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.

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.

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.

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.

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.

Daclatasvir as a hepatitis C infection treatment option: an up-to-date evaluation.

INTRODUCTION: Globally, it is estimated that 290,000 patients infected with hepatitis C virus (HCV) died from hepatitis C consequences, including cirrhosis and hepatocellular carcinoma in 2019. Although daclatasvir (DCV), combined with sofosbuvir (SOF), is effective in HCV patients, the new pan-genotypic combinations are considered by many as more cost-effective and successful in eradicating HCV infection. AREAS COVERED: This review discusses the safety, efficacy, and cost-effectiveness of DCV as an HCV treatment option based on real-world studies and pharmacoeconomic evaluations. EXPERT OPINION: Real-life studies suggest that SOF/DCV has acceptable sustained virological response and can be used successfully to manage HCV. Nonetheless, the use of SOF/DCV is limited by the longer treatment duration in genotype (GT)-3 patients and the need for ribavirin (RBV) in treatment-experienced patients which increases the likelihood of adverse effects. DCV is likely to remain as a therapeutic option for the management of GT-1, GT-2, and GT-4 patients in resource limited settings, while GT-3 patients are more likely to benefit from RBV-free direct-acting antiviral combinations such as SOF/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks. The introduction of generics for these new pan-genotypic drugs would likely eliminate the need for SOF/DCV in the near future.

Relation of Depression and Anxiety Disorders in Choosing Obesity Management in Obese Patients.

Background: Obesity is a chronic medical illness with a higher risk of physical and mental cascade. People who seek obesity treatment were reported to have some psychiatric disorders affecting their disease and selection of management. Aims of the Study: This study aims to estimate the prevalence of depressive and anxiety disorders in obese patients seeking obesity management and explore the relationship between common psychiatric disorders (depression and anxiety disorders) and selection of the type of obesity management (surgical or non-surgical). Methods: Patients were recruited from Alazhar Universityhospitals, Egypt, and the total number completing the study was 1115 patients. All subjects underwent psychiatric interview through Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (SCID-5 for DSM-5) for diagnosis of psychiatric disorders and completed two questionnaires, Hamilton Rating Scale for Depression (HRSD) and Hamilton Rating Scale for Anxiety (HRSA). Results: The prevalences of depressive and anxiety disorders were 29.23% and 25.56%, respectively, in all subjects. The most prevalent diagnoses were dysthymic disorder (20.7%), general anxiety disorder (16.95%), major depressive disorder (13.04%), and social phobia (12.4%). Our sample was divided into two groups (surgical and non-surgical). Dysthymia was more common in the surgical group (21.4% versus 19.8% P = 0.560), whereas major depressive disorder was more common in the non-surgical group (7.4% versus 5.4 P = 0.593); also, the non-surgical group was more likely to have "anxiety disorders" (29.23% versus 22.4%, P = 0.840), but severity of anxiety was higher in the surgical group according to HRSA score with a highly significant difference. Conclusions: A high prevalence of depression and anxiety disorders was found among patients who sought obesity treatment. Severity of anxiety was higher in the surgical group according to HRSA score with a highly significant difference, which may affect selection of treatment, so psychiatric evaluation and management are needed before and after obesity management to improve the outcome.

Boosting amygdaloid GABAergic and neurotrophic machinery via dapagliflozin-enhanced LKB1/AMPK signaling in anxious demented rats.

Anxiety is a neuropsychiatric disturbance that is commonly manifested in various dementia forms involving Alzheimer's disease (AD). The mechanisms underlying AD-associated anxiety haven't clearly recognized the role of energy metabolism in anxiety represented by the amygdala's autophagic sensors; liver kinase B1 (LKB1)/adenosine monophosphate kinase (AMPK). Dapagliflozin (DAPA), a SGLT2 inhibitor, acts as an autophagic activator through LKB1 activation in several diseases including AD. Herein, the propitious yet undetected anxiolytic potential of DAPA as an autophagic enhancer was investigated in AD animal model with emphasis on amygdala's GABAergic neurotransmission and brain-derived neurotrophic factor (BDNF). Alzheimer's disease was induced by ovariectomy (OVX) along with seventy-days-D-galactose (D-Gal) administration (150 mg/kg/day, i.p). On the 43rd day of D-Gal injection, OVX/D-Gal-subjected rats received DAPA (1 mg/kg/day, p.o) alone or with dorsomorphin the AMPK inhibitor (DORSO, 25 µg/rat, i.v.). In the amygdala, LKB1/AMPK were activated by DAPA inducing GABAB2 receptor stimulation; an effect that was abrogated by DORSO. Dapagliflozin also replenished the amygdala GABA, NE, and 5-HT levels along with glutamate suppression. Moreover, DAPA triggered BDNF production with consequent activation of its receptor, TrkB through activating GABAB2-related downstream phospholipase C/diacylglycerol/protein kinase C (PLC/DAG/PKC) signaling. This may promote GABAA expression, verifying the crosstalk between GABAA and GABAB2. The DAPA's anxiolytic effect was visualized by improved behavioral traits in elevated plus maze together with amendment of amygdala' histopathological abnormalities. Thus, the present study highlighted DAPA's anxiolytic effect which was attributed to GABAB2 activation and its function to induce BDNF/TrkB and GABAA expression through PLC/DAG/PKC pathway in AMPK-dependent manner.

Poor implementation of tobacco control measures and lack of education influences the intention to quit tobacco: a structural equation modelling approach.

BACKGROUND: Tobacco consumption remains a public health issue and is one of the major causes of death in India. This study presents a validated conceptual model to assess the interaction between education, perceived application of tobacco control measures, type of tobacco and their effects on the intention to quit tobacco. Additionally, the direct and mediating roles of tobacco use -frequency, -duration, and -dependency on the intention to quit is also investigated. METHODS: An analytical cross-sectional study was carried out, and data from tobacco users of six randomly selected states in India was collected via face-to-face interviews. Structural equation modeling (SEM) was performed using R v 3.6.3 to test the model fit and to explore the association between tobacco control measures and the intention to quit tobacco. RESULTS: From 1962 tobacco users, 43.7% wanted to quit tobacco immediately. Tambakoo (57.7%) was the most common type of tobacco used and 68.9% said that minors could buy tobacco. Findings from SEM showed that that one standard deviation (SD) increase in the perceived application of tobacco control measures is directly associated with a 0.181 SD increase in the intention to quit tobacco (B = 0.181, P < 0.001), and this effect was partially mediated by frequency of tobacco consumption (B = 0.06, P < 0.05). Also, a better education level was associated with a higher intention to quit tobacco (B = 0.14, P < 0.001). CONCLUSIONS: To conclude, the application of tobacco control measures and a better education level may positively affect the intention to quit tobacco. The frequency of tobacco use and the number of influencers play an essential role in deciding to quit. In future, longitudinal studies are recommended to further substantiate the evidence.

Therapeutic Potential of Artichoke in the Treatment of Fatty Liver: A Systematic Review and Meta-Analysis.

Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disease that can lead to liver cirrhosis, liver cancer, and death. Artichoke leaf extract (ALE) is well known in folk medicine for its hepatoprotective effect. Till recent times, no sufficient data from randomized clinical trials (RCTs) exist to support such use. This meta-analysis summarizes evidence from recent RCTs that evaluated ALE in NAFLD patients. Electronic databases were searched for RCTs that used ALE in NAFLD patients. The random-effects model was used to pool effect sizes (standardized change score). Data synthesis from five RCTs (333 patients) showed that ALE resulted in a significant reduction in alanine aminotransferase (standardized mean difference [SMD]: 1.1; 95% confidence interval [CI], 0.79-1.73; P < .001) and aspartate aminotransferase levels (SMD: 1.01; 95% CI, 0.52-1.51; P < .001) compared with the control group. ALE also resulted in a significant reduction in total cholesterol (SMD: 0.98; 95% CI, 0.53-1.43; P = .004), low-density lipoprotein (SMD: 0.96; 95% CI, 0.3-1.62; P < .001) and triglycerides (SMD: 0.95; 95% CI, 0.58-1.32; P < .001). The current review provides evidence from RCTs to support the use of ALE as a hepatoprotective agent in NAFLD patients. The study was registered on the PROSPERO database with the Registration No. CRD42020182502 (https://www.crd.york.ac.uk/prospero).

A randomised trial comparing transurethral to percutaneous cystolithotripsy in boys.

OBJECTIVE: To compare the efficacy and morbidity of transurethral cystolithotripsy (TUCL) and percutaneous CL (PCCL) in the management of bladder stones in male children. PATIENTS AND METHODS: A total of 100 boys, aged <14 years with a single bladder or urethral stone of <30 mm, were randomised into two equal groups. Initial diagnostic urethro-cystoscopy and push back of urethral stones were done for patients in both groups. Patients in Group A had TUCL, while those in Group B had PCCL through a 20-F sheath using a 12-F nephroscope. The two groups were compared regarding preoperative criteria, intraoperative details, and postoperative outcomes. RESULTS: The patients in this study had a median (range) age of 36 (4-144) months and stone size of 10 (5-26) mm. There was no statistically significant difference between the two groups for preoperative criteria. The assigned procedure was successful in 48 (96%) patients in Group A and 49 (98%) in Group B (P = 1). Complications were encountered in 11 (22%) patients in Group A and five (10%) in Group B (P = 0.171). The median (range) operative time was 21.5 (4-90) min in Group A and 13 (5-70) min in Group B (P < 0.001). In all, 47 (94%) stones needed disintegration in Group A vs 22 (44%) in Group B (P < 0.001). CONCLUSION: Both techniques have comparable success and complications rates. However, PCCL has a shorter operative time and less need for stone disintegration.

Prognostic significance of the ratio of surgically resected to radiologically detected lung nodules in patients with metastatic osteosarcoma.

The factors that affect the prognosis of patients' metastatic osteosarcoma are still poorly understood. In this study, we investigated a new prognostic factor, the ratio of surgically resected to radiologically detected osteosarcoma lung nodules (SR/RD), which may have predictive value. PATIENTS AND METHODS: Data from patients with metastatic osteosarcoma who underwent metastasectomy between January 2009 and December 2020, in a single center, were reviewed. The relationships between survival and the SR/RD ratio, timing of lung metastases, number of nodules, laterality, and presence of tumor necrosis at first metastasectomy were investigated. RESULTS: Among the 125 metastatic osteosarcoma patients, 80 patients had an SR/RD ratio ≤1. The median duration of follow-up was 72 months, ranging from 6 to 118 months. The five-year overall survival (OS) and postmetastasectomy event-free survival (EFS) for all patients were 36.5% and 18.1%, respectively. The five-year OS of patients with a low SR/RD ratio was 49.6% and that of patients with a high SR/RD ratio was 11.8 (P = 0.001). The two-year postmetastasectomy EFS rates of the high and low ratio groups were 24.1% and 9.4%, respectively (P = 0.001). The SR/RD ratio, number of nodules, and tumor necrosis had significant effects on OS and postmetastasectomy EFS in univariate analysis. A Cox proportional hazard model demonstrated that tumor necrosis and an SR/RD ratio >1 were associated with OS (HR = 1.8 and 2.01) and postmetastasectomy EFS (HR = 1,69 and 1.97). CONCLUSIONS: A high SR/RD ratio of greater than 1 and poor tumor necrosis were significantly associated with poor survival among patients with metastatic osteosarcoma who had lung metastasectomy. The high SR/RD ratio may be a surrogate outcome for incomplete metastatic tumor resection.

Role of PI3K/Akt axis in mitigating hippocampal ischemia-reperfusion injury via CB1 receptor stimulation by paracetamol and FAAH inhibitor in rat.

AIMS: Acetaminophen or paracetamol (PAR), the recommended antipyretic in COVID-19 and clinically used to alleviate stroke-associated hyperthermia interestingly activates cannabinoid receptor (CB1) through its AM404 metabolite, however, to date, no study reports the in vivo activation of PAR/AM404/CB1 axis in stroke. The current study deciphers the neuroprotective effect off PAR in cerebral ischemia/reperfusion (IR) rat model and unmasks its link with AM404/CB1/PI3K/Akt axis. MATERIALS AND METHODS: Animals were allocated into 5 groups: (I) sham-operated (SO), (II) IR, (III) IR + PAR (100 mg/kg), (IV) IR + PAR (100 mg/kg) + URB597; anandamide degradation inhibitor (0.3 mg/kg) and (V) IR + PAR (100 mg/kg) + AM4113; CB1 Blocker (5 mg/kg). All drugs were intraperitoneally administered at the inception of the reperfusion period. KEY FINDINGS: PAR administration alleviated the cognitive impairment in the Morris Water Maze as well as hippocampal histopathological and immunohistochemical examination of GFAP. The PAR signaling was associated with elevation of anandamide level, CB1 receptor expression and survival proteins as pS473-Akt. P(tyr202/thr204)-ERK1/2 and pS9-GSK3ß. Simultaneously, PAR increased hippocampal BDNF and ß-arrestin1 levels and decreased glutamate level. PAR restores the deranged redox milieu induced by IR Injury, by reducing lipid peroxides, myeloperoxidase activity and NF-κB and increasing NPSH, total antioxidant capacity, nitric oxide and Nrf2 levels. The pre-administration of AM4113 reversed PAR effects, while URB597 potentiated them. SIGNIFICANCE: PAR poses a significant neuroprotective effect which may be mediated, at least in part, via activation of anandamide/CB1/PI3K/Akt pathway in the IR rat model.

Prognostic value of detection of CD99+ , CD45- cells in peripheral blood by flow cytometry in children with Ewing sarcoma.

BACKGROUND: Early detection of metastasis and recurrence of Ewing sarcoma (ES) is important for early management. This work aimed to detect CD99+ , CD45- cells in peripheral blood by flow cytometry (FC) before and during chemotherapy and evaluate their prognostic significance. PROCEDURE: This prospective cohort study was carried out on 60 children newly diagnosed with ES at Children Cancer Hospital-Egypt 57357 and 40 healthy children control group. Detection of CD99+ , CD45- cells in peripheral blood was accomplished by FC at baseline before treatment and after five cycles of chemotherapy. Samples were classified as positive if they had more than the upper limit of cells observed in the control cases. Correlation between FC results and relapse and overall survival (OS) after one year was performed. RESULTS: Median percentage of CD99+ , CD45- cells was significantly increased in patients compared with controls (0.002% vs 0%, respectively, P < 0.001). Post-cycle 5 CD99+ , CD45- cells were increased in 12 patients, of them 11 patients' disease had either relapsed or progressed. Post-cycle 5 CD99+ ; CD45- cells had a 73.3% sensitivity and 97.8% specificity for predicting relapse or progression, whereas baseline only had 6.7% sensitivity and 77.8% specificity. The hazard ratio for mortality in the post-cycle 5 positive group was 18.4 [95% confidence interval (1.86 to 181.46)] times that of the negative group. One year OS was 91.67%. CONCLUSION: Post-cycle 5 CD99+ , CD45- cells in peripheral blood by FC is a strong predictor for relapse, progression, and mortality whereas baseline is a poor predictor in newly diagnosed patients with ES.

Wide Resection of Primary Malignant Bone Tumors of the Hand in Children and Reconstruction Using Nonvascularized Fibular Bone Graft: Case Series and Literature Review.

PURPOSE: Primary malignant bone tumors of the hand are rare in children. Resection and reconstruction of the digit are challenging and have been described in case reports. This retrospective study describes the functional and oncologic outcomes of resection and reconstruction using a nonvascularized fibular bone graft in a cohort of children. METHODS: A total of 5 children were included. The mean age at diagnosis was 7.6 years (range, 1.6-12 years). Histologic diagnosis showed Ewing sarcoma in 3 and osteosarcoma in 2 patients. Four tumors were located in the metacarpal bones of the fingers, and 1 was located in the thumb. Four patients were treated with chemotherapy. All the patients were treated with wide resection and a cement spacer. This was followed by second stage reconstruction using a nonvascularized fibular bone graft. In tumors of the fingers, carpometacarpal joint fusion with a neighboring carpal bone was performed, whereas a pseudoarthrosis was created between the graft and the base of the proximal phalanx. In the thumb's case, the opposite was done, with fusion at the metacarpophalangeal joint and a pseudoarthrosis at the carpometacarpal joint. RESULTS: The mean follow-up duration was 5.5 years (range, 2-9 years). Surgical margins were negative in all the patients. At their latest follow-up visit, none of the patients developed systemic or local recurrence. Two complications required a revision surgery, one due to graft subluxation and the other due to nonunion. At their final follow-up examination, the mean total arc of movement was 80° (range, 60°-100°), and all the patients were able to resume their grasping and writing capabilities. CONCLUSIONS: The resection and reconstruction of primary malignant bone tumors of the metacarpals using a nonvascularized fibular bone graft in children can preserve the cosmesis and function of the digit without jeopardizing oncologic outcomes. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Feto-Maternal Outcomes of Breastfeeding during Pregnancy: A Systematic Review and Meta-Analysis.

BACKGROUND: Breastfeeding is beneficial to both mother and infant. However, overlap of lactation with pregnancy and short recuperative intervals may impact mothers nutritionally. We aimed to investigate the possible effects of pregnancy during breastfeeding. METHODS: In October 2018, we searched systematically in nine electronic databases to investigate any association of breastfeeding during pregnancy with fetal and/or maternal outcomes. The study protocol was registered in PROSPERO (CRD41017056490). A meta-analysis was done to detect maternal and fetal outcomes and complications during pregnancy. Quality assessment was performed using the Australian Cancer Council bias tool for included studies. RESULTS: With 1992 studies initially identified, eight were eligible for qualitative analysis and 12 for quantitative analysis. Our results showed no significant difference in different abortion subtypes between lactating and non-lactating ones. In delivery, no difference between two groups regarding the time of delivery in full-term healthy, preterm delivery and preterm labor. No significant difference was detected in rates of antepartum, postpartum hemorrhage and prolonged labor between two groups. The women with short reproductive intervals may have higher supplemental intake and greater reduction fat store. The present studies showed that breastfeeding during pregnancy does not lead to adverse outcomes in the mother and her fetus in normal low-risk pregnancy, although it may lead to the nutritional burden on the mother. CONCLUSION: The present studies showed that breastfeeding during pregnancy did not lead to the adverse outcomes in the mother and her fetus.

Sesquiterpene lactones; Damsin and neoambrosin suppress cytokine-mediated inflammation in complete Freund's adjuvant rat model via shutting Akt/ERK1/2/STAT3 signaling.

ETHNOPHARMACOLOGIAL RELEVANCE: Although Damsissa (Ambrosia maritima) is traditionally used as anti-inflammatory and diuretic, the biological activity and mechanism of action of its major constituents are to be elucidated. AIM: to decipher the anti-arthritic potential of damsin (DMS) and neoambrosin (NMS) and to unfold their molecular signaling in complete Freund's adjuvant (CFA)-induced arthritis model. MATERIALS AND METHODS: the right hind paw was inoculated with CFA (0.1 ml) at day 0 and 7 while treatments were started from the 14th day and continued for 2 weeks. Rats were randomly assigned into 4 groups; normal group (NRML), CFA-induced arthritis group, CFA-induced arthritis treated with DMS and NMS (10 mg/kg/day) as 3rd and 4th group; respectively. RESULTS: Throughout experimental period, treatments ameliorated the increase of paw volume, knee joint diameter and nociception tests as reflected in open field arena. Also, DSM and NMS suppressed phosphorylation of Akt, STAT-3, ERK1/2 which was further mirrored by inactivation of GSK3ß and downregulation of MCP-1 together with CCN1 and NF-kß in hind paw tissue. Concomitantly, inflammation markers; TNF-α, IL-6, -12 were lowered as confirmed microscopically during examination of hind paw tissue. CONCLUSION: DSM and NMS-induced suppression of NF-kß subdues clinical features of RA most probably through repression of Akt/ERK1/2/STAT3 pathway. Therefore, DMS and NMS can serve as safe and effective treatment for rheumatoid arthritis, one of the most disabling chronic, inflammatory and painful autoimmune disease.

The role of ultrasound in prediction of intra-operative blood loss in cases of placenta accreta spectrum disorders.

PURPOSE: To assess the value of various grey-scale ultrasound, 2D color Doppler, and 3D power Doppler sonographic markers in predicting major intraoperative blood loss during planned cesarean hysterectomy for cases diagnosed with placenta accreta spectrum (PAS) disorders. METHODS: 50 women diagnosed with PAS were scanned the day before planned delivery and hysterectomy for various sonographic markers indicative of placental invasion. These women were then later divided according to blood loss in two groups: group A (minor hemorrhage, < 2500 ml), and group B (major hemorrhage, > 2500 ml), and the data were analyzed. RESULTS: The odds ratio (OR) for major hemorrhage was as follows for the following sonographic markers: 'number of lacunae > 4' OR 3.8 95% CI (1.0-13.8) (p = 0.047); 'subplacental hypervascularity' OR 10.8 95% CI (1.2-98.0) (p = 0.035); 'tortuous vascularity with 'chaotic branching' OR 10.8 95%CI (1.2-98.0) (p = 0.035); 'numerous coherent vessels involving the serosa-bladder interface OR 14.6 95% CI (2.7-80.5) (p = 0.002); and 'presence of bridging vessels OR 2.9 95% CI (1.4-6.9) (p = 0.005). Only the presence of numerous coherent vessels involving the bladder-serosal interface (p = 0.002) was proven to be independent predictor of major hemorrhage during hysterectomy. CONCLUSION: The use of 2D color Doppler and 3D power Doppler can help predict massive hemorrhage in cases of PAS disorders.

Immunomodulatory effect of diallyl sulfide on experimentally-induced benign prostate hyperplasia via the suppression of CD4+T/IL-17 and TGF-ß1/ERK pathways.

Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of the prostate common in older men. Diallyl sulfide (DAS), a major component of garlic, has been reported to possess antioxidant, anti-inflammatory, and antiproliferative effects. However, the underlying protective immunomodulatory mechanism of DAS on BPH remains vague. Herein, experimental BPH was induced in rats by daily subcutaneous injection of testosterone propionate (TP) (3 mg/kg, s.c.) for 4 weeks. In parallel, finasteride (Fin) (5 mg/kg, p.o) or DAS (50 mg/kg, p.o.) was administered orally during BPH induction. TP-induced histological alterations and the immune-inflammatory cascade. On the other hand, DAS or Fin administration alleviated all abnormalities induced testosterone. Fin and DAS administration markedly reduced prostate weight by 53% with Fin, and by 60% with DAS. Moreover, serum testosterone and DHT were reduced by 55% and 52%, respectively, with Fin and by 68% and 75%, respectively, with DAS, in concordance with decreased protein expression of androgen receptor (AR), and prostate-specific antigen (PSA). Furthermore, both regime lessen immune-inflammatory milieu, as evidenced by decrease CD4+ T-cells protein expression and associated inflammatory cytokines. Concomitantly, Fin and DAS exhibited marked mitigation in insulin-like growth factor-1 (IGF-1), transforming growth factor-beta1 (TGF-ß1), and phosphorylated extracellular signal-regulated kinase (ERK1/2) signaling. Besides alleviating oxidative stress by 53% and 68% in prostatic MDA and by 27% and 7% in prostatic iNOS with Fin and DAS, respectively. In conclusion, this work highlighted a potential therapeutic approach of DAS as a dietary preventive agent against BPH via its anti-inflammatory and immunomodulatory effect along with suppression of the ERK pathway.

The effect of early administration of rectal progesterone in IVF/ICSI twin pregnancies on the preterm birth rate: a randomized trial.

BACKGROUND: The rate of multiple pregnancies in IVF/ICSI ranges from 20 to 30%. The incidence of preterm birth in multiple pregnancies is as high as 60% and is even higher in pregnancies conceived after IVF & ICSI. The effect of progesterone on prevention of preterm birth in twins is controversial. Our group has proven a positive effect in reduction of preterm birth, by starting progesterone from the mid-trimester, in exclusively IVF/ICSI singleton pregnancies but not twins. The purpose of our current study was to explore the effect of earlier administration of natural progesterone, in IVF/ICSI twin pregnancies starting at 11-14 weeks for prevention of preterm birth. METHODS: This is a double-blind, placebo controlled, single center, randomized clinical trial. Women with dichorionic twin gestations, having an IVF/ICSI trial were randomized to receive natural rectal progesterone (800 mg daily) vs placebo, starting early from 11 to 14 weeks. They also received oral and vaginal antimicrobial agents as part of our routine treatment for vaginitis and urinary tract infection. They were randomized regardless of cervical length and had no previous history of preterm birth or known Mullerian anomalies. The primary outcome was spontaneous preterm birth rate before 37 weeks. The secondary outcome was; spontaneous preterm birth before 34, 32, 28 weeks and neonatal outcome. RESULTS: A total of 203 women were randomized to both groups, final analysis included 199 women as 4 were lost to follow up. The base line characteristics as well as gestational age at delivery were not significantly different between the study and the placebo group (34.7 ± 3.6 vs 34.5 ± 4.5, P = 0.626). Progesterone administration was not associated with a significant decrease in the spontaneous preterm birth rates before 37 weeks (73.5% vs 68%, P = 0.551), before 34 (20.6% vs 21.6%, P = 0.649), before 32 (8.8% vs 12.4%, P = 0.46) & before 28 (4.9% vs 3.1%, P = 0.555) weeks. CONCLUSIONS: Rectal natural progesterone starting from the first trimester in IVF/ICSI twin pregnancies did not reduce spontaneous preterm birth. TRIAL REGISTRATION: The trial was registered on 31 January 2014 at www.ISRCTN.com, number 69810120.