Hydrophilic catheters for intermittent catheterization and occurrence of urinary tract infections. A retrospective comparative study in patients with spinal cord Injury.

BACKGROUND: Neurogenic bladder dysfunction is a major problem for spinal cord injury (SCI) patients not only due to the risk of serious complications but also because of the impact on quality of life. The main aim of this study is to compare the rate of urinary tract infection (UTI) associated with hydrophilic-coated catheters versus uncoated polyvinyl chloride (PVC) catheters among SCI patients presenting with functional neurogenic bladder sphincter disorders. METHODOLOGY: This was a retrospective cohort study from 2005 to 2020 including adult male or female patients who have an SCI at least more than 1 month ago with neurogenic bladder dysfunction and were using intermittent catheterization (single-use hydrophilic-coated or the standard-of-care polyvinyl chloride uncoated standard catheters) at least 3 times a day to maintain bladder emptying. RESULTS: A total of 1000 patients were selected and recruited through a stratified random sampling technique with 467 (47.60%) patients in the uncoated catheter arm and 524 (52.60%) in the coated catheter groups. The three outcome measures, namely: symptomatic UTI, Bacteriuria, and pyuria were significantly higher in the group using uncoated polyvinyl chloride (PVC) catheters compared to hydrophilic-coated catheters at the rate of 79.60% vs.46.60%, 81.10% vs. 64.69, and 53.57% versus 41.79% respectively. Males, elder patients, longer duration, and severity of SCI were associated with increased risk of symptomatic UTI. CONCLUSIONS: The results indicate a beneficial effect regarding clinical UTI when using hydrophilic-coated catheters in terms of fewer cases of symptomatic UTI. Bacteriuria is inevitable in patients with long-term catheterization, however, treatment should not be started unless the clinical symptoms exist. More attention should be given to the high-risk group for symptomatic UTIs.

Predicting COVID-19 outcomes with the Edmonton Obesity Staging System.

BACKGROUND: Multiple studies have demonstrated a correlation between a high body mass index and discriminatory COVID-19 outcomes. Studies appear to indicate that there is a correlation between obesity-related comorbidities and less favorable outcomes. OBJECTIVES: The primary aim of the current investigation is to conduct a thorough assessment of the correlation between BMI and comorbidities associated with obesity, and their potential impact on the severity and consequences of COVID-19 infection among patients receiving care in a tertiary healthcare setting. DESIGN: Retrospective cohort. SETTINGS: Tertiary rehabilitation center, Riyadh, Saudi Arabia. PATIENTS AND METHODS: The study included all individuals who received medical treatment and tested positive for COVID-19 by means of RT-PCR during the period from March to September 2020. COVID-19 patients were classified using Edmonton Obesity Staging System (EOSS). MAIN OUTCOME MEASURES: COVID-19-related complications, including pneumonia and cytokine release syndrome, as well as the time length to COVID-19 negativization. SAMPLE SIZE: 315 patients. RESULTS: The median (25th-75th percentiles) age of the patients was 38 (31.5-49) years old. Males outnumbered females, and 66% of patients were non-Saudis. Forty-eight patients (15.2%) had obesity class I, whereas 13 patients (4.1%) had class II. Thirty-two patients (10.2%) were classified as EOSS stage 1, 105 patients (33.3%) were classified as EOSS stage 2, and 25 patients (7.9%) were assigned to EOSS stage 3. Males predominated in EOSS stages 1 and 2, whereas females predominated in stage 3. In EOSS stage 3, 52% of cases had moderate severity and 48% had severe illness. CONCLUSIONS: EOSS distinguishes the COVID-19 risks of poor outcomes beyond BMI. Patients who were overweight or obese but remained in the stage 1 of the EOSS had a lower risk of a poor COVID-19 outome than normal-weight patients. The health status of obese patients is a more precise indicator of the progression of COVID-19 during hospitalization than BMI alone. LIMITATIONS: Given the limited capacity of urgent care facilities to conduct a comprehensive evaluation of comorbidities and other relevant outcomes in all patients, it is plausible that certain patients may have been erroneously classified with an EOSS stage 2 diagnosis, when in fact they ought to have been assigned a stage 3 diagnosis.

Galantamine mitigates testicular injury and disturbed spermatogenesis in adjuvant arthritic rats via modulating apoptosis, inflammatory signals, and IL-6/JAK/STAT3/SOCS3 signaling.

Rheumatoid arthritis (RA) affects the joints and the endocrine system via persistent immune system activation. RA patients have a higher frequency of testicular dysfunction, impotence, and decreased libido. This investigation aimed to evaluate the efficacy of galantamine (GAL) on testicular injury secondary to RA. Rats were allocated into four groups: control, GAL (2 mg/kg/day, p.o), CFA (0.3 mg/kg, s.c), and CFA + GAL. Testicular injury indicators, such as testosterone level, sperm count, and gonadosomatic index, were evaluated. Inflammatory indicators, such as interleukin-6 (IL-6), p-Nuclear factor kappa B (NF-κB p65), and anti-inflammatory cytokine interleukin-10 (IL-10), were assessed. Cleaved caspase-3 expression was immunohistochemically investigated. Protein expressions of Janus kinase (JAK), signal transducers and activators of transcription (STAT3), and Suppressors of Cytokine Signaling 3 (SOCS3) were examined by Western blot analysis. Results show that serum testosterone, sperm count, and gonadosomatic index were increased significantly by GAL. Additionally, GAL significantly diminished testicular IL-6 while improved IL-10 expression relative to CFA group. Furthermore, GAL attenuated testicular histopathological abnormalities by CFA and downregulated cleaved caspase-3 and NF-κB p65 expressions. It also downregulated JAK/STAT3 cascade with SOCS3 upregulation. In conclusion, GAL has potential protective effects on testicular damage secondary to RA via counteracting testicular inflammation, apoptosis, and inhibiting IL-6/JAK/STAT3/SOCS3 signaling.

The enteroprotective effect of nifuroxazide against methotrexate-induced intestinal injury involves co-activation of PPAR-γ, SIRT1, Nrf2, and suppression of NF-κB and JAK1/STAT3 signals.

Methotrexate (MTX) has long manifested therapeutic efficacy in several neoplastic and autoimmune disorders. However, MTX-associated intestinal toxicity restricts the continuation of treatment. Nifuroxazide (NIF) is an oral antibiotic approved for gastrointestinal infections as an effective antidiarrheal agent with a high safety profile. The current study was designed to explore the potential efficacy of NIF in alleviating intestinal toxicity associated with MTX chemotherapy with the elucidation of the proposed molecular mechanisms. Rats were administered NIF (50 mg/kg; p.o.) for ten days. On day five, a single i.p. injection of MTX (20 mg/kg) was given to induce intestinal intoxication. At the end of the experiment, duodenal tissue samples were isolated for biochemical, Western blotting, immunohistochemical (IHC), and histopathological analysis via H&E, PSA, and Alcian blue stains. NIF showed antioxidant enteroprotective effects against MTX intestinal intoxication through enhanced expression of the redox-sensitive signals of PPAR-γ, SIRT1, and Nrf2 estimated by IHC. Moreover, NIF down-regulated the pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6), NF-κB protein expression, and the phosphorylation of JAK1/STAT3 proteins, leading to mitigation of intestinal inflammation. In accordance, the histological investigation revealed that NIF ameliorated the intestinal pathological changes, preserved the goblet cells, and reduced the inflammatory cells infiltration. Therefore, NIF could be a promising candidate for adjunctive therapy with MTX to mitigate the associated intestinal injury and increase its tolerability.

Prevalence of Multidrug-Resistant and ESBL-Producing Bacterial Pathogens in Patients with Chronic Wound Infections and Spinal Cord Injury Admitted to a Tertiary Care Rehabilitation Hospital.

A pressure ulcer is defined as a skin lesion of ischemic origin, a condition that contributes to morbidity and mortality in patients with spinal cord injuries. The most common complication of ulcers is a bacterial infection. Antimicrobial therapy should be selected with caution for spinal cord injury patients since they have a high risk of developing multidrug-resistant (MDR) infections. The aim of this study was to determine the prevalence of different bacterial pathogens in patients with pressure ulcers admitted with spinal cord injuries. This was a retrospective single-center study that included adult patients aged 18 years and above, admitted with chronic pressure wounds after a spinal cord injury requiring hospitalization between 2015 and 2021. A total of 203 spinal cord injury patients with pressure ulcers were included in the study. Ulcers were commonly infected by Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, and they were mostly located in the sacral and gluteal areas. More than half of the bacteria isolated from patients were sensitive to commonly tested antibiotics, while 10% were either MDR- or pan-drug-resistant organisms. Of the MDR bacterial isolates, 25.61% were methicillin-resistant S. aureus, and 17.73% were extended-spectrum beta-lactamase Enterobacteriaceae. The most prevalent bacteria in pressure ulcers of spinal cord injury patients were S. aureus. Other antibiotic-resistant organisms were also isolated from the wounds.

Metabolic control and incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy: an analysis of the Saudi Arabia data from the DISCOVER Observational Study programme.

OBJECTIVES: The aim of the global DISCOVERing Treatment Reality of Type 2 Diabetes in Real World Settings (DISCOVER) Study was to provide a comprehensive real world assessment of the treatment pattern changes for patients with type 2 diabetes. The aim of this analysis was to assess the metabolic control and the annual incidence of hypoglycaemia, hospitalisation and complications among Saudi patients with type 2 diabetes initiating second-line therapy. DESIGN: This study is part of the observational, longitudinal, prospective multinational DISCOVER Study. SETTING: Governmental and private health sectors from different regions within Saudi Arabia. PARTICIPANTS: The study recruited 519 patients with type 2 diabetes aged ≥18 years who were switching to second-line therapy. Patients who were already using insulin/injectable agents, patients with type 1 diabetes, pregnant women, and patients undergoing dialysis or with a history of renal transplantation were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Metabolic control among patients with type 2 diabetes mellitus; fear of hypoglycaemia; quality of life; and the incidence of complications, hypoglycaemic events and/or hospitalisations. Data were analysed using descriptive statistics. RESULTS: A total of 519 patients were recruited with a mean age of 52.4±11 years. Of these participants, 54.7% were male and 45.3% were female. The incidence of hypoglycaemia was 56.72/1000 patient-years. The Hypoglycemia Fear Survey II showed a significant increase in patient worry related to hypoglycaemia from 6.4±11.9 at baseline to (p=0.0446) at the 36-month follow-up. The incidence of hospitalisation was 30.81/1000 patient-years. There was a moderate improvement in glycaemic control, represented as an HbA1c reduction from 8.8% at baseline to 8.2% at the 36-month follow-up. The incidence of macroangiopathy was 24.51/1000 patient-years and the incidence of microvascular complications such as retinopathy and albuminuria was 47.00/1000 patient-years and 221.71/1000 patient-years, respectively. The mean score of fear of hypoglycaemia showed an increase with 13.0±21.5 at baseline to 16.1±22.2 at the 36-month follow-up. When assessing the patients' quality of life, there was an improvement in the mental component score from 47.4±9.1 at baseline to 53.0±6.7 at the 36-month follow-up. CONCLUSIONS: Treatment intensification decisions should be made individually, weighing the benefit of good glycaemic control against the risk of hypoglycaemia. TRIAL REGISTRATION NUMBER: NCT02322762 and NCT02226822.

The remission rate, metabolic changes, and quality of life assessment among patients with type 2 diabetes post-bariatric surgery in Riyadh, Saudi Arabia: A cross-sectional study.

OBJECTIVES: To assess the remission rate, metabolic changes, and quality of life after bariatric surgery among Saudi patients with type 2 diabetes (T2DM). METHODS: This cross-sectional study was conducted in 2 main centers in the Riyadh, Saudi Arabia. The study included patients with T2DM who underwent either laparoscopic sleeve gastrectomy (LSG) or Roux-en-Y gastric bypass (RYGB) surgery from 2014 to 2018. The remission rate was defined based on the American Diabetes Association (ADA) and the International Diabetes Federation (IDF) criteria. Quality of life was assessed using the World Health Organization Quality of Life (WHOQOL)-BREF. RESULTS: A total of 232 patients were included with a mean age of 44.3 ± 10.3 years. 93.4% of the patients had LSG, while only 6.6% had RYGB surgery. Among patients who underwent either LSG or RYGB surgery, there was a significant improvement in metabolic and glycemic markers compared to the baseline. According to the ADA criteria, 48.5% of the patients had complete remission, while 18.9% had partial remission. Overall, 7% of the patients met the IDF optimization criteria, while 5.7% met the IDF improvement criteria. The mean score for all the QOL domains exceeded 63 ± 13, with the environmental and physical health domains having the highest scores. CONCLUSION: Among Saudi patients, bariatric surgery was associated with high remission rates and a better quality of life.

Zafirlukast protects against hepatic ischemia-reperfusion injury in rats via modulating Bcl-2/Bax and NF-κB/SMAD-4 pathways.

Hepatic ischemia/reperfusion injury (IRI) is a clinical problem commonly during liver transplantation and other liver surgery. This study aimed to evaluate the protective effect of zafirlukast (ZFK) on IR-induced hepatic injury and investigate its relevant protective mechanism. Thirty-two male Wistar albino rats were randomly allocated to four groups: sham, IRI, ZFK, and ZFK + IR groups. ZFK was administered orally in a dose of 80 mg/kg/day for 10 consecutive days. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) levels, and gamma glutamyl transferase (GGT) activity were estimated. Liver tissues were used to assess oxidative stress biomarkers including malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx), and reduced glutathione (GSH) contents. Inflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-33 (IL-33), in addition to apoptosis biomarkers, BCL2 associated X protein (Bax), B-cell lymphoma 2 (Bcl2) and galactine-9 (GAL9) proteins were also assessed. Western blot analysis was performed for vascular endothelial growth factor (VEGF) and fibrinogen expressions. Immunohistochemical analysis for hepatic nuclear factor-kappa B (NF-κB) and SMAD-4 was done in addition to histopathological examination. Our study revealed that ZFK pre-treatment resulted in liver function restoration and oxidative stress correction. Moreover, inflammatory cytokines were significantly reduced and a remarkable reduction of apoptosis, angiogenesis, and clotting formation has been indicated. Additionally, a significant reduction in SMAD-4 and NF-kB protein expressions was observed. These results were supported by hepatic architecture improvement. Our findings revealed that ZFK possesses a potential protective effect against liver IR possibly through its antioxidant, anti-inflammatory and anti-apoptotic properties.

Early Cytokine Signatures of Hospitalized Mild and Severe COVID-19 Patients: A Prospective Observational Study.

Background: The severe manifestation of coronavirus disease 2019 (COVID-19) is known to be mediated by several cytokines and chemokines. The study aimed to compare the early cytokine profile of mild and severe COVID-19 patients to that with COVID-19-like symptoms and tested negative for Severe Acute Respiratory Syndrome Coronavirus-2 in the Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) test. Methods: This was a prospective, observational study on COVID-19 patients admitted to King Khalid University Hospital, King Saud University Medical City from June to November 2020. Clinical and biochemical data were collected from hospital charts. Blood samples were collected at the time of hospital admission to measure cytokines. A Cytokine and Growth Factor High-Sensitivity Array was used to quantitatively measure cytokines. Results: The study included 202 RT-PCR-positive individuals and 61 RT-PCR-negative individuals. C-Reactive protein (CRP) and Interleukin-10 (IL-10) levels were found significantly elevated in the RT-PCR positive group compared to the RT-PCR negative group (p=0.001). Patients with severe COVID-19 had significantly longer median hospital stays than those with mild COVID-19 cases (7 vs 6 days). They also had higher CRP and Vascular Endothelial Growth Factor (VEGF) levels and lower Interleukin-4 (IL-4) levels compared to the mild cases. CRP, interleukin-6, IL-10, VEGF, and Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly elevated in men and IL-10 was significantly higher and interleukin-8 was significantly lower in women compared to negative controls. Elevated Interferon-É£ (IFN-γ) and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital. Conclusion: CRP and IL-10 levels were elevated in the RT-PCR positive group. People with severe COVID-19 had higher CRP and VEGF levels and lower IL-4 levels. Elevated IFN-γ and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.

LCZ696 (sacubitril/valsartan) mitigates cyclophosphamide-induced premature ovarian failure in rats; the role of TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway.

AIM: Cyclophosphamide (CP) is used to treat a variety of cancers and autoimmune illnesses. CP has been found to frequently cause premature ovarian failure (POF). The study's objective was to assess LCZ696's potential for protection against CP-induced POF in a rat model. MAIN METHODS: Rats were randomly assigned into seven groups as follows: control, valsartan (VAL), LCZ696, CP, CP + VAL, CP + LCZ696, and CP + triptorelin (TRI). Ovarian malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-18 (IL-18), IL-1ß, and tumor necrosis factor-alpha (TNF-α) were assessed using ELISA. Serum anti-mullerian hormone (AMH), estrogen, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also measured using ELISA. The expression of NLRP3/Caspase-1/GSDMD C-NT and TLR4/MYD88/NF-B P65 proteins was estimated using western blot assay. The histopathology of the ovaries was also investigated. The estrous cycle, body, and ovarian weights were also monitored. KEY FINDINGS: CP treatment significantly elevated levels of MDA, IL-18, IL-1ß, TNF-α, FSH, LH, and up-regulated TLR4/NF-κB/NLRP3/Caspase-1 proteins, as compared to the control group, however, ovarian follicles count, and levels of GSH, SOD, AMH, and estrogen were reduced with CP administration. All the aforementioned biochemical and histological abnormalities were considerably alleviated by the LCZ696 therapy compared to valsartan alone. SIGNIFICANCE: LCZ696 effectively mitigated CP-induced POF, offering promising protection that could be related to its suppression power on NLRP3-induced pyroptosis and TLR4/NF-B P65 pathway.

Effect of an antimicrobial stewardship program in the prevention of antibiotic misuse in patients with spinal cord injury undergoing minor urologic procedures: a single-group, quasi-experiment study.

BACKGROUND: Antimicrobial stewardship programs (ASPs) are an internationally recognized strategy for reducing antimicrobial resistance while maintaining patient safety. ASP activities include the restriction of broad-spectrum antibiotics, the establishment of hospital guidelines based on antibiograms, and the promotion of appropriate antibiotic use. This study aimed to determine whether the implementation of antimicrobial stewardship practices improved the effects of a peri-procedure antibiotic prophylaxis prescribed by urologists for patients with spinal cord injury/disease (SCI/D) undergoing minor urological procedures at a tertiary care hospital. METHODS: This single-group, quasi-experiment study included adult patients with SCI/D who required minor urological procedures (cystoscopy, cytobotox, cystolitholapaxy, and urodynamic study) and who were hospitalized between 2012 and 2020. RESULTS: In total, 233 patients were included in each of the pre- and post-ASP implantation groups. There was a significant reduction in antibiotic use among patients who received a pre-procedure antimicrobial prophylaxis in the post- compared to the pre-implementation group (45.9% vs. 24.46%, p < 0.0001), and there was a highly significant reduction in the post- compared to the pre-implementation group in the number who received a post-procedure prophylaxis (16.7% vs. 1.2%, p < 0.0001). CONCLUSION: ASP implementation is a highly effective strategy for reducing the use of peri-procedure antimicrobial prophylaxes in patients with SCI/D injuries undergoing minor urological procedures.

Longitudinal assessment of the quality of life and patterns of antidiabetic medication use in patients with type 2 diabetes, Saudi Arabia perspective, DISCOVER study.

OBJECTIVES: Patients with type 2 diabetes nowadays have a wide range of new antidiabetic medications with better efficacy and safety. Physicians' attitude toward selecting antidiabetic medications to reach targeted glycemic control and better quality of life (QOL) has not been studied prospectively. The global DISCOVER study aims to comprehensively provide a real-world assessment of the treatment pattern changes for patients with type 2 diabetes, in addition to QOL assessment. The Kingdom of Saudi Arabia was one of the countries participating in the DISCOVER study program. METHODS: This study is a part of the prospective, longitudinal multinational DISCOVER study conducted in 38 countries including Saudi Arabia, a country facing an epidemic of type 2 diabetes, recruited 519 adult patients with type 2 diabetes with a mean age of 52.4 ± 11 years, where, they were followed up for three years period, where 477 patients completed the follow-up period. The clinical, biochemical, and patient lifestyle data were assessed periodically during the study period. DISCOVER study is registered with ClinicalTrials.gov identifiers: NCT02322762. RESULTS: The most frequently used antidiabetic medications (ADMs) initially and during the follow-up were biguanides (metformin) and sulfonylureas (gliclazide, glibenclamide, glimepiride, glipizide, and glyclopyramide). Insulin (premix Insulin, basal insulin, and basal/bolus insulin) and dipeptidyl peptidase-4 (DPP-4) inhibitors (sitagliptin, vildagliptin, saxagliptin, and linagliptin) were the most frequent second and alternative of therapy. Other medications namely thiazolidinediones (TZds) (pioglitazone and rosiglitazone), incretins (exenatide and liraglutide), and Sodium-glucose co-transporter-2 (SGLT-2) inhibitors (canagliflozin) were used at a lesser rate. Drug availability, efficacy, and safety were the main determinants for choosing antidiabetic medications. The physical component score of the QOL had shown a significant decrease, while the mental component score has demonstrated an increase in QOL using SF36v2 Survey. CONCLUSIONS: There is an increasing trend of using of newly available ADMs, mainly DPP-4 inhibitors. The major limitation of ADMs use is related to efficacy, availability, and safety. This warrant taking all the measures to overcome these limitations through adopting a multidisciplinary team approach for close monitoring of the patients and any unfavorable side effects. Additionally, global insurance coverage for all patients with type 2 diabetes could be a solution for the drug availability factor.

Protective effects of rivaroxaban against cisplatin-induced testicular damage in rats: Impact on oxidative stress, coagulation, and p-NF-κB/VCAM-1 signaling.

Coagulation is a main pathway in various diseases pathogenesis including testicular damage. This study evaluated rivaroxaban (RVX) protective effects in testicular impairment by cisplatin (CP). Rats were randomly allocated into five groups: Control, RVX (7 mg/kg/day), CP (10 mg/kg), RVX 5 mg + CP and RVX 7 mg + CP. Serum testosterone and testicular ALT, AST, and ALP were assessed. Testicular oxidative stress and antioxidant parameters and inflammatory indicators including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were assessed. qRT-PCR was used to determine mRNA expression of 3ß-hydroxysteroid dehydrogenase (3ß-HSD), 17ß-hydroxysteroid dehydrogenase (17ß-HSD), and steroidogenic acute regulatory protein (stAR). Protein expressions of p-Nuclear factor kappa B (p- NF-κB) and vascular cell adhesion protein-1 (VCAM-1) were analyzed by Western blot analysis. Tissue factor (TF) expression was immunohistochemically analyzed. Results revealed that RVX significantly increased serum testosterone and sperm count while significantly reduced IL-1ß and TNF-α. It significantly decreased tissue MDA and NO contents while increased SOD and GPx. In addition, RVX attenuated CP-induced histopathological aberrations and normalized TF. It also decreased the VCAM-1 and p-NF-κB expression and showed strong expression of 3ß-HSD, 17ß-HSD, and stAR, indicating improvement of steroidogenesis. In conclusion, RVX counteracted testicular damage by CP via suppressing oxidative stress, inflammation, and coagulation and downregulating p-NF-κB/VCAM-1 signaling.

Novel therapeutic modalities target cell signaling of Renin-Angiotensin system/NF-κB-induced cell cycle arrest and apoptosis in urethane-induced lung cancer in mice: An in vivo study.

BACKGROUND: Lung cancer has risen to the top of the list of cancer-related deaths worldwide. Aliskiren is a direct renin inhibitor. AIM: This study aims to investigate the impact of cell signaling of Renin-Angiotensin system (RAS)/NF-κB on lung cancer by investigating the potential therapeutic effects of aliskiren for lung cancer treatment in urethane-induced lung cancer in mice. METHODS: Male BALB/c mice were randomly assigned to one of five treatment groups for 150 days, including (1) normal control; (2) aliskiren (25 mg/kg/i.p) daily, (3) urethane at a dose of 1.5 g/kg (i.p) at Day 1 and 60 (nonsmall cell lung cancer[NSCLC] group) (4) NSCLC mice received carboplatin (15 mg/kg/i.p) every other day for the last 4 successive weeks and (5) NSCLC mice treated with aliskiren daily. Tumor size was determined based on blood sampling, and lungs were isolated for biochemical analysis, western blot analysis assay, and histopathological examination. RESULTS: Urethane demonstrated significant changes in all biochemical and molecular parameters and histological patterns. Aliskiren-treated mice had significantly lower levels of NF-κB p65, Bcl-2, cyclin D1, ICAM-1, MMP-2, and Nrf2, with an increase in the catalytic activity of caspase-3 due to its RAS inhibitory mechanism. The combined urethane administration with aliskiren demonstrated a significant improvement in the histopathological examination. CONCLUSION: RAS/NF-B cell signaling is a potential therapeutic target for preventing and treating lung adenocarcinoma, evidenced by the fundamental cytotoxic mechanism and attenuation of metastasis and angiogenesis induced by the treatment of NSCLC mice with aliskiren.

Ameliorate impacts of scopoletin against vancomycin-induced intoxication in rat model through modulation of Keap1-Nrf2/HO-1 and IκBα-P65 NF-κB/P38 MAPK signaling pathways: Molecular study, molecular docking evidence and network pharmacology analysis.

Nephrotoxicity is an indication for the damage of kidney-specific detoxification and excretion mechanisms by exogenous or endogenous toxicants. Exposure to vancomycin predominantly results in renal damage and losing the control of body homeostasis. Vancomycin-treated rats (200 mg/kg/once daily, for seven consecutive days, i.p.) revealed significant increase in serum pivotal kidney function, oxidative stress, and inflammatory biomarkers. Histologically, vancomycin showed diffuse acute tubular necrosis, denudation of epithelium and infiltration of inflammatory cells in the lining tubular epithelium in cortical portion. In the existing study, the conservative consequences of scopoletin against vancomycin nephrotoxicity was investigated centering on its capacity to alleviate oxidative strain and inflammation through streamlining nuclear factor (erythroid-derived-2) like 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling and prohibiting the nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (p38 MAPK) pathway. With respect to vancomycin group, scopoletin pretreatment (50 mg/kg/once daily, i.p.) efficiently reduced kidney function, oxidative stress biomarkers and inflammatory mediators. Moreover, histological and immunohistochemical examination of scopoletin-treated group showed remarkable improvement in histological structure and reduced vancomycin-induced renal expression of iNOS, NF-κB and p38 MAPK. In addition, scopoletin downregulated (Kelch Like ECH Associated Protein1) Keap1, P38MAPK and NF-κB expression levels while upregulated renal expression levels of regulatory protein (IκBα), Nrf2 and HO-1. Furthermore, molecular docking and network approach were constructed to study the prospect interaction between scopoletin and the targeted proteins that streamline oxidative stress and inflammatory pathways. The present investigations elucidated that scopoletin co-treatment with vancomycin may be a rational curative protocol for mitigation of vancomycin-induced renal intoxication.

Prevalence, phenomenology and personality characteristics of premenstrual dysphoric disorder among female students at Zagazig University, Egypt.

BACKGROUND: Premenstrual dysphoric disorder (PMDD) is a female psychiatric disorder affecting the behaviour, cognitive abilities, mental health status and academic performance of female students. It includes: mood symptoms, behaviour symptoms and physical symptoms. AIM: To assess phenomenology, measure the prevalence of PMDD among university students and assess the relationship between PMDD and socio-demographic and personality characteristics. SETTING: This study was conducted at Zagazig University, Sharqia Governorate, Egypt. METHODS: A cross-sectional study was conducted from September 2020 to December 2020. It included 755 university students. They filled several questionnaires covering Diagnostic and Statistical Manual of Disorders (DSM-5) criteria to diagnose PMDD, socio-demographic, menstrual factors, physical activity and personality traits. RESULTS: Premenstrual dysphoric disorder was found in 159 out of 755 students (21.1%). Overall, the most frequently reported premenstrual symptoms were overeating/food cravings (84.2%), fatigue/lack of energy (83.6%), depressed mood/hopelessness (82.0%) and hypersomnia (78.9%). Binary logistic regression model revealed that significantly related PMDD risk factors include: being a medical student, having a duration of menstrual bleeding ≥ 7 days, the average length of one cycle ˂ 28 days, high menstrual blood loss, presence of dysmenorrhea and positive family history of premenstrual syndrome (sister/mother). Regarding personality traits, low extroversion and agreeableness, and high neuroticism were also significant PMDD risk factors. CONCLUSION: Prevalence of PMDD was high among university students, especially medical students, and it can have a detrimental effect on both academic life and educational accomplishments, quality of life and daily living activities.

Empagliflozin and neohesperidin protect against methotrexate-induced renal toxicity via suppression of oxidative stress and inflammation in male rats.

Kidney injury from chemotherapy is one of the worsening problems associated with methotrexate (MTX) use. This work aims to examine the nephroprotective effects of empagliflozin (EMPA) and neohesperidin dihydrochalcone (NHD) provoked by MTX. A rat model was implemented by a single administration of MTX (20 mg/kg, i.p.). EMPA and NHD were administered in two doses (10 and 30 mg/kg, p.o.) and (40 and 80 mg/kg, p.o.), respectively for 14 consecutive days, using N-acetylcysteine (150 mg/kg, p.o.) as a reference standard. Pretreatment with EMPA and NHD showed significant attenuation in the renal function biomarkers, histopathological abrasions, and renal oxidative parameters. Also, EMPA and NHD pretreatment produced marked reductions in the expression of IL-6 and TNF-α level as proinflammatory biomarkers. Furthermore, EMPA and NHD pretreatment revealed marked decreases in the expression level of NF-ĸB, Keap1, HSP70, and caspase-3 and notable increases in Nrf2, PPARγ and HO-1 expression levels. EMPA and NHD can constrain oxidative stress liberation, inflammatory mediators proliferation, and apoptotic reactions in the renal tissue, which may be promising for further clinical applications to protect against MTX-induced renal injury or at least to reduce its adverse effects.

Hearing loss among patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Hearing loss is an underestimated comorbid condition in type 2 diabetes. OBJECTIVES: Investigate hearing loss as a comorbidity associated with type 2 diabetes mellitus and evaluate the factors associated with hearing loss. DESIGN: Cross-sectional. SETTING: Tertiary care center, diabetes clinic. PATIENTS AND METHODS: Patients with type 2 diabetes, aged 30 to 60 years, were randomly selected to participate. All patients underwent clinical ear examinations and were referred for full audiological evaluation. Otoacoustic emission was used to assess inner function, tympanometry to assess middle-ear function, and pure tone air/bone audiometry to assess hearing sensitivity. Risk factors for hearing loss were assessed by multivariate logistic regression. MAIN OUTCOME MEASURE: Frequency, severity and risk factors for hearing loss. SAMPLE SIZE: 157 RESULTS: Of the 157 patients, 77 had hearing loss in both ears (49.0%), 13 in the right ear only (8.3%), 14 in the left ear only (8.9%), and 53 (33.8%) had normal hearing. In the 181 ears with sensorineural hearing loss, 90 had mild loss (49.7%), 69 moderate loss (38.2%), 16 severe loss (8.8%) and 6 had profound loss (3.3%). Disabling hearing loss was observed in 46 (29%) patients. A higher frequency of hearing loss was present in patients with glycated hemoglobin levels ≥8%. In the multivariate logistic regression analysis, the most important factors associated with hearing loss were longer diabetes duration, poor glycemic control and the presence of hypertension. CONCLUSIONS: Hearing loss is an underestimated comorbid condition in type 2 diabetes that warrants frequent hearing assessments and management. Strict glycemic and hypertension control is essential for the minimization of the effects of diabetes on hearing sensitivity. LIMITATIONS: Small sample size, limited age window (30-60 years), which was chosen to eliminate the natural aging effect on hearing. Cross-sectional nature was not ideal for the assessment of causality. CONFLICT OF INTEREST: None.

RETRACTED: Empagliflozin and neohesperidin mitigate methotrexate hepatotoxicity via Nrf2/PPARγ/HO-1 signalling initiation and suppression of NF-κB/Keap1/HSP70/caspase-3 axis in rats.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. A reader reported several mistakes in the paper including duplicated images in Figures 9 and 10, incorrect names of primer sequences and reference gene, as well as unclear description of the statistical analysis. The authors requested that a corrigendum be published, however, due to the large number of corrections applied, it cannot be concluded that these changes would not alter the conclusions of the paper. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.