Neonatal inhibition of androgen activity alters the programming of body weight and orexinergic peptides differentially in male and female rats.

The involvement of androgens in the regulation of energy metabolism has been demonstrated. The main objective of the present research was to study the involvement of androgens in both the programming of energy metabolism and the regulatory peptides associated with feeding. For this purpose, androgen receptors and the main metabolic pathways of testosterone were inhibited during the first five days of postnatal life in male and female Wistar rats. Pups received a daily s.c. injection from the day of birth, postnatal day (P) 1, to P5 of Flutamide (a competitive inhibitor of androgen receptors), Letrozole (an aromatase inhibitor), Finasteride (a 5-alpha-reductase inhibitor) or vehicle. Body weight, food intake and fat pads were measured. Moreover, hypothalamic Agouti-related peptide (AgRP), neuropeptide Y (NPY), orexin, and proopiomelanocortin (POMC) were analyzed by quantitative real-time polymerase chain reaction assay. The inhibition of androgenic activity during the first five days of life produced a significant decrease in body weight in females at P90 but did not affect this parameter in males. Moreover, the inhibition of aromatase decreased hypothalamic AgRP mRNA levels in males while the inhibition of 5α-reductase decreased hypothalamic AgRP and orexin mRNA levels in female rats. Finally, food intake and visceral fat, but not subcutaneous fat, were affected in both males and females depending on which testosterone metabolic pathway was inhibited. Our results highlight the differential involvement of androgens in the programming of energy metabolism as well as the AgRP and orexin systems during development in male and female rats.

Obesity-associated microglial inflammatory activation paradoxically improves glucose tolerance.

Hypothalamic gliosis associated with high-fat diet (HFD) feeding increases susceptibility to hyperphagia and weight gain. However, the body-weight-independent contribution of microglia to glucose regulation has not been determined. Here, we show that reducing microglial nuclear factor κB (NF-κB) signaling via cell-specific IKKß deletion exacerbates HFD-induced glucose intolerance despite reducing body weight and adiposity. Conversely, two genetic approaches to increase microglial pro-inflammatory signaling (deletion of an NF-κB pathway inhibitor and chemogenetic activation through a modified Gq-coupled muscarinic receptor) improved glucose tolerance independently of diet in both lean and obese rodents. Microglial regulation of glucose homeostasis involves a tumor necrosis factor alpha (TNF-α)-dependent mechanism that increases activation of pro-opiomelanocortin (POMC) and other hypothalamic glucose-sensing neurons, ultimately leading to a marked amplification of first-phase insulin secretion via a parasympathetic pathway. Overall, these data indicate that microglia regulate glucose homeostasis in a body-weight-independent manner, an unexpected mechanism that limits the deterioration of glucose tolerance associated with obesity.

l-Glutamine supplementation reduces gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves.

l-Glutamine supplementation improves gastrointestinal and immune function in dairy calves during controlled immune and stress challenges. However, it is unknown whether supplementing milk replacer (MR) with l-glutamine improves preweaning dairy calf health and welfare under production conditions. Therefore, the study objective was to evaluate the effects of supplementing MR with l-glutamine on gastrointestinal permeability, immune function, growth performance, postabsorptive metabolic biomarkers, and physiological stress response in preweaning dairy calves. In 3 repetitions, Holstein heifer calves (n = 30; 1.5 ± 0.5 d old; 37.1 ± 0.86 kg body weight) were blocked by serum total protein, body weight, and age, and provided MR (3.8 L/calf per d; 24% CP, 17% fat, 12.5% solids) supplemented with l-glutamine (GLN; 10g/kg MR powder; n = 5 calves/repetition) or nonsupplemented (NSMR; n = 5 calves/repetition). Calves were individually housed with ad libitum starter grain and water access until weaning (56.4 ± 0.5 d old). At 1 and 6 wk of age, urinary catheters were placed, and calves were orally dosed with 1 L of chromium (Cr)-EDTA. Urine samples were collected over a 24-h period for Cr output analysis as an in vivo biomarker of gastrointestinal permeability. Blood was collected on study d 1, 5, 7, 14, 21, 42, and 56 to measure white blood cell counts, cortisol, insulin, glucose, nonesterified fatty acids, serum amyloid A, haptoglobin, and neutrophil: lymphocytes. Two study intervals were used in the statistical analyses, representing greater (P1; wk 1-3) and reduced (P2; wk 4-8) enteric disease susceptibility. Data were analyzed using PROC GLIMMIX in SAS 9.4 (SAS Institute Inc.) with calf as the experimental unit. Overall, total urinary Cr output was reduced in GLN versus NSMR calves. Total Cr output was reduced at 1 wk of age in GLN versus NSMR calves, but no differences were detected at 6 wk of age. Neutrophil:lymphocyte was decreased both overall and during P2 in GLN versus NSMR calves, and neutrophil counts tended to be reduced in GLN versus NSMR calves during P2. No MR treatment differences were detected for average daily feed intake, average daily gain, body measurements, postabsorptive metabolic biomarkers, disease scores, and therapeutic treatments between GLN and NSMR calves. In summary, l-glutamine supplementation reduced gastrointestinal permeability and biomarkers of physiological stress in preweaning Holstein heifer calves.

Atletas de Taekwondo apresentam desequilíbrio muscular entre os músculos flexores e extensores do joelho: achados preliminares / Taekwondo athletes have muscle imbalance between knee flexors and extensions: preliminary findings / Los atletas de Taekwondo presentan un desequilibrio muscular entre los flexores y los extensores de la rodilla: hallazgos preliminares

Durante a prática de taekwondo com movimentos repetitivos, sistematizados e com certa sobrecarga de treino, o indivíduo pode gerar possíveis adaptações orgânicas que resultam em problemas posturais com grandes chances de desencadear desequilíbrio muscular. Objetivo: Verificar a presença de desequilíbrio entre os grupos musculares agonistas e antagonistas da articulação do joelho e entre membros dominantes e não dominantes de praticantes de taekwondo por meio da dinamometria isocinética. Método: Estudo transversal, observacional e descritivo realizado com nove praticantes de taekwondo do sexo masculino. Utilizou-se um dinamômetro isocinético para investigar o pico de torque, pico de torque por peso corporal, trabalho total, potência média, relação agonista/antagonista e índice de fadiga. Os dados dos membros dominante e não dominante foram comparados por meio do teste t-student para amostras pareadas. Foram calculados o intervalo de confiança de 95% da diferença média, o tamanho de efeito e o poder das análises. Resultados: Os músculos extensores dos membros dominante e não dominante apresentaram diferença média significante de 15,49 Nm (IC95% 7,27; 23,70; p=0,002) para pico de torque e de 22,64% (IC95% 11,83; 33,46; p=0,001) para pico de torque por peso corporal a 60°/s, representando tamanho de efeito médio. Conclusão: Os atletas de taekwondo apresentaram maior pico de torque e maior pico de torque por peso corporal dos músculos extensores do joelho a 60º/s no lado dominante. A relação agonista/ antagonista foi inferior a 60% e mais da metade dos atletas apresentaram uma diferença maior que 10% no pico de torque flexor no lado não dominante.

During taekwondo practice with the repetitive motions, systematized and with certain training overload, the person can generate possible organic adaptations that result in postural problems with a great chances of triggering muscle imbalance. Objective: To verify the presence of imbalance between agonist and antagonist muscle groups of knee joint and between dominant and non-dominant limbs through isokinetic dynamometry. Methods: Cross-sectional, observational and descriptive study realized with nine male taekwondo practitioners. An isokinetic dynamometer was used to investigate the peak torque, peak torque by body weight, total work, average power, agonist/antagonist ratio and fatigue index. Data from the dominant and non-dominant limbs were compared by t-student test for pared samples. The 95% confidence interval of the mean difference, the effect size and the power of analyses power were calculated. Results: The extensor muscles of the dominant and non-dominant limbs showed mean difference of 15,49 Nm (IC95% 7,27; 23,70; p=0,002) for peak torque and of 22,64% (IC95% 11,83; 33,46; p=0,001) for peak torque by body weight at 60°/s, representing average effect size. Conclusion: The taekwondo athletes had higher peak torque and higher peak torque by body weight of the knee extensors muscles in the dominant side. The agonist/ antagonist ratio was less than 60% and more than half of the athletes showed a difference greater than 10% in the peak flexor torque on the non-dominant side.

Durante la práctica de taekwondo con los movimientos repetitivos, sistematizados y con cierta sobrecarga de entrenamiento, la persona puede generar posibles adaptaciones orgánicas que deriven en problemas posturales con grandes posibilidades de desencadenar desequilibrios musculares. Objetivo: Verificar la presencia de desequilibrio entre grupos musculares agonistas y antagonistas de la articulación de la rodilla y entre miembros dominantes y no dominantes mediante dinamometría isocinética. Métodos: Estudio transversal, observacional y descriptivo realizado con nueve practicantes masculinos de taekwondo. Se utilizó un dinamómetro isocinético para investigar el par máximo, el par máximo por peso corporal, el trabajo total, la potencia media, la relación agonista/antagonista y el índice de fatiga. Los datos de las extremidades dominantes y no dominantes se compararon mediante la prueba t- student para muestras de pared. Se calcularon el intervalo de confianza del 95% de la diferencia media, el tamaño del efecto y la potencia de los análisis. Resultados: Los músculos extensores de los miembros dominantes y no dominantes mostraron una diferencia media de 15,49 Nm (IC95% 7,27; 23,70; p=0,002) para el par máximo y de 22,64% (IC95% 11,83; 33,46; p=0,001) para el par máximo por peso corporal a 60°/s, lo que representa el tamaño medio del efecto. Conclusiones: Los atletas de taekwondo presentaron un mayor par máximo y un mayor par máximo por peso corporal de los músculos extensores de la rodilla en el lado dominante. La relación agonista/antagonista fue inferior al 60% y más de la mitad de los atletas mostraron una diferencia superior al 10% en el pico de par flexor en el lado no dominante.

Examination of a nutritional treatment pathway according to pretreatment health status and stress levels of patients undergoing hematopoietic stem cell transplantation.

INTRODUCTION: This study aimed to validate hematopoietic stem cell transplantation (HSCT) treatment via a tailored nutritional pathway in myeloablative conditioning (MAC), determine its efficacy in terms of remission, and explore associations between clinical outcomes and nutritional indicators. METHODS: We included patients who underwent MAC for HSCT at the Shizuoka Cancer Center Stem Cell Transplantation between 2015 and 2019. We evaluated outcomes from the day before treatment initiation (transplant date: day 0) to day 42. RESULTS: Among the 40 MAC cases (participant characteristics: 20/40 males, mean age of 52 years, and mean body mass index of 21.9 kg/m2), we found that the percent loss of body weight and loss of skeletal muscle mass were correlated with the basal energy expenditure rate (BEE rate; r = 0.70, p<0.001 and r = 0.49, p<0.01, respectively). Based on the receiver operating characteristics curves, the cutoff value for the BEE rate in terms of weight loss was 1.1. Salivary amylase levels did not significantly change during the treatment course. Continuous variables, including oral caloric intake and performance status, showed statistically significant correlations with nutrition-related adverse events during treatment (r = -0.93, p<0.01 and r = 0.91, p<0.01, respectively). Skeletal muscle mass before treatment initiation was an independent predictive variable for reduced 2-year survival (p = 0.04). CONCLUSION: Our results support the validity of a safe nutritional pathway with a BEE rate of 1.1 for HSCT patients pretreated with MAC. Specifically, we found that this pathway could prevent weight loss in response to nutrition-related adverse events. Skeletal muscle mass before treatment was identified as an independent risk factor for reduced 2-year survival.

Yogurt Enriched with Inulin Ameliorated Reproductive Functions and Regulated Gut Microbiota in Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Mice.

The effects of synbiotic yogurt supplemented with inulin on the pathological manifestations and gut microbiota-bile acid axis were investigated using a dehydroepiandrosterone (DHEA)-induced polycystic ovary syndrome (PCOS) mice model. Female C57BL/6J mice were injected subcutaneously with DHEA at a dose of 6 mg/100 g BW for 20 days to establish a PCOS mouse model. Then, the PCOS mice were treated with yogurt containing inulin (6% w/w) at 15 mL/kg BW for 24 days. Results showed that supplementation of synbiotic yogurt enriched with inulin to PCOS mice decreased the body weight gain, improved estrus cycles and ovary morphology, and reduced the levels of luteinizing hormone while increasing the levels of follicle-stimulating hormone and interleukin-22 in serum. At the genus level, synbiotic yogurt increased the relative abundance of Lactobacillus, Bifidobacterium, and Akkermansia. PICRUSt analysis indicated that KEGG pathways including bile acid biosynthesis were changed after inulin-enriched synbiotic yogurt supplementation. Synbiotic yogurt enriched with inulin also modulated the bile acid profiles. In conclusion, inulin-enriched synbiotic yogurt alleviated reproductive dysfunction and modulated gut microbiota and bile acid profiles in PCOS mice.

Inhibition of POMC neurons in mice undergoing activity-based anorexia selectively blunts food anticipatory activity without affecting body weight or food intake.

Anorexia nervosa (AN) is a debilitating eating disorder characterized by severely restricted eating and significant body weight loss. In addition, many individuals also report engaging in excessive exercise. Previous research using the activity-based anorexia (ABA) model has implicated the hypothalamic proopiomelanocortin (POMC) system. Using the ABA model, Pomc mRNA has been shown to be transiently elevated in both male and female rodents undergoing ABA. In addition, the POMC peptide ß-endorphin appears to contribute to food anticipatory activity (FAA), a characteristic of ABA, as both deletion and antagonism of the µ opioid receptor (MOR) that ß-endorphin targets, results in decreased FAA. The role of ß-endorphin in reduced food intake in ABA is unknown and POMC neurons release multiple transmitters in addition to ß-endorphin. In the current study, we set out to determine whether targeted inhibition of POMC neurons themselves rather than their peptide products would lessen the severity of ABA. Inhibition of POMC neurons during ABA via chemogenetic Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology resulted in reduced FAA in both male and female mice with no significant changes in body weight or food intake. The selective reduction in FAA persisted even in the face of concurrent chemogenetic inhibition of additional cell types in the hypothalamic arcuate nucleus. The results suggest that POMC neurons could be contributing preferentially to excessive exercise habits in patients with AN. Furthermore, the results also suggest that metabolic control during ABA appears to take place via a POMC neuron-independent mechanism.

Fluid intake, hydration status and body mass changes in U-15 judo athletes during a training day

Despite numerous studies related to dehydration there is still a lack of scientific literature presenting hydration status and fluid intake of judo athletes during different periods. Therefore, the aim of this study was to investigate, fluid intake, hydration status and body weight changes of young judo athletes during a typical day of training in preparation period. Twenty-two young judo athletes (age: 12 ± 0.7 y, experience: 3.5 ± 1.1) voluntarily participated in this study. Hydration status and weight were examined in the morning, before and immediately after the training. All athletes trained 90 min and they consumed fluids ad libitum during the exercise. According to morning urine specific gravity (USG) values, 81.2% of the athletes were dehydrated while only 18.8% of the athletes were euhydrated. Pre-training urine measurements showed that 63.64% of the athletes presented dehydration and 77.27% of the athletes completed the training in dehydrated condition despite fluid availability during the training. Mean body weight loss during training was -0.64 ± 0.66%. It can be concluded that young judo athletes presented high prevalence of dehydration as indicated by USG values. Most of the athletes were dehydrated during a typical training day and completed the training in more dehydrated conditions compared to pre training values despite ad libitum fluid intake. It is of great importance to evaluate hydration status of the athletes before training to refrain from common practice of fluid restriction for weight loss and adverse effects of a persistent state of fluid deficit on physical and health related state.

Leptin, the brain and energy homeostasis: From an apparently simple to a highly complex neuronal system.

Leptin, produced and secreted by white adipose tissue in tight relationship with adipose mass, informs the brain about the status of the energy stores serving as the main peripheral signal for energy balance regulation through interaction with a multitude of highly interconnected neuronal populations. Most obese patients display resistance to the anorectic effect of the hormone. The present review unravels the multiple levels of complexity that trigger hypothalamic response to leptin with the objective of highlighting those critical hubs that, mainly in the hypothalamic arcuate nucleus, may undergo obesity-induced alterations and create an obstacle to leptin action. Several mechanisms underlying leptin resistance have been proposed, possibly representing useful targets to empower leptin effects. Among these, a special focus is herein dedicated to detail how leptin gains access into the brain and how neuronal plasticity may interfere with leptin function.

Effects of Tea Consumption on Anthropometric Parameters, Metabolic Indexes and Hormone Levels of Women with Polycystic Ovarian Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: Our aim was to conduct a systematic review and meta-analysis to assess the effectiveness and safety of tea supplements for patients with polycystic ovary syndrome (PCOS). Methods: We conducted searches of the published literature in PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure (CNKI), VIP database, and Wanfang Database in 1985 to September 2021. Data from randomized controlled trials (RCTs) were obtained to assess the effects of tea versus placebo in women with PCOS. Weighted mean differences (WMDs) were pooled using a random-effects model or risks ratios (RRs) using a random-effects model. Results: Six RCTs (235 participants) were included in our systematic review. Tea supplements as adjuvant therapy led to greater improvement in body weight (WMD -2.71, 95% CI -4.95 to -0.46, P = 0.02, I2 = 0%), fasting blood glucose (FBG: WMD -0.40, 95% CI -0.59 to -0.20, P < 0.0001, I2 = 0%) and fasting insulin (FINS: WMD -3.40, 95% CI -4.76 to -2.03, P < 0.00001, I2 = 0%) when compared with placebo. There were no significant differences of body mass index, waist circumference, hip circumference, waist-to-hip ratio (WHR), body fat rate, total testosterone, free testosterone (FT), dehydroepiandrosterone, luteinizing hormone or follicular-stimulating hormone (FSH) between the two groups. In addition, subgroup analysis suggested that green tea was effective on body weight, FINS, FBG, FT, and FSH, and herbal tea can also reduce FT levels, tea supplements had a significant impact on FBG and FSH in trials with intervention duration ≥ 3 months, and intervention lasting less than 3 months can improve FINS. Tea had significant effect on reducing WHR, FBG and FSH in Asian PCOS patients, but not in Caucasians. And there was no statistically significant effect of tea on weight and FINS in Asians, but it was effective for Caucasian participants. Compared with placebo, tea supplements did not cause significant adverse reactions (RR 1.45, 95% CI 0.30 to 6.90, P = 0.65, I2 = 0%). Conclusion: This meta-analysis suggests that consumption of tea supplementation in women with PCOS could significantly decrease the levels of FBG and FINS as well as reduce body weight. Especially green tea, not only has the above effects, but also has a significant effect on improving a variety of reproductive hormone indexes. Furthermore, tea supplementation is a relatively safe therapy for PCOS patients. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=212755, identifier CRD42021249196.

Effects of dairy and plant protein on growth and growth biomarkers in a piglet model.

The increasing world population with improved living conditions has increased the demand for food protein. This has intensified the search for sustainable alternative plant-derived high-quality protein sources for human nutrition. To study the effect of plant and milk proteins on growth in weaned pigs as a model for humans, 96 weaned pigs were divided into 48 pens and fed one of 4 different diets for 3 weeks. The dietary protein originated from either 50% rice + 50% 00-rapeseed protein (RICE + RAPE), 50% milk protein (MPC) + 50% 00-rapeseed protein (MPC + RAPE), 50% milk + 50% rice protein (MPC + RICE), or 100% MPC, and were supplemented with crystalline amino acids to meet the amino acid requirements. Weekly feed intake and body weights were recorded and after 3 weeks, a blood sample was taken 1 hour after a fixed meal, while organ weights were measured, and liver- and muscle tissue, and bone samples were collected at euthanasia. All pigs had a high daily gain and a low feed-to-gain ratio (F : G, feed intake per kg weight gain), but feed intake and daily gain was lowest and F : G highest in the RICE + RAPE diet. Metacarpal bones were longer and heavier in MPC + RICE and MPC fed pigs compared to pigs fed diet RICE + RAPE (P < 0.05), and intermediate in MPC + RAPE fed pigs, with no differences in bone thickness (P > 0.05). Plasma levels of all essential amino acids except Cys and Lys decreased markedly when fed a diet containing only plant protein. The differences were not associated with differences in plasma insulin or IGF-1, nor in the abundance of mRNA related to growth in liver and longissimus dorsi muscle. In conclusion, the growth of piglets fed a combination of milk and rice protein did not differ from the pure dairy-based diet, whereas the pure plant-based diet consisting of rice and rapeseed protein led to reduced growth. This was most likely caused by a lower feed intake and a lower than expected amino acid digestibility of the 00-rapeseed protein. There were no indications that the milk protein, beyond a favourable amino acid composition and high digestibility, specifically stimulated growth factors or other biomarkers of growth via the IGF-1 and insulin signalling pathways.

The anti-fatigue potential of water-soluble polysaccharides of Semen cassiae on BALB/c mice.

Fatigue syndrome is a major health problem that affects the voluntary activities of an individual. Particularly, exercise-induced fatigue has become a serious concern in people's health. Since polysaccharides from various medicinal plants have been reported for anti-fatigue effect, the current study deals with the anti-fatigue potential of water-soluble polysaccharides of the Chinese medicinal plant Semen cassiae (Cassia obtusifolia L.) in BALB/c mice. Water-soluble polysaccharides from Semen cassiae were extracted using aqueous solvent (water). An orthogonal test design was employed for the optimization of polysaccharide extraction. The conditions optimized through this design unveiled the raw materials to solvent ratio as 1:30. The optimal temperature and time duration were found to be 80°C and 3.5 h, respectively. The yield of soluble polysaccharides at these specified conditions was 5.42%. Strikingly, the water-soluble polysaccharide from S. cassiae exhibited strong anti-fatigue activity at 100 mg/kg in BALB/c mice. S. cassiae polysaccharide extended the weight-loaded swimming duration in BALB/c mice. In addition, it ameliorated the level of antioxidant enzymes (SOD, GPX) while decreased the blood urea nitrogen, creatine phosphokinase, triglyceride, lactic acid, lactate dehydrogenase, and malondialdehyde levels in blood serum. Moreover, the assessment of the immunomodulatory effect of S. cassia polysaccharides unveiled the enhancement of B-cell and T-cell lymphocytes, denoting the positive effect on physical immunity.

Psidium guajava leaf extract improves gastrointestinal functions in rats and rabbits: an implication for ulcer and diarrhoea management.

PURPOSE: Psidium guajava L. (Family, Myrtaceae) is reportedly used in ethnomedicine for the treatment of diarrhoea, inflammation, and gastroenteritis. OBJECTIVE: This study evaluated the gastrointestinal function of Psidium guajava leaf extract (PGLE) in rats and rabbits. MATERIALS AND METHODS: Crude ethanolic PGLE was subjected to phytochemical and toxicity tests (acute and sub-acute). Standard analytical procedures were employed to evaluate the in vivo gastrointestinal motility, and gastroprotective effect of PGLE against aspirin-induced ulcers. RESULTS: In the phytochemical analysis, phenols were the highest (48.32 mg) followed by flavonoids (32.74 mg) and least in tannins (7.31 mg). The acute toxicity of PGLE was >6000 mg/kg. Administration of PGLE decreased significantly (p < 0.05) the body weight, while the liver biomarkers were not significantly altered (p > 0.05) when compared to the control. PGLE significantly increased extractible mucus weight and lowered gastric acid secretion in rats (p < 0.05). PGLE decreased significantly (p < 0.05) ulcer scores and indexes, and increased percentage ulcer inhibition in a dose-dependent manner compared to the negative and omeprazole-treated groups. PGLE dose-dependently inhibited basal amplitudes of contractions, and significantly inhibited acetylcholine-induced contractions, terminating them completely at higher doses. CONCLUSION: PGLE may be a good anti-ulcer and anti-diarrhoeal agent, raising the prospect of novel drug development for such applications.

Optimal loading dose of meropenem before continuous infusion in critically ill patients: a simulation study.

The aim of this study was to investigate optimal loading doses prior to continuous infusion of meropenem in critically ill patients. A previously published and successfully evaluated pharmacokinetic model of critically ill patients was used for stochastic simulations of virtual patients. Maintenance doses administered as continuous infusion of 1.5-6 g/24 h with preceding loading doses (administered as 30 min infusion) of 0.15-2 g were investigated. In addition to the examination of the influence of individual covariates, a best-case and worst-case scenario were simulated. Dosing regimens were considered adequate if the 5th percentile of the concentration-time profile did not drop at any time below four times the S/I breakpoint (= 2 mg/L) of Pseudomonas aeruginosa according to the EUCAST definition. Low albumin concentrations, high body weight and high creatinine clearances increased the required loading dose. A maximum loading dose of 0.33 g resulted in sufficient plasma concentrations when only one covariate showed extreme values. If all three covariates showed extreme values (= worst-case scenario), a loading dose of 0.5 g was necessary. Higher loading doses did not lead to further improvements of target attainment. We recommend the administration of a loading dose of 0.5 g meropenem over 30 min immediately followed by continuous infusion.

Health Aspects, Growth Performance, and Meat Quality of Rabbits Receiving Diets Supplemented with Lettuce Fertilized with Whey Protein Hydrolysate Substituting Nitrate.

Lettuce (Lactuca sativa) was grown using a foliar spray with whey protein hydrolysate (WPH) as opposed to normal nitrate fertilization. Lettuce juice was prepared from lettuce cultivated without any fertilization, nitrate fertilization, or WPH. Sixty weaned, 4-week-old male V-line rabbits with an average 455 ± 6 g body weight were randomly divided into 4 groups (n = 15) and administered different lettuce juices. Rabbits administered WPH-fertilized lettuce showed significantly higher (n = 5, p < 0.05) body weight and carcass weight than those receiving nitrate-fertilized lettuce. Rabbits administered nitrate-fertilized lettuce were associated with significantly (p < 0.05) higher levels of liver enzyme activities (AST, ALT, and ALP), bilirubin (total, direct, and indirect), and kidney biomarkers (creatinine, urea, and uric acid). Rabbits administered WPH-fertilized lettuce avoided such increases and exhibited normal levels of serum proteins. Rabbits administered nitrate-fertilized lettuce manifested significantly (p < 0.05) lower RBCs and Hb levels than that of the other groups, while those receiving WPH-fertilized lettuce showed the highest levels. Liver and kidney sections of rabbits receiving WPH-fertilized lettuce witnessed the absence of the histopathological changes induced by feeding on nitrate-fertilized lettuce and produced higher quality meat. WPH-lettuce can substitute nitrate-fertilized lettuce in feeding rabbits for better performance and health aspects.

Effects of cereal fibers on short-chain fatty acids in healthy subjects and patients: a meta-analysis of randomized clinical trials.

Short-chain fatty acids (SCFAs) are involved in the regulation of a wide array of diseases. However, the effect of cereal dietary fibers on SCFA production remains unclear. We reviewed relevant clinical studies between 1950 and 2021 and aimed to evaluate the effect of cereal fiber consumption on SCFA production in healthy subjects and patients. PubMed, Web of Science, and the Cochrane Library databases were used for systematically searching published relevant trials with adults and a minimum intervention duration of 2 weeks. The effect size was estimated using standardized mean difference (SMD) and 95% confidence interval (CI). Of the 555 identified studies, 14 intervention groups involving 205 participants aged between 20 and 69 years are eligible. The results of meta-analysis revealed that cereal fiber supplementation significantly increased acetate [SMD: 0.86, 95% CI (0.46, 1.25), p < 0.0001], propionate [SMD: 0.48, 95% CI: (0.15, 0.81), p = 0.004], butyrate [SMD: 0.61, 95% CI: (0.20, 1.01), p = 0.003], and total SCFA [SMD, 0.96, 95% CI: (0.54, 1.39), p < 0.00001] concentrations. Subgroup analysis suggested that a long intervention duration (>4 weeks) significantly promoted acetate and propionate production, whereas a short intervention duration (≤4 weeks) significantly facilitated butyrate production. Cereal fiber supplementation had a more significant impact on overweight and obese subjects with body mass index (BMI) >29 kg m-2 than on individuals with BMI ≤29 kg m-2. Furthermore, we found that cereal fibers and wheat/rye arabinoxylan oligosaccharides, rather than wheat bran fibers, barley fibers, and barley ß-glucan, could significantly elevate the SCFA concentration. Overall, our meta-analysis demonstrated that cereal fiber supplementation is helpful in increasing the SCFA concentration, which provided strong proof for the beneficial role of cereal fibers.

Brown Seaweed Sargassum siliquosum as an Intervention for Diet-Induced Obesity in Male Wistar Rats.

The therapeutic potential of Sargassum siliquosum grown in Australian tropical waters was tested in a rat model of metabolic syndrome. Forty-eight male Wistar rats were divided into four groups of 12 rats and each group was fed a different diet for 16 weeks: corn starch diet (C); high-carbohydrate, high-fat diet (H) containing fructose, sucrose, saturated and trans fats; and C or H diets with 5% S. siliquosum mixed into the food from weeks 9 to 16 (CS and HS). Obesity, hypertension, dyslipidaemia, impaired glucose tolerance, fatty liver and left ventricular fibrosis developed in H rats. In HS rats, S. siliquosum decreased body weight (H, 547 ± 14; HS, 490 ± 16 g), fat mass (H, 248 ± 27; HS, 193 ± 19 g), abdominal fat deposition and liver fat vacuole size but did not reverse cardiovascular and liver effects. H rats showed marked changes in gut microbiota compared to C rats, while S. siliquosum supplementation increased gut microbiota belonging to the family Muribaculaceae. This selective increase in gut microbiota likely complements the prebiotic actions of the alginates. Thus, S. siliquosum may be a useful dietary additive to decrease abdominal and liver fat deposition.

Key role for hypothalamic interleukin-6 in food-motivated behavior and body weight regulation.

The pro-inflammatory role of interleukin-6 (IL-6) is well-characterized. Blockade of IL-6, by Tocilizumab, is used in patients with rheumatoid arthritis and those diagnosed with cytokine storm. However, brain-produced IL-6 has recently emerged as a critical mediator of gut/adipose communication with the brain. Central nervous system (CNS) IL-6 is engaged by peripheral and central signals regulating energy homeostasis. IL-6 is critical for mediating hypophagia and weight loss effects of a GLP-1 analog, exendin-4, a clinically utilized drug. However, neuroanatomical substrates and behavioral mechanisms of brain IL-6 energy balance control remain poorly understood. We propose that the lateral hypothalamus (LH) is an IL-6-harboring brain region, key to food intake and food reward control. Microinjections of IL-6 into the LH reduced chow and palatable food intake in male rats. In contrast, female rats responded with reduced motivated behavior for sucrose, measured by the progressive ratio operant conditioning test, a behavioral mechanism previously not linked to IL-6. To test whether IL-6, produced in the LH, is necessary for ingestive and motivated behaviors, and body weight homeostasis, virogenetic knockdown by infusion of AAV-siRNA-IL6 into the LH was utilized. Attenuation of LH IL-6 resulted in a potent increase in sucrose-motivated behavior, without any effect on ingestive behavior or body weight in female rats. In contrast, the treatment did not affect any parameters measured (chow intake, sucrose-motivated behavior, locomotion, and body weight) in chow-fed males. However, when challenged with a high-fat/high-sugar diet, the male LH IL-6 knockdown rats displayed rapid weight gain and hyperphagia. Together, our data suggest that LH-produced IL-6 is necessary and sufficient for ingestive behavior and weight homeostasis in male rats. In females, IL-6 in the LH plays a critical role in food-motivated, but not ingestive behavior control or weight regulation. Thus, collectively these data support the idea that brain-produced IL-6 engages the hypothalamus to control feeding behavior.

Clinical efficacy of Curcuvet and Boswellic acid combined with conventional nutraceutical product: An aid to canine osteoarthritis.

INTRODUCTION: Osteoarthritis is a progressive degenerative joint disease which is high prevalent in dogs. In the late stage of the disease, it determines chronic neuropathic pain which leads to reduced quality-of-life in affected patients. To date it has not yet been identified a specific treatment, but it has been proved that nutraceutical and dietary supplements may play an important role in controlling inflammation and pain. The aim of this study was to evaluate, by the use of force plate gait analysis, the clinical efficacy of Boswellia and Curcuvet® combined with conventional nutraceutical therapy compared with conventional nutraceutical alone in dogs affected by osteoarthritis. MATERIALS AND METHODS: Twenty client-owned dogs, over 12 months old and 20 kg of body-weight, with a confirmed diagnosis of Osteoarthritis, were included in this randomized, double-blinded study. The dogs were randomly divided into two groups: the first group (A) received a conventional nutraceutical (consisted in a preparation of glucosamine, chondroitin sulfate, fish-oil containing 80% of omega 3-fatty acid, vitamin C and E, saccharomyces Cerevisiae) with a combination of acid boswellic and Curcuvet®, while the second group (B) received a conventional nutraceutical. All the enrolled dogs underwent a washout period before starting the treatment with nutraceuticals products which were the only admitted treatment over the study period. A full orthopaedic and neurologic examination, and force plate gait analysis were performed before starting the treatment, at 45, 90, and 60 days post-treatment. Ground reaction forces were recorded and analyzed. RESULTS: Twenty dogs were enrolled in the study. In both groups there was an increasing values of ground reaction forces. These results might indicate that both nutraceutical products determined a better condition in terms of pain feeling but that effect is much more visible after 60 days from the end of the administration in treated group. DISCUSSION: In conclusion Curcuvet in combination with Boswellic acid could be considered a valid aid in a multimodal treatment for canine osteoarthritis.

Is Probiotic Supplementation Useful for the Management of Body Weight and Other Anthropometric Measures in Adults Affected by Overweight and Obesity with Metabolic Related Diseases? A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis is to assess the effectiveness of probiotics in inducing body weight loss in patients with overweight or obesity with related metabolic diseases. The research was carried out on PubMed and Scopus, focusing on studies reporting the effect on anthropometric measures (weight, body mass Index (BMI), waist circumference (WC), and hip circumference (HC) after administration of various probiotic strains compared to placebo. Twenty randomized controlled trials, that included 1411 patients, were considered. The meta-analyzed mean differences (MD) for random effects showed no significant decrease in body weight after probiotic supplementation (-0.26 kg [-075, 0.23], p = 0.30), while a significant BMI decrease was found (-0.73 kg/m2 [-1.31, -0.16], p = 0.01). For WC and HC, the meta-analyzed MD for random effects showed a significant decrease (WC: -0.71 cm [-1.24; -0.19], p = 0.008 and HC: -0.73 cm [-1.16; -0.30], p = 0.0008). The risk of bias was also evaluated considering a high risk and a low risk according to PRISMA criteria. In conclusion, the results of this meta-analysis highlight a positive trend of probiotics supplementation on the amelioration of anthropometric measures of overweight and obese patients with related metabolic diseases. However, further research is needed before recommending the use of probiotics as a therapeutic strategy for these patients. The focus of the future research should be to evaluate the efficacy of different probiotic strains, the quantities to be administered, and the duration of the intervention.