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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.

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012–2020. Two community‐based interventions were implemented in 2012–2013 and 2018–2020 with repeated sero‐behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti‐HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012–2013 and 2018–2020. Αnti‐HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012–2013 to 40.0% [31.3, 49.1%] in 2018–2020 (25.4% reduction, p =.007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person‐years (PYs) [29.6, 51.5] (30.5% reduction, p =.020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012–2013 and 9/55 in 2018–2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p <.001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high‐coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012–2020. [ABSTRACT FROM AUTHOR]

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.

Background and Aims: Hepatitis D virus (HDV) underdiagnosis remains common. We assessed the HDV screening and prevalence rates in HBsAg‐positive patients seen at tertiary liver centres throughout Greece as well as factors affecting HDV diagnosis. Methods: All adult HBsAg‐positive patients seen within the last 5 years were included. Non‐screened patients who visited or could be recalled to the clinics over a 6‐month period were prospectively tested for anti‐HDV. Results: Of 5079 HBsAg‐positive patients, 53% had anti‐HDV screening (41% before and 12% after study initiation). Pre‐study (8%–88%) and total screening rates (14%–100%) varied widely among centres. Screening rates were associated with older age, known risk group, elevated ALT, centre location and size and period of first visit. Anti‐HDV prevalence was 5.8% without significant difference in patients screened before (6.1%) or after study initiation (4.7%, p = 0.240). Anti‐HDV positivity was associated with younger age, parenteral drug use, born abroad, advanced liver disease and centre location. Overall, HDV RNA detectability rate was 71.6% being more frequent in anti‐HDV‐positive patients with elevated ALT, advanced liver disease and hepatitis B therapy. Conclusions: Anti‐HDV screening rates and recall capabilities vary widely among Greek liver clinics being higher in HBsAg‐positive patients of known risk group with active/advanced liver disease seen at smaller centres, while non‐medical factors are also important. Anti‐HDV prevalence varies throughout Greece being higher in patients born abroad with younger age, parenteral drug use and advanced liver disease. Viremia is more frequently but not exclusively detected in anti‐HDV‐positive patients with elevated ALT and advanced liver disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Summary: Background: Tenofovir alafenamide (TAF) has exhibited a favourable safety profile on estimated glomerular filtration (eGFR) and bone mineral density (BMD), but has not been extensively studied in patients with renal impairment and/or BMD disorders. Aims: To assess predictors of eGFR changes and other safety and efficacy outcomes during 24‐month TAF therapy in patients with chronic hepatitis B with renal and/or BMD disorders/risks. Methods: Adult patients who started TAF at 13 clinics throughout Greece were prospectively included. Main exclusion criteria were hepatitis D, active malignancy and bisphosphonates recent use. MDRD formula was used for eGFR estimation. Results: TAF was initiated in 176 patients (91% switched from another agent). At 12 and 24 months, HBV DNA was undetectable in 97% and 100%, and ALT was normal in 96% and 95% of patients. Median ALT decreased from baseline to month 12/24 (p < 0.001). Mean eGFR decreased from previous treatment initiation to baseline (p < 0.001), increased at 12 months and remained stable at 24 months (p ≤ 0.001). An increase in eGFR of >3 ml/min at 12 month was observed in 50% of patients and was associated mainly with baseline eGFR 30–60 ml/min. In patients with baseline phosphate <2.5 mg/dl, mean serum phosphate increased at month‐12/24 (p < 0.001). Median BMD did not change significantly from baseline to 12 months but improved at 24 months (p = 0.001). Conclusions: In mostly switched patients with renal and/or BMD disorders/risks, eGFR improved after 12‐24 months of TAF treatment, especially in patients with baseline eGFR 30–60 ml/min. TAF may also improve low serum phosphate, BMD and ALT, whereas it maintains or induces virological suppression. [ABSTRACT FROM AUTHOR]

Mycoplasma hominis was isolated in pure culture from septic synovial aspirates from an individual (patient A) during 16 different bouts of exacerbation over a 70-month period of observation. Two isolates, 107 and also 106 color-changing units (CCU) of the 1620 isolate and 5 × 104 CCU of the 1628 isolate, caused inflammation in chimpanzees inoculated intraarticularly. Inflammation was also induced with 107 CCU of the 2010B isolate, serovar VII of Ureaplasma urealyticum, recovered from an agammaglobulinemic individual (patient B) with septic polyarthritis and with 3 × 106 CCU of the PI-1428 isolate of Mycoplasma pneumoniae. Inflammation persisted for up to 36 days and was self-limiting. The aspirates contained up to 220,000 white blood cells/mm3 and up to 107 CCU/mL. There was good correlation between the severity of inflammation and the numbers of organisms, but antibody was not detected in aspirates during the peak severity of disease. As the numbers of organisms decreased, detectable levels of antibody increased, thus suggesting that antibody may have been bound to antigen. Chimpanzees previously infected with either the 1628 isolate of M. hominis or the 2010B isolate of U. urealyticum were protected on challenge with >100 times the minimal dose causing arthritis. Chimpanzees showed little or no inflammation when inoculated intraarticularly with 5 × 108 CCU of the type strain PG-21 of M. hominis or with the type strain CO of U. urealyticum or when inoculated intravenously with 3 × 108 CCU of the arthrogenic 1620 isolate of M. hominis. [ABSTRACT FROM PUBLISHER]