Significant Differences In Control Research Articles

Synthesis, Preclinical Toxicity, and Biodistribution of [18F]AVT-011 to Assess the P-Glycoprotein Function.

Introduction: Many studies have reported the role of P-glycoprotein (Pgp) in chemoresistance in various pathological conditions such as cancer and neurodegenerative diseases, such as Alzheimer's. In this study, we are reporting the high-performance liquid chromatography (HPLC)-based purification of fluorine-18 [18F]AVT-011 and its preclinical evaluation. Methods: AVT-011 was labeled with 18F using the nucleophilic substitution method by heating the reaction mixture at 110°C for 10 min, followed by purification using preparative HPLC and C18ec cartridge. The in vitro cell uptake study was carried out in U87 cells with and without an inhibitor. The preclinical toxicity was carried out in CD1 mice in three groups, including control, AVT-011 treated, and [18F]AVT-011 treated. The biodistribution study was done in CD1 mice (n = 12) after intravenous injection of 4-6 MBq [18F]AVT-011, and mice were sacrificed at various time intervals. A dose of 3.7 ± 0.7 MBq of [18F]AVT-011 was injected intravenously in the healthy Swiss albino mice, and the whole-body micro-positron emission tomography was acquired at 0-, 30-, 60-, and 120-min postinjection. Results: The radiochemical purity of [18F]AVT-011 was 97 ± 1.5% as evaluated by radio-HPLC with a yield of 14 ± 2% and was stable up to 95% under in vitro conditions in blood and invivo conditions up to 4 h. The in vitro cell uptake study showed a significant difference in control (27.4 ± 2.1%) and blocked U987 cells (73.2 ± 3.2%) after incubation of 120 min. The tissue distribution in mice showed the highest uptake in the liver (17.3 ± 2.4%), kidneys (16.6 ± 3.1%), lungs (10.4 ± 2.9%), and spleen (5.6 ± 0.8%) at 15 min, and the activity was washed out with time. The radioactivity cleared through the hepatorenal pathway. The animal imaging study also demonstrates a similar biodistribution pattern. Conclusions: [18F]AVT-011 showed higher specific activity than the cartridge-based method but showed similar biological activity.

Inducible deletion of the prostaglandin EP3 receptor in kidney tubules of male and female mice has no major effect on water homeostasis.

The prostaglandin E2 (PGE2) receptor EP3 has been detected in the thick ascending limb (TAL) and the collecting duct of the kidney, where its actions are proposed to inhibit water reabsorption. However, EP3 is also expressed in other cell types, including vascular endothelial cells. The aim here was to determine the contribution of EP3 in renal water handling in male and female adult mice by phenotyping a novel mouse model with doxycycline-dependent deletion of EP3 throughout the kidney tubule (EP3-/- mice). RNAscope demonstrated that EP3 was highly expressed in the cortical and medullary TAL of adult mice. Compared with controls EP3 mRNA expression was reduced by >80% in whole kidney (RT-qPCR) and nondetectable (RNAscope) in renal tubules of EP3-/- mice. Under basal conditions, there were no significant differences in control and EP3-/- mice of both sexes in food and water intake, body weight, urinary output, or clinical biochemistries. No differences were detectable between genotypes in handling of an acute water load or in their response to the vasopressin analog 1-deamino-8-d-arginine-vasopressin (dDAVP). No differences in water handling were observed when PGE2 production was enhanced using 1% NaCl load. Expression of proteins involved in kidney water handling was not different between genotypes. This study demonstrates that renal tubular EP3 is not essential for body fluid homeostasis in males or females, even when PGE2 levels are high. The mouse model is a novel tool for examining the role of EP3 in kidney function independently of potential developmental abnormalities or systemic effects.NEW & NOTEWORTHY The prostanoid EP3 receptor is proposed to play a key role in the kidney tubule and antagonize the effects of vasopressin on aquaporin-mediated water reabsorption. Here, we phenotyped a kidney tubule-specific inducible knockout mouse model of the EP3 receptor. Our major finding is that, even under physiological stress, tubular EP3 plays no detectable role in renal water or solute handling. This suggests that other EP receptors must be important for renal salt and water handling.

Thermal fixation technologies affect phenolic profile, ginkgolides, bilobalide, product quality, and ginkgolic acids in Ginkgo biloba leaf tea.

Ginkgo biloba leaves (GBLs) contain high phytoconstituents, but ginkgolic acids (GAs, the main toxic compound in GBLs) have limited its applications. Processing Ginkgo biloba dark tea (GBDT) using fixation technology could decrease the toxic compounds; retain flavonoids, ginkgolides, and bilobalide; and improve the product quality. For the first time, various thermal fixations (hot air fixation [HAF], iron pot fixation [IPF], and boiled water fixation [BWF]) followed by rolling, fermentation, and drying were applied to produce GBDT. A comprehensive analysis of the toxicants (GAs), main bioactive compounds (ginkgolides and bilobalide, flavonoids, antioxidants, and phenolic profiles), and product qualities (moisture content, reducing sugar [RS], free amino acids [FAAs], enzyme activity, color properties, antioxidant capacity, etc.) were evaluated. The results revealed that thermal fixations BWF and HAF significantly reduced the GA contents (41.1%-34.6%). Most terpene lactones showed significant differences in control, IPF, and HAF. The HAF had lower total flavonoid content (TFC) than BWF and IPF. The control group (unfixated) had the highest toxic components (GA), terpene trilactones, and TFC compared with various fixations. Adding different fixations to rolling, fermentation, and drying had various impacts on GBDT, and principal component analysis supported the results. Among four thermal fixations, HAF yielded the best results in RS, FAA, total phenolic content, and antioxidant activities, while IPF had the highest TFC. BWF had the lowest content for GA. In conclusion, HAF (6) was chosen as the best technique for producing GBDT since it preserved GBDT's bioactive components while lowering its toxic components.

Effects of Early Mobilization on Pain Among Children Post Appendectomy at Children Hospital Lahore

Early mobilization means interval starting with initial physiologic mobilization and continuing through the hospital stay. Mobilization includes the activities that help critical patients to move, and ambulate with or without assistance using a walker and/or support from staff. Objective: To assess the effect of Early Mobilization on pain and wound healing among children post appendectomy. Methods: A randomized control study was conducted from December 2022 to August 2023 at the Children hospital Lahore. The target population consisted of children undergone appendectomy at Children hospital Lahore. A random sample of n=26 was recruited. Validated tool was used for data collection from participants to assess the pain in the control and interventional group. Initially, Pre-assessment was conducted to obtain pain scores, then the intervention as early mobilization was provided to the interventional group while the control group was observed with usual care. After the intervention in the post assessment, the data were collected from the control and interventional group to compare the effect of intervention. Results: The study results revealed that after the intervention, the assessment at 1st follow-up showed somewhat significant difference in control and interventional group scores of pains. A significant mean difference was found on pain between control and interventional group scores at the 2nd follow up where z (-2.056) =, p value=0.040. Conclusions: Overall, these findings suggest that early mobilization intervention has a positive and statistically significant impact on reducing mean pain scores.

Supplementation of potassium in aquaculture wastewater and its effect on growth performance of basil (Ocimum basilicum L) and pangasius (Pangasianodon hypophthalmus) in NFT-based aquaponics

An experiment was conducted for 120 days to optimize the potassium dose and investigate its effects on the growth performance of basil and pangasius in a nutrient film technique-based aquaponics. Potassium was supplemented as four different dosages assigned as T1 (90 mg/L), T2 (120 mg/L), T3 (150 mg/L), and T4 (180 mg/L) were compared to an unsupplemented control (C). Basil and pangasius were stocked at 24 plants/m² and 3.00 kg/m³, respectively. The highest basil yield occurred during the 3rd harvest in T4 (390.50 ± 4.25 g), followed by T3, T2, T1, and control. No significant difference in plant yield was observed between T4 and T3. Similarly, highest plant height, leaf length, leaf width, SFW, SDW, RFW, and RDW was recorded in T4 and T3 compared to control and other treatments. Potassium supplementation resulted in increased uptake of macro-micro nutrients viz., phosphorous, nitrogen, sulfur, potassium, copper, iron, zinc, and manganese in basil. The physico-chemical parameters and nutrient profile of culture water were found to be within the permissible limits for aquaponics. The body weight of fish didn't show any significant difference in control, T1, T2 and T3 while significantly lower body weight was recorded in T4. Significantly higher serum cortisol and glucose levels were found in T4. Considering the basil yield, nutrient and chlorophyll content of basil plant, water quality, body weight of fish, and fish stress parameters, supplementation of 150 mg/L (T3) of potassium was found to be the optimum dose for basil and pangasius culture in NFT-based aquaponic system.

Neurofeedback for obsessive compulsive disorder: A randomized, double-blind trial

We aim to develop fMRI neurofeedback as a treatment for obsessive compulsive disorder (OCD). In prior work, we found that providing neurofeedback of activity in the anterior prefrontal cortex (aPFC) improved control over contamination anxiety in a subclinical population. Here, we present the results of a randomized, double-blind clinical trial (NCT02206945) testing this intervention in patients with OCD. We recruited patients with primary symptoms in the fear-of-harm/checking or contamination/washing domains. During neurofeedback, they viewed symptom provocative images and attempted to up- and down-regulate the aPFC during different blocks of time. The active group received two sessions of neurofeedback and the control group received yoked sham feedback. The primary outcome measure was the Yale-Brown Obsessive-Compulsive Symptom scale. The secondary outcome was control over aPFC. Thirty-six participants completed feedback training (18 active, 18 control). The active group had a slightly but significantly greater reduction of obsessive-compulsive symptoms after neurofeedback compared to the control group (p<.05) but no significant differences in control over the aPFC. These data demonstrate that neurofeedback targeting the aPFC can reduce symptoms in OCD. Future investigations should seek to optimize the training protocol to yield larger effects and to clarify the mechanism of action.

1567-P: Hepatic ALKBH5 Regulation of Glucose and Lipid Metabolism

Obesity is a worsening global health crisis leading to increased risk of long-term complications such as type 2 diabetes (T2D), nonalcoholic steatohepatitis (NASH), dyslipidemia and cardiovascular disease. Identifying novel molecular mechanisms regulating the connection between obesity, hepatic insulin resistance and progression of NASH is critical to develop new therapeutic options for these patients. Previous work has shown that reversible N6-methyladenosine (m6A) RNA methylation patterns are altered in and regulate metabolic disease in the pancreatic beta cell and liver. However, these studies have primarily focused on the m6A writer proteins that direct placement of m6A methyl groups, while our study explores the role of m6A eraser protein AlkBH5 in regulating metabolic pathways in the liver. To test the hypothesis that hepatic ALKBH5 is required to maintain normal glucose homeostasis, insulin sensitivity and lipid metabolism under physiologic conditions and in response to metabolic stress we used liver-specific Alkbh5 knockout (A5KO) mice and evaluated changes in weight gain, body composition, glucose tolerance, insulin sensitivity, fasting insulin levels, and gluconeogenesis in response to a chow versus Western diet (WD). In physiologic conditions (chow), A5KO mice have decreased glucose tolerance with no other significant phenotypic changes compared to controls. Exposure to metabolic stress (WD) caused (1) greater weight gain with increased visceral fat in control compared to A5KO mice, (2) decreased glucose tolerance compared to chow in both genotypes, (3) decreased glucose mobilization in A5KO mice on WD compared to chow, with no significant differences in controls, and (4) no significant differences in global insulin sensitivity. These studies demonstrate that A5KO mice are protected against weight gain upon exposure to metabolic stress with decreased glucose tolerance and mobilization compared to controls, establishing a role for hepatic ALKBH5 in regulating glucose and lipid metabolism. Disclosure K.Aamodt: None. M.Polay: None. V.R.Salerno gonzales: None. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK007699-39, 5T32DK007260-45); Pediatric Endocrine Society

Effects of Pilot Nutrition Curriculum on Medical Student Knowledge and Ability at the University of Minnesota Medical School Duluth Campus

Purpose: Undergraduate medical education is facing an increasing need to bridge the longstanding gap between basic nutrition knowledge and its application to patient care. In an effort to improve upon knowledge and confidence in this area, the University of Minnesota Medical School Duluth Campus implemented a pilot curriculum to increase content and exposure in the dimensions of food, food systems, nutrition, and clinical application. Methods: Two classes of outgoing second-year medical students at the University of Minnesota Duluth Campus were surveyed about personal health, knowledge of nutritional topics, and confidence in implementing these topics in patient care. The control group consisted of outgoing second-year medical students (MS2s) during the 2019-2020 academic year (n=28) prior to pilot nutrition curriculum inception. The cohort group (n=29) consisted of outgoing MS2s from the 2020-2021 academic year who received the new pilot curriculum. Findings: Survey findings did not yield statistically significant differences in control versus cohort responses in students' personal health and knowledge of nutritional concepts. However, over 90% of the cohort group, versus 54% of control, agreed that they were able to discuss and recommend healthy dietary modifications to a patient with a chronic disease. The cohort group also reported higher confidence in talking with patients about dietary patterns (69% vs 39%), whole-food plant-rich diets (90% vs 50%), as well as working inter-professionally with other members of the healthcare team around issues of food and nutrition (97% vs 71%). Conclusion: Results demonstrate that the pilot curriculum increased medical student confidence in evaluating the multidimensionality of food, food systems, and nutrition content as well as the application of this content to patient care. This pilot curriculum may have relevance to other medical schools who are also wishing to bridge this long-standing gap in medical education.

VEGF Genotype and Allele Frequency of Diabetes Mellitus and Diabetic retinopathy in Lahore, Pakistan

Diabetic retinopathy is characterized as basement membrane (BM) thickening, pericyte loss, endothelial cell (EC) dysfunction, microaneurysms, microvascular infarcts and neovascularization in a patient with diabetic retinopathy. Objectives: To determine the VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy in Lahore, Pakistan. Methods: A total of 100 blood samples were taken including diabetes mellitus (50) and diabetic retinopathy patients (50). Diseased and control subjects were selected for blood sampling. Demographic and clinical characteristics was evaluated. The BMI, HbA1c and the blood pressure of both groups were also examined. The VEGF genotype and allele frequency of diabetes mellitus and diabetic retinopathy was done. The statistical analysis was done by chi-square test and SPSS to study significant differences in control and diabetic retinopathy subjects. Results: The normal estimation of DM group was 46.18 ± 1.23 years while of DR class was 52.86 ± 1.36 years. The mean value of BMI of DM group was 26.0±0.62 while of DR group was 26.57±0.70.&#x0D; DD genetic mutation was substantially higher in diabetic retinopathy bunch (p&lt;0.05) relative to the II gene mutation, the huge contrasts (p&lt;0.05) were seen in diabetic group. Conclusions: This study concluded that Vascular endothelial growth factor gene was detected in both group of diabetes. In retinopathy people with T2DM the substantial elevated VEGF DD genetic variation was seen relative to retinopathy people without diabetes.

Generation of forward angular impulse with different initial conditions

Generation of angular impulse during foot contact is regulated by controlling the relative orientation between the total body center of mass (CoM) and the reaction force (RF) applied to the feet. Between-task differences in initial CoM horizontal momentum were hypothesized to alter how forward angular impulse was generated during two forward translating tasks. Five skilled athletes performed standing (SFS) and running (RFS) forward somersaulting dives. Sagittal plane kinematics and RFs were obtained during the take-off phase of both tasks. The initial CoM momentum differences resulted in significant differences in control of the CoM relative to the RF, RF generation mechanisms, and knee and hip net joint moments (NJMs). During the RFS, angular impulse was generated by positioning the feet anterior to the CoM at initial contact so that the RF passed posterior to the CoM throughout the take-off phase. During the SFS, angular impulse was generated by positioning the CoM anterior to the feet prior to the push interval so that the RF passed posterior to the CoM. Task-specific differences in segment kinematics and RF direction contributed to the redistribution of knee and hip NJMs. These results suggest that initial conditions influence strategies the nervous system uses to satisfy task objectives.

Intraobserver Assessment of Shear Wave Elastography in Tensor Fasciae Latae and Gluteus Maximus Muscle: The Importance of the Hip Abductor Muscles in Runners Knee Compared to Healthy Controls.

Background: Iliotibial band syndrome (ITBS) represents one of the most common running related injuries. The pathophysiology is postulated to be caused by excessive ITB tension, impingement and irritation of soft tissues at the lateral femoral epicondyle. However, direct evidence has yet to be found and the multifactorial etiology is under discussion. The purpose was to evaluate stiffness of ITB, gluteus maximus (GM) and tensor fasciae latae (TFL) muscles using shear wave elastography (SWE). Methods: In 14 patients with clinically verified ITBS and 14 healthy controls, three SWE measurements each of ITB, GM and TFL in both legs was performed to determine measurement reliability and between-group and -leg differences. Results: The mean value of ITB was 12.8 m/s with ICC of 0.76, whereas the values measured in the GM were 3.02 m/s with an ICC of 0.87. No statistically significant difference in controls compared to patients were found (p = 0.62). The mean value of TFL was 5.42 m/s in healthy participants, compared to 3.89 m/s patients with an ICC of 0.98 (p = 0.002). Conclusion: Although SWE showed no difference in ITB stiffness, significant differences for TFL muscle stiffness in runner’s knee was found, suggesting that the hip abductor muscles might play a bigger role in the pathophysiology of ITBS. We aimed to implement baseline values for stiffness assessments and prove reliability for further prospective studies of SWE in runner’s knee.

Effects of probiotic adjuncts on physicochemical properties, organic acids content, and proteolysis in cheese prepared from buffalo milk

The aim of the current study was to assess the effects of probiotic adjuncts on physiochemical characteristics, organic acids, water-soluble nitrogen percentage (WSN%), total free amino acids (TFAA), and proteolytic patterns in buffalo milk probiotic Cheddar cheese during 120 days of ripening at 4°C. Cheddar cheese was prepared with commercially available mesophilic cheese starter cultures (control), Lactobacillus acidophilus, and Bifidobacterium bifidum individually as well as in synergistic manner to prepare probiotic cheese. The results appeared with a significant difference in control and probiotic cheese with reference to citric, lactic, butyric, and acetic acids, WSN%, and TFAA production. The proteolytic pattern of probiotic bacteria modified the proteolysis and expedited the formation of bioactive peptides in Cheddar cheese. Among probiotic adjuncts, Cheddar having B. bifidum exhibited higher WSN% and TFAA as compared to the other two probiotic cheese samples. Hence, it can be concluded that B. bifidum is slightly more proteolytic as compared to other probiotic adjuncts and the incorporation of probiotic adjuncts enhanced the hydrolysis of αs1− casein in Cheddar cheese. Practical applications Bioactive peptides remain inactive within the protein molecule. When milk undergoes enzymatic hydrolysis (protein), fermentation (through the proteolytic starter), or enzymatic proteolysis, bioactive compounds become active and capable to exhibit their therapeutic potential. Probiotic adjuncts modify the proteolysis, balance bio-diversity removed by pasteurization and expedite the formation of bioactive peptides in Cheddar cheese. Regarding probiotic adjuncts, cheese serves as one of the most efficient carriers of probiotic bacteria owing to its matrix efficiency and ability to maintain the viability of bacteria and facilitate their entry into the human gut.

SIGNIFICANCE OF DETECTION OF FREE/TOTAL PSA RATIO AND OTHER BIOCHEMICAL PARAMETERS IN PATIENTS WITH BPH, CARCINOMA PROSTATE AND ITS CLINICOPATHOLOGIC CORRELATION

Background. Benign prostatic hyperplasia (BPH) can raise prostate-specific antigen (PSA) levels two to three times higher than the normal level. An increased PSA level does not indicate Prostate Cancer (PCa), but the higher the PSA level, the higher the chance of having PCa. Detection and treatment have been profoundly affected by the advent of Free/Total PSA ratio testing. Objectives. The aim of the study was to estimate free, total PSA levels and its ratio for serum levels of calcium, acid phosphatase and alkaline phosphatase in patients with BPH and PCa; to correlate clinical, biochemical and histopathological findings in the above patients. Methods. PSA levels were detected by Chemiluminescent assay; serum calcium – by Modified Arsenazo method; serum acid phosphatase – by Doumas et al method; and Alkaline phosphatase – by Lowry et al method. Results. Present study found high levels of total PSA in BPH and PCa. Levels of free PSA were high in BPH as compared to PCa rate. Free/Total PSA ratio is reduced considerably in PCa as compared to BPH. Serum acid phosphatase and alkaline phosphatase were considerably higher in PCa as compared to BPH. Serum calcium levels did not show significant difference in control and study groups. Conclusions. It was established that patients with PCa have a greater fraction of bound PSA and a lower percentage of free PSA than in those without PCa. Therefore, in clinical practice Free/Total PSA ratio helps clinicians to decide if a biopsy is necessary. Objectives: The study was carried out with the following objectives: to estimate free, total PSA levels and calculate Free/Total PSA ratio in patients with BPH and Carcinoma Prostate, to study the serum levels of calcium, acid phosphates, and alkaline phosphatase in patients with BPH and PCa. and to correlate clinical, biochemical and histopathological findings in the above patients. Methods. Free and total PSA levels were detected by Chemiluminescent assay; Serum Calcium was detected by Modified Arsenazo method. Serum acid phosphatase was detected by Doumas et al method and Alkaline phosphatase were detected by Lowry et al method Results: Present study found high levels of Total PSA in BPH and PCa. Levels of free PSA were high in BPH as compared to PCa ate. Free /Total PSA ratio is reduced considerably in PCa as compared to BPH. Serum acid phosphatase and alkaline phosphatase were slightly raised in PCa as compared to BPH. Serum calcium levels did not show a significant difference in control and study groups. Conclusion: We concluded that patients with PCa have a greater fraction of bound PSA and a lower percentage of free PSA than in men without PCa. There was a negative correlation found between the free/total PSA ratio and the histopathologic findings. The lower the ratio higher is the grade of malignancy. Therefore in clinical practice Free/Total PSA ratio helps clinicians to decide if a biopsy is necessary

Evaluation of Danzhi Xiaoyao powder and amlodipine sustained-release tablets in follow-up treatment of the hypertensive crisis and the interleukin-6 gene expression.

Danzhi Xiaoyao powder (DXP) is an herbal formula with eight different herbs. This herbal medicine can play multiple roles in various disease treatments through its several components. In this study, the effect of DXP was evaluated on the treatment of hypertensive patients with and without amlodipine. For this purpose, 252 patients were studied with high blood pressure. The 126 patients received DXP, and the others received DXP + amlodipine for four weeks. Besides demographic and biochemical assessments (gender, BMI, age, SBP, DBP, etc.), the expression of the interleukin-6 gene was evaluated in these two groups. The results showed that the blood pressure decreased by DPX, and there was no significant difference in control of blood pressure by DPX and DXP + amlodipine. But it did not affect interleukin-6 gene expression. Therefore, it can be concluded that this drug probably uses a different mechanism than amlodipine to control blood pressure.

Utilization of Wood Vinegar as Nutrient Availability Enhancer in Eggplant (Solanum melongena L.)

The study aims to evaluate the effect of different levels of wood vinegar as a nutrient availability enhancer in eggplant. The treatments used in the study were Treatment 1 (No application of wood vinegar), Treatment 2 (0.5% of wood vinegar), Treatment 3 (0.67% of wood vinegar), and Treatment 4 (1% of wood vinegar).&#x0D; Based on the study results, the average height of plants showed a significant difference among the treatments. The other parameters, average growth increment, average stem diameter, average number of days to flower initiation, the average length of fruits, and an average weight of fruits, showed high significance among treatments. The result was supported by LSD that showed significant differences in control and among the treatments. Therefore, the application of Treatment 4 is the recommended ratio in eggplant production.&#x0D; Hence, researchable areas need to be addressed, such as evaluating the continuous use of wood vinegar in eggplant production, and challenge literature stating that wood vinegar should be stopped one week before harvesting. Additional research on time and level of wood vinegar for insect control is recommended.

Damage to the Testicular Structure of Rats by Acute Oral Exposure of Cadmium.

Cadmium (Cd) is one of the most important heavy metal toxicants, used throughout the world at the industrial level. It affects humans through environmental and occupational exposure and animals through the environment. The most severe effects of oral exposure to Cd on the male reproductive system, particularly spermatogenesis, have not been discussed. In this study, we observed the damage to the testes and heritable DNA caused by oral exposure to Cd. Adult male Sprague–Dawley rats were divided into four groups: a control group and three groups treated with 5, 10, and 15 mg Cd/kg/day for 17 days by oral gavage. Our results revealed that Cd significantly decreases weight gain in 10 and 15 mg/kg groups, whereas the 5 mg/kg groups showed no difference in weight gain. The histopathology showed adverse structural effects on the rat testis by significantly reducing the thickness of the tunica albuginea, the diameter of the tubular lumen, and the interstitial space among seminiferous tubules and increasing the height of the epithelium and the diameter of the seminiferous tubules in Cd treated groups. Comet assay in epididymal sperms demonstrated a significant difference in the lengths of the head and comet in all the 3 Cd treated groups, indicating damage in heritable DNA, although variations in daily sperm production were not significant. Only a slight decrease in sperm count was reported in Cd-treated groups as compared to the control group, whereas the tail length, percentage of DNA in head, and tail showed no significant difference in control and all the experimental groups. Overall, our findings indicate that Cd toxicity must be controlled using natural sources, such as herbal medicine or bioremediation, with non-edible plants, because it could considerably affect heritable DNA and induce damage to the reproductive system.

Adherence at 2 years with distribution of essential medicines at no charge: The CLEAN Meds randomized clinical trial.

BackgroundAdherence to medicines is low for a variety of reasons, including the cost borne by patients. Some jurisdictions publicly fund medicines for the general population, but many jurisdictions do not, and such policies are contentious. To our knowledge, no trials studying free access to a wide range of medicines have been conducted.Methods and findingsWe randomly assigned 786 primary care patients who reported not taking medicines due to cost between June 1, 2016 and April 28, 2017 to either free distribution of essential medicines (n = 395) or to usual medicine access (n = 391). The trial was conducted in Ontario, Canada, where hospital care and physician services are publicly funded for the general population but medicines are not. The trial population was mostly female (56%), younger than 65 years (83%), white (66%), and had a low income from wages as the primary source (56%). The primary outcome was medicine adherence after 2 years. Secondary outcomes included control of diabetes, blood pressure, and low-density lipoprotein (LDL) cholesterol in patients taking relevant treatments and healthcare costs over 2 years. Adherence to all appropriate prescribed medicines was 38.7% in the free distribution group and 28.6% in the usual access group after 2 years (absolute difference 10.1%; 95% confidence interval (CI) 3.3 to 16.9, p = 0.004). There were no statistically significant differences in control of diabetes (hemoglobin A1c 0.27; 95% CI −0.25 to 0.79, p = 0.302), systolic blood pressure (−3.9; 95% CI −9.9 to 2.2, p = 0.210), or LDL cholesterol (0.26; 95% CI −0.08 to 0.60, p = 0.130) based on available data. Total healthcare costs over 2 years were lower with free distribution (difference in median CAN$1,117; 95% CI CAN$445 to CAN$1,778, p = 0.006). In the free distribution group, 51 participants experienced a serious adverse event, while 68 participants in the usual access group experienced a serious adverse event (p = 0.091). Participants were not blinded, and some outcomes depended on participant reports.ConclusionsIn this study, we observed that free distribution of essential medicines to patients with cost-related nonadherence substantially increased adherence, did not affect surrogate health outcomes, and reduced total healthcare costs over 2 years.Trial registrationClinicalTrials.gov NCT02744963.

Function of miR-24 and miR-27 in Pediatric Patients With Idiopathic Nephrotic Syndrome.

Purpose: We investigated the pathogenesis of idiopathic nephrotic syndrome (INS) by measuring the effects two specific miRNAs on Th2 cells in children with this disease.Methods: After informed consent, we enrolled 20 children with active INS before steroid initiation, 20 children with INS in remission after steroid therapy, and 20 age-matched healthy controls. Flow cytometry was used to measure the levels of Th2 cells and a cytometric bead array was used to measure the levels of IgE, interleukin (IL)−4, and IL-13. RT-PCR was used to measure the levels of miR-24 and miR-27 in CD4+TCD25− cells. PBMCs were isolated using Ficoll density gradient centrifugation, and transfected with different mimic or inhibitor miRNAs. RT-PCR was used to measure the expression of different RNAs, and flow cytometry was used to determine the percentage of Th2 cells.Results: Relative to healthy controls, children with active INS had higher percentages of Th2 cells (P < 0.05), but there was no significant difference in controls and children in remission. The plasma levels of IgE, IL-4, and IL-13 were significantly increased in children with active INS (P < 0.05). There were lower levels of miR-24 and miR-27 in children with active non-atopic INS (P < 0.05). Transfection experiments indicated that upregulation of each miRNA decreased the percentage of Th2 cells and the level of IL-4 (P < 0.05), and down-regulation of each miRNA had the opposite effects (P < 0.05).Conclusion: Children with active INS, with or without atopy, had higher levels of IgE, possibly related to their higher levels of IL-13 and IL-4 due to a drift toward Th2 cells. miR-24 and miR-27 suppressed the expression of Th2 cells and have a critical function regulating Th2 cell expression in INS.

EMBRYOGENESIS, LEUKOCYTIC PROFILE AND LIVER MORPHOLOGY OF PREGNANT RATES UNDER THE ACTION OF CITRIC ACID

The article presents the results of studies on the effects of citric acid on the female’s body. The studies were performed on white laboratory rats of the Wistar line, which at the age of 3 - 3.5 months with a body weight of 192 - 210 g were divided into two groups of 4 individuals in each. The animals of the experimental group were fed by citric acid at a concentration of 80 mg/l of drinking water during the period physiological and puberty, fertilization and pregnancy. A control group of female rats was fed by water. The animals had free access to drinkers and food. Indicators of embryogenesis, leukocyte profile of blood and body weight of animals, weighting factor, histological changes of the liver were determined.&#x0D; Female rats were found to have no abortions or premature births, however, the number of corpora lutea of pregnancy decreased by 19.2%, although there was no significant difference in control. The number of implantation sites per female was significantly lower by 28.8%. The mortality rate of embryos was 15.8%, which is 3.8 times higher than in intact animals. Regarding white blood cells, the analysis of the results indicates a tendency to increase the percentage of eosinophils in 2 times in the relation to the animals in the control group on the background of a probable increase in leukocytes by 42.4%.&#x0D; The applied dose of citric acid caused certain changes in the macro- and microstructure of the liver. It is macroscopically established that under the influence of citric acid the organ is slightly enlarged, sluggish consistency and changed its color from light red to light brown. The relative weighting factors of the liver are probably higher in the relation to the control (52.12 ± 8.16 g/kg vs 43.38 ± 1.96 g/ kg).&#x0D; The results of morphological studies indicate a partial violation of the lamellar structure of the organ in the centro-lobular region, which is due to turbid swelling of the cytoplasm of hepatocytes. In most cells, the contours are blurred, the cytoplasm is poorly stained, their nuclei are weakly basophilic, and hepatocytes with a lysed nucleus in a necrobiosis condition also occur. However, among dystrophic altered cells are clearly isolated hepatocytes with a uniformly colored basophilic cytoplasm, nucleus, rich in chromatin, which indicated the activation of reparative processes. Kupffer cells in this area are mostly round, located in the lumen of the sinusoid. Therefore, occurs a violation of lipoprotein complexes of cells and increase the permeability of cell membranes, which is reflected in the development of protein dystrophy with varying degrees of severity. Activation of reparative processes of hepatocytes is also determined.

Comparison of Serum Lipid Profiles of Women with or Without Hormonal Contraceptives Users at a Tertiary Care Hospital in Dhaka City

Background: Both oral and injectable hormonal contraceptives are the most popular type of birth control measures used in Bangladesh.&#x0D; Objective: The purpose for the present study was to see the effects of hormonal contraceptives on serum lipid profiles.&#x0D; Methodology: This was case-control study which was carried out in the Department of Obstetrics &amp; Gynaecology at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from July 2004 to December 2005 for eighteen (18) months. Women of reproductive age group who had given the history of taking low-dose OCP containing 30 meg EE plus 150 meg LNG were included as case group and women who were presented without the history of hormonal contraceptives use were included as control group. Blood was collected from each woman in fasting state and serum was sent for estimation of serum lipids profiles like serum triglycerides, total cholesterol, LDL and HDL.&#x0D; Result: The study included 40 women (control) who were not using OCP and 40 women (case) who were using OCP for more than one year. Comparison of age between control (31.75±4.85 years) and case (30.43±5.44 years) groups showed no significant difference (p&gt;0.05). No significant difference with raised cholesterol levels (207.50±3.54 and 254.71± 45.54 mg/dl) was reported. Comparison of normal (136.16±39.46 and 154.05±35.33 mg/dl) and raised (229.00±24.52 and 246.32±35.98 mg/dl) triglyceride levels between control and case groups did not statistically significant. Comparison of normal and raised HDL levels did not show statistically any significant difference in control (32.07±3.02 mg/dL) and case (32.48±1.76 mg/dL) groups. Mean (±SD) of normal and raised levels of LDL was significantly high in case group. Normal LDL level was 82.71±26.82 and 111.05±15.40 mg/dl and raised LDL level was 138.55±3.03 and 188.82±40.37 mg/dL.&#x0D; Conclusion: In conclusion use of low-dose OCP containing 30 meg EE plus 150 meg LNG significantly increases serum cholesterol, serum triglyceride and LDL-cholesterol levels but not HDL-cholesterol.&#x0D; Journal of Science Foundation, January 2020;18(1):19-24