Potential exacerbation of polycystic ovary syndrome by saccharin sodium Via taste receptors in a letrozole rat model.

The most common cause of anovulatory infertility is polycystic ovarian syndrome (PCOS), which is closely associated with obesity and metabolic syndrome. Artificial sweetener, notably saccharin sodium (SS), has been utilized in management of obesity in PCOS. However, accumulating evidence points towards SS deleterious effects on ovarian physiology, potentially through activation of ovarian sweet and bitter taste receptors, culminating in a phenotype reminiscent of PCOS. This research embarked on exploration of SS influence on ovarian functions within a PCOS paradigm. Rats were categorized into six groups: Control, Letrozole-model, two SS groups at 2 dose levels, and two groups receiving 2 doses of SS with Letrozole. The study underscored SS capability to potentiate PCOS-related anomalies. Elevated cystic profile with outer thin granulosa cells, were discernible. This owed to increased apoptotic markers as cleaved CASP-3, mirrored by high BAX and low BCL-2, with enhanced p38-MAPK/ERK1/2 pathway. This manifestation was accompanied by activation of taste receptors and disruption of steroidogenic factors; StAR, CYP11A1, and 17ß-HSD. Thus, SS showed an escalation in testosterone, progesterone, estrogen, and LH/FSH ratio, insinuating a perturbation in endocrine regulation. It is found that there is an impact of taste receptor downstream signaling on ovarian steroidogenesis and apoptosis instigating pathophysiological milieu of PCOS.

Influence of incorporating L-carnitine or Moringa oleifera leaves extract into semen diluent on cryosurvival and in vitro fertilization competence of buck sperm.

This study aimed at scrutinizing efficiency of incorporating L-carnitine or M. oleifera leaves extract into semen diluent on improving cryopreservation capacity and in vitro fertilization ability of buck spermatozoa. Ejaculates (n=48) were collected by an artificial vagina from six adult Damascus bucks twice weekly during the breeding season (September-October). Following initial evaluation, ejaculates of each collection session from the same bucks were pooled, diluted (1:10) with glycerolized (3 % glycerol, v/v) tris-citric acid egg yolk diluent and were split into three aliquots. The first aliquot served as control, whereas the second and third aliquots were supplemented with 4 µL/mL L-carnitine and 400 µL/mL moringa leaves extract (v/v), respectively. Thereafter, all specimens were processed for cryopreservation and were stored in liquid nitrogen (-196 °C) for 12 months before post-thaw sperm criteria were analyzed by a computer-assisted sperm analysis (CASA) system. Integrity of sperm DNA post thawing was visualized in all semen groups by fluorescence imaging, and in vitro fertilization ability of spermatozoa was also determined. Inclusion of L-carnitine or moringa leaves extract into the diluent improved (P<0.05) post-thaw sperm physical, morphofunctional and kinematic attributes, whilst maintaining (P<0.05) integrity of sperm DNA throughout the freezing and thawing cycle. Consequently, both supplemented groups yielded higher (P<0.05) in vitro fertilization rates compared to control. These results accentuate the protective roles of these antioxidants on buck sperm against consequences of cryopreservation-induced oxidative stress, hence ameliorating post-thaw sperm quality and fertilization competence. This is crucial for successful application of AI and IVF in goat selective breeding programs.

Smokeless tobacco and periodontitis: A systematic review with meta-analysis.

AIM: The present systematic review with meta-analysis aimed to investigate the global association between smokeless tobacco (SLT) use and periodontitis, considering significant effect size variation based on the income levels of countries. METHODS: We searched seven databases to identify studies that assessed the prevalence of periodontitis in adult SLT users compared to non-users. The quality of studies was evaluated using the 10-item risk-of-bias tool, and publication bias was addressed through the trim-and-fill method. Sensitivity analysis utilized the leave-one-out approach. Meta-analysis and meta-regression, stratified by country income, SLT type, and smoking status, employed robust variance estimation. RESULTS: From an initial pool of 484 studies, 29 studies met the selection criteria and were subjected to qualitative synthesis. Subsequently, data from 19 studies were included in the meta-analysis. SLT users exhibited a nearly threefold greater likelihood of periodontitis compared to non-users (OR = 2.99; 95% CI: 2.10, 4.27; p < .01). The pooled estimate did not vary significantly based on the type of SLT used or concurrent smoking. However, the odds of periodontitis varied according to the economic level of the country; the pooled estimate was higher in high-income countries (OR = 1.69; 95% CI: 1.20, 2.37; p < .01) and even higher in lower-middle-income and lower-income countries (OR = 3.91; 95% CI: 2.66, 5.77; p < .01). CONCLUSIONS: Smokeless tobacco users have a higher likelihood of developing periodontitis. This study underscores global disparities in the SLT-periodontitis relationship, highlighting the need for targeted interventions, particularly in economically challenged areas where SLT use is largely unregulated.

Vilazodone Alleviates Neurogenesis-Induced Anxiety in the Chronic Unpredictable Mild Stress Female Rat Model: Role of Wnt/ß-Catenin Signaling.

Defective ß-catenin signaling is accompanied with compensatory neurogenesis process that may pave to anxiety. ß-Catenin has a distinct role in alleviating anxiety in adolescence; however, it undergoes degradation by the degradation complex Axin and APC. Vilazodone (VZ) is a fast, effective antidepressant with SSRI activity and 5-HT1A partial agonism that amends somatic and/or psychic symptoms of anxiety. Yet, there is no data about anxiolytic effect of VZ on anxiety-related neurogenesis provoked by stress-reduced ß-catenin signaling. Furthermore, females have specific susceptibility toward psychopathology. The aim of the present study is to uncover the molecular mechanism of VZ relative to Wnt/ß-catenin signaling in female rats. Stress-induced anxiety was conducted by subjecting the rats to different stressful stimuli for 21 days. On the 15th day, stressed rats were treated with VZ(10 mg/kg, p.o.) alone or concomitant with the Wnt inhibitor: XAV939 (0.1 mg/kg, i.p.). Anxious rats showed low ß-catenin level turned over by Axin-1 with unanticipated reduction of APC pursued with elevated protein levels of neurogenesis-stimulating proteins: c-Myc and pThr183-Erk likewise gene expressions of miR-17-5p and miR-18. Two weeks of VZ treatment showed anxiolytic effect figured by alleviation of hippocampal histological examination. VZ protected ß-catenin signal via reduction in Axin-1 and elevation of APC conjugated with modulation of ß-catenin downstream targets. The cytoplasmic ß-catenin turnover by Axin-1 was restored by XAV939. Herein, VZ showed anti-anxiety effect, which may be in part through regaining the balance of the reduced ß-catenin and its subsequent exaggerated response of p-Erk, c-Myc, Dicer-1, miR-17-5p, and miR-18.

Sulforaphane's role in Redefining autophagic Responses in depression associated with polycystic ovarian syndrome: Unveiling the SIRT1/AMPK/LKB1 pathway connection.

Polycystic ovarian syndrome (PCOS) has been associated with depression and suicidal ideations in females. Studies have highlighted the role of autophagic deficiency in depression pathogenesis. Sulforaphane (SFN) is a natural product that improved autophagic deficiency and showed antidepressant activity in depressed patients. Herein, the study aimed to evaluate the impact of using SFN on depression-associated with PCOS via hippocampal energy sensors and cellular bioenergetics. PCOS was induced by administering letrozole (1 mg/kg, p. o.) for 21 days, followed by SFN treatment (0.5 mg/kg, i. p.) for one week. Two days before euthanasia, PCOS rats showed anhedonic behavior in the sucrose preference test and increased immobility time in the forced swimming test. Depressed rats showed a reduction in nuclear SIRT1 and an elevated cytoplasmic one. This was associated with a reduction in phosphorylation of energy sensors, liver kinase B1 (LKB1), and adenosine monophosphate kinase (AMPK), along with an imbalance of autophagic markers such as Beclin-1, microtubule-associated protein I/II light chain 3, autophagy enzyme 7 and selective autophagy receptor P62. Additionally, Nrf2 and KEAP1 levels were decreased. These abnormalities were alleviated by SFN treatment, as evidenced by the nuclear translocation of SIRT1 and the repression of downstream proteins, including FOXO1, NF-κB, and TNF-α production. These changes were reflected in improved behavioral performance in the sucrose preference test (SPT) and forced swimming test (FST). The antidepressant effects of SFN were counteracted by an autophagic inhibitor, 3-methyladenine. Eventually, SFN, as a nutraceutical, has a promising antidepressant effect via restoring autophagic-related depression in the PCOS rat model.

Real-time combined safety-mobility assessment using self-driving vehicles collected data.

The study presents a real-time safety and mobility assessment approach using data generated by autonomous vehicles (AVs). The proposed safety assessment method uses Bayesian hierarchical spatial random parameter extreme value model (BHSRP), which can handle the limited availability and uneven distribution of conflict data and accounts for unobserved spatial heterogeneity. The approach estimates two real-time safety metrics: the risk of crash (RC) and return level (RL), using Time-To-Collision (TTC) as conflict indicator. Additionally, a Risk Exposure (RE) index was developed to reflect the risk of an individual vehicle to travel through a corridor. In parallel, the mobility of corridor were assessed based on the highway Capacity manual methodology using real-time traffic data (Highway Capacity Manual, 2010). The study used a 440-hour AVs' dataset of a corridor in Palo Alto, California. After normalizing for each LOS representation in the dataset, LOS E was identified as the most hazardous operating condition with the highest average crash risk. However, the time spent under different operating condition would affect the safety of individual vehicles traveling through a road facility (i.e., vehicle's exposure time). Accounting for exposure time, the vehicle has the highest chance of encountering an extremely risky driving condition at intersections and segments under LOS D and E, respectively.

Influence of ß-catenin signaling on neurogenesis in neuropsychiatric disorders: Anxiety and depression.

It has been proven that stress, mainly in the early years of life, can lead to anxiety and mood problems. Current treatments for psychiatric disorders are not enough, and some of them show intolerable side effects, emphasizing the urgent need for new treatment targets. Hence, a better understanding of the different brain networks, which are involved in the response to anxiety and depression, may evoke treatments with more specific targets. One of these targets is ß-catenin that regulates brain circuits. ß-Catenin has a dual response toward stress, which may influence coping or vulnerability to stress response. Indeed, ß-catenin signaling involves several processes such as inflammation-directed brain repair, inflammation-induced brain damage, and neurogenesis. Interestingly, ß-catenin reduction is accompanied by low neurogenesis, which leads to anxiety and depression. However, in another state, this reduction activates a compensatory mechanism that enhances neurogenesis to protect against depression but may precipitate anxiety. Thus, understanding the molecular mechanism of ß-catenin could enhance our knowledge about anxiety and depression's pathophysiology, potentially improving clinical results by targeting it. Herein, the different states of ß-catenin were discussed, shedding light on possible drugs that showed action on psychiatric disorders through ß-catenin.

The preferential effect of Clemastine on F3/Contactin-1/Notch-1 compared to Jagged-1/Notch-1 justifies its remyelinating effect in an experimental model of multiple sclerosis in rats.

Clemastine (CLM) is repurposed to enhance remyelination in multiple sclerosis (MS) patients. CLM blocks histamine and muscarinic receptors as negative regulators to oligodendrocyte differentiation. These receptors are linked to the canonical and non-canonical Notch-1 signaling via specific ligands; Jagged-1 and F3/Contactin-1, respectively. Yet, there are no previous studies showing the influence of CLM on Notch entities. Herein, the study aimed to investigate to which extent CLM aligns to one of the two Notch-1 arms in experimental autoimmune encephalomyelitis (EAE) rat model. Three groups were utilized where first group received vehicles. The second group was injected by spinal cord homogenate mixed with complete Freund's adjuvant on days 0 and 7. In the third group, CLM (5 mg/kg/day; p.o) was administered for 15 days starting from the day of the first immunization. CLM ameliorated EAE-associated motor and gripping impairment in rotarod, open-field, and grip strength arena beside sensory anomalies in hot plate, cold allodynia, and mechanical Randall-Selitto tests. Additionally, CLM alleviated depressive mood observed in tail suspension test. These findings harmonized with histopathological examinations of Luxol-fast blue stain together with enhanced immunostaining of myelin basic protein and oligodendrocyte lineage gene 2 in corpus callosum and spinal cord. Additionally, CLM enhanced oligodendrocyte myelination and maturation by increasing 2',3'-cyclic nucleotide 3'-phosphodiesterase, proteolipid protein, aspartoacylase as well. CLM restored the level of F3/Contactin-1 in the diseased rats over Jagged-1 level; the ligand of the canonical pathway. This was accompanied by elevated gene expression of Deltex-1 and reduced hairy and enhancer-of-split homologs 1 and 5. Additionally, CLM suppressed microglial and astrocyte activation via reducing the expression of ionized calcium-binding adaptor molecule-1 as well as glial fibrillary acidic protein, respectively. These results outlined the remyelinating beneficence of CLM which could be due to augmenting the non-canonical Notch-1 signaling over the canonical one.

Effect of Metformin on Oxidative Stress and Left Ventricular Geometry in Nondiabetic Heart Failure Patients: A Randomized Controlled Trial.

Introduction: There is an increasing interest in using metformin in cardiovascular diseases and its potential new roles. Only two randomized controlled trials investigated the effect of metformin in nondiabetic heart failure (HF) patients. However, none of these studies assess the role of metformin in reducing oxidative stress. We hypothesized that metformin might improve oxidative stress and left ventricular remodeling in nondiabetic HF patients with reduced ejection fraction (HFrEF). Methods and Methods: Seventy HFrEF patients (EF 37% ± 8%; median age 66 years) were randomized to metformin (n = 35) or standard of care (SOC) for HF (n = 35) for 6 months in addition to standard therapy. Outcomes included the difference in the change (Δ) in total antioxidant capacity (TAC) and malondialdehyde (MDA), both assessed colorimetrically and left ventricular mass index (LVMI) assessed through transthoracic echocardiography. Results: Compared with the SOC, metformin treatment increased TAC [Δ = 0.12 mmol/L, confidence intervals (95% CIs): 0.03-0.21; P = 0.007]. TAC increased significantly only in the metformin group (0.90 ± 0.08 mmol/L at baseline vs. 1.04 ± 0.99 mmol/L at 6 months, P < 0.05). Metformin therapy preserved LVMI (Δ = -23 g/m2, 95% CI: -42.91 to -4.92; P = 0.014) and reduced fasting plasma glucose (Δ = -6.16, 95% CI: -12.31 to -0.02, P = 0.047) compared with the SOC. Results did not change after adjusting for baseline values. Changes in MDA left ventricular ejection fraction (LVEF) and blood pressure were not significantly different between groups. Conclusion: Metformin treatment in HF patients with reduced LVEF improved TAC and prevented the increase in LVMI compared with the SOC. These effects of metformin warrant further research in HF patients without diabetes to explore the potential benefits of metformin. Trial Registration Number: This protocol was registered in ClinicalTrials.gov under the number NCT05177588.

Novel quinazolinone Derivatives: Design, synthesis and in vivo evaluation as potential agents targeting Alzheimer disease.

Since Alzheimer disease is one of the most prevalent types of dementia with a high mortality and disability rate, so development of multi-target drugs becomes the major strategy for battling AD. This study shows the development of a series of quinazolinone based derivatives as novel, multifunctional anti-AD drugs that exhibit both cholinesterase inhibitoryand anti-inflammatory properties. The preliminary results of the in vitro AChE inhibition activity showed that compounds 4b, 5a, 6f, 6h and 7b were better represented for further evaluation. Furthermore, in-vivo AChE inhibition activity and behavior Morris water maze test against donepezil as reference drug were evaluated. Additionally, hippocampal inflammatory markers; TNF-α, NFĸB, IL-1ß and IL-6 and antioxidant markers; SOD and MDA were assessed to evaluate the efficacy of quinazolinone derivatives against AD hallmarks. The results showed that 6f, 6h and 7b have promising anti-acetylcholinesterase, anti-inflammatory and antioxidant activities thus, have a significant effect in treatment of AD. Moreover, Histopathological examination revealed that 6f, 6h and 7b derivatives have neuroprotective effect against neuronal damage caused by induced scopolamine model in mice. Finally, the binding ability of the synthesized derivatives to the target, AChE was investigated through molecular docking which reflected significant interactions to the target based on their docking binding scores. Hence, the newly designed quinazolinone derivatives possess promising anti-acetylcholinesterase activity and challenging for the management of AD in the future.

Pilot Demonstration of a New Tip for Effective Gas Flaring in the Permian Basin: Part 1.

In the oil and gas industry, gas flaring through flare stacks plays a critical role in safely and efficiently releasing and burning gases and other materials from pressure-relief and vapor-depressurizing systems. Gas flaring is a contentious and formidable environmental challenge, both regionally and globally. Its adverse impacts encompass pollution, contribution to global warming, and substantial economic losses. Shockingly, gas flaring squanders approximately 5% of the global gas supply, resulting in the annual production of over 350 million tons of CO2 gas. While alternatives to gas flaring exist, they are either undergoing investigation or currently lacking economic viability. Consequently, the development of a more efficient gas flaring system is imperative. In addition, the reliable and efficient operation of flares is paramount, as they are expected to function seamlessly over extended periods under various service conditions. In this paper, a novel gas flaring tip to address the limitations of existing flaring systems is introduced. This innovative tip features a distinctive configuration, incorporating a bullet-shaped device positioned atop the flare. This bullet device boasts four strategically placed apertures equipped with internal deflectors, facilitating the convergence of gases into a single vortex outlet at its apex. For operational flexibility, the bullet is affixed to the flare tip using a system of three springs, enabling it to elevate at a pressure of 2.0 psig and achieve full extension at 8 psig. This dynamic design harnesses the Coanda effect, promoting efficient oxygen utilization. The comprehensive evaluation of this tip spanned a wide range of gas capacities, 4.0 and 10.0 MMSCFD. In this analysis, parameters such as the fraction of heat radiated, transmissivity, atmospheric humidity level, solar radiation adjustment, ambient temperature, and horizontal wind velocity were factored. The evaluation included both theoretical analysis and experimental investigation. The theoretical analysis employed a simplified open pipe flare tip approach to predict thermal radiation levels around the tip using the Brzustowski and Sommer model. The experimental setup included equipment such as thermocouple thermometers, heat flux sensors, digital sound level meters, mass flowmeters, and portable flue gas analyzers. Throughout testing, thermal radiation levels, isopleths, noise levels, and flue gas composition were measured. The collected data were subsequently compared to predictions generated using the Brzustowski and Sommer model for identical gas flow rates, flare heights, and flare diameters. Due to technical challenges and safety concerns, flue gas composition was not available. The authors are exploring different alternatives to overcome these obstacles and data should be available in the near future. The resulting data of heat radiation and noise levels unequivocally demonstrate the superiority of the new tip when compared to conventional gas flaring systems. With its cost-effectiveness, smokeless operation, heightened efficiency, and cleaner flame characteristics, the authors, due to the groundbreaking design of this tip, strongly advocate its adoption as a means to mitigate the environmental impact of gas flaring.

Preclinical Evidence for the Role of the Yin/Yang Angiotensin System Components in Autism Spectrum Disorder: A Therapeutic Target of Astaxanthin.

Autism spectrum disorder (ASD) prevalence is emerging with an unclear etiology, hindering effective therapeutic interventions. Recent studies suggest potential renin-angiotensin system (RAS) alterations in different neurological pathologies. However, its implications in ASD are unexplored. This research fulfills the critical gap by investigating dual arms of RAS and their interplay with Notch signaling in ASD, using a valproic acid (VPA) model and assessing astaxanthin's (AST) modulatory impacts. Experimentally, male pups from pregnant rats receiving either saline or VPA on gestation day 12.5 were divided into control and VPA groups, with subsequent AST treatment in a subset (postnatal days 34-58). Behavioral analyses, histopathological investigations, and electron microscopy provided insights into the neurobehavioral and structural changes induced by AST. Molecular investigations of male pups' cortices revealed that AST outweighs the protective RAS elements with the inhibition of the detrimental arm. This established the neuroprotective and anti-inflammatory axes of RAS (ACE2/Ang1-7/MasR) in the ASD context. The results showed that AST's normalization of RAS components and Notch signaling underscore a novel therapeutic avenue in ASD, impacting neuronal integrity and behavioral outcomes. These findings affirm the integral role of RAS in ASD and highlight AST's potential as a promising treatment intervention, inviting further neurological research implications.

COVID-19 vaccine hesitancy in Egypt: a cross-sectional study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) vaccine hesitancy is a major problem. This study aimed to determine the factors associated with COVID-19 vaccine acceptance. METHODOLOGY: A cross-sectional survey-based study was conducted on a sample of the Egyptian population using an online survey distributed through social media platforms, including Facebook, WhatsApp, and LinkedIn. The questionnaire was composed of five parts: part I describing the research questionnaire and its aim, part II assessing the demographic data, part III assessing knowledge and attitude towards COVID-19 infection, and part IV and V evaluating knowledge regarding COVID-19 vaccines, factors affecting vaccine acceptance and participants' attitude toward vaccination. Regression models were used to assess factors associated with vaccine acceptability. RESULTS: A total of 24376 responses were included in the statistical analysis. Females represented more than two-thirds of the study sample (70.5%,) and 18-24 years was the most commonly reported age group. Around one-third of the sample were healthcare professionals (HCPs). Only 14.3% of the participants received or registered to receive the vaccine, while 47% refused to be vaccinated. Regression analysis revealed that male gender, secondary education, older age, married or divorced status, presence of comorbidities, and higher level of knowledge regarding the vaccine were significantly associated with high vaccine acceptance. The most important vaccine attributes influencing vaccine selection in the current work were efficacy and safety. CONCLUSIONS: Vaccine hesitancy is currently a major challenge. Governments should design educational campaigns that provide trusted data related to vaccine efficacy and safety to encourage vaccination and enhance awareness.

The Expression of Triticum aestivum Cysteine-Rich Receptor-like Protein Kinase Genes during Leaf Rust Fungal Infection.

Understanding the role of cysteine-rich receptor-like kinases (CRKs) in plant defense mechanisms is crucial for enhancing wheat resistance to leaf rust fungus infection. Here, we identified and verified 164 members of the CRK gene family using the Triticum aestivum reference version 2 collected from the international wheat genome sequencing consortium (IWGSC). The proteins exhibited characteristic features of CRKs, including the presence of signal peptides, cysteine-rich/stress antifungal/DUF26 domains, transmembrane domains, and Pkinase domains. Phylogenetic analysis revealed extensive diversification within the wheat CRK gene family, indicating the development of distinct specific functional roles to wheat plants. When studying the expression of the CRK gene family in near-isogenic lines (NILs) carrying Lr57- and Lr14a-resistant genes, Puccinia triticina, the causal agent of leaf rust fungus, triggered temporal gene expression dynamics. The upregulation of specific CRK genes in the resistant interaction indicated their potential role in enhancing wheat resistance to leaf rust, while contrasting gene expression patterns in the susceptible interaction highlighted potential susceptibility associated CRK genes. The study uncovered certain CRK genes that exhibited expression upregulation upon leaf rust infection and the Lr14a-resistant gene. The findings suggest that targeting CRKs may present a promising strategy for improving wheat resistance to rust diseases.

Nano-crystallization of flubendazole for enhanced dissolution rate and improved in vivo efficacy against Trichinella spiralis.

The aim was to enhance the dissolution rate and in vivo efficacy of flubendazole against trichinella spiralis. Flubendazole nanocrystals were developed by controlled anti-solvent recrystallization. Saturated flubendazole solution was prepared in DMSO. This was injected into phosphate buffer (pH 7.4) containing Aerosil 200, Poloxamer 407 or sodium lauryl sulphate (SLS) while mixing using paddle mixer. The developed crystals were separated from DMSO/aqueous system by centrifugation. The crystals were characterized using DSC, X-ray diffraction and electron microscopy. The crystals were suspended in Poloxamer 407 solution and dissolution rate was monitored. Optimal formulation was administered to Trichinella spiralis infected mice. Administration protocol attacked the parasite in intestinal, migrating and encysted phases. The crystals were spherical nanosized with formulation employing 0.2% Poloxamer 407 as stabilizer being optimum with size of 743.1 nm. DSC and X-ray supported particle size reduction with partial amorphization. Optimal formulation showed fast dissolution to deliver 83.1% after 5 min. Nanocrystals provided complete eradication of intestinal Trichinella and reduced larval count by 90.27 and 85.76% in migrating and encysted phases compared with marginal effect in case of unprocessed flubendazole. The efficacy was clearer from improved histopathological features of the muscles. The study introduced nano-crystallization for enhanced dissolution and in vivo efficacy of flubendazole.

Dentofacial effects of miniscrew-anchored maxillary protraction on prepubertal children with maxillary deficiency: a randomized controlled trial.

BACKGROUND: The introduction of bone-anchored maxillary protraction eliminated the side effects of facemask in the early treatment of patients with maxillary retrusion. This study aimed to evaluate the effects of miniscrew-anchored maxillary protraction (MAMP) and compare them with the growth changes in an untreated control group in growing patients with Class III malocclusion. METHODS: Forty growing patients with Class III malocclusion and retrognathic maxilla were randomly allocated into two groups: treated and control groups. In the treated group, patients were treated with full-time intermaxillary Class III elastics (C3E) anchored by a hybrid hyrax (HH) in the maxilla and a bone-supported bar in the mandible. Protraction was stopped after obtaining a positive overjet. Cephalometric radiographs were acquired before and after the treatment. Data were statistically analyzed on an intention-to-treat basis. Intergroup comparisons were also made using analysis of covariance with the readings at T0 as a covariate. RESULTS: Forty patients agreed to participate, and 30 of them completed the study (treated group, n = 17; control group, n = 13). The average treatment duration was 11.9 months. MAMP resulted in a significant maxillary advancement (A-VR, 4.34 mm) with significant control over the mandibular growth. No significant increase in the mandibular plane angle was found in the treated group compared with the control group. The upper and lower incisors showed significant protrusion in the treated group. CONCLUSIONS: Within the limitations of this study and high attrition rate, the MAMP protocol can effectively increase maxillary forward growth with good control over the growth of the mandible antero-posteriorly and vertically.

Total Antioxidant Capacity and Prediabetes Are Associated with Left Ventricular Geometry in Heart-Failure Patients with Reduced Ejection Fraction: A Cross-Sectional Study.

Introduction: Few studies explored the association between total antioxidant capacity (TAC) and left ventricular (LV) geometry in patients with heart failure and reduced ejection fraction (HFrEF). The current study aimed to assess factors associated with LV geometry in HFrEF patients with particular emphasis on oxidative stress and glycemic status. Methods: A cross-sectional study was conducted from July 2021 to September 2022. All consecutive patients with HFrEF who were stabilized on optimal or maximally tolerated heart failure medications were recruited. Patients were classified into tertiles based on TAC and malondialdehyde for correlation with other parameters. Results: TAC was significantly associated with LV geometry (P = 0.01), with higher TAC levels observed in patients with normal LV geometry (0.95 ± 0.08) and concentric hypertrophy (1.01 ± 0.14) than in patients with eccentric hypertrophy (EH) (0.90 ± 0.10). There was a significant positive trend in the association between glycemic state and LV geometry (P = 0.002). TAC showed a statistically significant positive correlation with EF (r = 0.29, P = 0.0064) and a negative correlation with LV internal diameter at end diastole (r = -0.26, P = 0.014), LV mass index (r = -0.25, P = 0.016), and LV mass (r = -0.27, P = 0.009). After adjusting for multiple confounders, prediabetes [odds ratio (OR) = 4.19, P = 0.032] and diabetes (OR = 7.47, P = 0.008) were associated with higher odds of EH than normoglycemic patients. A significant inverse trend was also observed in the association between TAC tertile and the odds of LV geometry (OR = 0.51, P = 0.046). Conclusions: TAC and prediabetes are significantly associated with LV geometry. TAC can be used as an additional marker in HFrEF patients to reflect the severity of the disease. Interventions aimed at managing oxidative stress might be useful in HFrEF patients to reduce oxidative stress and improve LV geometry and quality of life. Trial Registration Number: This study is part of an ongoing randomized clinical trial (ClinicalTrials.gov identifier NCT05177588).

Concerns about stone free rate and procedure events of percutaneous nephrolithotripsy (PCNL) for 2-4 cm kidney stones by standard-PCNL vs mini-PCNL- comparative randomised study.

BACKGROUND: To compare the efficacy and safety of standard percutaneous nephrolithotomy (PCNL) with mini- PCNL for kidney stones 2-4 cm. METHODS: Eighty patients were enrolled in a comparative study, they were randomly divided into mini-PCNL group (n = 40) and standard-PCNL (n = 40). Demographic characteristics, perioperative events, complications, stone free rate (SFR) were reported. RESULTS: Both groups showed no significant difference in clinical data about age, stone location, back pressure changes, and body mass index. The mean operative time was (95 ± 17.9 min) in mini-PCNL, and (72.1 ± 14.9 min). Stone free rate were 80% and 85% in mini-PCNL and standard-PCNL respectively. Intra-operative complications, post-operative need for analgesia, hospital stay were significantly higher in standard-PCNL compared to mini-PCNL (85% vs. 80%). The study followed CONSORT 2010 guidelines for reporting parallel group randomization. CONCLUSION: Mini-PCNL is an effective and safe treatment of kidney stones 2-4 cm, it has the advantage over standard-PCNL being has less intra-operative events, less post-operative analgesia, shorter hospital stay, while operative time and stone free rate are comparable when considering multiplicity, hardness, and site of stones.

Dapagliflozin modulates neuronal injury via instigation of LKB1/p-AMPK/GABAB R2 signaling pathway and suppression of the inflammatory cascade in an essential tremor rat model.

BACKGROUND: However, disturbances in cellular energy demarcate neuronal hyperexcitability in essential tremor (ET); nevertheless, no available data relates energy sensors and GABAergic neurotransmission in ET. Noteworthy, reports have asserted dapagliflozin's (DAPA) role in enhancing autophagic sensors in other disorders. Herein, this study aims to investigate DAPA's impact on the GABAB receptor subunit (GABAB R2), notwithstanding the GABA A involvement, in an ET model. METHODS: ET was induced by a single dose of harmaline (30 mg/kg; i.p.), while DAPA (1 mg/kg/day; p.o.) was given for 5 days before ET induction. The autophagic sensors were examined by injecting a single dose of dorsomorphin (DORSO) AMPK inhibitor (0.2 mg/kg; i.p.) on the 5th day before ET induction. RESULTS: DAPA decreased the HAR-induced tremor score and alleviated motor disabilities observed in the open field, rotarod, wire grip strength, and gait kinematics confirmed by reduced electrical activity in electroencephalogram. In the cerebella, DAPA curbed HAR-evoked inflammatory cytokines, apoptotic markers, and glutamate while restoring the disturbed GABA, BDNF, LKB1, p-AMPK, and GABAB R2 levels. DAPA's effect was mostly obliterated by DORSO. CONCLUSION: DAPA offers a potential neuroprotective effect in ET by augmenting the neuronal inhibitory machinery via suppressing the inflammatory and excitotoxicity systems through LKB1/p-AMPK/GABAB R2 signaling.

The effect of COVID-19 on the in-hospital outcomes of percutaneous coronary intervention in patients with acute coronary syndrome: A large scale meta-analysis.

Aim: We aimed to study the effect of COVID-19 on the in-hospital outcomes of percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). Method: A systematic literature search was performed in 2nd February 2022 updated in 12th December 2022 for recruiting relevant papers. The effect size was computed via the odds ratio (OR) for dichotomous data or standardized mean difference (SMD) for continuous data along with the 95% confidence interval (95%CI). Results: After the screening of 1075 records, we found 11 relevant papers that included 2018 COVID-19 patients and negative controls 21,207. ACS patients with COVID-19 had a significant higher mortality rate (OR: 4.95; 95%CI: 3.92-6.36; p <0.01), long hospital stay (days) (SMD: 1.17; 95%CI: 0.92-1.42; p <0.01), and reduced post TIMI 3 score (OR: 0.55; 95%CI: 0.41-0.73; p <0.01) rather than controls. However, we found no significant differences in terms of thrombus aspiration prevalence (OR: 1.88; 95%CI: 0.97-3.65; p = 0.06) or door to balloon time (SMD: 0.11; 95%CI: -0.43-0.66; p = 0.7). Conclusion: Despite that we found a significant association between COVID-19 and high mortality, more length of hospital stay and reduced post TIMI 3 score, in ACS patients after PCI, a rigorous analysis of the adjusted hazard ratio -that was absent in most of the included studies- by further meta-analysis is recommended to confirm this association. However, close monitoring of COVID-19 in patients with a high risk of developing ACS, is recommended due to the associated hypercoagulability of COVID-19 infection.