The NTD mutant that mimics the non-phosphorylated state (N2A) was competent in all steps of viral replication tested from capsid assembly, pgRNA packaging, reverse transcription, to virion secretion, except for a decrease in CCC DNA formation. On the other hand, the phosphor-mimetic mutant N2E showed a defect in the early step of pgRNA packaging but enhanced the late step of mature NC uncoating and consequently, increased CCC DNA formation. N2E also enhanced phosphorylation in CTD and possibly elsewhere in HBc. Furthermore, inhibition of the cyclin-dependent kinase 2 (CDK2), which is packaged into viral capsids, could block CCC DNA formation. These results prompted us to propose a model whereby rephosphorylation of HBc at both NTD and CTD by the packaged CDK2, following CTD dephosphorylation during NC maturation, facilitates uncoating and CCC DNA formation by destabilizing mature NCs.BACKGROUND The notion that smoking cannabis may damage the respiratory tract has been introduced in recent years but there is still a paucity of studies on this subject. The aim of this study was to investigate the relationship between cannabis smoking, pneumothorax and bullous lung disease in a population of operated patients. METHODS AND FINDINGS We performed a retrospective study on patients operated on for spontaneous pneumothorax. Patients were divided into three groups according to their smoking habit cannabis smokers, only-tobacco smokers and nonsmokers. Cannabis lifetime exposure was expressed in dose-years (1d/y = 1 gram of cannabis/week for one year). Clinical, radiological and perioperative variables were collected. The variables were analyzed to find associations with smoking habit. The impact of the amount of cannabis consumption was also investigated by ROC curves analysis. Of 112 patients, 39 smoked cannabis, 23 smoked only tobacco and 50 were nonsmokers. Median cannabis consumption was 28 dose/years, median tobacco consumption was 6 pack/years. Cannabis smokers presented with more severe chronic respiratory symptoms and bullous lung disease and with a higher incidence of tension pneumothorax than both tobacco smokers and nonsmokers. Cannabis smokers also developed a larger pneumothorax, experienced prolonged postoperative stay and demonstrated a higher incidence of pneumothorax recurrence after the operation than nonsmokers did. The risk of occurrence of chronic respiratory symptoms and bullous lung disease in cannabis smokers was dose-related. CONCLUSIONS Cannabis smoking seems to increase the risk of suffering from respiratory complaints and can have detrimental effects on lung parenchyma, in a dose-dependent manner. Cannabis smoking also negatively affected the outcome of patients operated for spontaneous pneumothorax. A history of cannabis abuse should always be taken in patients with pneumothorax. There may be need for a specific treatment for pneumothorax in cannabis smokers.OBJECTIVE To systematically review outcomes in patients with refractory overactive bladder (OAB) patients who underwent sacral neuromodulation therapy (SNM) therapy after unsuccessful onabotulinumtoxinA (BTX) therapy, and to compare outcomes with those who SNM as initial therapy. METHODS A systematic search of Cochrane Library, Pubmed and Embase databases from July 2002 to November 2019, to analyze randomized controlled trials and retrospective studies of SNM therapy after failed initial BTX therapy. Two reviewers independently screened the studies and extracted data. A quality assessment of the included literature was conducted using Newcastle-Ottawa Scale (NOS), and Stata 12.0 software was used to conduct a meta-analysis of the collected data. RESULTS A total of seven studies involving 319 patients were finally included. The success rate in refractory OAB patients who used SNM therapy after failed BTX therapy was 58.5%, 95% CI (0.47-0.70). There was no significant difference between refractory OAB patients who chose SNM as replacement therapy after failed BTX therapy and those who used SNM therapy as first choice [RR = 0.96, 95%CI (0.72-1.26), P = 0.735]. CONCLUSION OAB patients for whom an initial choice of BTX therapy ends in failure or dissatisfaction may consider switching to SNM therapy. There is no difference in outcomes between these patients and those whose first choice was SNM therapy.BACKGROUND Although combined antiretroviral therapy has substantially improved the prognosis of people living with HIV (PLHIV), mortality remains higher compared to the general population, mainly due to higher prevalence of non-HIV-related comorbidities, including cardiovascular diseases (CVD). We assessed the prevalence of CVD risk and its contributing factors in adult PLHIV versus general population controls in Greece. SETTINGS Cross-sectional comparison of PLHIV (Athens-Multicenter-AIDS-Cohort-Study; AMACS) versus general population controls (National health examination survey; EMENO). METHODS All HIV-infected adults with ≥1 measurement of interest (blood pressure, lipids, glucose, weight, height) between 2012-2014 and all EMENO participants (2014-2016) were included.  https://www.selleckchem.com/products/isa-2011b.html  Ten-year total CVD risk was estimated using the Framingham (FRS) or the Systematic Coronary Risk Evaluation (SCORE) equations. RESULTS 5839 PLHIV (median age41.6 years, 85.4% males) and 4820 controls (median age48 years, 48.4% males) were included. Adjusting for age, sex and origin, PLHIV were more likely to be current smokers (adjusted OR1.53 [95% CI1.35-1.74]) and dyslipidemic (aOR1.18; [1.04-1.34]), less likely to be obese (aOR0.44 [0.38-0.52], with no differences in hypertension, diabetes or high (≥20%) FRS but with greater odds of high (≥5%) SCORE (aOR1.55 [1.05-2.30]). Further adjustment for educational level, anti-HCV positivity and BMI showed higher prevalence of hypertension in PLHIV. CONCLUSIONS Despite the relative absence of obesity, PLHIV have higher prevalence of traditional CVD risk factors and higher risk of fatal CVD compared to general population. Regular screening and early management of CVD risk factors in PLHIV should be of high priority for CVD prevention.Knee osteoarthritis (KOA) is closely related with ageing, physical disability and functional dependency. The course of KOA is considered progressive and irreversible. Engagement with self-management may, however, minimize the impact of KOA. To be fully engaged with self-management activities, knowledge about KOA is a prerequisite. There is limited empirical data on older adults' understanding on KOA and their information needs about KOA. Therefore, the aims of this study were to explore older adults' knowledge about KOA and their perspectives on the information required to enable self-management. Three focus groups were conducted with 16 older adults with KOA. The sample consisted of three men and thirteen women with the mean age 73.2 years (range from 61 to 89). Thematic content analysis revealed two themes which were understanding about KOA and information needed about KOA. Participants' knowledge about KOA varied between individuals with many expressing that they needed more information about KOA. A targeted strategy is needed to educate older adults about KOA in order to support and prepare them for self-management.