Altered serum adiponectin and interleukin-8 levels are associated in the pathophysiology of major depressive disorder: A case-control study.

BACKGROUND: Major depressive disorder (MDD) is a complex mental health condition that results in several obstacles including disabilities, loss of productivity, and economic burdens on both patients and society. Etiopathogenesis of MDD involves several factors such as sociodemographic, genetic, and biological determinants. However, any suitable biomarkers for risk assessment of depression have not been established yet. Alterations of cytokine are assumed to be involved in the pathophysiology and severity of the depressive disorder. Therefore, we aimed to evaluate serum adiponectin and interleukin-8 (IL-8) among MDD patients in Bangladesh. METHODS: We recruited a total of 63 MDD patients and 94 age-sex matched healthy controls (HCs) in the present study. MDD patients were enrolled from a tertiary care teaching hospital, Dhaka, Bangladesh, and HCs from surrounding parts of Dhaka city. A psychiatrist assessed all the study participants following the criteria mentioned in the DSM-5. We applied the Hamilton depression (Ham-D) rating scale to assess the depression severity. Serum adiponectin and IL-8 levels were determined using ELISA kits (BosterBio, USA). RESULTS: The mean serum concentration of adiponectin was decreased (30.67±4.43 µg/mL vs. 53.81±5.37 µg/mL), and the IL-8 level was increased (160.93±14.84 pg/mL vs. 88.68±6.33 pg/mL) in MDD patients compared to HCs. Sex-specific scatters plot graphs showed the distribution of adiponectin and IL-8 levels with Ham-D scores in MDD patients. Also, ROC curve analysis demonstrated good predictive performances of serum adiponectin and IL-8 for MDD with the area under the curve (AUC) as 0.895 and 0.806, respectively. CONCLUSION: The present study findings suggest that alterations of serum adiponectin and IL-8 levels in MDD patients might be involved in the disease process. Therefore, we can use these changes of cytokines in serum levels as early risk assessment tools for depression. The present study findings should be considered preliminary. We propose further interventional studies to evaluate the exact role of adiponectin and IL-8 in depression.

Comparative evaluation of authorized drugs for treating Covid-19 patients.

Background and Aims: Vaccines are the first line of defense against coronavirus disease 2019 (Covid-19). However, the antiviral drugs provide a new tool to fight the Covid-19 pandemic. Here we aimed for a comparative evaluation of authorized drugs for treating Covid-19 patients. Methods: We searched in PubMed and Google Scholar using keywords and terms such as Covid, SARS-CoV-2, Coronavirus disease 2019, therapeutic management, hospitalized Covid-19 patients, Covid-19 treatment. We also gathered information from reputed newspapers, web portals, and websites. We thoroughly observed, screened, and included the studies relevant to our inclusion criteria. We included only the United States Food and Drug Administration (FDA) authorized drugs for this review. Results: We found that molnupiravir and paxlovid are available for oral use, and remdesivir is for only hospitalized patients. Paxlovid is a combination of nirmatrelvir and ritonavir, nirmatrelvir is a protease inhibitor (ritonavir increases the concentration of nirmatrelvir), and the other two (remdesivir and molnupiravir) are nucleoside analog prodrugs. Remdesivir and molnupiravir doses do not need to adjust in renal and hepatic impairment. However, the paxlovid dose adjustment is required for mild to moderate renal or hepatic impaired patients. Also, the drug is not allowed for Covid-19 patients with severe renal or hepatic impairment. Preliminary studies showed oral antiviral drugs significantly reduce hospitalization or death among mild to severe patients. Moreover, the US FDA has approved four monoclonal antibodies for Covid-19 treatment. Studies suggest that these drugs would reduce the risk of hospitalization or severity of symptoms. World Health Organization strongly recommended the use of corticosteroids along with other antiviral drugs for severe or critically hospitalized patients. Conclusion: All authorized drugs are effective in inhibiting viral replication for most SARS-CoV-2 variants. Therefore, along with vaccines, these drugs might potentially aid in fighting the Covid-19 pandemic.

New Coronavirus Variants are Creating More Challenges to Global Healthcare System: A Brief Report on the Current Knowledge.

The coronavirus is naturally mutating over time and producing new variants. Some of them are more contagious and destructive than previous strains. Also, some variants are capable of therapeutic escaping. Earlier SARS-CoV-2 variants proved that some are supercritical, and newly mutated strains are creating new challenges to the global healthcare systems. Here we aimed to evaluate different coronavirus variants and associated challenges for healthcare systems. We searched for information online and on the PubMed, Scopus, and Embase databases. We found the wild-type virus is more sensitive for neutralization and more controllable than newer variants. The Delta and Omicron variants are more highly transmissible than Alpha, Beta, and Gamma variants. Also, few strains are resistant to neutralization. Therefore, there is a chance of reinfection among the vaccinated population. The transmissibility and resistance of the recently identified Omicron variant is still unclear. The Delta variant is the most dangerous among all variants due to its high transmissibility, disease severity, and mortality rate. For poor and developing countries, oxygen supply, medication, vaccination, and device supply are challenging during epidemic waves. Slowing down the transmission, mass vaccination, vaccine redesign, re-compiling action plans, and following safety guidelines can be effective solutions to the new challenges.

Infectious Etiologies of Intussusception Among Children <2 Years Old in 4 Asian Countries.

BACKGROUND: The etiology of intussusception, the leading cause of bowel obstruction in infants, is unknown in most cases. Adenovirus has been associated with intussusception and slightly increased risk of intussusception with rotavirus vaccination has been found. We conducted a case-control study among children <2 years old in Bangladesh, Nepal, Pakistan, and Vietnam to evaluate infectious etiologies of intussusception before rotavirus vaccine introduction. METHODS: From 2015 to 2017, we enrolled 1-to-1 matched intussusception cases and hospital controls; 249 pairs were included. Stool specimens were tested for 37 infectious agents using TaqMan Array technology. We used conditional logistic regression to estimate odds ratio (OR) and 95% confidence interval (CI) of each pathogen associated with intussusception in a pooled analysis and quantitative subanalyses. RESULTS: Adenovirus (OR, 2.67; 95% CI, 1.75-4.36) and human herpes virus 6 (OR, 3.50; 95% CI, 1.15-10.63) were detected more frequently in cases than controls. Adenovirus C detection <20 quantification cycles was associated with intussusception (OR, 18.59; 95% CI, 2.45-140.89). Wild-type rotavirus was not associated with intussusception (OR, 1.07; 95% CI, 0.52-2.22). CONCLUSIONS: In this comprehensive evaluation, adenovirus and HHV-6 were associated with intussusception. Future research is needed to better understand mechanisms leading to intussusception, particularly after rotavirus vaccination.

Consumer preferences for electronic cigarettes: results from a discrete choice experiment.

INTRODUCTION: E-cigarettes present a formidable challenge to regulators given their variety and the rapidly evolving nicotine market. The current study sought to examine the influence of e-cigarette product characteristics on consumer perceptions and trial intentions among Canadians. METHODS: An online discrete choice experiment was conducted with 915 Canadians aged 16 years and older in November 2013. An online commercial panel was used to sample 3 distinct subpopulations: (1) non-smoking youth and young adults (n=279); (2) smoking youth and young adults (n=264) and (3) smoking adults (n=372). Participants completed a series of stated-preference tasks, in which they viewed choice sets with e-cigarette product images that featured different combinations of attributes: flavour, nicotine content, health warnings and price. For each choice set, participants were asked to select one of the products or indicate 'none of the above' with respect to the following outcomes: interest in trying, less harm and usefulness in quitting smoking. The attributes' impact on consumer choice for each outcome was analysed using multinomial logit regression. RESULTS: Health warning was the most important attribute influencing participants' intentions to try e-cigarettes (42%) and perceived efficacy as a quit aid (39%). Both flavour (36%) and health warnings (35%) significantly predicted perceptions of product harm. CONCLUSIONS: The findings indicate that consumers make trade-offs with respect to e-cigarette product characteristics, and that these trade-offs vary across different subpopulations. Given that health warnings and flavour were weighted most important by consumers in this study, these may represent good targets for e-cigarette regulatory frameworks.

The Impact of Cigarette Packaging Design Among Young Females in Canada: Findings From a Discrete Choice Experiment.

INTRODUCTION: The tobacco industry uses various aspects of cigarette packaging design to market to specific groups. The current study examined the relative importance of five cigarette packaging attributes--pack structure (eg, "slims"), brand, branding, warning label size, and price--on perceptions of product taste, harm, and interest in trying, among young females in Canada. METHODS: A discrete choice experiment was conducted with smoking and nonsmoking females, aged 16 to 24 (N = 448). Respondents were shown 10 choice sets, each containing four packs with different combinations of the attributes: pack structure (slim, lipstick, booklet, traditional); brand ("Vogue," "du Maurier"); branding (branded, plain); warning label size (50%, 75%); and price ($8.45, $10.45). For each choice set, respondents chose the brand that they: (1) would rather try, (2) would taste better, and (3) would be less harmful, or "none." For each outcome, the attributes' impact on consumer choice was analyzed using a multinomial logit model. RESULTS: The multinomial logit analyses revealed that young females weighted pack structure to be most important to their intention to try (46%), judgment of product taste (52%), and judgment of product harm (48%). Price and branding were weighted important in trial intent decisions (23% and 18%, respectively) and product taste judgments (29% and 15%, respectively). Whereas warning label size and brand were weighted important when judging product harm (23% and 17%, respectively). CONCLUSION: The findings suggest that standardized cigarette packaging may decrease demand and reduce misleading perceptions about product harm among young females.

NADPH oxidase 2 mediates angiotensin II-dependent cellular arrhythmias via PKA and CaMKII.

RATIONALE: Angiotensin II (Ang II) signaling has been implicated in cardiac arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which regulates similar targets as CaMKII has recently been shown to be redox-sensitive as well. OBJECTIVE: This study aims to investigate the distinct molecular mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the individual contribution of PKA vs. CaMKII. METHODS AND RESULTS: Isolated ventricular cardiac myocytes from rats and mice were used. Ang II exposure resulted in increased NOX2-dependent ROS generation assessed by expression of redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell patch clamp measurements showed that Ang II significantly increased peak Ca and Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/-)). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak INa and ICa were also absent. In contrast, genetic knockout of CaMKIIδ (CaMKIIδ(-/-)) did not influence the Ang II-dependent increase in peak ICa and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark measurements) in a CaMKIIδ-, but not PKA-dependent manner. Surprisingly, only the increase in diastolic SR Ca leak was absent in gp91phox(-/-)myocytes suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII- but not on NOX2. Finally, we show that Ang II increased the propensity for cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on NOX2. CONCLUSION: Ang II activates PKA and CaMKII via NOX2, which results in disturbed Na and Ca currents (via PKA) and enhanced diastolic SR Ca leakage (via CaMKII). Oxidative activation of PKA and CaMKII via NOX2 may represent important pro-arrhythmogenic pathways in the setting of increased Ang II stimulation, which may be relevant for the treatment of arrhythmias in cardiac disease.