the humoral immune system in response to antigen injection (SRBC Antibody against sheep red blood cell) or antibody titer against Newcastle virus and influenza (P≥0.05). Nevertheless, according to the data, the highest antibody titer against Newcastle virus and SRBC antigen was associated with this treatment. These results also showed that high levels of licorice led to an increase in the number of Bifidobacterium. Villi width and crypt depth decreased at the high dose of licorice, but the ratio of villi length to crypt depth increased. In addition, the use of different levels of licorice could not reduce the ratio of saturated to unsaturated fatty acids compared to the control group. Therefore, based on the results of this research, it is recommended to use the level of 400 mg/kg of licorice to supplement the diet of broilers of Ross 308 strain.

Drugs used in psychiatry causing an increase in body weight in children-a review.

Body weight gain is a prevalent adverse effect observed in psychiatric medication therapy. With the notable increase in mental health diagnoses among children and adolescents over the last decade, exacerbated by the COVID-19 pandemic, the use of medications associated with weight gain poses an additional risk for obesity development. This study aimed to identify psychiatric drugs that may induce weight gain in children as a side effect. Twenty-nine publications were included in this systematic review, investigating the effects of nineteen different drugs on children's weight. The majority of these drugs belonged to atypical antipsychotics and anticonvulsants. Nearly all included articles reported that the examined substances resulted in weight gain in children. As childhood obesity has become a significant problem with various metabolic, psychological and social consequences, it is crucial to carefully consider therapy options. In addition to evaluating effectiveness, it is important to also assess the potential for weight gain. Clinicians and nutrition specialists should individually evaluate patients' nutritional needs, evaluate obesity risk, and provide appropriate dietary guidance to minimalize the risk of weight gain.

Lifestyle and BMI Changes after the Release of COVID-19 Restrictions: Do Humans Go ‘Back to Normal’?

Humans adapt their life history strategy and lifestyle behavior to the environment. The social restrictions during the COVID-19 pandemic in the years 2020–2021 led to changes in diet and physical activity habits in large parts of populations worldwide. Additionally, many people reported an increase in body weight during the pandemic. We investigated how diet quality, physical activity, and BMI changed since the end of the COVID-19 restrictions in Switzerland (2019–2023). We assessed diet and physical activity using a standardized questionnaire. We measured anthropometry and BMI using a stadiometer and a balance of a medical bioimpedance analyzer. Our results show a stable BMI in men and women during the pandemic. In both sexes, diet quality and physical activity levels did not change significantly during this time. Among women, physical activity and age were associated with BMI, while in men, apart from physical activity, high diet quality and living in the agglomeration were associated with BMI. Overall, we did not find evidence for a transient “unhealthier” lifestyle immediately after the COVID-19 pandemic. However, we found constituent sex differences in BMI determinants. Our results could indicate a higher resilience in highly educated persons and might contribute to more personalized approaches to prevent obesity.

Determinants of poor health-related quality of life among outpatients with rheumatoid arthritis in Jordan.

The purpose of this study was to assess the health-related quality of life (HRQOL) and investigate the variables contributing to reduced HRQOL in patients with rheumatoid arthritis. The present cross-sectional study was conducted on patients diagnosed with rheumatoid arthritis at two teaching hospitals in Jordan using a convenience sampling technique. The participants were interviewed face-to-face during the scheduled appointment at the outpatient rheumatology clinic. The HRQOL was evaluated by the validated EuroQol-5 Dimension (EQ-5D) questionnaire, which included the EQ-5D utility index that evaluated HRQOL in terms of 5 domains, including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, and the EQ-5D visual analogue scale (EQ-5DVAS), which evaluated HRQOL on a vertical scale ranging from 0 (worst imaginable health) to 100 (best imaginable health). The validated short version of the 19-item Compliance Questionnaire for Rheumatology (CQR-5) was used to evaluate medication adherence. The Clinical Disease Activity Index (CDAI) was used to assess disease activity among the study participants. A stepwise quantile regression model (q = 0.5) was conducted to explore the factors associated with the EQ-5DUtility Index and EQ-5DVAS scores. In total, 261 patients with RA participated in the study. The median (interquartile range) of the EQ-5DUtility Index and EQ-VAS scores was 0.552 (0.006-0.726) and 0.506 (0.233-0.690), respectively. Regression analysis results demonstrated that medication non-adherence (regression coefficient (β) = -0.348, P<0.01), not performing regular physical activity (β = -0.209, P<0.01), and higher disease activity as measured by the CDAI score (β = -0.015, P<0.01) were significant predictors of a lower EQ-5DUtility Index score. In addition, medication non-adherence (β = -0.199, P<0.01), not performing regular physical activity (β = -0.117, P<0.01), increased body mass index (BMI) (β = -0.009, P<0.01), and higher CDAI score (β = -0.009, P<0.01) were significant predictors of low EQ-5DVAS score. Patients with RA experienced significantly impaired HRQOL. Medication non-adherence, not performing regular physical activity, increased body weight, and increased disease activity were identified as determinants of poor HRQOL among patients with RA in the present study. Treating physicians should encourage regular physical activity, maintaining a healthy body weight, and controlling disease activity to improve HRQOL in patients with RA.

Dynamic Hydration and Viscosity Control of Konjac Glucomannan Enhance Long-Term Antiobesity Effects by Reducing Food Intake in High-Fat-Diet-Fed Mice.

The purpose of this study was to investigate the necessity and importance of dynamic hydration rate and ultimate viscosity control of konjac glucomannan (KGM) for long-term antiobesity effects in C57BL/6J mice on high-fat (HF) diets. KGM supplementation effectively attenuated HF-diet-induced increases in body and tissue weights. The hydration rate and viscosity changes of KGM in the digestive tract were found to have marked impacts on antiobesity effects. KGM with medium hydration and viscosity slowed gastric emptying and intestinal transit, leading to prolonged presence in the lower ileum, increased satiety-related hormones (GLP-1 and PYY), and an 18.27% reduction in daily food intake over 10 weeks (p < 0.05). This resulted in the greatest reduction in weight gain among HF-fed mice. In contrast, KGM with faster hydration and higher viscosity provided only short-term satiety due to rapid dilution. Furthermore, KGM improved metabolic health and altered glycolipid metabolism gene transcription while enriching beneficial gut bacteria; however, no significant differences were observed among the KGM groups in these effects. These findings highlight that synchronizing KGM's hydration rate and viscosity with digestive processes is crucial for regulating satiety and achieving long-term weight loss.

Deficiency of GPR10 and NPFFR2 receptors leads to sex-specific prediabetic syndrome and late-onset obesity in mice.

GPR10 and neuropeptide FF receptor 2 (NPFFR2) play important role in the regulation of food intake and energy homeostasis. Understanding the interaction between these receptors and their specific ligands, such as prolactin-releasing peptide, is essential for developing stable peptide analogs with potential for treating obesity. By breeding and characterizing double knockout (dKO) mice fed standard or high-fat diet (HFD), we provide insights into the metabolic regulation associated with the GPR10 and NPFFR2 deficiency. Both WT and dKO mice were subjected to behavioral tests and an oral glucose tolerance test. Moreover, dual-energy X-ray absorptiometry (DEXA) followed by indirect calorimetry were performed to characterize dKO mice. dKO mice of both sexes, when exposed to an HFD, showed reduced glucose tolerance, hyperinsulinemia, and insulin resistance compared with controls. Moreover, they displayed increased liver weight with worsened hepatic steatosis. Mice displayed significantly increased body weight, which was more pronounced in dKO males and caused by higher caloric intake on a standard diet, while dKO females displayed obesity characterized by increased white adipose tissue and enhanced hepatic lipid accumulation on an HFD. Moreover, dKO females exhibited anxiety-like behavior in the open field test. dKO mice on a standard diet had a lower respiratory quotient, with no significant changes in energy expenditure. These results provide insights into alterations associated with disrupted GPR10 and NPFFR2 signaling, contributing to the development of potential anti-obesity treatment.

Folic acid supplementation during fattening period affects growth and nutritional metabolism in Japanese Black beef cattle

The folate requirements for beef cattle have not been established. Therefore, we investigated whether rumen-unprotected folic acid supplementation during the fattening period affects carcass traits and nutritional metabolism in Japanese Black beef cattle. Eighteen Beef cattle aged 16 months were divided into three groups: control, low folic acid supplementation (0.43 g DM/day), and high folic acid supplementation (0.86 g DM/day). Treatment was administered for 12 months. Folic acid supplementation dose-dependently increased serum folate levels, suggesting that supplemental folic acid can be absorbed into the body. Folic acid supplementation dose-dependently decreased serum vitamin B12 levels, while plasma total homocysteine and methylmalonic acid levels—markers for deficiency of folate and/or vitamin B12—were unaffected. Thus, the treatment did not clearly affect the nutritional status of these vitamins. Supplementation increased body weight, with no negative effects on other carcass traits. The levels of insulin-like growth factor 1, retinol, albumin, and some amino acids in serum or plasma were affected by supplementation. These results suggest that rumen-unprotected folic acid supplementation during the fattening period could increase the body weight of Japanese Black beef cattle and the mechanism of action may be related to growth-related hormones and/or the metabolism of some nutrients, including folate.

CREB coactivator CRTC1 in melanocortin‐4 receptor‐expressing cells regulate dietary fat intake

AbstractCyclic adenosine monophosphate‐response element‐binding protein‐1‐regulated transcription coactivator‐1 (CRTC1), a cytoplasmic coactivator that translocates to the nucleus in response to cAMP, is associated with obesity. We previously reported that CRTC1 deficiency in melanocortin‐4 receptor (MC4R)‐expressing neurons, which regulate appetite and energy metabolism in the brain, causes hyperphagia and obesity under a high‐fat diet (HFD). HFD is preferred for mice, and the dietary fat in HFD is the main factor contributing to its palatability. These findings, along with our previous results, suggest that CRTC1 regulates the appetite for dietary fat. Therefore, in this study, we aimed to investigate the dietary fat intake behavior and energy metabolism of MC4R neuron‐specific CRTC1 knockout mice fed soybean oil or lard. CRTC1 deficiency increased the intake of soybean oil and significantly increased body weight gain. Furthermore, obesity induced by soybean oil intake was partially due to leptin resistance. No significant changes in soybean oil intake were observed between young CRTC1‐deficient and wild‐type mice; however, soybean oil intake increased with age. Moreover, lard intake did not significantly affect the body weight. Overall, our findings highlighted the crucial role of CRTC1 in the regulation of spontaneous dietary fat intake. Furthermore, the role of CRTC1 becomes increasingly significant with age.

A Multicenter, Open-Label Study to Evaluate the Long-term Safety and Efficacy of Adjunctive Brexpiprazole 2 mg Daily in Japanese Patients with Major Depressive Disorder.

Inadequate response to antidepressant monotherapy is common among patients with major depressive disorder (MDD). The efficacy and safety of adjunctive brexpiprazole 2 mg/day has recently been confirmed during the 6-week, randomized, placebo-controlled phase 2/3 (BLESS) study, which evaluated brexpiprazole at 1 mg/day and 2 mg/day versus placebo as adjunctive therapy to antidepressant therapies in 740 Japanese patients with MDD and an inadequate response to antidepressant monotherapy. This study evaluated the long-term safety and efficacy of adjunctive fixed-dose brexpiprazole 2 mg/day in Japanese patients with MDD. An open-label, 52-week study enrolled rollover patients who completed the 6-week, double-blind, randomized, placebo-controlled phase 2/3 BLESS study (NCT03697603), and de novo patients aged ≥ 65 years. Patients were titrated to fixed-dose brexpiprazole 2 mg/day from Week 1. Safety assessments included treatment-emergent adverse events (TEAEs; primary outcome) and clinical and laboratory variables. Efficacy was assessed using the Montgomery-Åsberg Depression Rating Scale(MADRS), Clinical Global Impression-Improvement (CGI-I) scale, Hamilton Depression Rating Scale (HAM-D) 17-item total score, and Sheehan Disability Scale (SDS) score. In total, 247 patients [rollover, n = 216; de novo (previously unexposed), n = 31] were included in the safety/efficacy populations, and 138 (rollover, n = 132; de novo, n = 6; 55.9%) completed the study. Common TEAEs (incidence ≥ 10%) were weight gain [33.2% (n = 82)], akathisia [23.5% (n = 58)], nasopharyngitis [21.1% (n = 52)], and somnolence [10.5% (n = 26)]. TEAEs leading to treatment discontinuation occurred in 26.7% of patients receiving brexpiprazole and 58.1% of de novo patients. The mean (SD) increase in body weight from baseline to Week 52 [observed cases (OC)] was 4.2 (6.5) kg (n = 138); 44.5% (n = 110) had weight gain ≥ 7% at any postbaseline visit. There were no cases of tardive dyskinesia and no AEs related to suicide/suicide attempts. One death occurred (unknown cause), which was unrelated to study treatment. Improvements in the MADRS total score were observed from baseline over the course of the 52-week study [mean (SD) change at Week 52 (OC): - 7.3 (8.7)] for all patients receiving brexpiprazole. The overall MADRS response rate and remission rate in patients receiving brexpiprazole was 41.3% (n = 57) and 34.8% (n = 48), respectively, at Week 52 (OC). Improvements in CGI-S, HAM-D 17 item total score, and SDS mean scores were also observed from baseline over the 52-week study, with a mean (SD) change from baseline at Week 52 (OC) of - 0.8 (1.0), - 5.9 (6.3), and - 1.0 (2.2), respectively, indicating a sustained improvement in symptoms with long-term brexpiprazole treatment. This is the first study to evaluate the safety profile of brexpiprazole 2 mg/day in Japanese patients with MDD, including older adults, which is similar to previous reports, with no new safety risks, and continued efficacy over 52 weeks. ClinicalTrials.gov (NCT03737474; registered on 29 July 2018).

The effect of baby touch on premature infants

Objective: Premature infants require special attention during nursing. This study aimed to explore the effects of baby touch on the growth, immunity, sleep and communication in premature infants. Methods: This was a retrospective study. A total of 64 premature infants with a gestational age of 30-36 weeks were selected at Maternity &amp; Child Care Center of Qinhuangdao from June 2022 to May 2023, and randomly divided into experimental group and control group. The control group received routine comprehensive nursing care for newborns, while the experimental group was additionally treated with touch intervention using the international standard touch method. The effects of the three months touch on the growth and development, immunological function, sleep quality, and emotional communication of the premature infants were observed. Results: No statistically significant differences were found in gender, gestational age, birth weight, birth length, or head circumference at birth between the two groups (p&gt; 0.05). In the third month, the increases in body weight, body length and head circumference were significantly more obvious, the immunological function indicators including CD3+, CD4+, CD8+, IgG, IgA and IgM were all significantly higher, the sleep time and sleep quality were both significantly superior, and the interaction time and intimacy with parents were significantly superior in the experimental group compared with the control group, with statistically significant differences (p&lt; 0.05). Conclusion: Baby touch can promote growth and development, strengthen immunological function, improve sleep quality and enhance the emotional communication abilities of premature infants, and help them better adapt to the environment and grow. doi: https://doi.org/10.12669/pjms.40.10.9275 How to cite this: Du Q, Zhu H, Guo M, Yang Q, Yang H, Ma Y. The effect of baby touch on premature infants. Pak J Med Sci. 2024;40(10):2256-2260. doi: https://doi.org/10.12669/pjms.40.10.9275 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Obesity-induced extracellular vesicles proteins drive the endometrial cancer pathogenesis: therapeutic potential of HO-3867 and Metformin.

Endometrial cancer (EC) is the leading gynecologic malignancy in the United States with obesity implicated in 57% of cases. This research investigates the molecular complexities of extracellular vesicles (EV) secretion as carriers of oncogenic protein and their involvement in obesity-mediated EC. An understanding of these mechanisms is pivotal for unraveling pathways relevant to obesity-associated EC, thereby guiding the development of innovative prevention and treatment strategies. Our exploration revealed a significant increase in EV secretion carrying oncogenic proteins (TMEM205, STAT5, and FAS) in adipose and uterine tissues/serum samples from obese EC patients compared to control (without cancer). We identified alterations in EV-regulating proteins (Rab7, Rab11, and Rab27a) in obesity-mediated EC patients, adipose/uterine tissues, and serum samples. Through a 24-week analysis of the effects of a 45% kcal high-fat diet (HFD) on mice, we observed increased body weight, increased adipose tissue, enlarged uterine horns, and increased inflammation in the HFD group. This correlated with elevated levels of EV secretion and increased expression of oncogenic proteins TMEM205, FAS, and STAT5 and downregulation of the tumor suppressor gene PIAS3 in adipose and uterine tissues. Furthermore, our study confirmed that adipocyte derived EV increased EC cell proliferation, migration and xenograft tumor growth. Additionally, we identified that the small molecule inhibitors (HO-3867) or Metformin inhibited EV secretion in vitro and in vivo, demonstrating significant inhibition of high glucose or adipocyte-mediated EC cell proliferation and a reduction in body weight and adipose tissue accumulation when administered to HFD mice. Moreover, HO-3867 or Metformin treatment inhibited HFD induced hyperplasia (precursor of EC) by altering the expression of EV-regulated proteins and decreasing oncogenic protein expression levels. This study provides critical insights into the mechanisms underpinning obesity-mediated EV secretion with oncogenic protein expression, shedding light on their role in EC pathogenesis. Additionally, it offers pre-clinical evidence supporting the initiation of novel studies for EV-targeted therapies aimed at preventing obesity-mediated EC.

Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice.

The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi's protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.

Effects of licorice root (Glycyrrhiza glabra) extract on the livers of obese rats.

We have investigated anti-obesity effects of the extract of licorice (Glycyrrhiza glabra) root in rats with diet-induced obesity and hyperlipidemia by using histopathological and biochemical methods. Thirty-two Wistar albino rats were divided to four groups of eight: normal control (C), high fat diet (HFD), high fat Diet + Glycyrrhiza glabra (HFD+M), and normal diet with Glycyrrhiza glabra (M). The high fat diet contained 300 g/kg fat (4000 kcal/kg); the daily dosage of Glycyrrhiza glabra extract was 1g/kg body weight by orogastric gavage. Supplementation of Glycyrrhiza glabra extract dramatically reduced increases in body weight caused by the induction of obesity. A hepatoprotective effect of Glycyrrhiza glabra extract was supported by the almost normal histology in the livers of the HFD+M rats, in contrast to the degenerative changes in the HFD rats, which included macrovesicular and microvesicular fat deposits, hydropic degeneration, dilatation of sinusoids and coagulation necrosis of some hepatocytes. Serum levels of alanine transaminase (ALT), aspartic transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), cholesterol (HDL and LDL) and triglycerides, were ameliorated by Glycyrrhiza glabra extract treatment. We conclude that Glycyrrhiza glabra extract given together with HFD could prevent obesity and reduce liver damage in rats.