Vitamin D Alleviates Heavy Metal-Induced Cytotoxic Effects on Human Bone Osteoblasts Via the Induction of Bioenergetic Disruption, Oxidative Stress, and Apoptosis.

Cadmium (Cd) and lead (Pb) are heavy metals (HMs) that persistently contaminate the ecosystem, and bioaccumulation in bones is a health concern. We used biochemical and molecular assays to assess the cytoprotective effect of vitamin D (VD) on Cd- and Pd-induced chemical toxicity of human bone osteoblasts in vitro. Exposing Cd and Pb to human osteoblast cultures at concentrations of 0.1-1000 µM for 24-72 h significantly reduced osteoblast viability in an exposure time- and concentration-dependent manner. The cytotoxic effect of Cd on osteoblasts was more severe than Pb's, with 72-h exposure estimated half maximal effective concentration (EC50) of 8 and 12 µM, respectively, and VD (1 and 10 nM) alleviated cytotoxicity. Bioenergetics assays of ATP, mitochondrial membrane potential, and mitochondrial complex I and III activity showed that both Cd and Pb (1 and 10 µM) inhibited cellular bioenergetics after 72-h exposure. Cd and Pb increased lipid peroxidation and reactive oxygen species with reduced catalase/superoxide dismutase antioxidant activities and increased activity of caspases -3, -8, and -9. Co-treatment with VD (1 and 10 nM) counteracted bioenergetic disruption, oxidative damage, and apoptosis in a concentration-dependent manner. These findings suggest that VD is effective in managing the toxic effects of environmental pollutants and in treating bone diseases characterized by oxidative stress, apoptosis, and bioenergetic disruption.

Acacia saligna extract alleviates quetiapine-induced sexual toxicity in male albino rats: Insights from UPLC-MS/MS metabolite profiling, structural and PI3K/NF-κB pathway assessments.

Background: Quetiapine (QET) abuse has increased due to its anxiolytic and hedonic effects, necessitating protective adjunct treatments. Acacia saligna (A. saligna) flowers, used in traditional medicine, have potential health benefits. Aim: To investigate the protective role of A. saligna flower extract against QET-induced sexual toxicity, and to elucidate the possible underlying mechanisms through metabolomic and physiological studies. Methods: A. saligna extract was subjected to metabolite profiling via High-Resolution Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-ESI-qTOF-MS). Forty-eight adult male albino rats were assigned into six groups for 30 days. The intracavernosal pressure (ICP), semen, biochemical, hormonal, histological, genetic and Western blot (WB) analyses were determined. Results: A. saligna extract is rich in phenolic compounds, flavonoids, tannins, and unsaturated fatty acids. QET significantly decreased ICP and negatively affected semen parameters. A. saligna mitigated decreased sperm motility and ameliorated overexpressed proinflammatory genes in QET-55 group. A. saligna ameliorated the reduction of the antioxidant biomarkers, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), concurrent with downregulation of the nuclear factor kappa B (NF-κB) protein. A. saligna counteracted the disrupted testicular and prostatic structures revealed by histological examination. Conclusion: The extract from A. saligna, which contains a high concentration of antioxidants and anti-inflammatory chemicals, effectively mitigates sexual toxicity caused by QET. This study provided the first known explanation of the hypothesized processes behind the protective properties of A. saligna through biological, biochemical, and histological parameters. The results emphasize the potential of A. saligna as a safeguarding agent against drug-induced sexual toxicity.

Cyberchondria and smartphone addiction: A correlation survey among undergraduate medical students in Egypt.

BACKGROUND: There is an increase in smartphone usage globally. Cyberchondria (CYB) is characterized by excessive Internet searches for health information. Smartphone addiction is constantly rising among medical students together with CYB as a collateral emerging risk, yet there is limited research available on the topic. METHODS: This cross-sectional study explores the rising phenomenon of smartphone addiction and its potential role in CYB among medical students in seven Egyptian universities. A total of 1435 medical students participated in completing online questionnaires that assessed smartphone addiction and CYB using the Smartphone Addiction Scale-Short Version (SAS-SV) and Cyberchondria Severity Scale (CSS-12). Multivariable regression analysis was applied to assess predictors of smartphone addiction and CYB. RESULTS: Based on the used scales, 57.6% of students were suffering from smartphone addiction, and 85.8% exhibited a moderate degree of CYB. There was a significant positive correlation between smartphone addiction scores and CYB (p < 0.05). The multivariable regression models revealed that four factors including using Facebook, using WhatsApp, increasing time spent on the Internet per day, and a higher CYB score increase the probability of smartphone addiction. The factors that increase the probability of CYB are using Facebook, an increase in the frequency of Internet searches, a higher degree of worry about one's health or a family member's health, and being a smartphone addict. CONCLUSION: Smartphone addiction among undergraduate medical students is prevalent. Social media use, time spent online, and smartphone addiction were linked with the risk of CYB. Regular physical activity decreases the probability of smartphone addiction. Awareness programs and increased mental and physical activities are required to help reduce smartphone addiction among youth.

Musculoskeletal pain among medical residents: role of workplace safety climate and sexual harassment.

BACKGROUND: Workplace factors are important predictors of occurrence of musculoskeletal pain among different occupational populations. In healthcare, a psychologically unsafe work environment can negatively affect the emotional, physical and psychological well-being of physicians. This study aimed to examine the relationship between workplace violence, sexual harassment and musculoskeletal pain among Egyptian physicians in their years of residency. METHODS: We distributed an online self-administered questionnaire to 101 residents working in various healthcare sectors in Egypt. It included sections on demographic data, working conditions, widespread pain index (WPI), pain interference short-form, workplace violence and harassment questionnaire, psychosocial safety climate questionnaire (PSC) and sexual harassment climate questionnaire. RESULTS: All residents had at least one painful site on the WPI (range 1-11). The mean WPI was 3.5 ± 2.4, and 39.6% satisfied the criteria of having widespread pain by having at least 4 pain sites. Widespread pain index showed a weak statistically significant negative correlation with workplace PSC score (rho = - 0.272, p = 0.006), and a statistically significant weak positive correlation with the calculated total abuse index (rho = 0.305, p = 0.002). Workplace violence and abuse, as measured by a calculated abuse index was the only significant predictors of widespread pain among residents. CONCLUSION: WPV was found to be a predictor of musculoskeletal pain among medical residents. Healthcare organizations need to address WPV by employing preventive strategies to minimize its hazardous effects and ensure a safe working environment for physicians.

Selenium alleviates modafinil-induced neurobehavioral toxicity in rat via PI3K/Akt/mTOR/GSK3B signaling pathway and suppression of oxidative stress and apoptosis: in vivo and in silico study.

Nonmedical use of modafinil (MOD) led to increased rates of overdose toxicity, road accidents, addiction, withdrawal, suicide, and mental illnesses. The current study aims to determine the probable MOD brain toxicity and elucidate the possible role of selenium (Se) in ameliorating the neurotoxicity in rat models. Fifty-four male Albino rats were randomly assigned into nine groups. The groups were G1 (control negative), G2 (Se0.1), G3 (Se0.2), G4 (MOD300), G5 (MOD600), G6 (Se0.1 + MOD300), G7 (Se0.2 + MOD300), G8 (Se0.1 + MOD600), and G9 (Se0.2 + MOD600). After finishing the experiment, blood and brain tissue were harvested for biochemical and histological investigation. Neurobehavior parameters were assessed. Tissue neurotransmitter levels and oxidative stress markers were assessed. Gene expression of PI3K/Akt/mTOR-GSK3B, orexin, and orexin receptor2 was measured by qRT-PCR. Histological and immunohistochemistry assessments, as well as molecular docking, were carried out. MOD-induced neurobehavioral toxicity exhibited by behavioral and cognitive function impairments, which are associated with decreased antioxidant activities, increased MDA levels, and decreases in neurotransmitter levels. Brain levels of mRNA expression of PI3K, Akt, and mTOR were decreased, while GS3K, orexin, and orexin receptors were significantly elevated. These disturbances were confirmed by histopathological brain changes with increased silver and Bax immunostaining and decreased crystal violet levels. MOD induced neurotoxic effects in a dose-dependent manner. Compared with the MOD groups, SE coadministration significantly attenuates MOD-induced toxic changes. Docking study shows the protective role of Se as an apoptosis inhibitor and inflammation inhibitor. In conclusion, Se could be used as a biologically effective antioxidant compound to protect from MOD neurobehavioral toxicity in Wistar rats by reversing behavioral alterations, inflammation, apoptosis, and oxidative injury.

Vaping, Environmental Toxicants Exposure, and Lung Cancer Risk.

Lung cancer (LC) is the second-most prevalent tumor worldwide. According to the most recent GLOBOCAN data, over 2.2 million LC cases were reported in 2020, with an estimated new death incident of 1,796,144 lung cancer cases. Genetic, lifestyle, and environmental exposure play an important role as risk factors for LC. E-cigarette, or vaping, products (EVPs) use has been dramatically increasing world-wide. There is growing concern that EVPs consumption may increase the risk of LC because EVPs contain several proven carcinogenic compounds. However, the relationship between EVPs and LC is not well established. E-cigarette contains nicotine derivatives (e.g., nitrosnornicotine, nitrosamine ketone), heavy metals (including organometal compounds), polycyclic aromatic hydrocarbons, and flavorings (aldehydes and complex organics). Several environmental toxicants have been proven to contribute to LC. Proven and plausible environmental carcinogens could be physical (ionizing and non-ionizing radiation), chemicals (such as asbestos, formaldehyde, and dioxins), and heavy metals (such as cobalt, arsenic, cadmium, chromium, and nickel). Air pollution, especially particulate matter (PM) emitted from vehicles and industrial exhausts, is linked with LC. Although extensive environmental exposure prevention policies and smoking reduction strategies have been adopted globally, the dangers remain. Combined, both EVPs and toxic environmental exposures may demonstrate significant synergistic oncogenicity. This review aims to analyze the current publications on the importance of the relationship between EVPs consumption and environmental toxicants in the pathogenesis of LC.

Type 2 diabetes and thyroid cancer: Synergized risk with rising air pollution.

Diabetes is a complex condition, and the causes are still not fully understood. However, a growing body of evidence suggests that exposure to air pollution could be linked to an increased risk of diabetes. Specifically, exposure to certain pollutants, such as particulate Matter and Ozone, has been associated with higher rates of diabetes. At the same time, air pollution has also been linked to an increased risk of thyroid cancer. While there is less evidence linking air pollution to thyroid cancer than to diabetes, it is clear that air pollution could have severe implications for thyroid health. Air pollution could increase the risk of diabetes and thyroid cancer through several mechanisms. For example, air pollution could increase inflammation in the body, which is linked to an increased risk of diabetes and thyroid cancer. Air pollution could also increase oxidative stress, which is linked to an increased risk of diabetes and thyroid cancer. Additionally, air pollution could increase the risk of diabetes and thyroid cancer by affecting the endocrine system. This review explores the link between diabetes and air pollution on thyroid cancer. We will discuss the evidence for an association between air pollution exposure and diabetes and thyroid cancer, as well as the potential implications of air pollution for thyroid health. Given the connections between diabetes, air pollution, and thyroid cancer, it is essential to take preventive measures to reduce the risk of developing the condition.

Assessment of the potential cerebellar toxicity of gold nanoparticles on the structure and function of adult male albino rats.

BACKGROUND: The regular use of gold nanoparticles (Au-NPs) may increase the likelihood of human exposure to these nanoparticles (NPs) and raises concerns about toxicity. AIM: This study investigated the short-term impact of exposure to Au-NPs on inducing cerebellar pathology in rats, and whether the dose or duration of exposure was more important. METHODOLOGY: The study used two concentrations of Au-NPs (25 and 50 particles per million) and 18 rats were randomly assigned to three groups. Assessments of the animals were done via behavioral, gene expression, histological, and immunohistochemistry analyses. RESULTS: Both concentrations of Au-NPs caused cerebellar pathology, as assessed through the investigation test battery. The Au-NPs50 group displayed more injury and decreased mobility compared with the control and the Au-NPs25 group. The Au-NPs25 group showed an increase in supported rearing and significant up-regulation of the Rgc32 gene compared with the control. The Trkb gene was insignificantly up-regulated in both Au-NPs groups compared with the control. CONCLUSION: The study indicates that exposure to Au-NPs can cause cerebellar pathology in rats and that the toxicity is more dependent on dose than the duration of exposure. These findings have significant implications for the safe use of Au-NPs in various applications.

Endomyocardial fibrosis related sudden cardiac death; two autopsied case-reports from Egypt.

Endomyocardial fibrosis (EMF) is an idiopathic tropical disorder that is characterized by the development of restrictive cardiomyopathy. Neglected EMF can cause sudden cardiac death (SCD) in adults. Conclusive diagnosis of EMF depends on autopsy after death. In an effort to attract the interest of the community for this rare disease, we report two cases of SCD that were diagnosed as EMF during autopsy in Egypt. Both cases were thoroughly investigated with emphasis on death circumstances and post-mortem anatomical and histopathological findings. The two cases were for adult males presented with SCD following a quarrel with a negative medical history and family history regarding cardiac diseases. No trauma or drug abuse. The autopsy revealed hypertrophied hearts, thick fibrosed endocardium, patchy myocardial fibrosis, and filling of the apex by fibrosis and calcifications. In one of them, there was a huge mural thrombus reaching the level of the mitral valve that totally occluded the cavity of the left ventricle. Histopathologically, fibrosis was confirmed, and no eosinophils were detected. In contrast to previously reported cases in Egypt, the left ventricle was solely affected. Despite the rarity of the disease outside the tropics, the frequency of EMF cases is more likely to be more than the number of reported cases. EMF should be considered as possible cause of SCD during autopsy. Further studies are needed to clarify the etiology and epidemiology of EMF.

Impact of workplace violence on anxiety and sleep disturbances among Egyptian medical residents: a cross-sectional study.

BACKGROUND: Workplace violence (WPV) against healthcare workers is a common occurrence worldwide, especially among young physicians and medical residents. This study aimed to explore the negative health impacts of WPV among medical residents in Egypt, and their perception regarding how safe it is to report violence. PURPOSE: To investigate the prevalence of WPV among medical residents, its possible negative health impacts, specifically on sleep quality and mental health, and the perceived workplace safety climate. METHODS: This is a cross-sectional analytic study, using a convenience sample through an online questionnaire. An abuse index was calculated, generalized anxiety disorder (GAD) and sleep quality were collected from the reported outcomes. RESULTS: The study sample included 101 residents (86.1% females). The most common reported form of abuse was verbal abuse, with the most common reported perpetrators being senior staff members (59.4%). About 86% of participants were classified as poor sleepers, while 59.4% had GAD, and there were significant positive correlations between GAD and Global Pittsburgh Sleep Quality Index (PSQI) scores with the abuse index. More than one third (35.6%) of residents reported a very high-risk Psychosocial Safety Climate (PSC) score, and 31.6% of them either strongly agreed or agreed that reporting a sexual harassment claim would be dangerous. CONCLUSION: Workplace violence is common among Egyptian medical residents, with a significant negative impact on sleep quality and a rising risk of GAD. The promotion of a safe workplace environment is essential in protecting the health and wellbeing of medical residents.

Thyroid Carcinoma: A Review for 25 Years of Environmental Risk Factors Studies.

Environmental factors are established contributors to thyroid carcinomas. Due to their known ability to cause cancer, exposure to several organic and inorganic chemical toxicants and radiation from nuclear weapons, fallout, or medical radiation poses a threat to global public health. Halogenated substances like organochlorines and pesticides can interfere with thyroid function. Like phthalates and bisphenolates, polychlorinated biphenyls and their metabolites, along with polybrominated diethyl ethers, impact thyroid hormones biosynthesis, transport, binding to target organs, and impair thyroid function. A deeper understanding of environmental exposure is crucial for managing and preventing thyroid cancer. This review aims to investigate the relationship between environmental factors and the development of thyroid cancer.

Domestic violence against women during coronavirus (COVID-19) pandemic lockdown in Egypt: a cross-sectional study.

BACKGROUND: While it is necessary to limit the spread of the coronavirus (COVID-19) pandemic, efforts including social isolation, restricted travel, and school closures are anticipated to raise the probability of domestic violence (DV). This study aimed to estimate the prevalence, pattern, risk factors, and physical health outcomes of domestic violence against women during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted using a convenient sample. The data collection tool was based on Sect. 11 of the Egyptian Demographic Health Survey, 2014, which is designed to measure domestic violence. We used a Google form-designed questionnaire and distributed the link to social media platforms from May 2020 to June 2020 till the collection of the required sample of 388 completed questionnaires. RESULTS: The prevalence of every form of DV was 31%. Emotional violence was the most prevalent (43.5%) followed by physical (38.9%) and sexual violence (17.5%). About 10.5% of women reported suffering from all types of violence. The husband was the most common perpetrator of DV. The determinants of ever experiencing any form of DV were low education level of women (OR = 7.3, 95% CI 2.8-18.8), unemployment (OR = 2.31, 95% CI 4-3.5), husband's use of alcohol or substance (OR = 14.4, 95% CI 4.1-50.2), and insufficient income (OR = 2.01, 95% CI 2-3.2). The most common health consequences of DV were injuries such as cuts, bruises, and aches. CONCLUSIONS: The prevalence of ever experiencing any form of DV was 31% which is considered high. Emotional violence was the most common whereas sexual violence was the least common. Identifying the risk factors of DV would support the development and implementation of preventive and screening programs for early identification and offering social support to the victims. Policies should be adopted for the early detection and protection of women suffering from violent behaviors. Access to adequate prompt support and health-care services is crucial in order to decrease the consequences of violence. It is necessary to implement alcohol or drug abuse interventions, preventive measures, and screening programs in families to reduce DV.

Subacute toxic effects of silver nanoparticles oral administration and withdrawal on the structure and function of adult Albino Rats' hepatic tissue.

Products containing Silver nanoparticles (Ag NPs) are becoming vastly used in our daily life. The widespread increased introduction of Ag NPs in many aspects of life has raised researchers' concerns regarding their safety and toxicity for biological and environmental life in the past few years. The current study aimed to explore the subsequent effects of Ag NPs withdrawal, following short-term oral administration. Eighteen rats were assigned randomly into three groups (control group "1" and AG NPs treated groups "2" and "3"; 6 animals each). The control group received normal food and tap water while groups 2 & 3 received 0.5 ml of a solution containing 25 ppm Ag NPs for 14 days. Group 2 rats were sacrificed on day 14 whereas group 3 was left for another 14 days of particle cessation followed by euthanasia on day 28. Functional assessment was done by liver enzyme assays, hydrogen peroxide activity, hepatic Bdnf expression, and P53 immunoreactivity. Hepatic tissue structural assessment was done via hematoxylin and eosin, periodic acid-Schiff as well as Masson's trichrome stains. The results revealed a significant elevation of Hydrogen peroxide in group 2 only compared to the control group. Hepatic Bdnf and liver enzymes were both insignificantly affected. Structural abnormalities and enhanced apoptosis in hepatic tissue were found 14 days after ceasing the nanoparticles. In conclusion: Structural and functional insults following Ag NPs oral administration continues after particle withdrawal, and interestingly they do not necessitate apparent reflection on liver enzyme assays.

Tigecycline and Gentamicin-Combined Treatment Enhances Renal Damage: Oxidative Stress, Inflammatory Reaction, and Apoptosis Interplay.

Although the combination of antibiotics is generally well-tolerated, they may have nephrotoxic effects. This study investigated whether tigecycline (TG) and gentamicin (GM) co-administration could accelerate renal damage. Male Wistar rats were randomly divided into six experimental groups: the control, TG7 (tigecycline, 7 mg/kg), TG14 (tigecycline, 14 mg/kg), GM (gentamicin, 80 mg/kg), TG7+GM, and TG14+GM groups. The combination of TG and GM evoked renal damage seen by the disruption of kidney function tests. The perturbation of renal tissue was mainly confounded to the TG and GM-induced oxidative damage, which was exhibited by marked increases in renal MDA (malondialdehyde) along with a drastic reduction in GSH (reduced-glutathione) content and CAT (catalase) activity compared to their individual treatments. More obvious apoptotic events and inflammation were also revealed by elevating the annexin-V and interleukin-6 (IL-6) levels, aside from the upregulation of renal PCNA (proliferating cell nuclear antigen) expression in the TG and GM concurrent treatment. The principal component analysis indicated that creatinine, urea, annexin-V, IL-6, and MDA all played a role in discriminating the TG and GM combined toxicity. Oxidative stress, inflammatory response, and apoptosis were the key mechanisms involved in this potentiated toxicity.

The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFß-Mediated p53/Smad2/3 Signaling.

Recent studies indicated renal toxicity and interstitial nephritis in patients receiving leflunomide (LEFN), but the exact mechanism is still unknown. The transforming growth factor ß (TGFß)/p53/Smad2/3 pathway crucially mediates renal fibrosis. We aimed to assess the nephrotoxic effect of LEFN in mice and the possible role of TGFß-stimulated p53/SMAD2/3 signaling. The study design involved distributing sixty male albino mice into four groups: (i) vehicle-treated mice, (ii) LEFN (2.5 mg/kg), (iii) LEFN (5 mg/kg), and (iv) LEFN (10 mg/kg). The drug was given orally every 48 h and continued for 8 weeks. Blood samples were then taken from mice for the determination of kidney function parameters. Right kidneys were used for histopathologic staining and immunohistochemistry, whereas left kidneys were frozen and used for Western blot analysis of the target proteins, p-p53 and Smad2/3. Results indicated that chronic administration of LEFN in mice resulted in a four- and nine-fold increase in serum urea and creatinine levels, respectively. Kidney specimens stained with hematoxylin and eosin or periodic acid-Schiff showed significant histopathological manifestations, such as cellular irregularity, interstitial congestion, and moderate lymphocytic inflammatory infiltrate in mice treated with LEFN. Western blotting indicated upregulation of the p-p53/Smad2/3 proteins. LEFN, especially in the highest dose (10 mg/kg), produced prominent nephrotoxicity in mice. This toxicity is mediated through stimulating fibrotic changes through TGFß-stimulated p53/Smad2/3 signaling and induction of glomerular and tubular apoptosis. An improved understanding of LEFN-induced nephrotoxicity would have great implications in the prediction, prevention, and management of leflunomide-treated rheumatic patients, and may warrant further clinical studies for following up these toxidromes.

Medico-legal assessment of acid attack (Vitriolage) injuries in Egypt: Fate, outcomes and permanent infirmity.

BACKGROUND: Vitriolage is an aggressive criminal act that results in different degrees of burn injuries and serious health consequences. Vitriolage has been known as a popular method of assault in some developing countries. To our knowledge, this is the first study in Egypt to study the medicolegal aspects of vitriolage crime. PURPOSE: The current study was designed to study the pattern of vitriolage injuries and to evaluate the permanent infirmity of vitriolage reported cases in Egypt. SUBJECTS AND METHODS: All cases of acid burn medicolegal reports throughout three years from 2015 to 2017 were included. 31 victims were studied as regards the demographic, medico-legal data and permanent infirmity assessment done on the victims. RESULTS: The male: female ratio of caustic burn victims was 1:2.9. Females were being assaulted at a higher rate than males. Most of the victims were young working women aged 20-30 years old and most of them lived in urban areas. Regarding the gender of the offenders, 23 were males and 6 were females. Almost 90.3% of the offenders were known to their victims. Most attacks occurred in public 22 cases (70.9%). Revenge was the most mentioned motive for assault (58.1%, n = 18). Ocular damage and dermal disfigurement were the most frequent injuries. CONCLUSION: Ensuring efficient implementation of multilevel policies is required to help survivors attain medical, psychological and community support. Legal socio-cultural reform with permanent infirmity evaluation modification is recommended to combat vitriolage.