Body Mass Research Articles

Effects of high-fat diet on the morphology and function of the thyroid gland and glycolipid metabolism in thyroid clock gene Bmal1 knockout mice

Objective: To investigate the changes in thyroid morphology and function in mice with thyroid-specific knockout of the clock gene Bmal1 under high-fat diet (HFD), and to examine its effects on glycolipid metabolism in mice. Methods: Construct a mouse model with specific knockout of the Bmal1 gene in the thyroid (T-Bmal1-/-) (knockout group, n=10), and use Bmal1flox/flox mice without thyroid peroxidase-cyclization recombination enzyme (T-Bmal1+/+) as the control group (non-knockout group, n=10). The mice were fed until 6 weeks (body weight 20-23 g), and then use the random number table method to evenly divide each group of mice into two subgroups. They were then fed either with normal diet (ND) or (HFD), resulting in four final groups: ND non-knockout group, HFD non-knockout group, ND knockout group, and HFD knockout group, with 5 mice in each group. From the 6th week onwards, the body weights of the mice were measured for 10 consecutive weeks. On the first day of the 14th week, the intraperitoneal glucose tolerance test (IPGTT) was conducted, and on the first day of the 15th week, the intraperitoneal insulin tolerance test (IPITT) was performed. On the first day of the 16th week after the mice were born, blood samples (0.2 ml) were taken from the eyes under anesthesia at 7∶00, 13:00, 19:00, and 1∶00 the next day, and the thyroid, liver, kidneys, spleen, inguinal white adipose tissue, and scapular brown adipose tissue were rapidly removed. Thyroid tissue morphology, thyroid function indexes, thyroid clock genes and thyroid hormone synthesis and secretion related genes expression, body weight, IPGTT and IPITT area under the curve (AUC) and lipid levels were detected and compared among all groups. Results: There was no significant difference in the number of thyroid follicles, the area of thyroid follicles and the height of thyroid follicle cavity between ND knockout group and ND non-knockout group (all P>0.05), but the height of thyroid follicle cavity in HFD knockout group was lower than that in HFD knockout group [(25.8±1.6) vs (54.4±9.5) μm, P=0.002]. The level of serum T4 in knockout group after ND or HFD feeding was higher than that in non-knockout group (all P<0.05). There was no significant difference in the mRNA expression level of sodium iodine transporter between ND knockout group and ND non-knockout group (P=0.550), but the mRNA expression level of sodium iodine transporter in HFD knockout group was higher than that in HFD non-knockout group [0.67±0.27 vs 0.20±0.09, P=0.006].There was no significant difference in weight gain and groin white fat weight between ND knockout group and ND non-knockout group (both P<0.05), but weight gain and groin white fat tissue weight in HFD knockout group were lower than those in HFD knockout group (both P<0.05). The IPGTT results showed no statistically significant difference in AUC between the ND knockout and ND non-knockout groups (P=0.226), but the HFD knockout group had a smaller AUC than the HFD non-knockout group (P=0.008). The IPITT revealed that the AUC of the ND knockout group was smaller than that of the ND non-knockout group (P=0.047). Lipid profiles were similar between the ND knockout and ND non-knockout groups (all P>0.05), but the HFD knockout group had lower levels of total cholesterol and high-density lipoprotein cholesterol than the HFD non-knockout group (both P<0.05). Conclusion: Thyroid-specific knockout of the clock gene Bmal1 can affect thyroid hormone levels and glycolipid metabolism in mice, with more pronounced effects after HFD feeding.

Relationship between the ratio of increase in lean tissue to body weight gain and energy required to gain body weight in growing rats.

Although the energy stored in the lean tissue (LT) and adipose tissue (AT) is well known, the energy required to synthesize these tissues is obscure. Theoretically, the energy at the point at which ΔLT/Δ body weight (BW) reaches 100% on a regression line, which indicates the relationship between ΔLT/ΔBW and the energy required for BW gain, is considered to be the energy expended to synthesize LT. Therefore, we investigated this relationship in rats. Rats were fed diets with different ratios of protein, fat, and carbohydrates because their ΔLT/ΔBW values were expected to be different. Six-week-old male Sprague-Dawley rats had ad libitum access to normal (N, n = 6), high-fat (HF, n = 7), or high-protein (HP, n = 8) diets for 4 weeks. The ΔLT/ΔBW was 0.77 in the N group, 0.70 in the HF, and 0.87 in the HP groups, respectively. The average energy required to gain BW was 8.8 kJ/g in the N group, 7.0 kJ/g in the HF group, and 11.3 kJ/g in the HP group. We observed a positive correlation between ΔLT/ΔBW and energy required for BW gain. The regression line demonstrated that the energy expended to synthesize LT was 13.9 kJ/g and AT was -7.9 kJ/g. Therefore, combined with the energy stored in LT, the energy required to accumulate LT is approximately 19 kJ/g, whereas the energy to accumulate AT could not be elucidated.

As, Cd, Hg, and Pb Biological Concentrations and Anthropometry in Slovak Adolescents.

Anthropometry provides a non-invasive technique for evaluating growth and obesity and serves as an indicator of health status. This cross-sectional study aims to investigate the association of internal arsenic (As), cadmium (Cd), total mercury (THg), methylmercury (MeHg), and lead (Pb) exposure with anthropometric parameters, including obesity, in adolescents. Participants (N = 320) were children aged 10-14 years (mean 11.8 years) from eastern Slovakia, at an early stage of adolescence characterized by growth acceleration. Metal concentrations in blood and urine were measured by ICP-MS (for As, Cd, and Pb), GC/ICP-MS (for MeHg) and amalgamation technique AAS (for THg). Median concentrations of the studied elements in whole blood (Cd: 0.16, Pb: 10.6, THg: 0.25, MeHg: 0.11µg/L) and urine (Cd: 0.25, Pb: 0.73, As: 3.38µg/g creatinine) were relatively low in our study group. The results showed that blood Cd and Pb concentrations were inversely associated with several anthropometric parameters (body weight, BMI, body fat percentage, chest circumference, and waist circumference) in both boys and girls. Conversely, blood THg concentration was positively associated with these parameters in boys. A positive relationship was also observed between blood MeHg concentration and height in boys, while negative associations between blood Cd and Pb concentrations and height were significant only in girls. No associations were found between metal concentrations (As, Cd, Pb) in urine and parameters of physical growth or obesity. This study demonstrates that even low-level exposure to Cd, Pb, and Hg can influence growth and obesity indicators in adolescents, with distinct sex-specific patterns, highlighting the need for ongoing monitoring and protection against environmental metal exposure.

Maternal swimming with overload allied to postnatal high-fat, high-sugar diet induce subtle impairment on rat offspring’s ovarian redox homeostasis

Context The Developmental Origins of Health and Disease (DOHaD) concept suggests that early-life interventions significantly influence the long-term health outcomes of offspring. Emerging evidence supports that maternal physical exercise and balanced nutrition can positively impact the health of the next generation. Aims This study investigated the effects of maternal swimming combined with postnatal high-fat, high-sugar (HFHS) diet on the ovarian health of adult female Wistar rat offspring. Methods Adult female Wistar rats performed swimming exercise in a controlled temperature environment (32°C, 2% bodyweight overload adjusted daily) during 4 weeks, starting 1 week prior mating. The female offspring received a control or HFHS diet from postnatal day (PND) 21 to PND 90. We analyzed offspring’s body weight, ovarian histomorphology, redox status, and associated molecular pathways 5′ adenosine monophosphate-activated protein kinase (AMPKα), forkhead box O3 (FoxO3), and mitofusin 1 (Mfn-1). Key results Our findings reveal that maternal swimming exerted an effect on offspring body weight gain, delaying it. Individually, maternal exercise reduced superoxide dismutase (SOD) activity and mitofusin-1 levels, while the postnatal HFHS diet alone decreased both SOD and glutathione peroxidase (GPx) activities and increased the pFOXO3a/FOXO3a ratio in the ovaries. Conclusions We showed that combination of maternal swimming with a 2% overload and a postnatal HFHS diet can negatively affect the ovarian redox balance in offspring. Implications Prenatal and postnatal lifestyle might affect reproductive function in females.

Limited preventive effects of empagliflozin against metabolic dysfunction-associated steatotic liver disease in a mouse model of fast food diet.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent disease with limited treatment options. The aim of this study was to evaluate the preventive effects of a sodium-glucose co-transporter (SGLT)-2 inhibitor, empagliflozin, on a dietary mouse model of MASLD. In total, 24 C57BL/6J mice of both sexes were randomly allocated to three groups, as follows: the fast food diet (FFD) group (eight mice, receiving a high-fat, high-cholesterol, high-fructose diet, FFD), the EMPA group (eight mice, fed a FFD with 10mg/kg/d empagliflozin), and the chow diet (eight mice, CD) group. The mice were weighed and blood samples were drawn every 4weeks; after 25weeks the mice were euthanized, at which point liver tissues were histologically evaluated. After 25weeks, there was no significant difference in body weight between the three groups, whereas liver-to-body weight ratio was greater in the EMPA compared to the CD group (p = 0.002). Hepatic fibrosis was marginally different between the three groups (p = 0.045). Fibrosis stage 1 was present in five mice on FFD (62.5%), in one mouse on EMPA (12.5%), and in one mouse on CD (12.5%). Lipogenic, inflammatory, and fibrogenic genes did not differ between the EMPA and FFD groups. Interestingly, mRNA encoding for SGLT-1 and SGLT-2 was detected in the mouse livers. Empagliflozin treatment in mice on a FFD did not result in any significant effects on morphological, biochemical, or histological features or on expression of hepatic genes associated with MASLD compared to those fed a FFD without empagliflozin. The observed effects on mild hepatic fibrosis warrant validation, possibly via studies of longer duration.

An Overview of Existing and Emerging Weight-Loss Drugs to Target Obesity-Related Complications: Insights from Clinical Trials.

Obesity requires treatment as it is associated with health problems such as type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, and some cancers, which increase mortality rates. Achieving sufficient weight loss to reduce obesity-related diseases requires a variety of interventions, including comprehensive lifestyle modification of diet and exercise, change in behavior, anti-obesity medications, and surgery. To date, anti-obesity agents with various mechanisms of action have been developed, and mostly reduce energy intake, resulting in weight loss of about 5% to 10% compared to baseline. Recently developed drugs and those currently under development have been shown to reduce body weight by more than 10% and are expected to reduce obesity-related complications. This article summarizes existing and emerging anti-obesity medications, with a particular focus on those evaluated in clinical trials.

Supaglutide alleviates hepatic steatosis in monkeys with spontaneous MASH

BackgroundGlucagon-like peptide 1 (GLP-1) is an incretin hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic agent. We demonstrated previously that supaglutide, a novel long-acting GLP-1 analog, exerted hypoglycemic, hypolipidemic, and weight loss effects in type 2 diabetic db/db mice, DIO mice, and diabetic monkeys. In the present study, we investigated supaglutide’s therapeutic efficacy in rhesus monkeys with spontaneous metabolic dysfunction-associated steatohepatitis (MASH).Methods15 rhesus monkeys with biopsy-confirmed MASH were divided into three groups, receiving supaglutide 50 µg/kg, supaglutide 150 µg/kg, and placebo, respectively, by weekly subcutaneous injection for 3 months. Liver fat content quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), liver pathology, and metabolic parameters were assessed.ResultsWe found that once-weekly subcutaneous injections of supaglutide for 3 months significantly reduced hepatic fat accumulation, with a 40% percentage decrease in MRI-PDFF from baseline (P < 0.001 vs. Placebo). Treatment with supaglutide alleviated hepatic histological steatosis (nonalcoholic fatty liver disease activity score P < 0.001 vs. Placebo) without worsening of fibrosis, as assessed by ultrasound-guided liver biopsy. Supaglutide concomitantly ameliorated liver injury exemplified by a lowering tendency of hepatic alanine aminotransferase levels. Supaglutide also decreased body weight in a dose-dependent fashion accompanied by decreased food intake, improved lipid profile and glycemic control.ConclusionsSupaglutide exerts beneficial effects on hepatic and metabolic outcomes in spontaneous MASH monkeys.

Effects of 4-week Eri silkworm cornflakes supplementation on oxidative stress and antioxidant status in male university athletes: A preliminary crossover study.

Aim: This study among moderately fit male athletes investigated changes in oxidative stress and antioxidant levels after supplementation with Eri silkworm cornflakes. Method: Male university athletes (n = 18, age 19-21 years) were enrolled in a randomized crossover trial. They participated in either the supplementation period (consuming 0.20 g protein/kg body weight Eri silkworm daily) or the control period (no supplementation). Each period lasted 4 weeks, with a washout period of 4 weeks in between. Results: Compared to the control period, reduced glutathione concentration (p = 0.019) and reduced/oxidized glutathione ratio (p < 0.001) were significantly higher, and oxidized glutathione (p = 0.018) and malondialdehyde (p = 0.002) concentrations were significantly lower in the supplementation period. Conclusion: Eri silkworm supplementation as cornflakes for 4 weeks improved oxidative stress and antioxidant status in male university athletes. This supplement may be an alternative to support optimal antioxidant status for athletic individuals. Thai Clinical Trials Registry (TCTR): TCTR20180303003.

Pediococcus acidilactici Y01 reduces HFD-induced obesity via altering gut microbiota and metabolomic profiles and modulating adipose tissue macrophage M1/M2 polarization.

Obesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.

Relationship Between Body Weight and Leukopenia in Non-Kidney Solid Organ Transplant Recipients With Normal Renal Function Who Are Receiving Valganciclovir for CMV Prophylaxis.

Cytomegalovirus (CMV) disease causes significant morbidity among solid organ transplant (SOT) recipients. To prevent CMV disease, eligible recipients are frequently started on valganciclovir (VGC) prophylaxis post-transplant. Leukopenia has been documented as a primary adverse events of the drug (1). This study's primary aim was to determine whether a patient's weight at the start of VGC prophylaxis was associated with the development of leukopenia. This was a single center, retrospective cohort study that included adults > 18 years of age, who had received an organ transplant (heart, liver, or lung) at an academic transplant center from January 1, 2018 through December 31, 2022. A creatinine clearance of > 60mL/min was required. All 294 included patients received 900mg/day of VGC for CMV prophylaxis, without dose adjustment. Fifty-two percent of the patients developed leukopenia while receiving VGC prophylaxis. The mean weight at initiation of VGC was higher in patients who did not develop leukopenia (97.9kg) compared to those who did (90.7kg; p = 0.0112). It was found that with each 1kg increase in body weight, the likelihood of developing leukopenia decreased by 1.7% (p = 0.004, odds ratio = 0.983, 95% confidence interval [CI], 0.972-0.994). Patients with a baseline body-mass index (BMI) > 25 had a longer median freedom time from leukopenia after initiation of VGC as compared to the group with baseline BMI < 25 (log-rank p = 0.035). These data suggest that in SOT recipients with normal renal function, receiving a fixed dose of VGC resulted in a significant, inverse relationship between body weight and the development of leukopenia.

Genetic Profiles of Purine, Uric Acid, Superoxide Dismutase, and Growth in Thai Slow-Growing Chickens

The objective of this study was to estimate genetic parameters and genetic correlations between growth characteristics and purine and uric acid in the breast and liver and superoxide dismutase (SOD) in the blood. The growth characteristics included body weight (BW) at hatching (BW0), BW at 2, 4, 6, 8, and 10 weeks of age, average daily gain (ADG) at 0–2, 2–4, 4–6, 6–8, and 8–10 weeks of age, and breast circumference at 6, 8, and 10 weeks of age (BrC6, BrC8, and BrC10) were recorded from 300 Thai native chickens (Shee breed). In total, 30 chickens (15 males and 15 females) were randomly euthanized to collect breast meat, liver, and blood samples to determine the purine content. A multiple-trait animal model and an average information-restricted maximum likelihood (AI-REML) were used to estimate the variance components and genetic parameters. The estimated heritability values for all growth traits were moderate and ranged from 0.304 to 0.485, 0.270 to 0.335, and 0.286 to 0.314 for BW, ADG, and BrC, respectively. The estimated heritability values for various biochemical traits, including purine content, uric acid, and SOD levels, were low to moderate and ranged from 0.035 to 0.143, and 0.050 to 0.213 in breast meat and liver, respectively. In genetic correlations, total purine content showed a strong negative correlation with growth traits, whereas uric acid and SOD levels exhibited varying degrees of correlation with BW and ADG. These results highlight the importance of genetic parameters between growth and biochemical traits in Thai native chickens and provide valuable insights for breeding programs aimed at improving growth performance and meat quality. This study indicated the potential use of heritability values and genetic correlations to enhance selective breeding strategies using the multiple-trait genetic evaluation method for optimal trait combinations in poultry.

Beyond Hunger: A Connection Between Diet and Gonadal Development of a Ladybird Beetle.

Food availability shapes morphology, physiology, growth, reproduction, and overall fitness of insects. Countless research in coccinellids reported the effect of diet in terms of quality and quantity on reproductive output. But fewer studies have reported the direct effects of food on the gonadal development in both sexes. In nature, ladybird beetle Cheilomenes sexmaculata exhibit food preference, favouring Aphis craccivora (nutritious prey) over Aphis nerii (poor prey). We hypothesized that beetles consuming nutritious prey in abundant quantity will have larger and heavier gonads. The current study assessed the effect of food preferred and its fluctuations on the gonadal development of C. sexmaculata. First instars were collected randomly from experimental stock and reared on two different diet regimes for a lifetime. After eclosion, beetles from each dietary regime were dissected daily to assess gonadal development until maturity. Here, we documented total developmental duration, body weight, weight of gonads, GSI, total area of gonads, length, and number of testicular lobules/ovarioles across different treatments. Both quality and quantity of diet significantly affected development period, body weight, and gonadal parameters in both sexes except for GSI in males and number of ovarioles in females that reared on varied diet quality, which were found to be similar. Aphis craccivora in abundant supply positively affected the growth and development of the gonads in C. sexmaculata. Beetles reared on the abundant supply of nutritious prey with larger and heavier gonads than those reared on limited supply or poor prey. This study improves our understanding of the development of gonads in ladybird beetles, which may be helpful in improving the mass rearing of ladybird beetles.

Effects of Isalo scorpion cytotoxic peptide on growth, immune performance, and intestinal flora of yellow-feathered broilers

IntroductionThis study aimed to investigate the effects of Isalo scorpion cytotoxic peptide (IsCT) on the growth performance, immune function, and gut microbiota of yellow-feathered broilers.MethodsThe experiment involved supplementing a corn-soybean meal-based diet with various dietary levels of IsCT. The experiment adopted a completely randomized design. A total of 240 one-day-old yellow-feathered broilers were randomly divided into six groups: a control group (CON), a chlortetracycline group (CTC), and four groups receiving a basal diet with 50, 100, 150, or 200 mg/ kg IsCT (IsCT50, IsCT100, IsCT150, and IsCT200). The trial period lasted 60 days.ResultsThe results showed that the average final body weight and average daily weight gain of the IsCT150 and IsCT200 groups were significantly higher than those of the CON group (p &amp;lt; 0.05). Compared to the CTC group, the average daily feed intake in group III was significantly lower (p &amp;lt; 0.05). The feed conversion ratios of the IsCT150 and IsCT200 groups were significantly lower than those of the IsCT50 and CON groups (p &amp;lt; 0.05). Albumin levels in the CTC and IsCT150 groups were significantly higher than those in the CON, IsCT100, and IsCT50 groups. Alanine transaminase levels in the IsCT150 group were significantly lower than those in the IsCT50, IsCT200, CON, and CTC groups (p &amp;lt; 0.05), but there was no significant difference compared with the IsCT100 group (p &amp;lt; 0.05). IgA levels in the IsCT150, IsCT200, and CTC groups were significantly higher than those in the IsCT50 group (p &amp;lt; 0.05). IgG levels in the CTC, IsCT100, IsCT150, and IsCT200 groups were significantly higher than those in the IsCT50 and CON groups (p &amp;lt; 0.05). 16S rRNA sequencing indicated significant differences in the caecal microbiota between the IsCT and CON groups (p &amp;lt; 0.05). The abundance of Bacteroidetes increased, whereas that of Firmicutes decreased in the IsCT groups; however, the difference was not significant (p &amp;lt; 0.05). The relative abundances of Actinobacteriota and Patescibacteria were significantly different in the IsCT100 group (p &amp;lt; 0.05).DiscussionIn conclusion, supplementing the basal diet with IsCT improved growth performance, immune function, and gut microbiota of yellow-feathered broilers at an optimal supplementation level of 150 mg/kg.

Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model

Background/Objectives: Fragile X Syndrome (FXS) is associated with intellectual disability, hyperactivity, social anxiety and signs of autism. Hyperactivation of NADPH oxidase has been previously described in the brain of the male Fmr1-KO mouse. This work aims to demonstrate the efficacy of Apocynin, a specific NADPH oxidase inhibitor, in treating Fragile X mouse hallmarks. Methods: Free radicals, lipid and protein oxidation markers and behavioural and learning paradigms were measured after chronic treatment with orally administered vehicle, 10 mg/kg/day or 30 mg/kg/day of Apocynin. Results: The results revealed a reduction in testis weight, an increase in peritoneal fat, and no variation in body weight after chronic treatment. Furthermore, a reduction in hyperactivity was detected in Apocynin-treated male Fmr1-KO mice. Additionally, the higher dose of 30 mg/kg/day also improves behaviour and learning in the male Fmr1-KO mice, normalising free radical production and oxidative parameters. Moreover, a reduction in phospho-EKR1 and P47-Phox protein signals was observed in specific brain areas. Conclusions: Thus, chronic treatment with Apocynin could lead to a new therapeutic option for the Fragile X Syndrome.

Mirikizumab pharmacokinetics and exposure-response in pediatric patients with moderate-to-severe ulcerative colitis.

Mirikizumab is a p19-directed anti-interleukin-23 antibody approved for the treatment of adults with moderate-to-severe ulcerative colitis (UC). Here, we report the first data of mirikizumab pharmacokinetics (PK) and exposure-response (E/R) relationships in pediatric participants (aged 2 to <18 years weighing >10 kg) with moderate-to-severe UC from the phase II, open-label study SHINE-1 (NCT04004611). PK parameters were analyzed using a model developed previously in adults with fixed-exponent allometry for body weight. Serum samples collected from 26 participants during the 12-week induction and 40-week maintenance periods of SHINE-1 were analyzed. Estimated body weight-adjusted systemic clearance, volume of distribution, and subcutaneous bioavailability were 0.021 L/h, 0.069 L/kg, and 49.8%, respectively. Covariate analysis identified no clinically significant covariates other than body weight. In the exposure range studied, E/R analysis using post hoc grouping by average concentration quartile and comparison of observed change from baseline in modified Mayo Score (MMS) at Week 12 with the adult model prediction revealed no obvious E/R relationship in clinical response, clinical remission, or endoscopic response, consistent with observations in adults. The E/R relationship for observed change from baseline in MMS at Week 12 is also similar to the adult model prediction. The PK modeling and E/R analyses suggested optimal doses of intravenous mirikizumab 300 mg for weight >40 kg, 5 mg/kg for weight ≤40 kg every 4 weeks (Q4W) during induction, and subcutaneous mirikizumab 200 mg (>40 kg), 100 mg (>20 to ≤40 kg), or 50 mg (≤20 kg) Q4W during maintenance therapy for pediatric patients with moderate-to-severe UC.

Psilocybin increases emotional empathy in patients with major depression.

Empathy plays a crucial role in interpersonal relationships and mental health. It is decreased in a variety of psychiatric disorders including major depression. Psilocybin, a promising candidate for treating depression, has been shown to acutely increase emotional empathy in healthy volunteers. However, no study has investigated this effect and its relevance for symptom improvement in a clinical population. This study examines the enduring effects of psilocybin-assisted therapy on empathy in depressed patients using a randomized, placebo-controlled design. Fifty-one depressed patients were randomly assigned to receive a single dose of psilocybin (0215 mg/kg body weight) or a placebo embedded in a 4-week psychological support intervention. Empathy was measured using the Multifaceted Empathy Test at baseline and 2 days, 1 week, and 2 weeks after substance administration. Changes in empathy were compared between treatment conditions. Patients who received psilocybin showed significant improvements in explicit emotional empathy driven by an increase in empathy towards positive stimuli compared to the placebo group for at least two weeks. This study highlights the potential of psychedelics to enhance social cognition in individuals living with depression and contributes to a better understanding of the psychological mechanisms of action of psychedelics. Further studies are necessary to investigate the interaction between social cognition and clinical efficacy.The trial is registered on clinicaltrials.gov (Identifier: NCT03715127) and KOFAM (Identifier: SNCTP000003139).

Evaluation of Response to Weight-based Dosing Strategies of Continuous, Fixed-Rate Atracurium Infusions in Critically Ill, Obese Adults With Acute Respiratory Distress Syndrome.

Fixed-rate infusions of weight-based neuromuscular blocking agents (NMBAs) were adopted during the COVID pandemic to limit caregiver exposure during titrations. Although fixed-rate infusions are supported in studies of acute respiratory distress syndrome (ARDS), the optimal scalar for weight-based NMBAs in patients with obesity remains controversial. This study sought to compare change in oxygenation using two weight-based dosing strategies for atracurium in obese patients with ARDS. Secondary outcomes included total atracurium dose, mortality, and intensive care unit (ICU) and ventilator-free days. Following an institutional practice update to use ideal body weight (IBW) for patients with obesity, we retrospectively compared adults (≥18 years) with ARDS and a body mass index (BMI) ≥ 30 kg/m2 who received atracurium (15 µg/kg/min) based on actual body weight (ABW) with those using IBW. The primary outcome was change in PaO2/FiO2 ratio (P/F) 48 hours after atracurium initiation. Analysis-of-covariance compared change in P/F between groups after adjustment for confounders. The IBW group (n = 123), compared with the ABW group (n = 133), had lower baseline P/F (85.0 [71.0, 118.3] vs 93.3 [76.0, 128.3], P = 0.025) and sequential organ failure assessment (SOFA) score (9.7 ± 2.6 vs 10.5 ± 2.6, P = 0.015), with greater use of steroids (96% vs 89%, P = 0.032) and prone positioning (72% vs 58%, P = 0.015). No difference was detected in change in P/F at 48 hours (adjusted least squares mean [95% confidence interval, CI]: 55.8 [37.0, 74.5] vs 56.9 [39.6, 74.1], P = 0.90). Atracurium doses were higher in the ABW group (97.4 mg/h [84.4, 110.3] vs 55.4 [47.2, 65.7], P < 0.001). There was no difference in hospital mortality, ICU mortality, and ICU-free days or ventilator-free days. In patients with obesity with ARDS receiving fixed-rate atracurium infusions, the change in P/F at 48 hours did not differ based on weight. Atracurium dosed on IBW may use less total drug without compromising ability to improve oxygenation. This is the first study comparing the dosing weight used for continuous infusion atracurium in hospitalized, critically ill ARDS patients with obesity. Additional studies are warranted to optimize dosing in obese patients.

Hydroxylated-Benz[a]anthracenes Induce Two Apoptosis-Related Gene Expressions in the Liver of the Nibbler Fish Girella punctata

Polycyclic aromatic hydrocarbons (PAHs) are known to have toxic effects on fish. In this study, we examined the effects of benz[a]anthracene (BaA), a type of PAH, on fish liver metabolism. Nibbler fish (Girella punctata) were intraperitoneally injected with BaA (10 ng/g body weight) four times over a 10-day period. BaA significantly decreased known bone metabolism-related plasma factors such as calcium and inorganic phosphorus. Moreover, significant reductions were observed in the plasma levels of known liver metabolism-related factors, including ferrous ions, total bile acids, total bilirubin, free bilirubin, aspartate aminotransferase, and alkaline phosphatase. Interestingly, mono-hydroxylated metabolites of BaA, such as 3 hydroxylbenz[a]anthracene (3-OHBaA), were detected in the bile of BaA-injected nibbler fish. This hydroxylated form of BaA was found in its free form, rather than conjugated with glucuronic acid or sulfuric acid. Due to the lack of whole-genome sequence data for the nibbler fish, two nibbler fish-specific apoptosis-related factors (TNF receptor superfamily member 1A: tnfrsf1a and TNF superfamily member 10: tnfsf10) were isolated by De novo RNA sequencing. In a liver tissue culture, 3-OHBaA (10−6 M) significantly upregulated the expression of tnfrsf1a and tnfsf10 in the liver. These results provide the first evidence that 3-OHBaA metabolites exhibit toxic effects on the liver in teleost.

Impact of rumen-protected glucose on performance, milk composition, and selected blood metabolites of early lactating Holstein Friesian cows

IntroductionHigh-producing dairy cows often face calving stress and reduced feed intake during the transition period, leading to body fat mobilization to meet production demands. Supplementing rations with energy-dense sources like rumen-protected glucose (RPG) may enhance production performance in early lactation.MethodsThis study evaluated the effects of RPG supplementation on feed intake, body condition score (BCS), production performance, and blood metabolites in 32 early-lactation Holstein Friesian cows (6 ± 1 DIM; milk yield: 30 ± 5 kg/day; body weight: 550 ± 50 kg; BCS: 3.00 ± 0.25). Cows were assigned to four groups (n = 8/group) and fed a basal diet (Control) or supplemented with 150 g (S-150), 300 g (S-300), or 450 g (S-450) of RPG for a 42-day trial after 2 weeks of adaptation.ResultsResults showed significant improvements (p &amp;lt; 0.05) in final body weight, milk yield, energy-corrected milk, and milk-to-feed ratio with RPG supplementation, with the highest effects observed at 450 g/day. Milk components, including solids-not-fat, lactose, and total solids, also increased significantly. While feed intake remained similar (p &amp;gt; 0.05), blood glucose levels rose, and non-esterified fatty acids and β-hydroxybutyric acid concentrations decreased (p &amp;lt; 0.05), indicating reduced ketosis and negative energy balance.ConclusionThese findings suggest RPG supplementation at 450 g/day improves milk production, quality, and metabolic health in early lactating cows, warranting further exploration of higher dosages like 500–550 g/day.

Dietary Supplementation of Turmeric Rhizome Promotes the Growth Performance, Serum Lipid Profile and Intestinal Microflora of Broilers

The injudicious use of antibiotics as growth promoters in poultry rations has caused great concern around the world. Scientists are currently trying to replace broadspectrum antibiotics in animal diets with alternative natural feed additives. The current study aimed to investigate the dietary effect of turmeric rhizome powder (TP) on the growth performance, serum lipid profiles, and intestinal microflora of broiler chickens. A total of 75 Cobb-15 broiler chicks (15-day-old) were randomly distributed into five groups offered with five experimental rations designated as T0 (control diet, without TP), T1 (1 g TP/kg feed), T2 (2.5 g TP/kg feed), T3 (5 g TP/kg feed), and T4 (7.5 g TP/kg feed). Parameters such as body weight gain, total feed intake, and feed conversion ratio (FCR) were used to assess the response of broiler chickens to feed turmeric powder. Supplementation with 5 g TP/kg feed (T3) resulted in the highest increase in body weight with a relatively lower FCR. Serum levels of cholesterol, triacylglycerol, and LDL-cholesterol decreased significantly when supplemented with 5 g TP/kg feed. The bacteriological investigation revealed that a turmeric-supplemented diet significantly lowered the total Salmonella spp. count. The antioxidant property of turmeric rhizome may alleviate stress in broiler chickens. Taken together, these findings indicate that supplementing broiler ration with 5 g TP/kg feed improved growth performance, lipid profiles, and intestinal microflora of broiler chickens, suggesting that turmeric rhizome can be a potential alternative feed additive to synthetic antibiotics for safe and organic poultry meat production. J. of Sci. and Tech. Res. 6(1): 117-124, 2024