The mitochondrial unfolded protein response: Signaling from the powerhouse

Mitochondria are multifaceted and indispensable organelles required for cell performance. Accordingly, dysfunction to mitochondria can result in cellular decline and possibly the onset of disease. Cells use a variety of means to recover mitochondria and restore homeostasis, including the activation of retrograde pathways such as the mitochondrial unfolded protein response (UPRmt). In this Minireview, we will discuss how cells adapt to mitochondrial stress through UPRmt regulation. Furthermore, we will explore the current repertoire of biological functions that are associated with this essential stress-response pathway

Prophylactic use of carvedilol to prevent ventricular dysfunction in patients with cancer treated with doxorubicin

Objective: Deterioration in ventricular function is often observed in patients treated with anthracyclines for cancer. There is a paucity of evidence on interventions that might provide cardio-protection. We investigated whether prophylactic use of carvedilol can prevent doxorubicin-induced cardiotoxicity and whether any observed effect is dose related. Methods: A prospective, randomized, double-blind study in patients treated with doxorubicin, comparing placebo (n = 38) with different doses of carvedilol [6.25 mg/day (n = 41), 12.5 mg/day (n = 38) or 25 mg/day (n = 37)]. The primary endpoint was the measured change in left ventricular ejection fraction (LVEF) from baseline to 6 months. Results: LVEF decreased from 62 ± 5% at baseline to 58 ± 7% at 6-months (p = 0.002) in patients assigned to placebo but no statistically significant changes were observed in any of the 3 carvedilol groups. At 6 months, only one of 116 patients (1%) assigned to carvedilol had an LVEF < 50% compared to four of the 38 assigned to placebo (11%), (p = 0.013). No significant differences were noted between carvedilol and placebo in terms of the development of diastolic dysfunction, clinically overt heart failure or death. Conclusions: Carvedilol might prevent deterioration in LVEF in cancer patients treated with doxorubicin. This effect may not be dose related within the studied range

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

Neurodegenerative diseases are a serious and widespread global public health burden amongst aging populations. The total estimated worldwide global cost of dementia was US$818 billion in 2015 and has been projected to rise to 2 trillion US$ by 2030. While advances have been made to understand different neurodegenerative disease mechanisms, effective therapeutic strategies do not generally exist. Several drugs have been proposed in the last two decades for the treatment of different types of neurodegenerative diseases, with little therapeutic benefit, and often with severe adverse and side effects. Thus, the search for novel drugs with higher efficacy and fewer drawbacks is an ongoing challenge in the treatment of neurodegenerative disease. Several natural compounds including polysaccharides have demonstrated neuroprotective and even therapeutic effects. Natural polysaccharides are widely distributed in plants, animals, algae, bacterial and fungal species, and have received considerable attention for their wide-ranging bioactivity, including their antioxidant, anti-neuroinflammatory, anticholinesterase and anti-amyloidogenic effects. In this review, we summarize different mechanisms involved in neurodegenerative diseases and the neuroprotective effects of natural polysaccharides, highlighting their potential role in the prevention and therapy of neurodegenerative disease

Therapeutic Properties of Vanadium Complexes

Vanadium is a hard, silver-grey transition metal found in at least 60 minerals and fossil fuel deposits. Its oxide and other vanadium salts are toxic to humans, but the toxic effects depend on the vanadium form, dose, exposure duration, and route of intoxication. Vanadium is used by some life forms as an active center in enzymes, such as the vanadium bromoperoxidase of ocean algae and nitrogenases of bacteria. The structure and biochemistry of vanadate resemble those of phosphate, hence vanadate can be regarded as a phosphate competitor in a variety of biochemical enzymes such as kinases and phosphatases. In this review, we describe the biochemical pathways regulated by vanadium compounds and their potential therapeutic benefits for a range of disorders including type 2 diabetes, cancer, cardiovascular disease, and microbial pathology

Medical students' perceptions of complementary and alternative medicine therapies: A pre- and post-exposure survey in Majmaah University, Saudi Arabia

Background: Evidently, Complementary and Alternative Medicine (CAM) is increasingly a recognized medical practice that efficiently uses multiple treatment therapies and techniques in promoting the health  and wellbeing of people as well as preventing and managing a variety of human disorders. Research in CAM, which courses exposure to diverse healthcare professionals, is important from many perspectives including improvement in teaching skills of faculty, enhancing capacity building, and  innovative curriculum development. This pre- and post-design crosssectional study aimed to assess perceptions, training needs, personal usage, use in office practice, and knowledge of two batches of medical students toward CAM therapies in Majmaah University, Saudi Arabia.Materials and Methods: The second year medical students of the first (year 2012-13) and second (year 2013-2014) batch [n=26 & 39, respectively] were selected for this study. A reliable 16-item  self-administered questionnaire was distributed among all students for answering before and after the 48-hour specific 19 CAM therapies course, in terms of CAM therapies are clearly conventional or  alternative, training needs, effectiveness, personal use, use in practice, management of two clinical cases by CAM or conventional therapies, and views about which evidence based approach strongly support individual CAM modalities.Results: Medical students' knowledge and perceptions of CAM therapies significantly improved across some sub-items of CAM questionnaire with a positive trend in the rest of its items including their views about CAM therapies, need for further training, personal use of therapies and advising patients regarding CAM practices strongly supported by randomized clinical controlled trials and published case studies.Conclusion: CAM course tends to have positive impact on the knowledge and perceptions of medical students, in addition to need for further training, and personal use and use of CAM therapies in practice in line with strong evidence-based data regarding therapeutic efficacy. The preliminary results of this study call for further research in specific CAM modalities with a larger sample in academic settings across the nation. Key words: Medical students; Complementary and Alternative Medicine; CAM course; CAM therapies; pre-post design study; Saudi Arabia

Cigarettes' use and capabilities-opportunities-motivation-for-behavior model:a multi-country survey of adolescents and young adults

The use of cigarettes among adolescents and young adults (AYA) is an important issue. This study assessed the association between regular and electronic-cigarettes use among AYA and factors of the Capability-Motivation-Opportunity-for-Behavior-change (COM-B) model. A multi-country survey was conducted between August-2020 and January-2021, Data was collected using the Global-Youth-Tobacco-Survey and Generalized-Anxiety-Disorder-7-item-scale. Multi-level logistic-regression-models were used. Use of regular and electronic-cigarettes were dependent variables. The explanatory variables were capability-factors (COVID-19 status, general anxiety), motivation-factors (attitude score) and opportunity-factors (country-level affordability scores, tobacco promotion-bans, and smoke free-zones) controlling for age and sex. Responses of 6,989-participants from 25-countries were used. Those who reported that they were infected with COVID-19 had significantly higher odds of electronic-cigarettes use (AOR = 1.81, P = 0.02). Normal or mild levels of general anxiety and negative attitudes toward smoking were associated with significantly lower odds of using regular-cigarettes (AOR = 0.34, 0.52, and 0.75, P < 0.001) and electronic-cigarettes (AOR = 0.28, 0.45, and 0.78, P < 0.001). Higher affordability-score was associated with lower odds of using electronic-cigarettes (AOR = 0.90, P = 0.004). Country-level-smoking-control policies and regulations need to focus on reducing cigarette affordability. Capability, motivation and opportunity factors of the COM-B model were associated with using regular or electronic cigarettes

Anxiety among adolescents and young adults during COVID-19 pandemic: A multi-country survey

(1) Background: Adolescents-and-young-adults (AYA) are prone to anxiety. This study assessed AYA's level of anxiety during the COVID-19 pandemic; and determined if anxiety levels were associated with country-income and region, socio-demographic profile and medical history of individuals. (2) Methods: A survey collected data from participants in 25 countries. Dependent-variables included general-anxiety level, and independent-variables included medical problems, COVID-19 infection, age, sex, education, and country-income-level and region. A multilevel-multinomial-logistic regression analysis was conducted to determine the association between dependent, and independent-variables. (3) Results: Of the 6989 respondents, 2964 (42.4%) had normal-anxiety, and 2621 (37.5%), 900 (12.9%) and 504 (7.2%) had mild, moderate and severe-anxiety, respectively. Participants from the African region (AFR) had lower odds of mild, moderate and severe than normal-anxiety compared to those from the Eastern-Mediterranean-region (EMR). Also, participants from lower-middle-income-countries (LMICs) had higher odds of mild and moderate than normal-anxiety compared to those from low-income-countries (LICs). Females, older-adolescents, with medical-problems, suspected-but-not-tested-for-COVID-19, and those with friends/family-infected with COVID-19 had significantly greater odds of different anxiety-levels. (4) Conclusions: One-in-five AYA had moderate to severe-anxiety during the COVID-19-pandemic. There were differences in anxiety-levels among AYAs by region and income-level, emphasizing the need for targeted public health interventions based on nationally-identified priorities

A multi-country study on the impact of sex and age on oral features of COVID-19 infection in adolescents and young adults

Background: Oral diseases are features of COVID-19 infection. There is, however, little known about oral diseases associated with COVID-19 in adolescents and young adults (AYA). Therefore, the aim of this study was to assess oral lesions’ association with COVID-19 infection in AYA; and to identify if sex and age will modify these associations. Methodology: Data was collected for this cross-sectional study between August 2020 and January 2021 from 11-to-23 years old participants in 43-countries using an electronic validated questionnaire developed in five languages. Data collected included information on the dependent variables (the presence of oral conditions- gingival inflammation, dry mouth, change in taste and oral ulcers), independent variable (COVID-19 infection) and confounders (age, sex, history of medical problems and parents’ educational level). Multilevel binary logistic regression was used for analysis. Results: Complete data were available for 7164 AYA, with 7.5% reporting a history of COVID-19 infection. A significantly higher percentage of participants with a history of COVID-19 infection than those without COVID-19 infection reported having dry mouth (10.6% vs 7.3%, AOR = 1.31) and taste changes (11.1% vs 2.7%, AOR = 4.11). There was a significant effect modification in the association between COVID-19 infection and the presence of dry mouth and change in taste by age and sex (P = 0.02 and < 0.001). Conclusion: COVID-19 infection was associated with dry mouth and change in taste among AYA and the strength of this association differed by age and sex. These oral conditions may help serve as an index for suspicion of COVID-19 infection in AYA

Involvement of Acetylcholine Receptors in Cholinergic Pathway-Mediated Protection Against Autoimmune Diabetes

Type I diabetes (T1D) is a T cell-driven autoimmune disease that results in the killing of pancreatic β-cells and, consequently, loss of insulin production. Using the multiple low-dose streptozotocin (MLD-STZ) model of experimental autoimmune diabetes, we previously reported that pretreatment with a specific acetylcholinesterase inhibitor (AChEI), paraoxon, prevented the development of hyperglycemia in C57BL/6 mice. This correlated with an inhibition of T cell infiltration into the pancreatic islets and a reduction in pro-inflammatory cytokines. The cholinergic anti-inflammatory pathway utilizes nicotinic and muscarinic acetylcholine receptors (nAChRs and mAChRs, respectively) expressed on a variety of cell types. In this study, we carried out a comparative analysis of the effect of specific antagonists of nAChRs or mAChRs on the development of autoimmune diabetes. Co-administration of mecamylamine, a non-selective antagonist of nAChRs maintained the protective effect of AChEI on the development of hyperglycemia. In contrast, co-administration of atropine, a non-selective antagonist of mAChRs, mitigated AChEI-mediated protection. Mice pretreated with mecamylamine had an improved response in glucose tolerance test (GTT) than mice pretreated with atropine. These differential effects of nAChR and mAChR antagonists correlated with the extent of islet cell infiltration and with the structure and functionality of the β-cells. Taken together, our data suggest that mAChRs are essential for the protective effect of cholinergic stimulation in autoimmune diabetes