Significant Increase In Weight Research Articles

Hesperidin & Apigenin Attenuates Diabetes & Lipid Levels in Experimentally Induced Diabetes Mellitus in Wistar Rats.

The aim of the present investigation is to study the antidiabetic potential of Hesperidin and Apigenin in Diabetic rats. Wistar Albino rats of either sex (150 to 200 g) were purchased from the CPCSEA approved vendor New Delhi. A total of three animals were used, which received a single oral dose in 500 mg/kg, body weight of different flavonoids. Doses equivalent to 25 mg and 50 mg per kilogram body weight were calculated, and suspended in 1% w/v Tween 80 solutions for the experiment. For OGTT, Different doses of both flavonoids i.e. Hesperidin & Apigenin were administered 60 min prior to oral glucose load (2.0 g/kg). Diabetes was induced in overnight fasted rats by Streptozotocin (60 mg/kg), 15 min. after the i.p. administration of Nicotinamide (120mg/kg). Streptozotocin was dissolved in citrate buffer (0.1 M, pH 4.5) & nicotinamide was dissolved in normal saline. During the study period of 21 days, animals was weighed at 0, 7, 14 and 21 day and effect of vehicle, standard drug and all solvent fractions on body weight was determined. Blood samples was collected by cardiac puncture and retroorbital plexus method into EDTA sprinkled tubes and centrifuged at 3000 rpm for 20 min. Serum was separated as supernatant and stored at -20°C until analysis performed. The biochemical parameters, namely hemoglobin, urea, creatinine, total protein, total cholesterol, triglycerides, HDL determined. The other biochemical tests were performed using kits from Erba Diagnostics. Hesperidin and Apigenin significantly prevented the increase in blood glucose levels after 60 min. of glucose administration at the doses of 25 and 50 mg/kg. After 21 days blood samples were collected by retro-orbital plexus under mild anesthesia. Diabetic control group with no drug treatment showed no significant difference in the fasting serum glucose level after 21 days treatment as compared to the initial day treatment. Hesperidin & Apigenin (25 mg/kg & 50 mg/kg) treated diabetic rat showed a significant (p < 0.05) increase in body weight. The diabetic rat treated with glibenclaimide (10mg/kg) showed gradual and consistent increase in body weight. Treated diabetic rat with Hesperidin & Apigenin showed significant fall in total cholesterol, triglycerides, HDL-C, LDL-C and VLDL-C level at dose of 25 and 50 mg/kg. The Hesperidin and Apigenin had the antidiabetic activity with effects on lipids and other kidney markers..

Anti-implantation and uterotonic properties of Mentha pulegium L. in female Sprague-Dawley rats

Background: Some traditional herbs disrupt endocrine-endometrial synchrony, affecting embryo-endometrium communication during fertility. Hormonal imbalances cause non-receptive conditions, leading to anti-implantation or abortion. Historically, Mentha pulegium has served for contraceptive and abortive purposes. Its effects on the post-coital contraceptive and hormonal activities were evaluated. Methods: Thirty-six Sprague-Dawley female rats were selected based on the presence of copulation plugs and received 200, 500, and 1000 mg/kg of Hydroethanolic leaf extract of Mentha pulegium L. (MPE) for seven days. Reproductive organ weights and serum estrogen and progesterone levels were measured. The resorption index, anti-implantation activity, and pre-implantation loss were also calculated using the number of implantation sites and resorptions in all treatments. Data were presented as mean±standard error mean (SEM), and significance was defined as p<0.05 using one-way ANOVA. Results: Post-coital administration of MPE resulted in resorptive, pre-implantation loss, and anti-implantation activity. A dose of 200 mg/kg reduced the number of implantations and exhibited a high resorption index, percentage pre-implantation loss, and anti-implantation activity. A marked decline in serum progesterone levels and a significant reduction in serum estrogen and progesterone ratio was observed at 200 mg/kg MPE. A significant increase in uterine weight was observed in the 500 mg/kg treatment. Doses of 500 and 1000 mg/kg resulted in a significant reduction in anti-implantation activity. Conclusions: The observed anti-implantation activity and pre-implantation loss suggest the abortifacient properties of MPE. However, its effects were seen to be dose-dependent.

Impact of dielectric barrier discharge plasma and plasma-activated water on cotton seed germination and seedling growth

Unfavorable environmental conditions during planting can reduce seed germination and hinder seedling growth. To address this issue, manufacturers are exploring innovative and cost-effective methods, such as cold plasma discharge. This simple, low-cost, and efficient physical technique induces significant biological responses in seeds and plants without the use of traditional, environmentally hazardous chemicals. This study investigated the impact of dielectric barrier discharge (DBD) plasma and plasma-activated water (PAW), produced by gliding arc plasma, on the germination and seedling growth of My344 cotton seeds. The seeds were pre-treated with 80 W of DBD plasma for 0, 1, 2, and 3 min, and subsequently soaked for 90 min in PAW with varying pH levels of 5.82, 3.88, 3.63, and 3.38. The results showed that plasma treatment positively influenced seed germination and seedling growth. The highest germination percentage (98.89 %) was observed with 1 min of DBD treatment, followed by PAW priming at pH levels of 3.63 and 3.38. Additionally, a 3-min DBD treatment followed by soaking in PAW with a pH of 3.63 led to significant increases in stem length (76.76 %), root length (48.77 %), and wet weight (76.44 %). Furthermore, it was observed that the electrical conductivity of the seeds in all groups decreased significantly with increased PAW acidity. The physical and chemical effects of cold DBD plasma on the seed surface, as well as changes in hydrophilicity, were further examined using scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and water contact angle imaging.

Beneficial effects of Haematococcus pluvialis on growth and hepatopancreas health status in crayfish (Procambarus clarkii) via remodeling the gut microbial metabolic functions

Plant proteins fulfill roles in low-fishmeal diets for crustaceans, but their overuse could have negative effects. Haematococcus pluvialis has the potential to be used as a functional additive due to its high astaxanthin. As such, this study aimed to investigate the effects of dietary H. pluvialis supplementation on growth, hepatopancreas health, and gut metabolic functions in crayfish. 720 crayfish with average weight around 9.20 g were randomized into six treatments (HP0, HP0.3, HP0.6, HP0.9, HP1.2, and HP1.5) in three replications each, and fed six different dosages of H. pluvialis over sixty days. Crayfish exposed to H. pluvialis at concentrations of 0.3, 0.6, and 0.9 % showed significant increases in final average weight, weight gain rate, and specific growth rate (P < 0.05) compared to the HP0 group, together with the highest contents of muscle and shell astaxanthin in the HP0.9 group. Furthermore, increasing H. pluvialis supplementation exhibited the potential to repair hepatopancreas, as demonstrated by the decrease in hemolymph malondialdehyde (MDA) content and activities of alanine aminotransferase and aspartate aminotransferase, as well as the increase in the total protein content, superoxide dismutase, and glutathione peroxidase (GSH-Px) activities. Moreover, high H. pluvialis diets improved microbial dysbiosis by increasing specific microbes, the alpha diversity index, and shifting prominent phyla such as Proteobacteria and Firmicutes. Specifically, dietary H. pluvialis inclusion significantly decreased Vibrio (Proteobacteria) compared to the HP0 group (P < 0.05), but Tyzzerella (Firmicutes) showed the opposite regulatory pattern. A further statistical check revealed that 20 differential OTUs were shared by all H. pluvialis groups compared to the HP0 group, with OTU1439 and OTU2941 identified as the main growth-liver health contributors. Accordingly, high H. pluvialis diets contributed to more complex and stable microbial networks, and down-regulated alanine, aspartate, and glutamate metabolism, as well as lipopolysaccharide biosynthesis. Taken above, the optimal dietary H. pluvialis inclusion level was recommended to be 0.78–0.86 % according to the growth and astaxanthin contents. High H. pluvialis feeding reversed gut microbial dysfunction and improved hepatopancreas antioxidant capacity.

Postnatally overfed mice display cardiac function alteration following myocardial infarction

BackgroundCardiovascular (CV) pathologies remain a leading cause of death worldwide, often associated with common comorbidities such as overweight, obesity, type 2 diabetes or hypertension. An innovative mouse model of metabolic syndrome induced by postnatal overfeeding (PNOF) through litter size reduction after birth was developed experimentally. This study aimed to evaluate the impact of PNOF on cardiac remodelling and the development of heart failure following myocardial infarction. MethodsC57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for normally-fed (NF) control and PNOF group respectively. After weaning, all mice had free access to standard diet and water. At 4 months, mice were subjected to myocardial infarction (MI). Echocardiographic follows-up were performed up to 6-months post-surgery and biomolecular analyses were carried-out after heart collection. FindingsAt 4 months, PNOF mice exhibited a significant increase in body weight, along with a basal reduction in left ventricular ejection fraction (LVEF) and an increase in left ventricular end-systolic area (LVESA), compared to NF mice. Following MI, PNOF mice demonstrated a significant decrease in stroke volume and an increased heart rate compared to their respective initial values, as well as a notable reduction in cardiac output 4-months after MI. After 6-months, left ventricle and lung masses, fibrosis staining, and mRNA expression were all similar in the NF-MI and PNOF-MI groups. InterpretationAfter MI, PNOF mice display signs of cardiac function worsening as evidenced by a decrease in cardiac output, which could indicate an early sign of heart failure decompensation.

Doublecortin-immunoreactive neurons in the piriform cortex are sensitive to the long lasting effects of early life stress.

The olfactory system is a niche of continuous structural plasticity, holding postnatal proliferative neurogenesis in the olfactory bulbs and a population of immature neurons in the piriform cortex. These neurons in the piriform cortex are generated during embryonic development, retain the expression of immaturity markers such as doublecortin, and slowly mature and integrate into the olfactory circuit as the animal ages. To study how early life experiences affect this population of cortical immature neurons, we submitted mice of the C57/Bl6J strain to a protocol of maternal separation for 3 h per day from postnatal day 3 to postnatal day 21. Control mice were continuously with their mothers. After weaning, mice were undisturbed until 6 weeks of age, when they were weighted and tested in the elevated plus-maze, a standard test for anxiety-like behavior, to check for phenotypical effects. Mice were then perfused, and their brains processed for the immunofluorescent detection of doublecortin and the endogenous proliferation marker Ki67. We found that maternal separation induced a significant increase in the body weight of males, but not females. Further, maternally separated mice displayed increased exploratory-like behavior (i.e., head dipping, velocity and total distance traveled in the elevated plus maze), but no significant differences in anxiety-like behavior or corticosterone levels after behavioral testing. Finally, we observed a significant increase in the number of complex doublecortin neurons in the piriform cortex, but not in the olfactory bulbs, of mice submitted to maternal separation. Interestingly, most doublecortin neurons in the piriform cortex, but not the olfactory bulb, express the epigenetic reader MeCP2. In summary, mild early life stress results, during adolescence, in a male-specific increase in body weight, alteration of the exploratory behaviors, and an increase in doublecortin neurons in the piriform cortex, suggesting an alteration in their maturation process.

Mild condition lignin modification enabled high-performance anticorrosive polyurethane coating

The diverse active hydroxyl groups of lignin pose challenges in the preparation of lignin-based polyurethane coatings with exceptional long-term anticorrosive properties. Here, the dense and defect-free lignin-based polyurethane coating with a thickness of 25 ± 5 μm was successfully synthesized using a mild hydroxypropyl lignin modification approach, exhibiting outstanding barrier properties (|Z| > 109 Ω cm2) and long-term anti-corrosion performance exceeding 120 d. Under ambient conditions (i.e., 25 °C and atmospheric pressure), propylene oxide was directly blended with the alkali solution of lignin to effectively convert phenolic hydroxyl groups into more reactive aliphatic hydroxyl groups, while also minimizing the significant increase in molecular weight caused by lignin condensation. As a result, the high crosslinking density of lignin polyurethane coatings effectively prevented the penetration of corrosive media and enhanced the long-term corrosion resistance of the coatings. Overall, the results demonstrate that a mild hydroxypropyl modification process is an effective and facile strategy to prepare highly reactive lignin-based polyols, which is crucial for the development of high-performance bio-based polyurethane anticorrosive coatings.

PSI-21 Limited impact of hypothyroidism on porcine fetal growth during mid to late gestation

Abstract In the fetal pig, both circulating thyroid hormone and growth rate are known to increase throughout gestation; however, the functional association between these coincident factors has not been established. Thus, the objective of this project was to investigate this cause-and-effect relationship by evaluating the impact of induced fetal hypothyroidism on fetal growth during mid to late gestation. To induce fetal hypothyroidism, n = 12 pregnant gilts were orally treated with the goitrogen methimazole (MMI) at a dose of 5 mg/kg/d for 21 d, with n = 3 gilts starting treatment on gestation d 34, 45, 55 and 65. An equivalent group n = 12 of gilts were sham treated for the same periods to produce gestationally age-matched euthyroid control litters (CON). Upon completion of the treatment period, gilts were humanely euthanized, and the resulting populations of n = 174 MMI and n = 166 CON fetuses deeply phenotyped. No meconium-stained fetuses were observed at any time point, and only 5 mummified fetuses were observed (3 CON, 2 MMI), indicating treatment has no effect on fetal viability. Fetal body weight (BW) and the weights of individual organs including thyroid, liver, heart, lung, kidney, spleen, and brain were collected. In addition, fetuses were imaged in both left and right lateral recumbency for subsequent morphometric assessment using a custom analysis pipeline in ImageJ. Image analysis yielded parameters including crown-rump length, girth, brow length, depth at the snout/skull junction, depth at the snout/nose junction, and area under the skull curvature (AUC). Left and right measurements for all morphometric parameters were found to be highly correlated (r2 &amp;gt; 0.9) indicating a repeatable measure using this approach. Statistical analysis of all phenotypic differences was carried out using a linear mixed effect model including gestational age and treatment as fixed effects and gilt as a random effect. A significant increase in both absolute and relative thyroid weights indicated the development of goiter and thus, successful induction of hypothyroidism within the MMI litters. In addition, a significant treatment by time interaction was observed, with 0.014 g and 0.21 g increase at d 55 and 66, respectively, indicating reduced compensatory action within the fetal hypothalamic-pituitary-thyroid axis during this earliest period. Liver weight as a percentage of BW decreased from 6.06% to 2.56% between d 55 and 86 in the CON group but was significantly increased at all time points in response to MMI induced hypothyroidism (P &amp;lt; 0.01). A corresponding increase in brain to liver weight ratio over time was suppressed in MMI fetuses (P &amp;lt; 0.05). While all other phenotypic parameters were significantly altered by gestational age, there was no significant impact of fetal hypothyroidism. Collectively, the results indicate that fetal growth during mid to late gestation is not driven by fetal thyroid hormone.

Postoperative Feeding in Cleft Surgery: A Systematic Review.

Postoperative feeding is crucial for the recovery of children after cleft surgery. The literature outlines diverse feeding methods with varying recommendations on the duration of non-nipple feeding postsurgery. This study aims to explore reported postoperative feeding modalities for infants undergoing primary cleft lip/palate repair, concentrating on their influence on feeding improvement and complication reduction. PubMed, Cochrane, and Web of Science databases were queried for original English articles without any date restrictions. This review was conducted in accordance with the 2020 PRISMA. The MINORS criteria was used to assess quality of studies. Of 696 abstracts, 9 full-text articles were included, consisting of 459 children with cleft lip (n = 221) & cleft lip/palate (n = 238). Feeding modalities included bottle, breastfeeding, spoon, syringe, and nasogastric tube. Two studies found a significant increase in weight with breastfeeding compared to spoon or cup. Two studies found partial wound dehiscence using spoons, and two studies reported dehiscence using bottles. Post-palatoplasty, two studies showed a decrease in hospital stay in infants breastfed (2.1 & 5.8 days) vs spoon-fed (6 days). Analgesia was reduced in the breastfed group vs spoon/nasogastric tube. This review highlights the importance of postoperative feeding in the recovery of infants with cleft lip/palate. Evidence suggests that breastfeeding may offer advantages in terms of weight gain and reduced hospital stay, while potentially minimizing the need for postoperative analgesia. The limited number of studies and variability in their outcomes underscore the need for further research to establish evidence-based guidelines for postoperative feeding.

Enhancing Soybean Growth with Phytohormone-enriched PGPR Bioinoculants and Biofertilizers in Plant Stress Physiology

Background: The present investigation aimed to evaluate the effects of plant growth-promoting rhizobacteria (PGPR) bioinoculants and their carrier-based biofertilizers on the physiology of soybean. Methods: Seeds of two soybean varieties (cv. NARC-1 and cv. William-82) were either soaked in broth cultures of two PGPR strains, Planomicrobium chinense (MF616408) and Pseudomonas putida (KX574857), containing 106 cells/mL, or coated with biofertilizers. Three biofertilizers, namely biostimulant, biozote and biofert, were used. Result: Significant increases in root and shoot weight were observed with both liquid bioinoculants and carrier-based biofertilizers compared to the control. The consortium of P. chinense and P. putida resulted in the highest proline content and superoxide dismutase (SOD) activity. Biostimulant-treated plants exhibited higher catalase (CAT) activity and phenolics content. Indole-3-acetic acid (IAA) and gibberellic acid (GA) levels were enhanced in plants treated with PGPR and biofertilizers. Specifically, P. chinense and the biostimulant significantly promoted IAA content in cv. William-82, while biozote and P. chinense treatments increased GA content in both varieties. The consortium of P. chinense and P. putida showed the lowest ABA levels. The highest IAA/ABA and GA/ABA ratios were observed in plants treated with P. chinense. Liquid bioinoculants had a more pronounced effect on plant growth than carrier-based biofertilizers, though biofertilizers had stronger residual effects on rhizosphere soil organic matter. The combined effects of phytohormones, sugar, protein and proline production and antioxidant enzyme activity influenced plant growth and development.

Sex-specific modulation of renal epigenetic and injury markers in aging kidney.

Sex differences in renal physiology and pathophysiology are now well established in rodent models and in humans. Epigenetic programming is known to be a critical component of renal injury, as studied mainly in male rodent models; however, not much is known about the impact of biological sex and age on the kidney epigenome. We sought to determine the influence of biological sex and age on renal epigenetic and injury markers, using male and female mice at 4 mo (4M; young), 12 mo (12M), and 24 mo (24M; aged) of age. Females had a significant increase in kidney and body weights and serum creatinine levels and a decrease in serum albumin levels from 4M to 24M of age, whereas minor changes were observed in male mice. Kidney injury molecule-1 levels in serum and renal tissue greatly enhanced from 12M to 24M in both males and females. Circulating histone 3 (H3; damage-associated molecular pattern molecules) levels extensively increased with age; however, males had higher levels than females. Overall, females had markedly high histone acetyltransferase (HAT) activity than age-matched males. Aged mice had decreased HAT activity and increased histone deacetylase activity than sex-matched 12M mice. Aged females had substantially decreased renal H3 methylation at lysine 9 and 27 and histone methyltransferase (HMT) activity than aged male mice. Antiaging protein Klotho levels were significantly higher in young males than age-matched females and decreased substantially with age in males, whereas epigenetic repressor of Klotho, trimethylated H3K27, and its HMT enzyme, enhancer of zeste homolog 2, increased consistently with age in both sexes. Moreover, nuclear translocation and activity of proinflammatory transcription factor nuclear factor-κB (p65) were significantly higher in aged mice. Taken together, our data suggest that renal aging lies in a range between normal and diseased kidneys but may differ between female and male mice, highlighting sex-related differences in the aging process.NEW & NOTEWORTHY Although there is evidence of sex-specific differences in kidney diseases, most preclinical studies have used male rodent models. The clinical data on renal injury have typically not been stratified by sex. Our findings provide convincing evidence of sex-specific differences in age-regulated epigenetic alterations and renal injury markers. This study highlights the importance of including both sexes for better realization of underlying sex differences in signaling mechanisms of aging-related renal pathophysiology.

A comparative metabolomics study of delayed-harvested and pumpkin grafted cucumbers

Cucumber is a widely consumed vegetable crop known for its rich nutrient composition and distinctive flavor, influenced by both volatile and non-volatile compounds. Grafting and delayed harvesting are crucial strategies for increasing cucumber yield. The present study investigates the impact of delayed harvesting at different developmental stages and grafting on the metabolic profile, flavor, and overall quality of cucumber fruits Yuxiu 2 (YX) using UPLC-MS/MS and GC-MS/MS techniques. The results indicate that delayed harvesting of YX led to significant increases in length, diameter, and weight from 12 to 24 days after pollination (DAP), with minimal growth beyond 24 DAP. However, grafting did not affect these physical parameters compared to self-rooted plants. Furthermore, metabolic profiling reveals that delayed harvesting enhances the concentration of certain non-volatile metabolites, including alkaloids, organic acids, and phenolic acids, while leading to a reduction in flavonoid contents. Overall, 140 non-volatile and 26 volatile differential metabolites were screened at three developmental stages. Notably, four new organic acids (6-amino hexanoic acid, 5-amino valeric acid, 1-hydroxy-2-naphthoic acid, and succinic semialdehyde) and three novel alkaloids (3-indole acetonitrile, epinephrine, and serotonin) were identified. Volatile compounds, such as aldehydes, esters, terpenes, alcohols, and ketones, exhibit a peak in concentration at 24 DAP, followed by a decline. The characteristic cucumber flavor compound, (E,Z)-2,6-nonadienal, remains consistent across all developmental stages. In grafted cucumber fruits, a total of 113 non-volatile and 11 volatile differential metabolites were screened, and among them, ten unique non-volatile metabolites were detected in grafted fruits, contributing to the sour and bitter taste of cucumbers. Moreover, some of the metabolites like (1S,4S,4aR)-1-isopropyl-4-methyl-7-methylene-1,2,3,4,4a,5,6,7-octahydronaphthalene with pentylenetetrazol contribute to an undesirable camphor-like odor. The study concludes that while delayed harvesting and grafting practices can increase cucumber yield, they also significantly alter the fruit’s metabolic profile, impacting taste and flavor.

Abstract MP07: Efficacy and safety of aprocitentan in patients with resistant hypertension and elevated NT-proBNP

Background and Objectives: The endothelin ETA/ETB receptor antagonist aprocitentan (APRO) decreased blood pressure (BP) in patients with confirmed resistant hypertension (RHT) in the PRECISION study. 19.6% of the overall population (143 subjects) had a reported history of Heart Failure (HF). It is well known that in subjects with RHT, HF is often underdiagnosed. In PRECISION, NT-proBNP (a marker of HF) was measured. Here we report the efficacy and safety of APRO in patients with increased NT-proBNP. Methods: 730 patients with RHT were switched to a standardized fixed-dose combination of amlodipine/valsartan/hydrochlorothiazide from their existing anti-hypertensive and diuretic medication and then randomized to APRO (12.5 mg or 25 mg) or placebo in PRECISION. This analysis considers subjects with baseline blood levels of NT-proBNP &gt;125 pg/mL. Change in BP, incident cases of edema/fluid retention and change in body weight were assessed. Descriptive statistics are presented. Results: 236 enrolled subjects (32.3%) had NT-proBNP levels from 125–1125 pg/mL. At Week 4, APRO 12.5 mg decreased trough sitting systolic BP (SiSBP) by mean (SD) 14.2 (16.7) mm/Hg, APRO 25 mg by 15.8 (13.5) mm/Hg and placebo by 9.9 (18.0) mm/Hg, confirming that the effect was greater for APRO than placebo with no apparent difference between 12.5 and 25 mg, as observed in the overall population enrolled in PRECISION. The effect was maintained with APRO 25 mg at Week 36 with a decrease of 18.4 (15.2) mm/Hg versus baseline. Adverse events of edema/fluid retention were reported with an incidence of 13.4%, 25.7% and 1.2% in the 12.5 mg, 25 mg and placebo group, respectively, at Week 4. During the SB part up to 36 weeks edema/fluid retention was reported by 26.1% of subjects with 25 mg. Body weight change at Week 4 was +0.5, +0.7 and -0.2 Kg with 12.5 mg, 25mg and placebo, respectively. This weight increase was reversible: a subsequent decrease resulted in a difference versus baseline of 0.4 kg at Week 36. NT-proBNP ratio vs baseline (geometric mean) was 0.94, 0.86 and 0.78 with 12.5 mg, 25 mg and placebo, respectively, at Week 4. There was no increase over time, the ratio vs baseline was still below 1 (0.91) at Week 36. Conclusion: Aprocitentan is effective in patients with RHT and elevated NT-proBNP. Edema and fluid retention are more common in this sub-group compared with the overall population included in PRECISION, but it is not linked to significant weight gain or increase of NT-proBNP.

Establishing and Characterizing the Molecular Profiles, Cellular Features, and Clinical Utility of a Patient-Derived Xenograft Model Using Benign Prostatic Tissues

Benign prostatic hyperplasia (BPH) is a common condition marked by the enlargement of the prostate gland, which often leads to significant urinary symptoms and a decreased quality of life. The development of clinically relevant animal models is crucial for understanding the pathophysiology of BPH and improving treatment options. This study aims to establish a patient-derived xenograft (PDX) model using benign prostatic tissues to explore the molecular and cellular mechanisms of BPH. PDXs were generated by implanting fresh BPH (transition zone) and paired normal (peripheral zone) prostate tissue from 8 patients under the renal capsule of immunodeficient male mice. Tissue weight, architecture, cellular proliferation, apoptosis, prostate-specific marker expression, and molecular profiles of PDXs were assessed after 1 week and 1, 2, or 3 months of implantation by immunohistochemistry, enzyme-linked immunosorbent assay, transcriptomics, and proteomics. Responses to finasteride, a standard-of-care therapy, were evaluated. PDXs maintained histologic and molecular characteristics of the parental human tissues. BPH, but not normal PDXs, demonstrated significant increases in weight and cellular proliferation, particularly at 1 month. Molecular profiling revealed specific gene and protein expression patterns correlating with BPH pathophysiology. Specifically, an increased immune and stress response was observed at 1 week, followed by increased expression of proliferation markers and BPH-specific stromal signaling molecules, such as BMP5 and CXCL13, at 1 month. Graft stabilization to preimplant characteristics was apparent between 2 and 3 months. Treatment with finasteride reduced proliferation, increased apoptosis, and induced morphologic changes consistent with therapeutic responses observed in human BPH. Our PDX model recapitulates the morphologic, histologic, and molecular features of human BPH, offering a significant advancement in modeling the complex interactions of cell types in BPH microenvironments. These PDXs respond to therapeutic intervention as expected, providing a valuable tool for preclinical testing of new therapeutics that will improve the well-being of BPH patients.

ORGAN WEIGHT VARIATIONS IN CASES OF DROWNING IN FRESH WATER IN COMPARISION WITH NON-DROWNING DEATHS

Background: Diagnosis of drowning as a cause of death still remains a challenge in forensic pathology due to scanty pathognomic signs. Traditional diagnostic methods have shown limitations, prompting interest and pursuit on alternative approaches. One such approach involves analysing the weight of internal organs, particularly the lungs and spleen, to provide additional supportive evidence. Objectives: This study aimed to investigate the variations in organ weights in wet fresh water drowning cases compared to deaths due to other causes and assess the utility of the drowning index as a diagnostic tool. Methods: The study analyzed the findings in 245 cases,that were brought to the Department of Forensic Medicine, Government Medical College, Kozhikode for medico-legal autopsy. It included 83 cases of hanging, 71 cases of wet fresh water drowning and 91 cases of traumatic brain injury. Lung, spleen and other organ weights were measured using an electronic scale. The data obtained were subjected to statistical analysis using SPSS version 18 with focus on comparative analysis across the different types. Results: The results showed a significant increase in weight of lungs and a decrease in spleen weight in persons who had died of drowning when compared to other causes of death. However, the drowning index, though elevated in drowning cases, did not consistently surpass the established diagnostic threshold, suggesting variability and potential limitations in its application as a reliable diagnostic marker. Conclusion: Variations in weights of lungs and spleen can provide valuable clues in the diagnosis of drowning, but their diagnostic utility as a stand alone criteria is limited to a certain extent by case-to-case variability. The drowning index demonstrates potential as a supplementary diagnostic tool but requires further validation through more extensive studies to improve its reliability and accuracy.

Reductions in functional muscle mass and ability to ambulate in Duchenne muscular dystrophy from ages 4 to 24 years.

Duchenne muscular dystrophy (DMD) results in a progressive loss of functional skeletal muscle mass (MM) and replacement with fibrofatty tissue. Accurate evaluation of MM in DMD patients has not previously been available. Our objective was to measure MM using the D3creatine (D3Cr) dilution method and determine its relationship with strength and functional capacity in patients with DMD over a wide range of ages. Subjects were recruited for participation in a 12month, longitudinal, observational study. Here, we report the baseline data. A 20mg dose of D3Cr dissolved in water was ingested by 92 patients with DMD (ages 4-25years) followed later with a fasting urine sample. Enrichment of D3creatinine was determined by liquid chromatography-mass spectrometry analysis. The North Star Ambulatory Assessment (NSAA) total score was determined for ambulatory participants, and the Performance of Upper Limb (PUL 2.0) total score and grip strength for all participants. We observed a significant age-associated increase in body weight along with a substantial decrease in MM/body weight (%MM). MM and %MM were associated with PUL score (r=0.517, P<0.0001 and r=0.764, P<0.0001 respectively). The age-associated decrease in MM and %MM was strongly associated with ambulatory status. We observed very little overlap in %MM between ambulant and non-ambulant subjects, suggesting a threshold of 18-22% associated with loss of ambulation. MM is substantially diminished with advancing age and is highly related to clinically meaningful functional status. The D3Cr dilution method may provide a biomarker of disease progression and therapeutic efficacy in patients with DMD or other neuromuscular disorders. KEY POINTS: The non-invasive D3creatine dilution method provides novel data on whole body functional muscle mass (MM) in a wide range of ages in patients with DMD and reveals profoundly low functional MM in older non-ambulant patients. The difference in %MM between ambulant and non-ambulant subjects suggests a threshold for loss of ambulatory ability between 18 and 22% MM. The data suggest that as functional MM declines with age, maintaining a lower body weight may help to conserve ambulatory ability.

Long-lasting effects of post-traumatic stress disorder in Yazidi women living in Northern Iraqi camps

The severity of post-traumatic stress disorder and its long-lasting effects among the Yazidi population has not yet been investigated. ObjectivesThis study evaluated the impact of PTSD severity and chronicity on physiological and anthropometric parameters in women survivors of the genocide-related events after the so-called Islamic State of Iraq and Syria (ISIS) attack in 2014. MethodsThe diagnosis PTSD was assessed using PTSD Checklist for DSM-5 (PCL-5). Participants were divided into: External control (healthy individuals living outside the camps), Internal control (healthy individuals living in the camps), and PTSD group (individuals diagnosed with PTSD). The PTSD group was subdivided according to chronicity <2 years, 2–5 years, and >5 years and subdivided according to PTSD severity into “Moderate”, “Severe” and “Extreme”. Systolic blood pressure (SBP), diastolic blood pressure (DBP), blood oxygen saturation (SPO2) and heart rate (HR) were evaluated. Weight, height and waist circumference were measured. Body mass index (BMI) and waist-to-height ratio (WHtR) were calculated. ResultsThe PTSD group showed significant increases in SBP, DBP, heart rate, BMI, WC, weight, and WHtR compared to the control groups. SPO2 values decreased in the PTSD group. As the disease progressed, there were further increases in SBP, DBP, heart rate, BMI, WC, WHtR, and weight. Similar increases were observed with the severity of the disease. ConclusionOur data indicates that a long-term impact on physiological and anthropometric parameters is present in women diagnosed with PTSD which might be aggravated by the severity and chronicity of the disease.

Pharmacodynamic interaction between tamsulosin and finasteride treatment in mice induced benign prostate hyperplasia using the Chou-Talalay method

This study was conducted to evaluate the efficacy and interaction of tamsulosin with finasteride treatment on induced benign prostate hyperplasia (BPH) in mice. BPH was induced by subcutaneous injection of testosterone propionate (20 mg/kg) for 30 days. Eighty-five mice were divided into five groups. The first group (G1): twenty-five mice induced BPH treated with tamsulosin orally and divided into five equal subgroups with doses (0.017, 0.052, 0.087, 0. 123, and 0.158) mg/kg, the second group (G2): twenty-five mice induced BPH treated with finasteride orally and divided into five equal subgroups with doses (0.175, 0.527, 0.878, 1.23, and 1.580) mg/kg, the third group (G3): twenty-five mice induced BPH treated with a combination of tamsulosin with finasteride orally, and divided into five equal subgroups with doses (0.0085, 0.0875), (0.026, 0.2635), (0.0435, 0.439) , (0.0615, 0.615) and ( 0.079 , 0.790 ) mg/kg respectively. Fourth group (G4): five mice induced BPH and treated distilled water. Fifth group (G5): five mice were not inducing BPH and without any treatment. The results showed a gradual significant increase in prostate weight % and prostate index % inhibitions until reached saturation in the last two doses of tamsulosin, finasteride, and combination groups, the maximum effective doses of tamsulosin and finasteride were (0.156) and (1.495) mg/kg respectively. Moreover, the effective dose of the combination (tamsulosin and finasteride) was estimated (0.06876, 0.6876) mg/kg respectively as well as the type of interaction was synergism and the value of the combination index was 0.046. The combination of tamsulosin with finasteride showed a synergistic effect in BPH treatment by minimizing the side effect of each drug as a result of decreasing the dose of each one.

Antidiabetic effects of aqueous leaf extract of Vernonia amygdalina on serum liver markers in streptozotocin-induced diabetic albino Rats: a new data to support its Anti-diabetic effect

BackgroundNumerous plants have been explored for their potential antidiabetic properties, and Vernonia amygdalina (VA) stands among them. This study aims to investigate the antidiabetic activities of VA and validate its efficacy.MethodsAn aqueous extract of Vernonia amygdalina leaves was obtained through maceration. The antidiabetic effects of this plant extract were evaluated in vivo using diabetic model rats. Albino Wistar rats were induced into a diabetic state through intraperitoneal injection of streptozocin and subsequently treated with an optimal dose of 250 mg/kg aqueous extract of VA over a 21-day period. Parameters such as body weight, blood glucose levels, and serum marker enzymes were measured.ResultsThe results demonstrated a significant reduction (p < 0.05) in the glucose levels of streptozocin-induced diabetic rats following treatment with VA extract, highlighting its potential as an antidiabetic agent that performed comparably to the reference drug, glimepiride. Additionally, a significant increase (p < 0.05) in the body weight of the treated diabetic rats was observed. Aqueous extracts also significantly (p < 0.05) altered the serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a manner similar to the glimepiride-treated group.ConclusionThis study affirms the anti-diabetic effects of the aqueous extract of Vernonia amygdalina in streptozotocin-induced diabetic rats and suggests that the extract holds promise as an important phytomedicine for the development of more effective treatments for diabetes.

Systematic review of randomised controlled clinical trials examining effectiveness of contingent financial rewards for smoking cessation during pregnancy: intention-to-treat and causal effects on birthweight.

Objective: To examine birth weight change caused by adding financial rewards for smoking cessation compared to no rewards for pregnant women. To estimate the average expected birth weight change for those who quit because of rewards. This study updates a previous systematic review and refocuses the outcome from smoking cessation to birth weight.Eligibility Criteria: Trials with an experimental design allowing treatment effects to be attributed to rewards were included. Trials involving non-pregnant participants, or with no report of magnitude, treatment duration, timing or where most rewards were contingent on another behaviour (e.g., treatment attendance) were excluded.Information sources: Medline, PsycInfo, Embase, Cochrane (Central Register of Controlled Trials, Tobacco Addiction Group Specialised Register and Database of Systematic Reviews), and PubMed searched to 5th December 2023.Risk of bias: Risk of bias and certainty of evidence used Cochrane 'Risk of bias 2' and GRADE assessments.Synthesis of results: Primary analysis estimated Intention-To-Treat (ITT) mean birthweight difference when randomised to offer of rewards versus control. Within-trial estimates and standard errors were derived from mean, standard deviation, and sample size data provided, or from publications. Pooled ITT estimates used common (fixed) and random effects models. Secondary analyses used trial team supplied data to derive Complier Average Causal Effect (CACE) estimate of smoking cessation on birth weight, and a standard error. Estimates were pooled using common and random effects models. Similar analyses were applied to low birth weight (<2500g), birth weight for gestational age z-scores, and small for gestational age (<10 th percentile). Included studies: Primary analysis included 8 trials (2351 participants) from the UK (2 trials, 1475 participants); France (1 trial, 407 participants), and the US (6 trials, 469 participants). Secondary analysis included 7 trials as data retrieval from one US trial (51 participants) was not possible.Synthesis of results: Primary ITT analysis (2351 participants) estimated a mean 46.3g (95% CI: 0.0 to 92.6) birth weight increase when offered financial rewards for smoking cessation. Secondary CACE analysis (2239 participants) estimated a mean 206.0g (95% CI: -69.1 to 481.1) increase for smokers who quit because of rewards. There was no effect on low birth weight (<2500g), or birth weight adjusted for gestational age, though less babies were born small for gestational age, particularly if cessation was because of rewards (CACE risk difference -17.7%; 95% CI: -34.9% to -0.4%). Limitation of evidence: Sample size led to imprecision - maximum 2351 participants. A single trial of 3712 participants would give 80% power at 5% significance to show a 46g increase from 3.1kg to 3.146kg with 0.5kg standard deviation in both groups. Consistency - trials where smoking cessation increased (7 of 8) all showed a mean birth weight increase. In one trial smoking cessation fell as did birth weight. Bias is unlikely as 3 of 4 trials with no birth weight data showed increased cessation consistent with higher mean birth weight. Interpretation: Trials of contingent financial rewards for smoking cessation have previously been shown to more than double pregnancy quit rates. We have uncovered a significant (46g) population level increase in mean birth weight, driven by a clinically important mean increase (206g) for those who quit because of financial rewards associated with a reduction in Small for Gestational Age births. Funding: Review update - The U.S. National Institute of Health, National Institute of General Medical Sciences Center of Biomedical Research Excellence Award P30GM149331. Data retrieval, synthesis and analysis - Scottish Cot Death Trust.Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024494262.