Viral MicroRNAs in Herpes Simplex Virus 1 Pathobiology.

Simplexvirus humanalpha1 infects millions of people globally, manifesting as vesiculo-ulcerative lesions of the oral or genital mucosa. After primary infection, the virus establishes latency in the peripheral neurons and reactivates sporadically in response to various environmental and genetic factors. A unique feature of herpesviruses is their ability to encode tiny noncoding RNAs called microRNA, (miRNAs). Simplexvirus humanalpha1 encodes eighteen miRNA precursors that generate twenty-seven different mature miRNA sequences. Unique Simplexvirus humanalpha1 miRNAs repertoire is expressed in lytic and latent stages and exhibits expressional disparity in various cell types and model systems suggesting their key pathological functions. This review will focus on elucidating the mechanisms underlying HSV-1 encoded viral miRNAs regulation of host-virus interaction. Numerous studies have demonstrated sequence-specific targeting of both viral and host transcripts by Simplexvirus humanalpha1 miRNAs. While these noncoding RNAs predominantly target viral genes involved in viral life cycle switch, they regulate host genes involved in antiviral immunity, thereby facilitating viral evasion and lifelong viral persistence inside the host. Expression of Simplexvirus humanalpha1 miRNAs has been associated with disease progression and resolution. Systemic circulation and stability of viral miRNAs compared to viral mRNAs can be harnessed to utilize their potential as diagnostic and prognostic markers. Moreover, functional inhibition of these enigmatic molecules may allow us to devise strategies that have therapeutic significance to contain Simplexvirus humanalpha1 infection.

Psychological impact and stress factors among Ha'il medical students post COVID19 pandemic.

The current COVID-19 pandemic frightfully threatened the whole world, and people in different countries were demanded to be quarantined due to possible contact with the infection. High mortality rate, the spread of COVID19 and the propagation of fake news in social media programs created fear and anxiety among majority of society especially, medical students. One of the most essential changes during the covid-19 was the termination of teaching lectures in physical presence and its replacement by virtual online lectures. Circumstances like these have negative impact on the mental health of medical students. Therefore, it is of interest to investigate the impact of the COVID19 pandemic on medical students' learning and the effect of distressing situation they experienced, psychological and educational variables specifically during return to physical attendance in college and the impact of these variables of probably affecting factors like age, gender, marital status, transition of preclinical years to clinical years. A Cross-sectional study was completed among medical students at UOH, KSA. The data are collected by distributing an online questionnaire. Statistical analysis has been done with Microsoft Power BI. 14.82% of 5th year female participants were unable to stop worrying for different things while 10.54% of male participant were in the 1st year. Large numbers of students who have increased the number of times they wash their hands are found in med3 and med4 while 27.92% agree and 29.05% strongly agree of whole years of study. 45.29% of students were having mental pressure before online session due to internet connection while 51.55% had decreased motivation since the shift to online learning. Data shows that highest numbers of participants who were having past illness and anxious were in age group 21-23 in both male and female. The majority of students was having fear toward returning in physical presence and preferred not to have on- college education. Hence, it is recommended to encourage students and reduce stress by providing with Personal Protective Equipment (PPE) course.

Short-term Effects of Metformin on Cardiac and Peripheral Blood Cells Following Cecal Ligation and Puncture-induced Sepsis.

AIM OF THE STUDY: Sepsis has well-documented inflammatory effects on cardiovascular and blood cells. This study is designed to investigate potential anti-inflammatory effects of metformin on cardiac and blood cells 12 and 24 h following cecal ligation and puncture (CLP)-induced sepsis. METHODS: For the purpose of this study, 36 male Wistar rats were divided into six groups: two groups underwent CLP, two groups underwent CLP and received metformin, and two groups only received sham operations. 12 h later, 18 rats (half of rats in each of the three aforementioned groups) were sacrificed and cardiac and blood cells were harvested. Subsequently, 12 h later, the rest of the rats were euthanatized. In all harvested blood and cardiac cells, oxidative stress indicators, antioxidant properties, count of blood cells, neutrophil infiltration, percentage of weight loss and pathological assessment were conducted. RESULTS: In our experiment, metformin elevated antioxidant levels, improved function of blood cells and percentage of weight loss. Moreover, in the groups which received metformin, oxidative stress and neutrophil infiltration markers were decreased significantly. Moreover, pathological investigations of cardiac cell injury were reduced in the metformin group. CONCLUSIONS: Our findings suggest that in CLP induced sepsis model, metformin can improve the function of blood and cardiac cells through alleviating inflammation, improvement of anti-inflammation properties, and enhancement of blood profile, and all these effects are more pronounced after 24 h in comparison with 12 h after induction of sepsis.

Validity, reliability and use of a Kuwait child nutrition knowledge assessment questionnaire

Background: Little is known about the nutritional knowledge of children in Kuwait and school-based nutrition interven-tions are scarce. No validated tool to assess the nutrition knowledge of schoolchildren in Kuwait is available. Aims: This study determined the validity and reliability of a nutrition knowledge questionnaire in Kuwaiti primary-school children, and measured children’s nutrition knowledge before and after a nutrition awareness intervention.Methods: The questionnaire included five questions to measure nutritional knowledge. The face and content validity were assessed by nutrition and paediatric experts. To assess questionnaire reliability and nutrition knowledge, 642 school-children (8–12 years) were assigned to an intervention, control or reliability group. Each group completed the question-naire twice, one or two weeks apart. Students in the intervention group attended a nutrition knowledge presentation before completing the questionnaire the second time. Independent and paired samples t-tests were used to assess score differences between and within the intervention and control groups for changes in nutrition knowledge. Pearson correla-tion coefficients were used to measure score consistency in the reliability group. Results: Overall, the questionnaire had good content validity and moderate to strong reliability (r = 0.44, P < 0.001). Stu-dents in the intervention group had significantly higher mean nutritional knowledge scores after the intervention (from 3.65 (SD 1.03) to 4.20 (SD 1.02); P = 0.17). Control group scores were mostly unchanged.Conclusions: The Kuwait child nutrition knowledge questionnaire is a valid and reliable tool to assess nutritional knowl-edge in schoolchildren in Kuwait. Nutrition knowledge of Kuwaiti schoolchildren should be improved using age-appro-priate interventions in school.

Contexte : Peu d’informations sont disponibles sur les connaissances des enfants koweïtiens en matière de nutrition, et les interventions d’éducation nutritionnelle dans les écoles sont rares. Aucun outil validé permettant d’évaluer les connaissances des écoliers koweïtiens à cet égard n’est disponible.Objectifs : La présente étude visait à déterminer la validité et la fiabilité d’un questionnaire d’évaluation des connaissances en matière de nutrition auprès d’écoliers du cycle primaire au Koweït, et à mesurer les connaissances des enfants à cet égard avant et après une intervention de connaissance nutritionnelle. Méthodes : Le questionnaire comportait cinq questions visant à évaluer le niveau de connaissance nutritionnelle. La validité apparente et de contenu du questionnaire a été évaluée par des experts en pédiatrie et en nutrition. Afin de mesurer la fiabilité du questionnaire et le niveau de connaissance en matière de nutrition, 642 écoliers (âgés de 8 à 12 ans) ont été répartis en trois groupes : un groupe d’intervention, un groupe témoin et un groupe servant à garantir la fiabilité. Chaque groupe a répondu deux fois au questionnaire, à une ou deux semaines d’intervalle. Les écoliers du grouped’intervention ont assisté à une présentation sur la nutrition avant de répondre une deuxième fois au questionnaire. Des tests t d’échantillons appariés et indépendants ont été utilisés pour évaluer les différences de scores entre le groupe d’intervention et le groupe témoin et au sein de ces deux groupes dans le but d’interpréter l’évolution des connaissances nutritionnelles. Les coefficients de corrélation de Pearson ont été utilisés pour mesurer la cohérence des scores dans le groupe de fiabilité. Résultats : Globalement, le questionnaire présentait une bonne validité de contenu et une fiabilité moyenne à élevée (r = 0,44, p < 0,001). Les écoliers du groupe d’intervention avaient des scores de connaissance nutritionnelle beaucoup plus élevés suite à l’intervention (passant de 3,65 (E.T. 1,03) à 4,20 (E.T. 1,02) ; p = 0,17). Les scores du groupe témoin étaient en grande partie restés inchangés. Conclusions : Le questionnaire d’évaluation des connaissances des enfants koweïtiens en matière de nutrition constitue un outil valide et fiable pour mesurer le niveau de connaissance nutritionnelle des écoliers au Koweït. Des interventions adaptées à l’âge devraient être organisées dans les écoles afin d’améliorer le niveau de connaissance des écoliers koweïtiens en matière de nutrition.

Healthcare Workers' Knowledge of HIV-Exposed Infant Feeding Options and Infant Feeding Counseling Practice in Northern Nigeria.

BACKGROUND: Despite the existence of evidence-based HIV-exposed infant feeding guidelines, infants in Africa still acquire HIV through inappropriate feeding practices. OBJECTIVE: To identify predictors of HIV-exposed infant feeding knowledge and counseling practice among health care workers (HCW) in Nigeria. METHODS: Structured, pretested questionnaires were administered to HCW (n=262) in a tertiary health facility in Kano, Nigeria. Multivariate logistic regression was used to determine predictors of HIV-exposed infant feeding knowledge and counseling practice. RESULTS: Of 262 respondents, (58.0%, n=152) had good knowledge of recommended feeding options. Respondents listed exclusive breastfeeding (57.6%, n=151), human milk substitutes (45.4%, n=119), HIV-negative wet-nursing (37.0%, n=97), heated expressed human milk (20.6%, n=54) and mixed feeding (13.4%, n=35) as appropriate feeding choices. Over half (57.3%, n=150) of the respondents have ever counseled a HIV-positive mother on infant feeding. Knowledge was predicted by female sex (Adjusted Odds Ratio (AOR)=2.47, 95% Confidence Interval (CI):1.35-4.52), profession (physician vs. laboratory scientist, AOR=4.00, 95%CI:1.25-12.87; nurse/midwife vs. laboratory scientist, AOR=2.75, 95%CI:1.17-9.28), infant feeding counseling training (AOR=3.27, 95%CI:1.87-5.71), and number of children (2-4 vs. 0, AOR=1.75, 95%CI:1.23-3.92). Infant feeding counseling was predicted by female sex (AOR=2.85, 95%CI:1.39-5.85), age (>40 vs. <30 years, AOR=3.87, 95%CI:1.27-15.65), knowledge of infant feeding options (good vs. fair/poor, AOR=3.96, 95%CI:2.07-7.59), training (AOR=2.60, 95%CI:1.42-5.32), and profession (physician vs. laboratory scientist, AOR=10.7, 95%CI:2.85-40.54; nurse/midwife vs. laboratory scientist, AOR=4.8, 95%CI:1.26-18.02). CONCLUSION: The practice of infant feeding counseling among HCW in Nigeria is associated with sex, knowledge, and profession. Our findings may inform the development of targeted training programs for HCW in similar settings.

The Role of Epigenetic Alterations Involved in Sepsis: An Overview.

BACKGROUND: Sepsis is among the leading causes of death with no specific etiology or treatment. Increase in health burden in terms of cost, morbidity, and mortality is the reason behind the continuous search for different treatment modalities which involve several targets/approach and one of them includes the involvement of epigenetics in sepsis. OBJECTIVE: This review was carried out to explain the epigenetic alterations involved in sepsis, as it affects the disease progression, diagnosis, and treatment. METHODS: Information used in this review was obtained from different databases including PUBMED, SCOPUS, Web of Science, and EMBASE. Keywords were used as search terms. RESULT: In this review, we provided a concise overview of the significant role of epigenetic alterations in sepsis pathophysiology as it relates to disease progression, diagnosis and treatment derived from in vitro, in vivo, and human studies. These mechanisms affected various targets and pathways involved in sepsis modulation, which correlates with morbidity and mortality. Change in DNA methylation pattern, histone modification, and microRNA regulation has been shown in sepsis models to silence or activate pro-inflammatory genes such as TNF-α and interleukins, anti-oxidant enzymes, and many signaling pathways. Drugs that target these pathways have proven effective in sepsis treatment. CONCLUSION: Epigenetic processes involve specific enzymes detected in the blood and other body fluids which can potentially serve as diagnostic, therapeutic, as well as prognostic tools in sepsis. Epigenetic mechanisms can provide a highly sensitive and accurate method for sepsis diagnosis using blood and other body fluids.

Comparative occurrence of diabetes in canine, feline, and few wild animals and their association with pancreatic diseases and ketoacidosis with therapeutic approach.

Diabetes mellitus (DM) is a chronic metabolic disorder in which blood glucose level raises that can result in severe complications. However, the incidence increased mostly by obesity, pregnancy, persistent corpus luteum, and diestrus phase in humans and animals. This review has focused on addressing the possible understanding and pathogenesis of spontaneous DM in canine, feline, and few wild animals. Furthermore, pancreatic associated disorders, diabetic ketoacidosis, hormonal and drug interaction with diabetes, and herbal remedies associated with DM are elucidated. Bibliographic search for the present review was done using PubMed, Scopus, and Google Scholar for articles on concurrent DM in small and wild animals. Persistent corpus luteal and pseudopregnancy in female dogs generate gestational DM (GDM). GDM can also be caused by extensive use of drugs/hormones such as glucocorticosteroids. Although many similarities are present between diabetic cats and diabetic humans which present islet amyloidosis, there was a progressive loss of ß- and α-cells and the normal number of δ-cells. The most prominent similarity is the occurrence of islet amyloidosis in all cases of diabetic cat and over 90% of human non-insulin dependent DM Type-2. Acute pancreatic necrosis (APN) occurs due to predisposing factors such as insulin antagonism, insulin resistance, alteration in glucose tolerance, obesity, hyperadrenocorticism, and persistent usage of glucocorticoids, as these play a vital role in the progression of APN. To manage such conditions, it is important to deal with the etiological agent, risk factors, diagnosis of diabetes, and hormonal and drug interaction along with its termination with suitable therapy (herbal) protocols. It should be noted that the protocols used for the diagnosis and treatment of human DM are not appropriate for animals. Further investigations regarding diabetic conditions of pets and wild animals are required, which will benefit the health status of all animals health worldwide.

The relation between rice consumption, arsenic contamination, and prevalence of diabetes in South Asia.

Rice is the major staple food for about two billion people living in Asia. It has been reported to contain considerable amount of inorganic arsenic which is toxic to pancreatic beta cells and disrupt glucose homeostasis. Articles and conference papers published between 1992 and 2017, indexed in Scopus, PubMed, EMBASE, Google, and Google scholar were used. Arsenic exposure has been associated with increased blood glucose and insulin levels, or decreased sensitization of insulin cells to glucose uptake. Several studies have shown the association between inorganic arsenic exposure and incidence of diabetes mellitus. Considerable amounts of arsenic have been reported in different types of rice which may be affected by cultivation methods, processing, and country of production. Use of certain microbes, fertilizers, and enzymes may reduce arsenic uptake or accumulation in rice, which may reduce its risk of toxicity. Combined exposure to contaminated rice, other foods and drinking water may increase the risk of diabetes in these countries. Maximum tolerated daily intake of arsenic contaminated rice (2.1 µg/day kg body weight) has been set by WHO, which may be exceeded depending on its content in rice and amount consumed. Hence, increased prevalence of diabetes in South Asia may be related to the consumption of arsenic contaminated rice depending on its content in the rice and daily amount consumed. In this review, we have focused on the possible relation between rice consumption, arsenic contamination, and prevalence of diabetes in South Asia.

Epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes.

BACKGROUND: Exposure to inorganic arsenic (iAs) is a major threat to the human health worldwide. The consumption of arsenic in drinking water and other food products is associated with the risk of development of type-2 diabetes mellitus (T2DM). The available experimental evidence indicates that epigenetic alterations may play an important role in the development of diseases that are linked with exposure to environmental toxicants. iAs seems to be associated with the epigenetic modifications such as alterations in DNA methylation, histone modifications, and micro RNA (miRNA) abundance. OBJECTIVE: This article reviewed epigenetic mechanisms underlying the toxic effects associated with arsenic exposure and the development of diabetes. METHOD: Electronic databases such as PubMed, Scopus and Google scholar were searched for published literature from 1980 to 2017. Searched MESH terms were "Arsenic", "Epigenetic mechanism", "DNA methylation", "Histone modifications" and "Diabetes". RESULTS: There are various factors involved in the pathogenesis of T2DM but it is assumed that arsenic consumption causes the epigenetic alterations both at the gene-specific level and generalized genome level. CONCLUSION: The research indicates that exposure from low to moderate concentrations of iAs is linked with the epigenetic effects. In addition, it is evident that, arsenic can change the components of the epigenome and hence induces diabetes through epigenetic mechanisms, such as alterations in glucose transport and/or metabolism and insulin expression/secretion.

Effect of styrene exposure on plasma parameters, molecular mechanisms and gene expression in rat model islet cells.

Styrene is an aromatic hydrocarbon compound present in the environment and have primary exposure through plastic industry. The current study was designed to evaluate styrene-induced toxicity parameters in rat plasma fasting blood glucose (FBG) level, oral glucose tolerance, insulin secretion, oxidative stress, and inflammatory cytokines in cellular and molecular levels. Styrene was dissolved in corn oil and administered at different doses (250, 500, 1000, 1500, 2000mg/kg/day and control) to each rat, for 42days. In treated groups, styrene significantly increased fasting blood glucose, plasma insulin (p<0.001) and glucose tolerance. Glucose tolerance, insulin resistance and hyperglycemia were found to be the main consequences correlating gene expression of islet cells. Styrene caused a significant enhancement of oxidative stress markers (p<0.001) and inflammatory cytokines in a dose and concentration-dependent manner in plasma (p<0.001). Moreover, the activities of caspase-3 and -9 of the islet cells were significantly up-regulated by this compound at 1500 and 2000mg/kg/day styrene administrated groups (p<0.001). The relative fold change of GLUD1 was downregulated (p<0.05) and upregulated at 1500 and 2000mg/kg, respectively (p<0.01). The relative fold changes of GLUT2 were down regulated at 250 and 1000mg/kg and up regulated in 500, 1500 and 2000mg/kg doses of styrene (p<0.01). The expression level of GCK indicated a significant upregulation at 250mg/kg and downregulation of relative fold changes in the remaining doses of styrene, except for no change at 2000mg/kg of styrene for GCK. Targeting genes (GLUD1, GLUT2 and GCK) of the pancreatic islet cells in styrene exposed groups, disrupted gluconeogenesis, glycogenolysis pathways and insulin secretory functions. The present study illustrated that fasting blood glucose, insulin pathway, oxidative balance, inflammatory cytokines, cell viability and responsible genes of glucose metabolism are susceptible to styrene, which consequently lead to other abnormalities in various organs.

Immunotoxicity of mercury: Pathological and toxicological effects.

Mercury (Hg) is toxic and hazardous metal that causes natural disasters in the earth's crust. Exposure to Hg occurs via various routes; like oral (fish), inhalation, dental amalgams, and skin from cosmetics. In this review, we have discussed the sources of Hg and its potential for causing toxicity in humans. In addition, we also review its bio-chemical cycling in the environment; its systemic, immunotoxic, genotoxic/carcinogenic, and teratogenic health effects; and the dietary influences; as well as the important considerations in risk assessment and management of Hg poisoning have been discussed in detail. Many harmful outcomes have been reported, which will provide more awareness.

Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer / 한국역학회지

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.

Smokeless tobacco (paan and gutkha) consumption, prevalence, and contribution to oral cancer / 한국역학회지

Smokeless tobacco consumption, which is widespread throughout the world, leads to oral submucous fibrosis (OSMF), which is a long-lasting and devastating condition of the oral cavity with the potential for malignancy. In this review, we mainly focus on the consumption of smokeless tobacco, such as paan and gutkha, and the role of these substances in the induction of OSMF and ultimately oral cancer. The list of articles to be examined was established using citation discovery tools provided by PubMed, Scopus, and Google Scholar. The continuous chewing of paan and swallowing of gutkha trigger progressive fibrosis in submucosal tissue. Generally, OSMF occurs due to multiple risk factors, especially smokeless tobacco and its components, such as betel quid, areca nuts, and slaked lime, which are used in paan and gutkha. The incidence of oral cancer is higher in women than in men in South Asian countries. Human oral epithelium cells experience carcinogenic and genotoxic effects from the slaked lime present in the betel quid, with or without areca nut. Products such as 3-(methylnitrosamino)-proprionitrile, nitrosamines, and nicotine initiate the production of reactive oxygen species in smokeless tobacco, eventually leading to fibroblast, DNA, and RNA damage with carcinogenic effects in the mouth of tobacco consumers. The metabolic activation of nitrosamine in tobacco by cytochrome P450 enzymes may lead to the formation of N-nitrosonornicotine, a major carcinogen, and micronuclei, which are an indicator of genotoxicity. These effects lead to further DNA damage and, eventually, oral cancer.

Effect of methanol leaf extract of Dalbergia saxatilis Hook.f (fabaceae) on renal function.

OBJECTIVE: Dalbegia saxatilis (D.saxatilis) is used as a decoction in traditional medicine for ailments such as cough, small pox, skin lesions, bronchial ailments and toothache. This study is aimed at evaluating the toxic effect of methanol leaf extract of D.saxatilis on renal function. MATERIALS AND METHODS: Wistar rats of both sexes were divided into four groups of five: control animals (group 1) received distilled water 1 ml/kg while groups 2, 3 and 4 were given graded doses of the extract (250, 500 and 1000 mg/kg body weight, respectively) daily for 28 days. Body weight changes were estimated by weighing the rats twice weekly using digital weighing balance. After 28 days, blood samples were obtained for evaluation of renal indices and the kidney was used for histopathology. Data were analysed using one-way and repeated measures ANOVA using SPSS version 20. RESULTS: Significant weight increase in all groups were observed (p<0.05). Significant reduction in electrolytes concentration was observed following treatment with extract (250 and 500 mg/kg) (p<0.05). Histopathological findings of the kidney revealed massive necrosis of the glomerulus with tubular distortion and lymphocyte hyperplasia at 250 and 500 mg/kg while intense glomerular and tubular necrosis was observed at 1000 mg/kg of the extract. CONCLUSION: Since different doses of the extract caused reduction in electrolyte concentration and damage to the kidney it is suggested that prolonged administration of the extract is associated with increased risk of kidney toxicity.