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Abstract Background Norethisterone acetate (NETA), also known as norethindrone acetate is a progestogens medication that is widely used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders as abnormal uterine bleeding and endometriosis. There is a lack of detailed histological information regarding the effects of NETA on the uterine structure. So, the present study focuses on the uterine histological, histochemical and ultrastructure changes following the exposure to NETA in the albino rats. To do this aim, fourteen adult female albino rats were used. They were randomly divided into two equally groups: Control group and NETA treated group. Albino rats of control group were administered daily food, water and orally distilled water only, while rats of NETA treated group were administered daily orally 20 µg of NETA dissolved in 2 ml distilled water, food, and water. The experiment was continued for three weeks. Results The findings of the present work indicated that the use of NETA has negative effects on the endometrial epithelium (proliferation, autophagy and apoptosis), glands (necrotic, apoptotic or pseudosecretory glands) and stromal and myometrial reactions (granulocytes, connective tissue remodeling, apoptosis, myocytes hypertrophy). Conclusion This work revealed that NETA has desynchronized progestogenic effect on the uterine tissues of the albino rat and thereby prevent implantation and pregnancy.

Abstract This study assessed the clinical effectiveness of orange peel polymethoxy-flavonoids rich fraction (OPMF) solid dispersion as a palatal dressing material, compared with Alveogyl, in a randomized clinical trial. After harvesting free gingival grafts for 18 patients in three groups, the donor site in group I received OPMF; group II received Alveogyl; and group III received placebo dough material. The visual analog scale (VAS) pain score in group I showed the lowest value in week one without a significant difference. In week 2, there was a substantial decrease in pain in group I compared to group III. Week 4 showed reduced pain scores in all groups without significant differences. The results of the number of analgesic pills revealed, after 1 week, the lowest number of pills consumed in group I, with a considerable difference compared to group III. Healing process results showed that group I had the highest healing values in each interval, with a significant difference between group I and group III at 1 and 2 weeks. Color matching parameter showed slight differences between the groups’ readings in favor of group I in all intervals without a statistically significant difference. The results suggest OPMF as a palatal dressing material that facilitates hemostasis, pain relief, and palatal wound healing.

Abstract Simvastatin (SV) is a poorly soluble drug; its oral administration is associated with a significant problem: Myopathy. The present study aims to formulate SV microsponges that have the potential to minimize the myotoxicity accompanying the oral administration of the drug. SV microsponges were prepared by exploiting the emulsion solvent evaporation technique. The % entrapment efficiency (%EE) of the drug approached 82.54 ± 1.27%, the mean particle size of SV microsponges ranged from 53.80 ± 6.35 to 86.03 ± 4.79 µm in diameter, and the % cumulative drug release (%CDR) of SV from microsponges was significantly higher than that from free drug dispersion much more, the specific surface area of the optimized microsponges formulation was found to be 16.6 m2/g revealed the porosity of prepared microsponges. Histological and glycogen histochemical studies in the skeletal muscles of male albino rats revealed that microsponges were safer than free SV in minimizing myotoxicity. These findings were proven by Gene expression of Mitochondrial fusion and fission (Mfn1) & (Fis1) and (Peroxisome proliferator-activated receptor gamma co-activator 1α) PGC-1α. Finally, our study ascertained that SV microsponges significantly decreased the myotoxicity of SV.

The dynamic regulation of endothelial pathophenotypes in pulmonary hypertension (PH) remains undefined. Cellular senescence is linked to PH with intracardiac shunts; however, its regulation across PH subtypes is unknown. Since endothelial deficiency of iron-sulfur (Fe-S) clusters is pathogenic in PH, we hypothesized that a Fe-S biogenesis protein, frataxin (FXN), controls endothelial senescence. An endothelial subpopulation in rodent and patient lungs across PH subtypes exhibited reduced FXN and elevated senescence. In vitro, hypoxic and inflammatory FXN deficiency abrogated activity of endothelial Fe-S-containing polymerases, promoting replication stress, DNA damage response, and senescence. This was also observed in stem cell-derived endothelial cells from Friedreich's ataxia (FRDA), a genetic disease of FXN deficiency, ataxia, and cardiomyopathy, often with PH. In vivo, FXN deficiency-dependent senescence drove vessel inflammation, remodeling, and PH, whereas pharmacologic removal of senescent cells in Fxn-deficient rodents ameliorated PH. These data offer a model of endothelial biology in PH, where FXN deficiency generates a senescent endothelial subpopulation, promoting vascular inflammatory and proliferative signals in other cells to drive disease. These findings also establish an endothelial etiology for PH in FRDA and left heart disease and support therapeutic development of senolytic drugs, reversing effects of Fe-S deficiency across PH subtypes.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0–90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non‐SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2. Conclusions This study examined one of the largest single‐center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A; postmortem whole exome sequencing identified 18 ultrarare variants.

Zohair Ahmed,1 Jinma Ren,2 Adam Gonzalez,3 Umair Ahmed,4 Saqib Walayat,4 Daniel K Martin,5 Harsha Moole,4 Sherri Yong,6 Sean Koppe,7 Sonu Dhillon5 1Department of Gastroenterology and Hepatology, University of Illinois at Chicago, IL, USA; 2Department of Center for Outcomes Research, University of Illinois College of Medicine, Peoria, IL, USA; 3University of Illinois College of Medicine, Peoria, IL, USA; 4Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL, USA; 5Department of Gastroenterology and Hepatology, University of Illinois College of Medicine, Peoria, IL, USA; 6Department of Pathology, University of Illinois College of Medicine, Peoria, IL, USA; 7Department of Hepatology, University of Illinois at Chicago, IL, USA Aim: The purpose of this study was to create and validate a novel serological diagnostic index to predict cirrhosis of all etiologies.Methods: This was a retrospective observational study of 771 patients, age >18 years, who underwent a liver biopsy. The stage of fibrosis and routine laboratory values were recorded. The data were randomly separated into 2 datasets (training 50% and testing 50%). A stepwise logistic regression model was used to develop the novel index. The area under the curve of receiver operating characteristic (AUROC) was applied to compare the new index to existing ones (Fibro-Q, FIB4, APRI, AAR), which was also validated in the testing dataset.Results: Variables associated with the presence of cirrhosis were first assessed by univariate analysis then by multivariable analysis, which indicated serum glutamic-oxaloacetic acid transaminase, serum glutamic-pyruvic transaminase, international normalized ratio, albumin, blood urea nitrogen, glucose, platelet count, total protein, age, and race were the independent predictors of cirrhosis (P

Zohair Ahmed,1 Umair Ahmed,2 Saqib Walayat,2 Jinma Ren,3 Daniel K Martin,4 Harsha Moole,2 Sean Koppe,5 Sherri Yong,6 Sonu Dhillon4 1Department of Gastroenterology and Hepatology, University of Illinois, Chicago, IL, USA; 2Department of Internal Medicine, University of Illinois College of Medicine, Peoria, IL, USA; 3Department of Center for Outcomes Research, University of Illinois College of Medicine, Peoria, IL, USA; 4Department of Gastroenterology and Hepatology, University of Illinois College of Medicine, Peoria, IL, USA; 5Department of Hepatology, University of Illinois at Chicago, Chicago, IL, USA; 6Department of Pathology, University of Illinois College of Medicine, Peoria, IL, USA Background and aims: Many patients with liver disease come to medical attention once they have advanced cirrhosis or acute decompensation. Most often, patients are screened for liver disease via liver function tests (LFTs). There is very limited published data evaluating laboratory values with biopsy-proven stages of hepatic fibrosis. We set out to evaluate whether any correlation exists between routine LFTs and stages of hepatic fibrosis.Methods: A large retrospective observational study on 771 liver biopsies was conducted for evaluating the stage of fibrosis with AST, ALT, INR, BUN, creatinine, platelets, alkaline phosphatase, bilirubin, and albumin. Mean and 95% confidence intervals were used to describe the distributions of serum markers in different fibrosis stages. Multivariable generalized linear models were used and a two-tailed P-value was calculated.Results: ALT was not statistically significant for any stage, and AST was statistically significant for stage 3 and 4 fibrosis. INR was statistically significant only in stage 4 disease but remained near the upper limit of normal range. Albumin failed to show a clinically relevant association. Platelets remained within normal laboratory range for all stages. The remaining laboratory values failed to show statistical and clinical significance.Conclusion: The health care burden from chronic liver disease (CLD) will likely continue to rise, unless clinicians are made aware that normal or near normal laboratory findings may be seen in asymptomatic patients. Earlier identification of asymptomatic patients will allow for treatment with new promising modalities and decrease morbidity and mortality from CLD. Our study shows that laboratory values correlate poorly with liver disease. Keywords: chronic liver disease, hepatic fibrosis, serum markers, cirrhosis, NAFLD, HCV