The Prospective Effect of Green Tea versus Pomegranate Peels Extracts on Submandibular Salivary Glands of Albino Rats after Methotrexate Administration (Histological and Immunohistochemical Study).

Background: There is curiosity in the use of substances that can stop cell damage. Antioxidants are substances that can prevent free radicals from damaging cells, and they can be used to treat and avoid a wide variety of illnesses. Objectives: The current investigation set out to evaluate the histological changes brought on by a single high dose of methotrexate in the submandibular glands of rats treated with green tea and pomegranate peel extract, both are well-known as antioxidants. Materials and Methods: Forty-eight healthy Albino rats were used in the current study. Animals were divided into six groups. Group 1: Vehicle group which is control group, Group 2: methotrexate treated group, Group 3: green tea control group, Group 4: pomegranate peel extract control group, Group 5: green tea + methotrexate group, and Group 6: pomegranate peel extract + methotrexate group. Rats of all groups were left 1 week after the end of the treatment. Cervical dislocation was used to kill all of the rats. Samples were gained from the rats' submandibular salivary glands of different groups for histological and immunohistochemical evaluation. Results: Green tea + methotrexate group showed improvement in the histological picture of the submandibular salivary gland compared to methotrexate group and the pomegranate peel extract + methotrexate group. Conclusion: The antioxidant activity of green tea is more potent than that of pomegranate peels extract in blocking methotrexate that induced cytotoxicity in the submandibular salivary glands of rats. As a result, it can be administered to people undergoing cancer treatment as a safeguard for their salivary glands.

The mechanistic interplay between Nrf-2, NF-κB/MAPK, caspase-dependent apoptosis, and autophagy in the hepatoprotective effects of Sophorolipids produced by microbial conversion of banana peels using Saccharomyces cerevisiae against doxorubicin-induced hepatotoxicity in rats.

BACKGROUND: Doxorubicin (DOX) is a well-known chemotherapeutic agent which causes serious adverse effects due to multiple organ damage, including cardiotoxicity, nephrotoxicity, neurotoxicity, and hepatotoxicity. The mechanism of DOX-induced organ toxicity might be attributed to oxidative stress (OS) and, consequently, activation of inflammatory signaling pathways, apoptosis, and blockage of autophagy. Sophorolipids (SLs) as a glycolipid type of biosurfactants, are natural products that have unique properties and a wide range of applications attributed to their antioxidant and anti-inflammatory properties. AIMS: Production of low-cost SLs from Saccharomyces cerevisiae grown on banana peels and investigating their possible protective effects against DOX-induced hepatotoxicity. MAIN METHODS: The yeast was locally isolated and molecularly identified, then the yielded SLs were characterized by FTIR, 1H NMR and LC-MS/MS spectra. Posteriorly, thirty-two male Wistar rats were randomly divided into four groups; control (oral saline), SLs (200 mg/kg, p.o), DOX (10 mg/kg; i.p.), and SL + DOX (200 mg/kg p.o.,10 mg/kg; i.p., respectively). Liver function tests (LFTs), oxidative stress, inflammatory, apoptosis as well as autophagy markers were investigated. KEY FINDINGS: SLs were produced with a yield of 49.04% and treatment with SLs improved LFTs, enhanced Nrf2 and suppressed NF-κB, IL-6, IL-1ß, p38, caspase 3 and Bax/Bcl2 ratio in addition to promotion of autophagy when compared to DOX group. SIGNIFICANCE: Our results revealed a novel promising protective effect of SLs against DOX-induced hepatotoxicity in rats.

The beneficial effects of l-carnitine and infliximab in methotrexate-induced hepatotoxicity: Emphasis on Notch1/Hes-1 signaling.

Methotrexate (MTX)-induced hepatotoxicity is a serious adverse effect that may limit its use. Therefore, eligible drugs to ameliorate MTX-induced hepatotoxicity are required. l-Carnitine (LC) is a natural molecule with beneficial metabolic effects and infliximab (INF) is an anti-inflammatory monoclonal antibody against tumor necrosis factor-alpha (TNF-α). Recently, Notch1/Hes-1 signaling was found to play a key role in the pathogenesis of liver injury. However, its role in MTX-induced hepatotoxicity is unclear. This study aimed to evaluate the modulatory effects of LC or INF on MTX-induced hepatotoxicity and to explore the underlying mechanism with emphasis on the Notch1/Hes-1 signaling pathway. Sixty rats were randomized into six groups (n = 10): (1) control (saline); (2) MTX (20 mg/kg MTX, intraperitoneal [ip], once); (3) LC group (500 mg/kg ip, 5 days); (4) INF (7 mg/kg INF ip, once); (5) MTX+LC (20 mg/kg ip, once, 500 mg/kg ip, 5 days, respectively); (6) MTX+INF (20 mg/kg ip, once, 7 mg/kg INF ip, once, respectively). Oxidative stress, inflammatory markers, and Notch1/Hes-1 were investigated. MTX induced the expression of Notch1 and Hes-1 proteins and increased the levels of TNF-α, interleukin (IL)-6, and IL-1ß in the liver. Cotreatment with LC or INF showed apparent antioxidant and anti-inflammatory effects. Interestingly, the downregulation of Notch1 and Hes-1 expression was more prominent in LC cotreatment as compared with INF. In conclusion, LC or INF attenuates MTX-induced hepatotoxicity through modulation of Notch1/Hes-1 signaling. The LC ameliorative effect against MTX-induced hepatotoxicity is significantly better than that of INF. Therefore, LC cotreatment may present a safe and therapeutically effective therapy in alleviating MTX-induced hepatotoxicity.

A national screening for the prevalence and profile of disability types among Egyptian children aged 6-12 years: a community-based population study.

AIM: This study aimed to determine the prevalence of disability domains among Egyptian children in the age group of 6-12 years as well as assess their socio-demographic, epidemiological, and perinatal predictors. METHODS: A national population-based cross-sectional household survey targeting 20,324 children from eight governorates was conducted. The screening questionnaire was derived from the WHO ten-question survey tool validated for the identification of disabilities. RESULTS: The prevalence of children with at least one type of disability was 9.2%. Learning/ comprehension was the most prevalent type (4.2%), followed by speech/communication (3.7%), physical/ mobility and seizures (2.2% for each), intellectual impairment (1.5%), visual (0.7%), and hearing (0.4%). The commonest predictors for disabilities were children who suffered from convulsions or cyanosis after birth and maternal history of any health problem during pregnancy. However, preterm and low birth weight (LBW) babies or being admitted to incubators for more than two days were strong predictors for all disabilities except hearing disability. A history of jaundice after birth significantly carried nearly twice the odds for seizures (AOR = 2.2, 95% CI:1.5-3.4). History of difficult labor was a predictor of intellectual impairment (AOR = 1.5, 95% CI:1.1-2.0). A disabled mother was a strong predictor for all disabilities except seizures, while a disabled father was a predictor for visual and learning/ comprehension disabilities (AOR = 3.9, 95% CI:2.2-7.1 & AOR = 1.6, 95% CI:1.1-2.4 respectively). Meanwhile, both higher maternal and paternal education decreased significantly the odds to have, physical/ mobility and Learning/ comprehension by at least 30%. CONCLUSION: The study found a high prevalence of disability among Egyptian children aged 6-12 years. It spotted many modifiable determinants of disability domains. The practice of early screening for disability is encouraged to provide early interventions.

Current and novel modalities for management of chronic hepatitis B infection.

Over 296 million people are estimated to have chronic hepatitis B viral infection (CHB), and it poses unique challenges for elimination. CHB is the result of hepatitis B virus (HBV)-specific immune tolerance and the presence of covalently closed circular DNA as mini chromosome inside the nucleus and the integrated HBV. Serum hepatitis B core-related antigen is the best surrogate marker for intrahepatic covalently closed circular DNA. Functional HBV "cure" is the durable loss of hepatitis B surface antigen (HBsAg), with or without HBsAg seroconversion and undetectable serum HBV DNA after completing a course of treatment. The currently approved therapies are nucleos(t)ide analogues, interferon-alpha, and pegylated-interferon. With these therapies, functional cure can be achieved in < 10% of CHB patients. Any variation to HBV or the host immune system that disrupts the interaction between them can lead to reactivation of HBV. Novel therapies may allow efficient control of CHB. They include direct acting antivirals and immunomodulators. Reduction of the viral antigen load is a crucial factor for success of immune-based therapies. Immunomodulatory therapy may lead to modulation of the host immune system. It may enhance/restore innate immunity against HBV (as toll-like-receptors and cytosolic retinoic acid inducible gene I agonist). Others may induce adaptive immunity as checkpoint inhibitors, therapeutic HBV vaccines including protein (HBsAg/preS and hepatitis B core antigen), monoclonal or bispecific antibodies and genetically engineered T cells to generate chimeric antigen receptor-T or T-cell receptor-T cells and HBV-specific T cells to restore T cell function to efficiently clear HBV. Combined therapy may successfully overcome immune tolerance and lead to HBV control and cure. Immunotherapeutic approaches carry the risk of overshooting immune responses causing uncontrolled liver damage. The safety of any new curative therapies should be measured in relation to the excellent safety of currently approved nucleos(t)ide analogues. Development of novel antiviral and immune modulatory therapies should be associated with new diagnostic assays used to evaluate the effectiveness or to predict response.

National screening for Egyptian children aged 1 year up to 12 years at high risk of Autism and its determinants: a step for determining what ASD surveillance needs.

This study aimed to provide a national estimate of the prevalence of the high risk of autism spectrum disorder (ASD) and their determinants. A national screening survey was conducted for 41,640 Egyptian children aged 1 to 12 years in two phases. Tools used were Vineland's Adaptive Behavior Scales, Modified Checklist for Autism in Toddlers, Gilliam Autism Rating scale, and Denver II Developmental screening test. The overall prevalence of children at high risk of ASD was 3.3% (95% CI:3.1%-3.5%). Children living without mothers in homes, suffered from convulsions (AOR = 3.67; 95%CI:2.8-4.8), a history of cyanosis after birth (AOR = 1.87; 95% CI:1.35-2.59) or history of LBW babies (AOR = 1.53; 95% CI:1.23-1.89) carried higher odds of being at high risk of ASD.

Impact of lifestyle modification on glycemic control and cognitive function among Type II diabetes mellitus patients.

Aim: Assessing impact of lifestyle modification on Type 2 diabetes mellitus (T2DM) glycemic control and cognitive function. Subjects & methods: Prospective study was conducted on T2DM patients (92 patients as interventional group and 92 patients conventional therapy). Results: After 6 months, significant improvements of HbA1c, oxidant and antioxidant, lipid profile, and cognitive function among only the interventional group (p < 0.05). Using logistic analysis, conventional therapy, DM duration >10 years, lower education, HbA1c baseline >7 were significant predictive risks for uncontrolled DM (AOR 4.2, 2.9, 2.7 and 2.2, respectively). While, conventional therapy, baseline mild cognitive impairment (MCI) and females were significant risks for MCI (AOR 11.5, 10.8 and 4.8, respectively). Conclusion: Lifestyle modification is a very important for glycemic control and cognitive function.Clinical Trial Registration: NCT04891887 (ClinicalTrials.gov).

The study aimed at assessing the effect of lifestyle modification program on Type 2 diabetes mellitus (T2DM) patients. The program contents include maintaining healthy diet depending on glycemic index and CHO counting, adjusting cholesterol level, regular physical activity for at least 30 minutes; 3­5 days per week, weight loss and maintaining an appropriate weight, controlling the blood pressure, smoking cessation and practicing mental activity. After 6 months, there was a significant improvement in glycemic control, cognitive function, oxidant and antioxidant and lipid profile levels among patients participating in the program but not among those remained on the conventional therapy.

Promoting weaning practices and growth of Egyptian infants by using communication for behavioral development approach.

BACKGROUND: Access to various affordable and nutritious foods is considered a challenging factor for households with limited resources affecting the proper weaning practices. In order to motivate communities to adhere to the right and proper weaning practices, the social aspect should be considered through close communication with the targeted communities. This study aimed to evaluate how impactful the use of the principles of Communication for Development (C4D) that respect parents' beliefs and their cultural norms is in improving the weaning practices and growth of infants in an Egyptian village. METHODS: An interventional three-phase study was conducted for three years. The intervention targeted 464 mothers of infants up to 2 years of age. C4D interventions encouraged each mother to provide her baby with nutritious and varied options through age-appropriate introduction and diversification of nutrient-rich complementary foods under the slogan " enjoy meals like a baby". The effectiveness of the approach was measured by five essential weaning practices: Introduction of solid, semi-solid, or soft foods, Minimum dietary diversity, minimum meal frequency, Minimum acceptable diet, and consumption of iron-rich foods. RESULTS: There was marked and significant improvement in the awareness and of the majority of the weaning practices' indicators as a result of the interventions. This was noticed for the timely introduction of complementary foods which increased from 36.7% to 82.0%, the minimum meal frequency indicator (3-5) which increased from 25.3% to 67.3%, iron-rich or fortified food (68.0% to 82%) as well as a regular checkup for baby health at the health unit (71.3%). Indicators that were improved but failed to achieve the target were the "Minimum Dietary Diversity" (reached 32%) and the minimum acceptable diet (reached 22.0%). A significant effect on linear growth especially for females is evidenced by the remarkable decrease in wasting (from 31.5% to 11.1%) and obesity (from 12.0% to 0%) associated with a considerable decrease in underweight (from 40% to 16.7%). CONCLUSION: Targeting caregivers through the C4D approach have succeeded in providing them with the support required for the provision of adequate nutrition for their infants that had significantly marked improvement in growth indices of their infants.

Impact of direct-acting antiviral regimens on hepatic and extrahepatic manifestations of hepatitis C virus infection.

Hepatitis C virus (HCV) is a common cause of liver disease and is associated with various extrahepatic manifestations (EHMs). This mini-review outlines the currently available treatments for HCV infection and their prognostic effect on hepatic manifestations and EHMs. Direct-acting antiviral (DAA) regimens are considered pan-genotypic as they achieve a sustained virological response (SVR) > 85% after 12 wk through all the major HCV genotypes, with high percentages of SVR even in advanced fibrosis and cirrhosis. The risk factors for DAA failure include old males, cirrhosis, and the presence of resistance-associated substitutions (RAS) in the region targeted by the received DAAs. The effectiveness of DAA regimens is reduced in HCV genotype 3 with baseline RAS like A30K, Y93H, and P53del. Moreover, the European Association for the Study of the Liver recommended the identification of baseline RAS for HCV genotype 1a. The higher rate of hepatocellular carcinoma (HCC) after DAA therapy may be related to the fact that DAA regimens are offered to patients with advanced liver fibrosis and cirrhosis, where interferon was contraindicated to those patients. The change in the growth of pre-existing subclinical, undetectable HCC upon DAA treatment might be also a cause. Furthermore, after DAA therapy, the T cell-dependent immune response is much weaker upon HCV clearance, and the down-regulation of TNF-α or the elevated neutrophil to lymphocyte ratio might increase the risk of HCC. DAAs can result in reactivation of hepatitis B virus (HBV) in HCV co-infected patients. DAAs are effective in treating HCV-associated mixed cryoglobulinemia, with clinical and immunological responses, and have rapid and high effectiveness in thrombocytopenia. DAAs improve insulin resistance in 90% of patients, increase glomerular filtration rate, and decrease proteinuria, hematuria and articular manifestations. HCV clearance by DAAs allows a significant improvement in atherosclerosis and metabolic and immunological conditions, with a reduction of major cardiovascular events. They also improve physical function, fatigue, cognitive impairment, and quality of life. Early therapeutic approach with DAAs is recommended as it cure many of the EHMs that are still in a reversible stage and can prevent others that can develop due to delayed treatment.

A national prevalence and profile of single and multiple developmental delays among children aged from 1 year up to 12 years: an Egyptian community-based study.

OBJECTIVE: This study aimed at providing a national prevalence of single and multiple developmental delays (DDs) among 41,640 Egyptian children aged 1 to 12 years and exploring DDs' associated risk and protective factors. METHODS: A national household survey from eight governorates of Egypt representing the four major subdivisions of Egypt was conducted through systematic probability proportionate to size. All enrolled children were assessed according to Vineland Adaptive Behavior Scales, (VABS) as a reliable screening questionnaire for identifying categories of DDs that were verified by pediatrics' specialists. RESULTS: The overall prevalence of children with DDs was 6.7%. The prevalence of a single DD was 3.9% versus 2.8% multiple DDs. Communication deficit was the most prevalent type (5.3%). Lower prevalence was identified for fine motor delay (1.0%), gross motor delay, and socialization deficit (1.5% each). Whereas deficits in daily life skills (self-help and adaptive behavior delay) amounted to 2.3%. Living without mothers and/or fathers in homes was associated with increased odds of having DDs by one and a half times (OR = 1.72 and OR = 1.34 respectively). Multiple logistic regression analysis revealed the most predictors for DDs including children who suffer from convulsions after birth (OR = 3.10), low birth weight babies (OR = 1.94), male sex (OR = 1.75), mothers having health problems during pregnancy (OR = 1.70) and belonging to middle socioeconomic status (OR = 1.41). Children who suffered from cyanosis after birth was found to be at risk for any or multiple DDs. Difficult labor was significantly associated with increased odds for multiple DDs (OR = 1.55). Higher paternal and maternal education was associated with decreased odds to have any DDs by 40% (OR = 0.60 and OR = 0.58 respectively). CONCLUSIONS: The detected prevalence of DDs is within the estimated range of prevalence of DDs for the pediatric population. The majority of the detected risk factors are preventable. Developmental screening is recommended to be implemented in all primary care settings as a routine practice.

Morus macroura Miq. Fruit extract protects against acetic acid-induced ulcerative colitis in rats: Novel mechanistic insights on its impact on miRNA-223 and on the TNFα/NFκB/NLRP3 inflammatory axis.

Nod-like receptor pyrin domain-1 containing 3 (NLRP3) inflammasome/tumor necrosis factor alpha (TNFα)/nuclear factor kappa B (NFκB) inflammatory pathway is known to be involved in the pathogenesis of ulcerative colitis (UC). Inversely, miRNA-223 can exert counter-regulatory effect on NLRP3 expression. The mulberry tree (Morus macroura) fruit is attaining increased importance for its antioxidant and anti-inflammatory activity in addition to its high safety profile. Accordingly, we attempted to explore the possible protective effect of mulberry fruit extract (MFE) in acetic acid (AA)-induced UC rat model. Phytochemical constituents of MFE were characterized using high performance liquid chromatography coupled to mass spectrometry (HPLC-MS). In the in vivo study, three doses of MFE were orally given for seven days before intra-rectal induction of UC by AA on day eight. Screening study revealed that MFE (300 mg/kg) significantly reduced macroscopic and microscopic UC scores. Biochemically, MFE ameliorated oxidative stress, levels of TNFR1, NLRP3, p-NFκB p65, TNFα, IL-1ß, and IL-18, caspase-1 activity, but enhanced miRNA-223 expression. In conclusion, our study provided a novel protective impact for MFE against UC, in which miRNA-223 and TNFα/NFκB/NLRP3 pathway are involved. These results provide a promising step that might encourage further investigations of MFE as a protective agent in UC patients.

Egyptian patients'/guardians' experiences and perception about clinical informed consent and its purpose: Cross sectional study.

BACKGROUND: Informed consent (IC) is a healthcare standard emphasizing the meaning of human dignity as clarified in the Universal Declaration of Human Rights. Data about IC practices in Egypt is insufficient. This study aimed to assess the Egyptian patients'/guardians' experiences about IC and their expectations about its practices' purposes in general and according to the type of the healthcare facility. METHODS: Self-administered questionnaire was carried out for 1092 participants who had undergone or were scheduled to a procedure requiring an IC at three studied types for Egyptian health care facilities. Ten statements were ranked twice by the participants to reflect their perception of IC purpose as per what is currently practiced and what they believe should be practiced. RESULTS: IC implementation varies significantly (p<0.05) across the health care facilities in Egypt. The percentage of its implementation at the non-governmental facilities, governmental facilities, and university hospital was 85.9%, 77.8%, and 63.8 respectively. The first three ranked purposes of the current IC practices were: "Helping patient/guardian decide (64.9%)", "Documenting patient's/guardian's decision (59.3%)", and "Having shared decision (57.3%)". The perceived purposes of IC to be practiced were: "Informing the patient/guardian (68.4%)", "Making sure patient/guardian understand (65.3%)" and "Documenting patients/guardians decisions (65.1%)". "Being a meaningless routine" was reported by the majority to be ranked as a low purpose for IC current and preferred practices. CONCLUSION: The practice of IC is common within the Egyptian medical community. Participants believe that information disclosure "Making sure patients understand" has to help in IC decision making and its main purpose. However, unfortunately, this is not perceived as a current purpose of IC. There was consensus agreement that documenting the patient's/guardian's decision and informing the patient/guardian are perceived as both important current and preferred purposes for IC practices.

Ameliorative effect of betanin on experimental cisplatin-induced liver injury; the novel impact of miRNA-34a on the SIRT1/PGC-1α signaling pathway.

The anticancer agent, cisplatin (CIS), is associated with hepatotoxic effects related to activation of oxidative stress and inflammation pathways. CIS-induced oxidative DNA damage reduces sirtuin 1 (SIRT1) activity, which in turn, modulates the activity of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α). Moreover, microRNA-34a (miRNA-34a) was shown to hinder both SIRT1 and nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Thus, targeting such a pathway can alleviate CIS-induced hepatotoxicity. Betanin (BET) is a natural red glycoside food dye obtained from beets, which is reported to exhibit antioxidant function. However, its role in CIS-induced liver injury and the molecular mechanism has not been fully elucidated. Thus, the aim of this study was to investigate the ameliorative effect of BET on CIS-induced acute hepatotoxicity through the SIRT1/PGC-1α signaling pathway and illustrate the impact of miRNA-34a. Seventy-two rats were divided into six equal groups: (1) Control, (2) BET, (3) CIS, (4) CIS/BET, (5) CIS/EX527, and (6) CIS/BET/EX527. CIS-induced liver injury was evidenced by deregulated BAX and BCL2 levels, decreased levels of AMP-activated protein kinase and PGC-1α expression, and decreased SIRT1 activity. Consequently, reduced levels of Nrf2 and the expression of associated heme oxygenase-1 and glutamate-cysteine ligase modifier subunit were observed. Intriguingly, BET succeeded in reducing the CIS-induced liver injury through reducing miRNA-34a expression and enhancing the SIRT1/PGC-1α pathway. These findings coincide with the molecular docking results and the histopathological picture. In conclusion, the current research provided novel findings of the BET ameliorative effect on CIS-induced liver injury through modulating miRNA-34a expression and the SIRT1/PGC-1α signaling cascade.

Accelerating Hepatitis C virus elimination in Egypt by 2030: A national survey of communication for behavioral development as a modelling study.

AIM OF THE WORK: This study aimed at assessing the dominance of risk practices associated with HCV endemicity in Egypt and detecting the behavioral development level concerning different aspects of HCV risk behaviors with respect to age and gender. The survey highlights the most cost-effective strategies that could accelerate HCV elimination in Egypt. SUBJECTS AND METHODS: A national household survey targeted 3780 individuals (age range: 10-85 years). The sample was a systematic probability proportionate to size from 6 governorates representing the six major subdivisions of Egypt. The indicators used for assessing the behavioral development level towards HCV included six domains: awareness (7 indicators), perceived risk (5 indicators), motivation with the intention to change (4 and 5 indicators for males and females respectively), trial, rejection or adoption (6 and 5 indicators for males and females respectively). RESULTS: The study revealed that along the continuum of behavior development, the percentage of the participants who acquired half of the scores was as follows: 73.1% aware, 69.8% developed perceived risk, 80.6% motivated with only 28.9% adopting the recommended behaviors, 32% rejected them, 2.3% were in the trial stage versus 35.8% who did not try any. Adolescents had significantly lower levels of development for almost all domains when compared to adults. Statistical higher significance was detected in favor of adults, employees, married, Lower Egypt governorates, and university-educated participants (p<0.001) regarding awareness, perceived risk, and motivation scores. More than half of the participants incorrectly believed that contaminated food, sharing food utilities, contaminated water, mosquitoes, and schistosomiasis would lead to HCV transmission. CONCLUSION: Egypt would be closer to HCV elimination when cost-effective strategies are directed not towards creating awareness, perceived risk or motivation to change- (at an acceptable level)- but towards motivating adopting risk-reduction behaviors for HCV, tackling misconceptions and reinforcement of social support.

A novel protective role of sacubitril/valsartan in cyclophosphamide induced lung injury in rats: impact of miRNA-150-3p on NF-κB/MAPK signaling trajectories.

Cyclophosphamide (CP) is a chemotherapeutic agent that induces oxidative stress causing multiple organ damage. Sacubitril/valsartan, is a combined formulation of neprilysin inhibitor (sacubitril) and angiotensin II receptor blocker (valsartan), that induces the protective effect of brain natriuretic peptide. The aim of the current study is to investigate the prophylactic impacts of sacubitril/valsartan versus valsartan against CP-induced lung toxicity in rats. Rats were assigned randomly into 6 groups; control; received corn oil (2 ml/kg/day; p.o. for 6 days), sacubitril/valsartan (30 mg/kg; p.o. for 6 days), valsartan (15 mg/kg; p.o. for 6 days), CP (200 mg/kg; i.p. on day 5), sacubitril/valsartan + CP (30 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively), valsartan + CP (15 mg/kg; p.o. for 6 days, 200 mg/kg; i.p. single dose on day 5, respectively). Both sacubitril/valsartan and valsartan produced a significant decrease in the inflammation and fibrosis markers in the BALF, in comparison with the CP group. Both sacubitril/valsartan and valsartan produced an apparent decrease in the relative genes expression of miR-150-3p and NF-κB, as well as a significant decrease in the relative expression of P38 and ERK1/2 MAPKs and an increase in the relative gene expression of Nrf-2, compared to CP group. Intriguingly, sacubitril/valsartan , showed subtle superiority in almost all investigated parameters, compared to valsartan. In conclusion, sacubitril/valsartan effectively abrogated the CP induced lung inflammation and fibrosis, providing a potential promising protection that could be linked to their ability to inhibit miR-150-3p via inhibition of NF-κB and MAPK signaling pathways.

Strengths of community and health facilities based interventions in improving women and adolescents' care seeking behaviors as approaches for reducing maternal mortality and improving birth outcome among low income communities of Egypt.

BACKGROUND: Provision of emergency obstetric care is considered the key for maternal mortality reduction worldwide. This study evaluated the impact of community- and facility-based educational programs on provision of emergency obstetric care in Egypt. The study focused on evaluating utilization of the available health services and care seeking behaviors of mothers in the childbearing period. METHODS: We implemented a package of community- and facility-focused educational interventions in two of Egypt's lowest income governorates. At facility level, health professionals at rural health units from 21 villages over 5 years were trained. Mass media gathering, individual teaching at health facilities, printed materials and home-based care sessions were provided. Collectively, these interventions were designed to focusing on recognition of the early warning signs during pregnancy, delivery and postpartum period for timely referral to hospitals for 20,494 women and adolescents mothers. RESULTS: The impact of the interventions was highly reflected on the percent of mothers received care during their pregnancy period. Proper antenatal care at governmental or private health facilities was raised dramatically from 0.6 to 59.3% and those who utilized at least one family planning method from 61.4 to 74.4%. Accordingly, the rate of complications significantly reduced during pregnancy (38.1 to 15.1%), during delivery (24.1 to 13.1%) and during postpartum (81.7 to 7.0%). As an impact to the improvement, there was a marked reduction in adolescent pregnancy by 55% and better birth outcome with a reduction in the percent of stillbirth by 11.5%. CONCLUSION: It is important to provide a comprehensive package that works at both improving qualities of care as well as empowering women by knowledge to first aid measures at the community level. The cost-effective way to empower mothers to provide first aid measures as emergency obstetric care is to adopt the outreach approach which could be more influential than mass media campaigns for the at-risk and vulnerable and low-income communities.

Egyptians' social acceptance and consenting options for posthumous organ donation; a cross sectional study.

BACKGROUND: Organ donation has become one of the most effective ways to save lives and improve the quality of life for patients with end-stage organ failure. No previous studies have investigated the preferences for the different consenting options for organ donation in Egypt. This study aims to assess Egyptians' preferences regarding consenting options for posthumous organ donation, and measure their awareness and acceptance of the Egyptian law articles regulating organ donation. METHODS: A cross sectional study was conducted among 2743 participants over two years. Each participant was required to rank eleven consenting options from 1 (most preferred) to 11 (least preferred), and to report his awareness and acceptance of the seven articles of the Egyptian law of organ donation. RESULTS: 47% of the participants expressed willingness to donate their organs after death. This percentage increased to 78% when consenting options were explained to participants. "Informed consent by donor only" was the most preferred type of consent for one third of respondents. Awareness of the law articles regulating organ donation was relatively low ranging from 56% to 23%. CONCLUSION: Currently, around half of the Egyptian population agree to posthumous organ donation. This percentage could be increased significantly by raising the awareness about how the process of donation could be regulated and how the patient's right of decision could be protected.

Assessment of Quality of Life of Primary Caregivers of Egyptian Asthmatic Children and Adolescents.

BACKGROUND: Asthma as a serious public health problem worldwide exerts a serious load on children's health-related quality of life (HRQOL) and their families. OBJECTIVE: We assess the HRQOL of the primary caregivers of Egyptian asthmatic children and adolescents and its relation to HRQOL of their children and asthma severity. MATERIALS AND METHODS: A cross-sectional study was conducted on 128 pairs of asthmatic children (7-16 years) and their primary caregivers. Pediatric asthma quality of life (QOL) questionnaire, pediatric asthma caregiver's QOL questionnaire, and asthma control questionnaire were used. RESULTS: Uncontrolled asthmatic patients had statistically significantly lower mean caregiver score compared to controlled asthmatic (P < 0.005). There was a statistically significant positive correlation between caregiver's individual and overall QOL scores and their children (individual and overall QOL scores) (P < 0.05). A statistically significant negative correlation between asthma severity and QOL scores of the caregivers of asthmatic children and adolescents was found (P < 0.05). CONCLUSION: The QOL of the primary caregivers of asthmatic children is significantly adversely affected by their children's illness severity.

Neuroprotective effect of crocin against rotenone-induced Parkinson's disease in rats: Interplay between PI3K/Akt/mTOR signaling pathway and enhanced expression of miRNA-7 and miRNA-221.

The complexity of Parkinson's disease (PD) pathogenesis is attributed to multiple pathways involved in the neurodegeneration process. Among these pathways arise the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), and mammalian target of rapamycin (mTOR) axis, where inhibition of this cascade has been implicated in the pathogenesis of PD. Crocin, a carotenoid found in saffron, has shown beneficial effects against neurodegenerative diseases via anti-apoptotic, anti-inflammatory, and antioxidant activities. However, the exact molecular pathways involved in crocin's neuroprotective effects have not been fully elucidated. This drove our attention to unravel the possible involvement of PI3k/Akt/mTOR pathway in the neuroprotective effect of crocin against rotenone (ROT)-induced PD in rats. Sixty adult male Wistar rats were divided into four groups: control, crocin (30 mg/kg/day; i.p.), ROT (1.5 mg/kg/day, i.p.) and ROT pre-treated with crocin for 30 days. Crocin administration showed a substantial behavioral improvement. At the cellular level, crocin significantly stimulated the PI3K/Akt pathway, augmented phospho-proline-rich Akt substrate 40 kDa (p-PRAS40), mTOR and p-p70S6K levels. Consequently, glycogen synthase kinase-3ß (GSK-3ß), forkhead box transcription factor of the O class (FoxO3a), and the downstream caspase-9 were decreased; thus, attenuating neurodegeneration, which was witnessed through increased tyrosine hydroxylase (TH) and dopamine (DA), and hampered α-synuclein levels. Moreover, crocin showed enhanced expression of microRNA-7 (miRNA-7) and miRNA-221, which contributed to Akt/mTOR activation. These results were verified by improved histopathological portrait and increased number of intact neurons. In conclusion, crocin showed promising neuroprotective effects in ROT-induced PD via activation of PI3K/Akt/mTOR axis and enhanced miRNA-7 and miRNA-221.

Enhancing the value of women's reproductive rights through community based interventions in upper Egypt governorates: a randomized interventional study.

BACKGROUND: In 2012, the WHO described the quality of health care as the route to equity and dignity for women and children. AIM OF THE WORK: To provide community based support and empowerment to women in childbearing period to seek optimal prenatal, natal and postnatal healthcare. Achieving this is anticipated to decrease maternal morbidity and mortality in Egypt. SUBJECTS AND METHODS: An interventional study was conducted among women in childbearing period in the poorest two governorates of Upper Egypt. The study passed through three stages over three and a half years; pre-interventional assessment of awareness (n = 1000), educational interventions targeting the health providers and all women in childbearing period in their communities (n = 20,494), and post-intervention evaluation of change in awareness of their rights for prenatal, natal and postnatal care (no = 1150). RESULTS: The studied indicators relating to receiving care in pregnancy, labor, and puerperium have changed dramatically as a result of the study interventions. Results of the study showed that before interventions, the surveyed women had inaccurate knowledge regarding most of the items related to their rights. The percentages of women aware of their right to have pregnancy card increased and those who possessed a pregnancy card were doubled with a significant percent change of more than 25%. Some indicators showed more than 75% improvement, including; percent of surveyed women who knew that it's their right to follow up their pregnancy and to deliver with a specialized doctor, a trained nurse or at an equipped health facility, and those who knew their right to have at least two home preparations necessary for safe delivery at home. CONCLUSION AND RECOMMENDATIONS: More work is needed in order to achieve the targeted reduction of maternal mortality. This could be achieved by ensuring accessible and high quality care provided by the governmental health facilities together with increasing the awareness of women regarding their rights in receiving such care.