Phthalate Exposure and Coronary Heart Disease: Possible Implications of Oxidative Stress and Altered miRNA Expression.

The relationship between phthalate exposure and coronary heart disease (CHD) is still unclear. This study aimed to investigate the association between phthalate exposure and CHD and determine the possible atherogenic mechanisms of phthalates by assessing oxidative stress and altering miRNA expression. This case-control study included 110 participants (55 CHD patients and 55 healthy controls). The levels of oxidative stress markers, malondialdehyde (MDA), and superoxide dismutase (SOD), and the expression of miRNA-155 (miR-155) and miRNA-208a (miR-208a), were measured and correlated with the urinary mono-2-ethylhexyl phthalate (MEHP). Highly significant differences were detected between the CHD cases and the control group regarding MEHP, MDA, SOD, miR-155, and miR-208a (p-value < 0.001). Spearman correlations revealed a significant positive correlation between MDA and MEHP in urine (P = 0.001 and rs = 0.316) and a significant negative correlation between SOD and MEHP in urine (P < 0.001 and rs = -0.345). Furthermore, significant positive correlations were observed between miR-155 and urinary MEHP (P = 0.001 and rs = 0.318) and miR-208a and urinary MEHP (P < 0.001 and rs = -0.352). This study revealed an association between phthalate exposure, as indicated by urinary MEHP and CHD; altered expression of miR-155 and miR-208a and oxidative stress could be the fundamental mechanisms.

Attitudes of parents towards influenza vaccine in the Eastern Mediterranean Region: A multilevel analysis.

BACKGROUND: Seasonal influenza vaccines (SIVs) can protect against influenza and substantially reduce the risk of influenza-related hospitalizations and fatalities in children. This study aimed to assess parental attitudes towards SIVs in the Eastern Mediterranean region (EMR). METHODS: Through an anonymous online survey conducted in 19 countries in the EMR, parents or caregivers over 18 years who had at least one child above 6 months filled out the Parent Attitudes about Childhood Vaccines questionnaire. As data had two levels; country and individual factors, we utilized multilevel binary logistic regression models. RESULTS: In total, 6992 respondents filled out the questionnaire. Of them, 47.4 % were residents of middle-income countries, 72.4 % of the mothers were between 26 and 45 years old, 56.5 % had at least a university degree, and approximately 51.6 % were unemployed. Nearly 50.8 % of the respondents were hesitant to vaccinate their children against seasonal influenza. Parental attitudes towards seasonal influenza vaccination differed significantly between countries, p < 0.001. The main predictors of parental seasonal influenza vaccine hesitancy (VH) were parents vaccination (odds ratio (OR) = 0.42, 95 % CI = 0.32-0.55, p < 0.001)), the mother's education if mother educated vs. who did not receive any education (OR ranged from 0.48 to 0.64, p < 0.05), living in low-income countries (OR = 0.52, 95 % CI = 0.35-0.77, p < 0.01), mountain residence (0.69, 95 % CI = 0.49-0.99, p < 0.05), health workers as a source of information (OR = 0.70, 95 % CI = 0.58-0.85, p < 0.001), children vaccination against COVID-19 (OR = 0.52, 95 % CI = 0.41-0.65, p < 0.001), not receiving routine vaccinations (OR = 1.93, 95 % CI = 1.09-3.44, p = 0.025), and if parents respondents could not remember whether their child had suffered from seasonal influenza in the previous year (OR = 1.57, 95 % CI = 1.33-1.84, p < 0.001). CONCLUSION: A high seasonal influenza VH rate was found in the EMR. Health authorities should implement different interventions targeting the identified modifiable risk factor to increase vaccine uptake among children, especially those at risk of complication from seasonal influenza infection.

External validation of the parental attitude about childhood vaccination scale.

Introduction: Internal validation techniques alone do not guarantee the value of a model. This study aims to investigate the external validity of the Parental Attitude toward Childhood Vaccination (PACV) scale for assessing parents' attitude toward seasonal influenza vaccination. Methods: Using a snowball sampling approach, an anonymous online questionnaire was distributed in two languages (English and Arabic) across seven countries. To assess the internal validity of the model, the machine learning technique of "resampling methods" was used to repeatedly select various samples collected from Egypt and refit the model for each sample. The binary logistic regression model was used to identify the main determinants of parental intention to vaccinate their children against seasonal influenza. We adopted the original model developed and used its predictors to determine parents' intention to vaccinate their children in Libya, Lebanon, Syria, Iraq, Palestine, and Sudan. The area under the curve (AUC) indicated the model's ability to distinguish events from non-events. We visually compared the observed and predicted probabilities of parents' intention to vaccinate their children using a calibration plot. Results: A total of 430 parents were recruited from Egypt to internally validate the model, and responses from 2095 parents in the other six countries were used to externally validate the model. Multivariate regression analysis showed that the PACV score, child age (adolescence), and Coronavirus disease 2019 (COVID-19) vaccination in children were significantly associated with the intention to receive the vaccination. The AUC of the developed model was 0.845. Most of the predicted points were close to the diagonal line, demonstrating better calibration (the prediction error was 16.82%). The sensitivity and specificity of the externally validated model were 89.64 and 37.89%, respectively (AUC = 0.769). Conclusion: The PACV showed similar calibration and discrimination across the six countries. It is transportable and can be used to assess attitudes towards influenza vaccination among parents in different countries using either the Arabic or English version of the scale.

Trends of HIV indicators in Egypt from 1990 to 2021: time-series analysis and forecast toward UNAIDS 90-90-90 targets.

BACKGROUND: Infection with Human immunodeficiency virus (HIV) and the development of acquired immunodeficiency syndrome (AIDS) pose severe threats to public health across the world. This study aimed to describe and forecast the trend of HIV indicators, including progress towards the 90-90-90 targets in Egypt since 1990. METHODS: The HIV indicators were graphically described, where the X axis is the time in a year and the Y axis is the value of the selected indicator for each year using data retrieved from UNAIDS. We used the Autoregressive Integrated Moving Average (ARIMA) model to forecast different HIV indicators from 2022 to 2024. RESULTS: Since 1990, HIV prevalence has been < 0.01, the number of people living with HIV (PLHIV) has increased from < 500 to 30,000 with a higher male predominance since 2010, and the number of children living with HIV has increased from < 100 to 1100. The number of pregnant women who needed antiretroviral treatment (ART) to prevent maternofetal HIV transmission increased from < 500 during 2010-2014 to 780 in 2021, the percentage of women who received ART increased from 3% in 2010 to 18% in 2021, the number of children exposed to HIV who did not get infection increased from < 100 in 1990-1991 to 4900 in 2021. The number of AIDS-related deaths increased from < 100 in 1990 to < 1000 in 2021. Based on forecasting, we expect that by 2024 the number of PLHIV will be 39,325(95%CI, 33,236-37,334), 22% (95%CI, 13.0%-32.0%) of pregnant females will have access to ART, 6100(95%CI, 5714-6485) HIV exposed children will not be infected, 77.0%(95% CI 66.0%-86.0%) of the population who knew their HIV status, and 71.0% (95%CI, 61.0%-81.0%) among those who know their HIV status will be on ART. CONCLUSION: HIV is moving forward fast, however, the Egyptian health authority implements different control measures to control its spread.

Efficacy and Effectiveness of SARS-CoV-2 Vaccines: A Systematic Review and Meta-Analysis.

The coronavirus disease 2019 (COVID-19) pandemic has threatened global health and prompted the need for mass vaccination. We aimed to assess the efficacy and effectiveness of COVID-19 vaccines to prevent mortality and reduce the risk of developing severe disease after the 1st and 2nd doses. From conception to 28 June 2021, we searched PubMed, Cochrane, EBSCO, Scopus, ProQuest, Web of Science, WHO-ICTRP, and Google Scholar. We included both observational and randomized controlled trials. The pooled vaccine efficacy and effectiveness following vaccination, as well as their 95 percent confidence intervals (CI), were estimated using the random-effects model. In total, 22 of the 21,567 screened articles were eligible for quantitative analysis. Mortality 7 and 14 days after full vaccination decreased significantly among the vaccinated group compared to the unvaccinated group (OR = 0.10, ([95% CI, 0.04-0.27], I2 = 54%) and (OR = 0.46, [95% CI, 0.35-0.61], I2 = 0%), respectively. The probability of having severe disease one or two weeks after 2nd dose decreased significantly (OR = 0.29 [95% CI, 0.19-0.46], I2 = 25%) and (OR = 0.08 [95% CI, 0.03-0.25], I2 = 74%), respectively. The incidence of infection any time after the 1st and 2nd doses diminished significantly (OR = 0.14 [95% CI, 0.07-0.4], I2 = 100%) and (OR = 0.179 [95% CI, 0.15-0.19], I2 = 98%), respectively. Also, incidence of infection one week after 2nd dose decreased significantly, (OR = 0.04, [95% CI (0.01-0.2], I2 = 100%). After meta-regression, the type of vaccine and country were the main predictors of outcome [non-mRNA type, ß = 2.99, p = 0.0001; country UK, ß = -0.75, p = 0.038; country USA, ß = 0.8, p = 0.02]. This study showed that most vaccines have comparable effectiveness, and it is purported that mass vaccination may help to end this pandemic.

A systematic review and meta-analysis on chloroquine and hydroxychloroquine as monotherapy or combined with azithromycin in COVID-19 treatment.

Many recent studies have investigated the role of either Chloroquine (CQ) or Hydroxychloroquine (HCQ) alone or in combination with azithromycin (AZM) in the management of the emerging coronavirus. This systematic review and meta-analysis of either published or preprint observational studies or randomized control trials (RCT) aimed to assess mortality rate, duration of hospital stay, need for mechanical ventilation (MV), virologic cure rate (VQR), time to a negative viral polymerase chain reaction (PCR), radiological progression, experiencing drug side effects, and clinical worsening. A search of the online database through June 2020 was performed and examined the reference lists of pertinent articles for in-vivo studies only. Pooled relative risks (RRs), standard mean differences of 95% confidence intervals (CIs) were calculated with the random-effects model. Mortality was not different between the standard care (SC) and HCQ groups (RR = 0.99, 95% CI 0.61-1.59, I2 = 82%), meta-regression analysis proved that mortality was significantly different across the studies from different countries. However, mortality among the HCQ + AZM was significantly higher than among the SC (RR = 1.8, 95% CI 1.19-2.27, I2 = 70%). The duration of hospital stay in days was shorter in the SC in comparison with the HCQ group (standard mean difference = 0.57, 95% CI 0.20-0.94, I2 = 92%), or the HCQ + AZM (standard mean difference = 0.77, 95% CI 0.46-1.08, I2 = 81). Overall VQR, and that at days 4, 10, and 14 among patients exposed to HCQ did not differ significantly from the SC [(RR = 0.92, 95% CI 0.69-1.23, I2 = 67%), (RR = 1.11, 95% CI 0.26-4.69, I2 = 85%), (RR = 1.21, 95% CI 0.70-2.01, I2 = 95%), and (RR = 0.98, 95% CI 0.76-1.27, I2 = 85% )] respectively. Exposure to HCQ + AZM did not improve the VQR as well (RR = 3.23, 95% CI 0.70-14.97, I2 = 58%). The need for MV was not significantly different between the SC and HCQ (RR = 1.5, 95% CI 0.78-2.89, I2 = 81%), or HCQ + AZM (RR = 1.27, 95% CI 0.7-2.13, I2 = 88%). Side effects were more reported in the HCQ group than in the SC (RR = 3.14, 95% CI 1.58-6.24, I2 = 0). Radiological improvement and clinical worsening were not statistically different between HCQ and SC [(RR = 1.11, 95% CI 0.74-1.65, I2 = 45%) and (RR = 1.28, 95% CI 0.33-4.99), I2 = 54%] respectively. Despite the scarcity of published data of good quality, the effectiveness and safety of either HCQ alone or in combination with AZM in treating COVID-19 cannot be assured. Future high-quality RCTs need to be carried out.PROSPERO registration: CRD42020192084.

Molecular and hormonal changes caused by long-term use of high dose pregabalin on testicular tissue: the role of p38 MAPK, oxidative stress and apoptosis.

In 1990, pregabalin was introduced as a novel antiepileptic drug that acts by binding selectively to the alpha-2-delta subunits of voltage-gated calcium channels resulting in increasing neuronal GABA levels and inhibiting the release of exciting neurotransmitters. The aim of our study is to assess the hazardous effects of prolonged high-dose pregabalin (like that abused by addicts) on testes and to clarify the potential causative mechanisms. The current study was conducted on 70 adult male Wistar albino rats which were divided into 7 groups. In our study we evaluated the effect of pregabalin, at concentrations 150 and 300 mg/kg/day for 90 days, on hormones; FSH, LH, testosterone and prolactin secretion. Our study also evaluated the expression of apoptosis-related genes BAX and BCL2 in testicular tissue in addition to the western blotted analysis of p38 Mitogen activated protein kinases (p38 MAPK). The levels of reduced glutathione, malondialdehyde and superoxide dismutase were also measured. Pregabalin decreased testosterone level while FSH, LH and prolactin showed a significant increase. It also produced genotoxicity through reversal of the BAX/BCL2 ratio; increased p38 MAPK level and induction of oxidative stress markers. The concomitant administration of vitamin E significantly reduced all the previously mentioned biochemical and hormonal adverse effects caused by pregabalin. Pregabalin can adversely affect male fertility particularly in addicts and patients who are being treated with it for long periods as those suffering from neuropathies and seizures. Antioxidants like vitamin E could have a role in amelioration.

The neurotoxic effect of long-term use of high-dose Pregabalin and the role of alpha tocopherol in amelioration: implication of MAPK signaling with oxidative stress and apoptosis.

Pregabalin abuse has become an emerging concern; thus, the current study has been designed to study the neurotoxic hazards of prolonged high-dose of pregabalin (akin to that abused by addicts) and to evaluate the effect of alpha tocopherol as a possible ameliorating agent. The current study evaluated the brain neurotransmitters; dopamine, glutamate, and norepinephrine. The study also assessed the expression of the apoptosis-related markers Bax, Bcl2, and caspase 3. Western-blotted analysis of the three major mitogen-activated protein kinases (MAPKs), the c-JUN N-terminal kinase (JNK), the p38 MAPK, and the extracellular signal-regulated kinase (ERK), has also been performed. The study also evaluated oxidative stress via assessment of the cortical tissue levels of reduced glutathione and malondialdehyde and the activity of superoxide dismutase. Histopathological examination and histomorphometric evaluation of the darkly degenerated cortical neurons have also been performed. Pregabalin in high doses (150 mg/kg/day and 300 mg/kg/day) disrupted the ERK/JNK/p38-MAPK signaling, reversed the bax/bcl2 ratio, and induced oxidative stress. It also diminished the release of dopamine, glutamate, and norepinephrine and increased the count of degenerated neurons. Alpha tocopherol treatment significantly attenuated the deleterious effects induced by pregabalin. The role of alpha tocopherol in ameliorating the oxidative stress injury, and apoptosis induced by pregabalin, along with its role in normalizing neurotransmitters, modulating the ERK/JNK/p38-MAPK signaling pathways and improving the histopathological cortical changes, offers alpha tocopherol as a promising adjunctive therapy in patients undergoing prolonged pregabalin therapy as those suffering from prolonged seizures and neuropathies.