Efficacy of Caffeic Acid on Diabetes and Its Complications in the Mouse

Diabetic dyslipidemia and hyperglycemia contribute to excessive reactive oxygen species (ROS) production, leading to deleterious complications, such as nephropathy, atherosclerosis and cardiac dysfunction, and target major organs in the body. The aim of this study was to investigate the effect of caffeic acid (CA) on mouse weight and survival, serum level of fasting blood glucose (FBG), serum lipid parameters and atherogenic indices, oxidative damage in blood, liver and kidney tissue, pathophysiological changes and their function markers in healthy and alloxan-induced type 1 diabetic mice. Diabetes was induced in mice with a single intravenous injection of alloxan (75 mg/kg). Two days later, CA (50 mg/kg) was given intraperitoneally for seven days in diabetic mice. Diabetes affected glucose level, lipid profile, hematological and biochemical parameters, induced DNA damage and apoptotic/necrotic death in whole blood cells, liver and kidney, leading to weight loss and a decreased lifespan. CA treatment of diabetic mice revealed a protective effect on the liver and kidney, hypoglycemic and hypolipidemic properties and high protection against atherogenic outcomes. The obtained results suggest that CA is a safe and potent agent against diabetes that acts as an effective antioxidant in reducing serum glucose, lipid profile and atherogenic indices, leading to increased lifespan in mice

Neurodegenerative changes caused by inhalation anesthetics

Mozak je ciljni organ djelovanja inhalacijskih anestetika. Osjetljivost mozga na oksidacijski stres povezana je sa njegovom izraženom metaboličkom aktivnošću, proizvodnjom ROSa (engl. reactive oxygen species, ROS), velikim brojem mitohondrija i smanjenom enzimskom antioksidativnom aktivnošću. Inhalacijski anestetici, poput Isoflurana i Sevoflurana, utječu na jačanje osjetljivosti mozga na oštećenja oksidativnim stresom te na povećanje aktivnost beta-sekretaze (BACE), enzima koji formira beta-amiloidne plakove i izaziva beta-amiloidnu ovisnu apoptozu živčanih stanica. Nadalje, beta-amiloidni plakovi, kao patološki produkt amiloidnog prekursorskog proteina (APP), predstavljaju važnu značajku za razvoj neurodegenerativnih promjena povezanih sa nastankom Alzheimerove bolesti. Istraživanje prooksidativnih, upalnih i neurotoksičnih učinaka inhalacijskih anestetika, te praćenje razine oksidativnog stresa u moždanom tkivu i nastalih patohistoloških promjena na mozgu štakora vezanih za neurodegenerativna oštećenja i upalu možemo povezati sa dugotrajnim izlaganjem inhalacijskim anesteticima, narušavanjem oksidacijsko/antioksidacijske homeostaze i stvaranje beta-amiloidnih plakova. Razumijevanjem povezanosti izloženosti inhalacijskim anesteticima i nastanku ireverzibilnih neurodegenerativnih promjena sugeriralo bi se poštednijim korištenjem inhalacijskih anestetika utjecati na ograničavanje neurodegenerativnihpromjena vezanih za nastanak Alzheimerove bolesti.Main target of inhalation anesthetics is the brain. The sensitivity of the brain to oxidative stress is associated with its pronounced metabolic activity, production of ROS (reactive oxygen species), large number of mitochondria and reduced enzymatic antioxidant activity. Inhaled anesthetics, such as Isoflurane and Sevoflurane, increase the sensitivity of the brain to oxidative stress damage and increase the activity of beta-secretase (BACE), an enzyme that forms beta-amyloid plaques and causes beta-amyloid-dependent apoptosis of nerve cells. Furthermore, beta-amyloid plaques, pathological product of amyloid precursor protein (APP), represent an important feature for the development of neurodegenerative changes associated with the development of Alzheimer’s disease. By investigation of prooxidative, inflammatory and neurotoxic effects of inhaled anesthetics and analyzing the parameters of oxidative stress levels in brain tissue and pathohistological changes in rat brain related to neurodegenerative damage and inflammation, connection with long-term exposure to inhaled anesthetics disruption of oxidative/antioxidant homeostasis and formation of beta amyloid plaques can be made. By understanding the relationship between exposure to inhaled anesthetics and the occurrence of irreversible neurodegenerative changes it could be suggested to reduce using inhaled anesthetics to limit the neurodegenerative changes associated with the development of Alzheimer’s disease

Antioxidative and Anti-Inflammatory Activities of Chrysin and Naringenin in a Drug-Induced Bone Loss Model in Rats

Oxidative stress (OS) mediators, together with the inflammatory processes, are considered as threatening factors for bone health. The aim of this study was to investigate effects of flavonoids naringenin and chrysin on OS, inflammation, and bone degradation in retinoic acid (13cRA)-induced secondary osteoporosis (OP) in rats. We analysed changes in body and uterine weight, biochemical bone parameters (bone mineral density (BMD), bone mineral content (BMC), markers of bone turnover), bone geometry parameters, bone histology, OS parameters, biochemical and haematological parameters, and levels of inflammatory cytokines. Osteoporotic rats had reduced bone Ca and P levels, BMD, BMC, and expression of markers of bone turnover, and increased values of serum enzymes alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). Malondialdehyde (MDA) production in liver, kidney, and ovary was increased, while the glutathione (GSH) content and activities of antioxidant enzymes were reduced and accompanied with the enhanced release of inflammatory mediators TNF-α, IL-1β, IL-6, and RANTES chemokine (regulated on activation normal T cell expressed and secreted) in serum. Treatment with chrysin or naringenin improved bone quality, reduced bone resorption, and bone mineral deposition, although with a lower efficacy compared with alendronate. However, flavonoids exhibited more pronounced antioxidative, anti-inflammatory and phytoestrogenic activities, indicating their great potential in attenuating bone loss and prevention of OP

Characteristics of post hoc subgroup analyses of oncology clinical trials: A systematic review

BACKGROUND: Subgroup analyses in clinical trials assess intervention effects on specific patient subgroups, ensuring generalizability. However, they are usually only able to generate hypotheses rather than definitive conclusions. This study examined the prevalence and characteristics of post hoc subgroup analysis in oncology. METHODS: We systematically reviewed published subgroup analyses from 2000 to 2022. We included articles presenting secondary, post hoc, or subgroup analyses of interventional clinical trials in oncology, cancer survivorship, or cancer screening, published separately from the original clinical trial publication. We collected cancer type, year of publication, where and how subgroup analyses were reported, and funding. RESULTS: Out of 16 487 screened publications, 1612 studies were included, primarily subgroup analyses of treatment trials for solid tumors (82%). Medical writers contributed to 31% of articles, and 58% of articles reported conflicts of interest. Subgroup analyses increased significantly over time, with 695 published between 2019 and 2022, compared to 384 from 2000 to 2014. Gastrointestinal tumors (25%) and lymphoid lineage tumors (39%) were the most frequently studied solid and hematological malignancies, respectively. Industry funding and reporting of conflicts of interest increased over time. Subgroup analyses often neglected to indicate their secondary nature in the title. Most authors were from high-income countries, most commonly North America (45%). CONCLUSIONS: This study demonstrates the rapidly growing use of post hoc subgroup analysis of oncology clinical trials, revealing that the majority are supported by pharmaceutical companies, and they frequently fail to indicate their secondary nature in the title. Given the known methodological limitations of subgroup analyses, caution is recommended among authors, readers, and reviewers when conducting and interpreting these studies

Oral manifestations in young adults infected with COVID-19 and impact of smoking:a multi-country cross-sectional study

Background: Oral manifestations and lesions could adversely impact the quality of people's lives. COVID-19 infection may interact with smoking and the impact on oral manifestations is yet to be discovered. Objectives: The aim of this study was to assess the self-reported presence of oral lesions by COVID-19-infected young adults and the differences in the association between oral lesions and COVID-19 infection in smokers and non-smokers. Methods: This cross-sectional multi-country study recruited 18-to-23-year-old adults. A validated questionnaire was used to collect data on COVID-19-infection status, smoking and the presence of oral lesions (dry mouth, change in taste, and others) using an online platform. Multi-level logistic regression was used to assess the associations between the oral lesions and COVID-19 infection; the modifying effect of smoking on the associations. Results: Data was available from 5,342 respondents from 43 countries. Of these, 8.1% reported COVID-19-infection, 42.7% had oral manifestations and 12.3% were smokers. A significantly greater percentage of participants with COVID-19-infection reported dry mouth and change in taste than non-infected participants. Dry mouth (AOR=, 9=xxx) and changed taste (AOR=, 9=xxx) were associated with COVID-19-infection. The association between COVID-19-infection and dry mouth was stronger among smokers than non-smokers (AOR = 1.26 and 1.03, p = 0.09) while the association with change in taste was stronger among non-smokers (AOR = 1.22 and 1.13, p = 0.86). Conclusion: Dry mouth and changed taste may be used as an indicator for COVID-19 infection in low COVID-19-testing environments. Smoking may modify the association between some oral lesions and COVID-19-infection

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

COPD care delivery pathways in five European Union countries: mapping and health care professionals&rsquo; perceptions

Background: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services. Objective: The aim of this study was to compare COPD patients’ care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals’ (HCPs) perceptions about the current pathways. Methods: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview. Results: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers. Conclusion: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients’ engagement could optimize current care pathways resulting in a better integrated system. Keywords: COPD, comorbidities, care delivery pathway, comparative analysi

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