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Selective ligands of the CB2 receptor are receiving considerable attention due to their potential as therapeutic agents for a variety of diseases. Recently, 7-hydroxy-5-oxopyrazolo[4,3-b]pyridine-6-carboxamide derivatives were shown to act at the CB2 receptor either as agonists or as inverse agonists/antagonists in vitro and to have anti-osteoarthritic activity in vivo. In this article, we report the synthesis, pharmacological profile, and molecular modeling of a series of twenty-three new 7-hydroxy-5-oxopyrazolo[4,3-b]pyridine-6-carboxamides with the aim of further developing this new class of selective CB2 ligands. In addition to these compounds, seven other analogs that had been previously synthesized were included in this study to better define the structure–activity relationship (SAR). Ten of the new compounds studied were found to be potent and selective ligands of the CB2 receptor, with Ki values ranging from 48.46 to 0.45 nM and CB1/CB2 selectivity indices (SI) ranging from >206 to >4739. In particular, compounds 54 and 55 were found to be high-affinity CB2 inverse agonists that were not active at all at the CB1 receptor, whereas 57 acted as an agonist. The functional activity profile of the compounds within this structural class depends mainly on the substitution pattern of the pyrazole ring.

AimsTo estimate all-cause mortality in a cohort of people who inject drugs (PWID) over the period 2018–2022 in the two major cities of Greece (Athens and Thessaloniki).MethodsPWID were recruited from two community-based seek-test-treat programs for HCV and HIV infections in Athens and Thessaloniki. Participants provided information on sociodemographic characteristics, injection practices, social security number, access to harm reduction and treatment. Data on the vital status and date of death were identified from the national HCV treatment registry. All-cause mortality rates (CMR) were estimated as well as age-, gender- and calendar-year standardized mortality ratios (SMR). Determinants of mortality were assessed using a Cox proportional-hazards model.ResultsOf 2,433 PWID, 243 (10.0%) died over a total of 6,649 person-years (PYs) of follow-up. The CMR [95% confidence interval (CI)] was 3.50 (3.08–3.97) deaths per 100 PYs; 3.03 (2.58–3.57) in Athens and 4.56 (3.74–5.57) in Thessaloniki. An increasing trend in CMR was identified over the period 2018–2022 in Athens (p for trend=0.004). The overall SMR (95% CI) was 17.17 (15.14–19.47) per 100 PYs in the combined cohort; 15.10 (12.85–17.75) in Athens and 21.72 (17.78–26.53) in Thessaloniki. The SMR was particularly increased in younger ages, females, those injecting daily, and HIV-infected PWID. Older age, living in Thessaloniki, Greek origin, homelessness, daily injecting drug use, HIV, and HCV infections were independently associated with all-cause mortality.ConclusionAll-cause mortality among PWID in Greece during 2018–2022 is high with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens might be the long-term impact of the pandemic on the health of PWID. Preventive programs such as take-home naloxone distribution and community involvement to increase harm reduction, screening, and uptake of antiretroviral and chronic hepatitis C treatment are urgently needed.

Objective: The present study was conducted to (1) investigate the role of emotion regulation difficulties among self-harming Lesbian, Gay, Bisexual, Transgender, Queer, or Questioning (LGBTQ+) individuals and (2) to test for a mediating role of emotion regulation difficulties in self-harm among LGBTQ + individuals. Method: This study investigated the relationship between LGBTQ + status, self-reported levels of emotion regulation difficulties, and self-harm in a community sample (N = 484, aged 16–63), using an online cross-sectional survey. Results: LGBTQ + individuals reported more emotion regulation difficulties and were almost seven times more likely to self-harm than non-LGBTQ + participants. Being an LGBTQ + participant was associated with greater self-harm frequency when controlling for age, income, and difficulties in emotion regulation. Emotion regulation difficulties mediated the association between LGBTQ + status and both self-harm status and frequency. Conclusions: The present findings suggest that treating emotion regulation difficulties might reduce both the prevalence and lifetime frequency of self-harm episodes among gender identity and sexual orientation minority individuals. Targeting emotion regulation might be used as an early prevention strategy among LGBTQ + individuals who are at risk for self-harm. Further, enhancing emotion regulation skills among self-harming LGBTQ + individuals might replace maladaptive emotion regulation strategies with healthy alternatives, and can, therefore, foster resilience. HIGHLIGHTS LGBTQ + individuals are at high risk for self-harm. ER-mediated the association between LGBTQ + status and self-harm. Targeting emotion regulation in LGBTQ + people may help reduce self-harm.

Introduction: The dissemination and adoption of healthy eating habits are crucial in promoting Public Health. Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease, a leading cause of death. Viral hepatitis causes a high morbidity burden and a high incidence of hepatocellular carcinoma.Objective: This case-control aims to investigate the impact of eating habits, especially functional food, on biomarkers of Metabolic Syndrome, Hepatitis B/C. The bibliographic lack of research on this matter was the impetus for this study.Methods: 90 (aged> 18 years) patients participated in the study, equally distributed in the three diseases and 90 healthy controls. The cardiovascular-hepatic biomarkers evaluated were: HbΑ1c, CHOL, TG, HDL, SGOT, SGPT, ΝΤ-proBNP, U, and CR.Results: The main groups of conventional and selected functional foods were recorded through their frequency of consumption and their effect on biomarkers (Statistically significant level, p-value

Individuals with a history of adverse childhood experiences (ACEs) display heightened symptoms of psychopathology during the COVID-19 pandemic. Yet, no study has investigated what aspects of the pandemic are of particular concern for this population and ways in which strategies to coping with pandemic stressors may exacerbate their clinical symptomatology.This study explores what pandemic stressors and coping strategies are associated with ACEs, depression, and posttraumatic stress disorder (PTSD) during the COVID-19 pandemic, before investigating whether the identified chief stressors and coping styles mediate the effects of ACEs on depression and PTSD.1107 Greek adults were sampled from the general population.Participants completed the Adverse Childhood Experiences Questionnaire, Patient Health Questionnaire, Primary Care PTSD Screen for DSM-5, Pandemic Stressor Scale, and Brief Cope Scale.ACEs and depression were both predominantly associated with difficult housing conditions as a stressor (b = 0.079, p .001 and b = 0.046, p .001, respectively), whereas PTSD was mainly related to fear of contracting the COVID-19 virus (b = 0.065, p .001). Self-blame was the main coping strategy associated with both ACEs (b = 0.046, p = .010), depression (b = 0.071, p .0005), and PTSD (b = 0.088, p .0005). Difficult housing conditions and self-blame further demonstrated a significant serial mediation effect in the relationship between ACEs with both depression (b = 0.105, 95% CI [0.0607, 0.158]) and PTSD (b = 0.019, 95% CI [0.011, 0.031]).The findings indicate that policy makers should identify ways of ameliorating challenging housing conditions, and that service providers should target self-blame in the psychological treatment of adults with ACEs during the COVID-19 pandemic.

Objectives: Eating Disorder symptoms are highly prevalent and persistent among university students, especially in societies that place high emphasis on body image and in countries where the weather conditions result in body revealing clothing such as Cyprus. The aim of this study is to investigate whether body image inflexibility moderates the relationship between weight concerns and eating disorder symptoms in a sample of Cypriot University students. Methodology: 440 students responded to a survey including measures of weight concerns, (WCS), body image inflexibility (BIIAAQ) and symptoms of eating disorders (EAT-26). Moderation analyses were conducted using the PROCESS Macro for SPSS. Results: The moderation model showed a significant interaction between weight concerns and body image inflexibility (95% CI .004 - .007). Discussion: Higher body image inflexibility seems to exacerbate the risk from weight concerns augmenting the experience of eating disorders symptoms. The findings suggest that interventions targeting body image inflexibility might help prevent and alleviate eating disorders symptoms., Mediterranean Journal of Clinical Psychology, Vol 9, No 2 (2021)

Erythrocytes from diabetic patients exhibit impaired viscoelastic properties when estimated by various methods. We determined erythrocyte filterability through 5-microm pores, in 51 patients with non-insulin-dependent diabetes mellitus, 18 healthy controls, 15 patients with homozygous beta-thalassemia and 15 with beta-thalassemia traits. The filtration measurements were made with a Hemorheometer, which uses the "initial flow rate" principle. To determine the Index of Rigidity (IR) of the red blood cells, we measured the passage time of white blood cell-free erythrocyte suspensions, 8% per volume, through the filter. Diabetic patients had significantly increased IR in comparison to healthy controls and to patients with beta-thalassemia trait, but not at the level found in patients with homozygous beta-thalassemia. In diabetic patients, a strong correlation between IR and the percentage of glycosylated haemoglobin was found (r=0.737, P < 0.0001), and a weaker one with serum unconjugated bilirubin (r=0.363, P=0.0097) and serum total lipids (r=0.321, P=0.0286). Patients with severe retinopathy also had significantly increased IR, in comparison to those with or without mild retinopathy. Anaemic diabetic patients, especially those with the anaemia of chronic disease, also had significantly increased IR in comparison to non-anaemic diabetics. No correlation between IR, MCV, MCH, MCHC, RDW, RBC morphology, serum LDH or the presence of erythrocyte inclusions after incubation with nitrous sodium solution was found. Our findings suggest that glycosylation of skeletal proteins probably contributes significantly to the increased membrane rigidity of diabetic erythrocytes.

This report analyses and reviews the corporate finance structure of non-financial corporations (NFCs) in the euro area, including how they interact with the macroeconomic environment. Special emphasis is placed on the crisis that began in 2007-08, thus underlining the relevance of financing and credit conditions to investment and economic activity in turbulent times. When approaching such a broad topic, a number of key questions arise. How did the corporate sector’s capital structure, internal and external financing sources, and its tendency to leverage, evolve in the euro area over the last decade and in the run-up to the financial crisis in particular? Did these developments contribute to and/or exacerbate the financial crisis? Did the corporate sector’s response to various shocks and vulnerabilities support or encumber the euro area economy, both during the financial crisis and in its aftermath? JEL Classification: E0, E5

This report analyses and reviews the corporate finance structure of non-financial corporations (NFCs) in the euro area, including how they interact with the macroeconomic environment. Special emphasis is placed on the crisis that began in 2007-08, thus underlining the relevance of financing and credit conditions to investment and economic activity in turbulent times. When approaching such a broad topic, a number of key questions arise. How did the corporate sector’s capital structure, internal and external financing sources, and its tendency to leverage, evolve in the euro area over the last decade and in the run-up to the financial crisis in particular? Did these developments contribute to and/or exacerbate the financial crisis? Did the corporate sector’s response to various shocks and vulnerabilities support or encumber the euro area economy, both during the financial crisis and in its aftermath?

Eight chimpanzees were examined. Two served as negative control and six inoculated with Mycoplasma pneumoniae became colonized. Colonization persisted for 28-68, 16-50 and 21 days with an average duration of 47, 32.5 and 21 days in the oropharyngeal, tracheal and lung tissues, respectively. Mycoplasma titers ranged from 10 8 to 10 1 color-changing units per specimen during the course of the infections. Seroconversion occurred within 12-15 days and peak antibody titers ranged from 1.256 to 1.1024 and developed between days 28 and 48 post-inoculation. Positive cold agglutinin titers were detected between 12 to 15 days and peak titers ranged from 1:80 to 1:640. Significant increases in sIgA and IgG immunoglobulin antibody levels were detected in lung lavage fluids. Unlike the many other experimentally infected animals examined, chimpanzees infected with M. pneumoniae had positive X-ray findings, developed cold agglutinins and showed overt signs of disease. These signs include persistent cough, low grade fever, rhinitis, oropharyngitis, diarrhea, and loss of appetite. Peak severity of disease corresponded with peak lung colonization, and the detection of cold agglutinins and positive X-ray findings. The microbiological, serological and clinical aspects of pneumonia induced in chimpanzees was similar to naturally occurring primary atypical pneumonia in humans.

We report two rare cases of hepatocellular carcinoma with invasion into the right atrium. In both our cases, the patients had liver cirrhosis and were admitted to our department due to symptoms such as worsening of the jaundice, ascites and edema of the lower extremities. The diagnosis of the HCC was established when we found high levels of alpha-fetoprotein, and the patients underwent MRI and CT-scan that were indicative of HCC. The clinical suspicion of invasion of the RA by the tumor emerged from the presence of heart-related symptoms, such as dyspnea and chest discomfort. The patients underwent two-dimensional transthoracic echocardiogram, which revealed from the sub-costal view a mobile atrial mass protruding from the inferior vena cava. In conclusion, when a patient with a history of chronic hepatic disease presents with symptoms of right heart failure one must be cautious and should bear in mind that right heart involvement from a malignant tumor may be present.