Increase In Weight Research Articles

Foliar applications of a Malvaceae-derived protein hydrolysate and its fractions differentially modulate yield and functional traits of tomato under optimal and suboptimal nitrogen application.

Protein hydrolysates (PHs) can enhance plant nitrogen nutrition and improve the quality of vegetables, depending on their bioactive compounds. A tomato greenhouse experiment was conducted under both optimal (14 mM) and suboptimal (2 mM) nitrogen (N-NO3) conditions. Tomatoes were treated with a new Malvaceae-derived PH (MDPH) and its molecular fractions (MDPH1, >10 kDa; MDPH2, 1-10 kDa and MDPH3, <1 kDa). Under optimal N conditions, the plants increased biomass and fruit yield, and showed a higher photosynthetic pigment content in leaves in comparison with suboptimal N, whereas under N-limiting conditions, an increase in dry matter, soluble solid content (SSC) and lycopene, a reduction in firmness, and changes in organic acid and phenolic compounds were observed. With 14 mM N-NO3, MDPH3 stimulated an increase in dry weight and increased yield components and lycopene in the fruit. The MDPH2 fraction also resulted in increased lycopene accumulation in fruit under 14 mM N-NO3. At a low N level, the PH fractions showed distinct effects compared with the whole MDPH and the control, with an increase in biomass for MDPH1 and MDPH2 and a higher pigment content for MDPH3. Regardless of N availability, all the fractions affected fruit quality by increasing SSC, whereas MDPH2 and MDPH3 modified organic acid content and showed a higher concentration of flavonols, lignans, and stilbenes. The molecular weight of the peptides modifies the effect of PHs on plant performance, with different behavior depending on the level of N fertilization, confirming the effectiveness of fractioning processes. © 2024 Society of Chemical Industry.

Novel Small Molecule, UTS-1401, as a Radioprotector for Total-Body Irradiation.

We report on a new radioprotector, UTS-1401, a small molecule that was synthesized (by one of us, JS) and evaluated here for its radioprotective effect against total-body irradiation (TBI). Female and male NIH Swiss mice were subjected to TBI at doses of 6.5, 7.5 and 8.5 Gy either with or without a 24 h pretreatment of UTS-1401 given ip and observed for 30 days. Survival rates were significantly increased when mice were treated with UTS-1401 compared to those not treated. The radioprotective effect of UTS-1401 was drug-dose dependent for male mice exposed to 8.5 Gy TBI with 150 mg/kg of UTS-1401 as the optimal dose. The radioprotective effect of UTS-1401 on female mice exposed to 8.5 Gy TBI was observed at 50, 100, and 150 mg/kg, with no dose response relationship noted. Female mice were more radioresistant than male mice with LD50/30 values of 7.8 Gy vs. 6.8 Gy, respectively. Weight changes after UTS-1401 alone showed a significant body weight increase at 150 mg/kg. Both the ip and iv route for UTS-1401 were similarly effective for male mice exposed to 8 Gy TBI. Further analysis using an endogenous spleen colony assay demonstrated that pretreatment of UTS-1401 for up to 72h prior to TBI protected both spleen weight and hematopoietic stem cells with a treated/untreated ratio between 2.0 and 3.2 for the latter for times between 0.5 h and 72 h. A separate invivo study showed that pretreatment of UTS-1401 protected bone marrow CFU-GM for mice exposed to TBI. In summary, UTS-1401 is a promising small-molecule radioprotective agent as demonstrated by whole animal, hematopoietic stem cell and bone marrow myeloid progenitor cell survival.

Protective Effects of Iraqi Propolis on Carbimazole-Induced Reduction of Sex Hormones in Female Adult Rats

Background:: Propolis (PR) is used as a health supplement and is widely used in foods and drinks in many parts of the world. This study aimed to know the possible reproductive toxicity effect of the antithyroid drug carbimazole (CZ) in adult female albino rats and to evaluate the possible protective role of Iraqi PR. Methods:: Twenty-four adult female albino rats were randomized into four groups: control, PR, CZ, and PR + CZ. Rats were orally treated for six weeks. Ovarian biochemical and histopathological analyses were performed. Results:: No change in appearance, no signs of toxicity, and no deaths of animals were reported throughout the study period. There was a significant body weight increase only in the PR group. The CZ group displayed a reduction in serum T3 and T4 levels and a rise in serum TSH levels compared to the control. Also, there was a significant decrease in serum T3, T4, and TSH levels after exposure to PR+ CZ compared to control. Exposure to 0.01mg/g body weight of CZ for six weeks results in a significant reduction of serum LH, FSH, and estradiol (E2) in female rats. At the same time, PR alone or with CZ was found to have no significant effect. Biochemical results were consistent with histopathological results. Conclusion:: Iraqi PR provides a protective effect against the reduction of serum sex hormones induced by CZ. Further studies are required to confirm this effect. PR has no effect on CZ activity in reducing thyroxin levels; however, PR might reduce the effects of CZ on TSH levels. Furthermore, PR alone demonstrated an elevation in the weight gain of animals compared to the control group.

Weight change does not impact the long-term outcomes following pulmonary vein isolation in obese patients with atrial fibrillation

Abstract Background Weight loss has been shown to reduce the burden of atrial fibrillation (AF) in obese patients. However, there are limited data on the impact of weight loss on long-term outcomes in patients with atrial fibrillation (AF) who undergo pulmonary vein isolation (PVI). Objective To understand the impact of weight change, as assessed by freedom from recurrent AF, in obese patients undergoing cryoballoon (CB) PVI. Methods We enrolled consecutive obese (BMI ≥ 30 kg/m2) patients with AF who underwent CB PVI; all patients had an implantable loop recorder (ILR) for long-term ECG monitoring. The cohort was divided into 3 groups based on their weight change 1-year after ablation: (1) weight loss (WL) &amp;gt; 3% weight decrease; (2) no weight change (NWC) - weight change &amp;lt; 3%, (3) weight gain (WG) &amp;gt; 3% weight increase. We assessed long-term AF recurrences, after excluding an initial 3-month post-ablation blanking period. Results Out of total of 137 pts with obesity, 61 pts had weight available at the ablation and at 1-year follow-up (65 ± 9 years; 41 [67%] male; 23 [38%] PAF; CHA2DS2-VASc 2.9 ± 1.7). There were no differences in baseline characteristics. At follow-up, 24 (39%), 26 (43%), and 11 (18%) pts lost, had no change, or gained weight, respectively. Of the 24 pts who lost weight, 3 pts lost &amp;gt; 10% body weight. During a follow-up of 964 ± 512 days, 41 (67%) pts had recurrent AF; the change in weight did not impact outcomes (Figure), including those who lost &amp;gt; 10% body weight. Conclusions During 3-years of follow-up, 2/3 of obese patients had objective evidence of AF recurrence following CB PVI. Weight change in the first-year post ablation did not alter long-term outcomes. Other strategies may be needed in these patients to improve outcomes.

Ovine KRT81 Variants and Their Influence on Selected Wool Traits of Commercial Value

Keratins are the main structural protein components of wool fibres, and variation in them and their genes (KRTs) is thought to influence wool structure and characteristics. The PCR–single strand conformation polymorphism technique has been used previously to investigate genetic variation in selected coding and intron regions of the type II sheep keratin gene KRT81, but no variation was identified. In this study, we used the same technique to explore the 5′ untranslated region of KRT81 and detected three sequence variants (A, B and C) that contain four single nucleotide polymorphisms. Among the 389 Merino × Southdown cross sheep investigated, variant B was linked to a reduction in clean fleece weight, while C was associated with an increase in both greasy fleece weight and clean fleece weight. No discernible effects on staple length or mean-fibre-diameter-related traits were observed. These findings suggest that variation in ovine KRT81 might influence wool growth by changing the density of wool follicles in the skin, the density of individual fibres, or the area of the skin producing fibre, as opposed to changing the rate of extrusion of fibres or their diameter.

#1665 Mechanisms underlying long-term weight changes and their impact on all-cause mortality among chronic hemodialysis patients

Abstract Background and Aims Observational studies have demonstrated a significant association between long-term weight loss and weight gain and an increased risk of mortality among chronic hemodialysis patients. However, underlying mechanisms of these associations remain insufficiently explored. To address this knowledge gap, we conducted an in-depth analysis using a cohort of hemodialysis patients, benefiting from comprehensive baseline data, regular six-month evaluations, and an extended follow-up period. We employed advanced statistical techniques, including Lasso regression, to construct predictive models for long-term weight loss and gain. Furthermore, we conducted mediation analyses to elucidate whether weight change mediates the impact of major risk factors on all-cause mortality. Method This post-hoc analysis utilized data from participants in a previous randomized controlled trial conducted between 2006 and 2011, named as the Olmesartan clinical trial in Okinawan patients under the OKIDS (OCTOPUS) study. Subsequently, we tracked participants' mortality outcomes until July 2018. At the time of enrollment, we collected comprehensive baseline information, encompassing demographics, medical history, and laboratory data. Throughout the trial, participants' body weights were meticulously recorded every six months. Our analysis was restricted to patients who survived for at least two years post-enrollment, ensuring a minimum of five body weight measurements during the trial. Lasso regression was employed in training datasets (comprising 60% of participants) to identify crucial risk factors associated with long-term weight gain (&amp;gt;1 kg per year) or weight loss (&amp;lt;−1 kg per year) among chronic hemodialysis patients. These selected models were subsequently applied to paired validation datasets (comprising 40% of participants), and receiver operating characteristic (ROC) curves were used to calculate the area under the curve (AUC), aiding in the identification of key risk factors for long-term weight changes. Subsequently, we conducted mediation analyses to investigate whether weight change mediated the relationship between risk factors and all-cause mortality. Results Our analysis included 404 out of 461 OCTOPUS participants, with 60.9% being male, a mean age of 59.2 years (±11.7), and a mortality rate of 41.6%. The median follow-up period extended to 10.3 years. In the training datasets, Lasso models identified critical predictors for weight increase, including a history of diabetes, younger age, normal cardio-thoracic ratio (CTR) (&amp;lt;50% for males and &amp;lt;53% for females), and BMI &amp;lt;20. Conversely, predictors for weight decrease included BMI ≥20, serum sodium &amp;lt;135 mEq/L, serum albumin &amp;lt;3.5 g/dL, and older age. Weight increase demonstrated higher predictability (mean AUC of 0.59) compared to weight decrease (mean AUC of 0.55) in the validation datasets. Mediation analyses revealed that weight loss mediated 30% of the impact of older age (≥70 years old) on all-cause mortality (P = 0.068). Conclusion Our findings suggest that, among chronic hemodialysis patients, long-term weight increase is associated with a history of diabetes and younger age, while long-term weight loss is linked to BMI (≥20), hyponatremia, hypoalbuminemia, and older age. Notably, long-term weight loss appears to explain 30% of the increased risk of all-cause mortality associated with older age (≥70 years old).

Exercise capacity and muscle strength in patients who have undergone the Fontan procedure: a retrospective follow-up study

Background. Due to their relationship with clinical progression, follow-up of exercise capacity and muscle strength is important for optimal disease management in patients who have undergone the Fontan procedure. We aimed to retrospectively analyze exercise capacity and muscle strength trajectory over approximately 2 years. Methods. Exercise capacity was assessed using an exercise stress test with the modified Bruce protocol on a treadmill, hand grip and knee extensor strength using a hand dynamometer, and body composition using a bioelectrical impedance device. Exercise capacity, muscle strength, and body composition follow-up data recorded between 2020 and 2022 were compared. Results. Fifteen patients [median age from 17 (first assessment) to 18 years (last assessment), 5 females)] with a 20-month median follow-up time were analyzed retrospectively. There was an increase in weight, height, body mass index, and body fat weight (p&lt;0.05). There was a tendency for increased handgrip strength (%) (p=0.069), but no significant difference was observed in the knee extensor strength of patients during the follow-up period (p&gt;0.05). The changes in heart rate (HR) and oxygen saturation were higher in the last test than in the first test (p&lt;0.05). Maximum HR (HRmax), % predicted HRmax and HR reserve recorded during the test and HR 1 minute after the test were similar between the first and last tests (p&gt;0.05). Conclusions. After 20 months of follow-up, exercise capacity and muscle strength did not decline; instead, the body mass index and fat weight increased. Patients who have undergone the Fontan procedure may not be experiencing a decline in exercise capacity and muscle strength over relatively short time periods during childhood, adolescence, and early adulthood.

Studying the efficiency of Gaprin application in sterlet farming

In the course of the experiment, the influence of new feed additives created on the basis of Gaprin and representing biomass of inactivated cell culture of non-pathogenic methane-oxidizing yeasts or bacteria on sturgeon fish productivity indicators was studied. The research was carried out in the Krasnodar Territory on sterlet fingerlings. The experiment lasted for 60 days. According to the scheme of the experiment, the 1st (control) group of fish received complete feeds without additives, i.e. containing 100.0% fish meal. In group 2 feeding, 50.0% fishmeal was replaced with 50.0% Gaprin. Group 3 diet contained 25.0% fishmeal and 75.0% Gaprin. In the feed for group 4, fish meal and Gaprin were in the ratio of 75/25%. In Group 5, fish meal was completely replaced by Gaprin, in this case the amount of additive was 10.5 kg. Sterlet fingerlings from Group 6 received feed with 10.0% Gaprin. The initial live weight in all groups was similar at 30 g. However, the inclusion of Gaprin in the diet by reducing the amount of fish meal contributed to an increase in the final live weight of sterlets in the experimental groups by 4.4–19.4% compared to the control. The exceptions were groups 5 and 6, which received 100.0 and 90.0% Gaprin instead of fishmeal. Final live weight in these groups was lower by 2.3 and 0.9%, respectively. Feed costs per 1 kg of live weight gain in the groups with partial or complete replacement of fish meal were lower relative to the 1st group (from 7.0 to 17.9%,).Inclusion of Gaprin in complete feeds contributed to the increase in profit from 553.00 to 1785.00 rubles.

A murine model of hypertensive heart disease in older women.

We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life. We observed that AngII effects on heart morphology were different in younger and adult mice (3- and 12-month-old; 20 and 19% increase in heart weight. P<0.01 for both) than in older animals (24-month-old; 6%; not significant). Ovariectomy at 12 months restored the hypertrophic response to AngII in elderly females (23%, p=0.0001). We performed a bulk RNA sequencing study of the left ventricle (LV) and left atrial gene expression in elderly animals, controls, and Ovx. AngII modulated (|Log2 fold change| ≥ 1) the LV expression of 170 genes in control females and 179 in Ovx ones, 64 being shared. In the left atrium, AngII modulated 235 genes in control females and 453 in Ovx, 140 shared. We observed many upregulated genes associated with the extracellular matrix regulation in both heart chambers. Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed Ankrd1, Nppb, Col3a1, Col1a1, Ctgf Col8a1, and Cilp. Several circadian clock LV genes were modulated differently by AngII between control and Ovx females (Clock, Arntl, Per2, Cry2, and Ciart). In conclusion, sex hormones, even in elderly female mice, modulate the heart's hypertrophic response to AngII. Our study identifies potential new markers of hypertensive disease in aging female mice and possible disturbances of their cardiac circadian clock.

Mendelian randomization shows causal effects of birth weight and childhood body mass index on the risk of frailty

BackgroundThe association between birth weight and childhood body mass index (BMI) and frailty has been extensively studied, but it is currently unclear whether this relationship is causal.MethodsWe utilized a two-sample Mendelian randomization (MR) methodology to investigate the causal effects of birth weight and childhood BMI on the risk of frailty. Instrumental variables (p &amp;lt; 5E-08) strongly associated with own birth weight (N = 298,142 infants), offspring birth weight (N = 210,267 mothers), and childhood BMI (N = 39,620) were identified from large-scale genomic data from genome-wide association studies (GWAS). The frailty status was assessed using the frailty index, which was derived from comprehensive geriatric assessments of older adults within the UK Biobank and the TwinGene database (N = 175,226).ResultsGenetically predicted one standard deviation (SD) increase in own birth weight, but not offspring birth weight (maternal-specific), was linked to a decreased frailty index (β per SD increase = −0.068, 95%CI = −0.106 to −0.030, p = 3.92E-04). Conversely, genetically predicted one SD increase in childhood BMI was associated with an elevated frailty index (β per SD increase = 0.080, 95%CI = 0.046 to 0.114, p = 3.43E-06) with good statistical power (99.8%). The findings remained consistent across sensitivity analyses and showed no horizontal pleiotropy (p &amp;gt; 0.05).ConclusionThis MR study provides evidence supporting a causal relationship between lower birth weight, higher childhood BMI, and an increased risk of frailty.

One anastomosis gastric bypass ameliorates diabetic nephropathy via regulating the GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

Diabetic nephropathy (DN), a complication of diabetes, is the most leading cause of end-stage renal disease. Bariatric surgery functions on the remission of diabetes and diabetes-related complications. One anastomosis gastric bypass (OAGB), one of popular bariatric surgery, can improve diabetes and its complications by regulating the glucagon-like peptide-1 (GLP-1) level. Meanwhile, GLP-1 can alleviate renal damage in high-fat-diet-induced obese rats. However, the effect of OAGB on renal injury remains uncertain in DN. A diabetes model was elicited in rats via HFD feeding and STZ injection. The role and mechanism of OAGB were addressed in DN rats by the body and kidney weight and blood glucose supervision, oral glucose tolerance test (OGTT), enzyme-linked immunosorbent assay (ELISA), biochemistry detection, histopathological analysis, and western blot assays. OAGB surgery reversed the increase in body weight and glucose tolerance indicators in diabetes rats. Also, OAGB operation neutralized the DN-induced average kidney weight, kidney weight/body weight, and renal injury indexes accompanied with reduced glomerular hypertrophy, alleviated mesangial dilation and decreased tubular and periglomerular collagen deposition. In addition, OAGB introduction reduced the DN-induced renal triglyceride and renal cholesterol with the regulation of fatty acids-related proteins expression. Mechanically, OAGB administration rescued the DN-induced expression of Sirt1/AMPK/PGC1α pathway mediated by GLP-1. Pharmacological block of GLP-1 receptor inverted the effect of OAGB operation on body weight, glucose tolerance, renal tissue damage, and fibrosis and lipids accumulation in DN rats. OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

Effects of different winter paddock management of Thoroughbred weanlings and yearlings in the cold region of Japan on physiological function, endocrine function and growth.

Effects of different winter paddock management of Thoroughbred weanlings and yearlings in Hokkaido, Japan, which is extremely cold in winter, on physiological function, endocrine function and growth were investigated. They were divided into two groups; those kept outdoors for 22 hr in the paddock (22hr group) and those kept outdoors for 7 hr in daytime with walking exercise for 1 hr using the horse-walker (7hr +W group), and the changes in daily distance travelled, body temperature (BT), heart rate (HR), HR variability (HRV), endocrine function and growth parameters were compared between the two groups from November at the year of birth to January at1 year of age. The 7hr+W group could travel almost the same distance as the 22hr group by using the horse-walker. The 22hr group had a lower rate of increase in body weight than the 7hr+W group in January. In addition, lower in BT and HR were observed, and HRV analysis showed an increase in high frequency power spectral density, indicating that parasympathetic nervous activity was dominant. And also, changes in circulating cortisol and thyroxine were not observed despite cold environment. On the other hand, the 7hr+W group had higher prolactin and insulin like growth factor than the 22hr group in January, and cortisol and thyroxine were also increased. Physiological and endocrinological findings from the present study indicate that the management of the 7hr+W group is effective in promoting growth and maintaining metabolism during the winter season.

Potato productivity on the background of the entomopathogenic fungus &lt;i&gt;Metarhizium robertsii&lt;/i&gt; application in production trials

For the first time in Western Siberia (Novosibirsk region), two-year production trials of an experimental prototype of a drug based on the entomopathogenic fungus Metarhizium robertsii have been conducted. Strain P-72 isolated from the dead larvae of Colorado potato beetle Leptinotarsa decemlineata Say from the collection of microorganisms of the Institute of Systematics and Ecology of Animals of the Siberian Branch of the Russian Academy of Sciences was used in this work. Species identification of the fungus was performed based on sequencing of the elongation factor gene region EF1α. The ability of the preparation to significantly increase the parameters of potato yield structure elements throughout the whole vegetation period was shown. A reliable increase in the number of surviving sprouts by 1.4 times, the number of stems and tubers by 1.5 times was found. The growth-stimulating effect of using the preparation based on entomopathogenic fungus was manifested in the increase of plant weight by the flowering phase. The average yield increase for two years amounted to 36.0% in the variant with application of M. robertsii significantly exceeding the productivity of potatoes in the control. The level of profitability of potato production with the use of entomopathogenic fungus M. robertsii increased to 92.0% (with 50.0% in the control) due to the increase in gross yield and improved quality of marketable products. Infestation of new harvest tubers with rhizoctoniose significantly decreased in the variant including treatment with entomopathogenic fungus: the number of tubers with sclerotia decreased 2.8 times compared to the control, which eventually led to an increase in the number of healthy tubers and a significant (2.5 times) decrease in the sclerotial index.

#1058 Causal discovery for the volume of white matter in patients undergoing haemodialysis

Abstract Background and Aims White matter hyperintensity is linked to adverse outcomes and a heightened risk of overt stroke and cognitive impairment, with its prevalence being more pronounced in patients undergoing haemodialysis than in the general population. Despite this, the determinants of white matter hyperintensity volume in patients undergoing haemodialysis remain unknown. Here, we aimed to utilise a statistical causal search approach to examine the factors influencing white matter hyperintensity volume, as measured by MRI, in patients undergoing haemodialysis. Method MRI measurements of white matter hyperintensity volumes were taken in 133 patients on outpatient maintenance haemodialysis for &amp;gt;1 year. Factors included in the statistical causal discovery model encompassed sex, underlying diseases that led to dialysis, total brain volume measured using MRI, and age and dialysis vintage at the time of MRI. Additionally, values calculated and averaged over the year before the MRI scan, such as pre-dialysis blood pressure, pulse, weight, blood pressure during dialysis, blood pressure after dialysis completion, the volume of water removed in one session, Kt/V, and URR and occurrences of sudden drops in blood pressure during dialysis, were considered. Missing measurements were supplemented using random forest. A statistical causal search using DirectLiNGAM was conducted, and clear temporal pre- and post-relationships were incorporated into the LiNGAM model as per prior knowledge. To enhance internal validity, 1000 bootstrap samplings were performed, and edges with a frequency of occurrence of ≥50% were considered valid for Directed Acyclic Graphs (DAGs). Factors directly linked to white matter volume were included in the model, and linear regression was executed. Results Patients had a mean age of 69.0 (Standard Deviation: 10.4) years, with 96 (72.2%) being male. The mean history of dialysis was 6.63 [Interquartile Range (IQR): 4.10, 10.78] years, and 40 (39.2%) patients had diabetes as the primary disease. The mean white matter hyperintensity volume was 14334.9 [IQR: 5262.4,30637.2]. Age, pre-dialysis body weight, post-dialysis mean blood pressure, and total brain volume were directly influenced by white matter volume. DAGs displaying causality obtained through bootstrapping are shown in the Fig. The regression model results revealed that white matter hyperintensity increased by 8376.3 [95% Confidence Intervals (CI): 4899.5 to 11853.1] for every 10 years of age, decreased by −2726.0 [95% CI: −4311.5 to −1140.5] with a 5 kg increase in pre-dialysis body weight, increased by 2089.7 [95% CI: 693.3 to 3540.0] with a 5-mmHg rise in post-dialysis mean blood pressure, and a 1 standard deviation increase in total cerebrum volume increased white matter volume by 13057.4 [95% CI: 8958.1 to 17156.8]. Conclusion The causal diagram indicated that age, pre-dialysis weight, post-dialysis mean blood pressure, and total cerebrum volume directly influenced white matter hyper intensity volume. The sudden drop in blood pressure during dialysis impacted white matter hyperintensity volume via post-dialysis mean blood pressure. Furthermore, age, post-dialysis mean blood pressure and total cerebrum volume had a facilitative effect on the increase in white matter hyperintensity volume, while pre-dialysis weight had a protective effect.

#362 Dosing low, winning high: unlocking the promise of endothelin antagonism for the treatment of CKD in the zibotentan/dapagliflozin ZENITH trials

Abstract Background and Aims The Phase 2b ZENITH-CKD trial demonstrated that combined treatment with the endothelin A receptor (ETAR) antagonist zibotentan and the sodium-glucose co-transporter-2 inhibitor (SGLT2i) dapagliflozin yields a robust and significant reduction in albuminuria in individuals with chronic kidney disease (CKD), compared to dapagliflozin treatment alone [1]. This is hypothesized to translate into a significant reduction of kidney function decline and may further confer cardiometabolic benefits including reducing blood pressure, LDL cholesterol and (in type 2 diabetes) HbA1c in the ongoing Phase 3 ZENITH High Proteinuria trial. The usage of ETAR antagonists has until now been limited by the class effect of fluid retention, which is associated with an increased risk of heart failure in the at-risk CKD population. Zibotentan has previously been investigated at 10 mg per day in Phase 3 for the treatment of prostate cancer. Method Model-Informed Drug Development (MIDD) was integrated with clinical pharmacology data to develop the dose strategy for both ZENITH trials. A low-dose strategy was selected considering the increased plasma exposure of zibotentan in kidney impairment. The Phase 2b dose steps were selected based on an exposure response model for the efficacy marker urinary albumin to creatinine ratio (uACR) and were supported using clinical trial simulations. The dose strategy for Phase 3 was defined based on a combined analysis of ZENITH-CKD results for both efficacy and tolerability: efficacy (uACR reduction on top of dapagliflozin) was analysed with a Dose-Response Mixed Model for Repeated Measures, and tolerability (fluid retention events, defined as a combination of specified body weight and BNP increase) was evaluated with Kaplan Meier analyses. Results Zibotentan doses of 0.25 mg and 1.5 mg (in a first, discontinued study part also 5 mg), in combination with dapagliflozin 10 mg, were selected for ZENITH-CKD. Clinical trial simulations indicated that inclusion of the low dose of 0.25 mg was crucial to characterise the dose-response relationship. Dose-uACR response modelling of ZENITH-CKD data predicted a zibotentan dose of 0.75 mg to result in a mean uACR reduction of around 25% in addition to the reduction with dapagliflozin. A post-hoc regression analysis of uACR mean changes from baseline, stratified by dose, showed a trend towards lower uACR reduction with higher eGFR levels. Kaplan-Meier analyses of the fluid retention risk in different eGFR subgroups indicated that the fluid retention risk increased with increasing zibotentan dose for eGFR levels &amp;lt;45 mL/min/1.73 m2, while for higher eGFR levels, no differences were observed between treatments with dapagliflozin alone and added zibotentan 0.25 mg or 1.5 mg. Therefore, a kidney-function based zibotentan dose strategy was selected for the ZENITH High Proteinuria trial: Combined zibotentan/dapagliflozin is being compared against dapagliflozin alone; within the combination treatment arm, 0.25 mg zibotentan is selected for participants with baseline eGFR levels &amp;lt;45 mL/min/1.73 m2, and 0.75 mg is selected for higher eGFR level, with a tolerance eGFR window for participants whose eGFR declines below this cut-off, and with the possibility to reduce the dose to 0.25 mg in case of tolerability findings. Conclusion The favourable benefit/risk profile that was demonstrated for combined zibotentan/dapagliflozin in ZENITH-CKD was enabled by the zibotentan low-dose strategy. The wide dose ranging and MIDD further enabled selection of a kidney-function based zibotentan dosing strategy for ZENITH High Proteinuria which is designed to further balance benefit/risk. The low-dose zibotentan strategy and the combination with dapagliflozin opened for the first time a therapeutic window for ETAR antagonists, with the potential to redefine their value for the treatment of CKD. This work was sponsored by AstraZeneca.

#1568 Cardiometabolic benefits of low dose zibotentan and dapagliflozin 10 mg in the ZENITH-CKD study

Abstract Background and Aims Positive effects of endothelin receptor antagonists on blood pressure and urinary albumin excretion have been well described, although their use in a wider population of patients with chronic kidney disease with increased cardiovascular risk has been limited by potential fluid retention. Here we present the effects of low dose zibotentan in combination with dapagliflozin on a range of cardiometabolic risk factors. Method In a post-hoc analysis of the ZENITH-CKD trial, a randomized, double-blind, active-controlled trial conducted in 170 clinical sites in 19 countries, adults with a urinary albumin-creatinine ratio (UACR) of 150 to 5000 mg/g and eGFR ≥20 mL/min/1.73 m2 not on SGLT2i were randomized to zibotentan/dapagliflozin, 0.25 mg/10 mg, zibotentan/dapagliflozin, 1.5 mg/10 mg, or placebo/dapagliflozin 10 mg. Effects on fluid retention events, defined as body weight increase from baseline &amp;gt;3% (of which at least 2.5% from total body water) or BNP increase &amp;gt;100% to &amp;gt;200 pg/mL without atrial fibrillation or 100% increase to &amp;gt;400 pg/mL with atrial fibrillation were assessed (NCT04724837). Results Data from the full analysis set is presented including 91 participants treated with 0.25 mg zibotentan and 10 mg dapagliflozin, and 177 participants treated with 10 mg dapagliflozin and placebo. UACR reduction for 0.25 mg zibotentan and 10 mg dapagliflozin was −47.7%, for 10 mg dapagliflozin alone it was −28.3%, making an adjusted mean difference for the combination versus dapagliflozin alone of −27.0%. Cardiometabolic markers are shown in the table. Conclusion In the ZENITH-CKD study zibotentan used at low dose combined with dapagliflozin had incremental effects versus dapagliflozin alone on a range of cardiometabolic risk markers including blood pressure, LDL cholesterol, HbA1c and uric acid, without a significant increase in fluid retention.

Body evaluation in men: the role of body weight dissatisfaction in appearance evaluation, eating, and muscle dysmorphia psychopathology.

Body image dissatisfaction is a significant concern among men, influencing appearance evaluation, eating behaviors, and muscle dysmorphia psychopathology. However, research on these correlations is notably deficient in men, largely because body image concerns are unevenly distributed between genders. Therefore, this study aims to assess the various dimensions of concerns about body image in men and explore their associations with characteristics such as sexual orientation. A cross-sectional study was conducted with 251 adult men from fitness centers in the Veneto Region, Italy. Participants completed self-report questionnaires, including the Eating Attitudes Test (EAT-26), the Appearance Schemas Inventory-Revised (ASI-R), and the Muscle Dysmorphic Disorder Inventory (MDDI). Body weight perception and dissatisfaction were evaluated using a Figure Rating Scale (FRS) with 12 male biometric silhouettes. Participants were divided into three subgroups based on the experienced levels of body weight dissatisfaction: those who rated a smaller body (BWsmaller), those who rated a larger body (BWlarger) more highly relative to their own estimated body size, and those who reported implicit neutrality with their current weight (BWneu). BWsmaller participants reported higher levels of eating-related concern, while BWlarger participants exhibited higher levels of muscle dysmorphia. Additionally, the BWlarger group showed the highest degree of quantitative perceptual underestimation of their body weight. Sexual orientation was found to have an impact on body weight dissatisfaction, with bisexual men more likely to desire an increase in weight and gay men more likely to desire a decrease. Body weight dissatisfaction significantly impacts appearance evaluation, eating behaviors, and muscle dysmorphia psychopathology in males. Tailored interventions that consider individual differences can support the well-being of men. The study provides useful insight into male body image issues, warranting further exploration to inform effective interventions and promote positive body image and mental health in this population.

The effect of exopolysaccharides from EMS-induced Porphyridium cruentum mutant on human epidermal and dermal layers

IntroductionMicroalgae biotechnology utilizes species like Porphyridium cruentum for their valuable phycobiliproteins and exopolysaccharides, which have potential industrial applications and health benefits, particularly in skin condition improvement.MethodsA mutant of P. cruentum LIMS-PS-1061 was developed through ethyl methanesulfonate mutagenesis and subsequent colony screening to study changes in its biomass production and pigment composition under different lighting conditions.Results and discussionThe mutant exhibited a 33.9% increase in dry weight under white light compared to the wild type. Despite maintaining the total pigment content, specific components changed significantly: chlorophyll content decreased 2.20- and 3.61-fold under white and blue light respectively, while phycobiliproteins increased 1.59- and 1.23-fold under the same conditions. These alterations suggest a compensatory mechanism for maintaining photosynthetic capacity. Furthermore, the exopolysaccharides of P. cruentum upregulated genes related to skin moisturization, barrier enhancement, and elasticity, and promoted wound healing through fibroblast migration. This supports the proposed mechanism of action for P. cruentum’s exopolysaccharides in improving human skin conditions by integrating the effects of aquaporin 3, filaggrin, involucrin, loricrin, elastin, and fibrillin-1.

Study the malnutrition status of children aged 6-24 months of the Cham ethnic group in Tan Chau town, An Giang province in 2018

Background: In recent years, according to the investigation report of the Institute of Nutrition, the malnutrition rate of children in remote, faraway, and ethnic minority areas is still high compared to children in other regions. Studying the malnutrition status of children aged 6 to 24 months of the Cham ethnic group in Tan Chau town, An Giang province is a practical need to provide some scientific evidence for interventions to reduce the malnutrition rate of children in the locality. This study aims to explore the nutritional status of children aged 6-24 months of the Cham ethnic group in Tan Chau town, An Giang province in 2018. Methods: Cross-sectional study. Subjects: Cham ethnic children from 6 to 24 months old at the time of the survey and the mothers of the children living in Tan Chau town, An Giang province. Results: Research shows that the average weight and length increase with age group, and boys have higher corresponding average values than girls. The malnutrition group has the highest malnutrition rate in the age group of 6-12 months at 27.2% and the lowest in the age group of 19-24 months at 2.6%. Undernourished group in the Stunted category has the highest undernourishment rate in the age group of 6-12 months at 44.1% and the lowest in the age group of 19-24 months at 25.7%. Undernourished group in the Wasted category has the highest undernourishment rate in the age group of 13-18 months at 13.9% and the lowest in the age group of 19-24 months at 2.6%. Conclusions: The malnutrition status of children aged 6-24 months of the Cham ethnic group in Tan Chau town, An Giang province in 2018 is still quite high.

Mitigation of drought stress effects on alfalfa (Medicago sativa L.) callus through CaO nanoparticles and graphene oxide in tissue culture conditions

Drought stress poses a significant threat to fertile soils worldwide, triggering profound physiological, biochemical, and molecular changes in plants that adversely impact agricultural productivity. This study explores the potential of nanotechnology, specifically Calcium Oxide Nanoparticles (CaO NPs) and Graphene Oxide (GO), to ameliorate the negative effects of drought stress on two distinct alfalfa ecotypes. Seeds from Erzurum and Konya regions were regenerated in the Murashige and Skoog (MS) medium, and ensuing callus formation was induced through 1 mg L−1 2,4-D and 1 mg L−1 kinetin MS medium. The callus samples underwent a one-month treatment with varying concentrations of mannitol (50 and 100 mM), CaO NPs, and GO (0.5 and 1.5 ppm). Results revealed a decrease in dry/wet weight with increasing mannitol concentration, contrasting with an increase in weight under CaO NPs and GO treatment. Proline, DNSA, MDA, and H2O2 exhibited proportional increases under drought stress, while CaO NPs and GO treatments mitigated these effects. Physiological and biochemical analyses identified optimal conditions for Erzurum as 50 mM mannitol/2 CaO NPs/0.5 ppm GO, and for Konya as 50 mM mannitol/0.5 ppm GO. Gene expression analysis indicated up-regulation of mtr-miR159 and mtr-miR393 with heightened drought stress, with down-regulation observed in CaO NPs and GO treatments. Scanning Electron Microscopy (SEM) and Confocal Laser Scanning Microscopy (CLSM) confirmed Ca2+ accumulation in alfalfa tissues. In conclusion, CaO NPs and GO treatments exhibited a significant reduction in the adverse effects of drought stress on alfalfa callus under tissue culture conditions. This research sheds light on the potential of nanotechnological interventions to alleviate the impact of environmental stressors on crop plants, opening avenues for sustainable agriculture in the face of changing climatic conditions. Further investigations are warranted to elucidate the underlying mechanisms and scalability of these findings for field applications.