Community-Based Assessment and Treatment of Hepatitis C Virus-Related Liver Disease, Injecting Drug and Alcohol Use Amongst People Who Are Homeless: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: We performed a systematic review and meta-analysis addressing community-based assessment and treatment of hepatitis C virus (HCV)-related liver disease, injecting drug use (IDU) and alcohol use amongst people who are homeless (PWAH). METHODS: Using systematic review methodology, databases were searched (MEDLINE/EMBASE/CINAHL) for studies combining PWAH, HCV-related liver disease and community assessment until December 2019. Studies with a sample size ≥ 30, with PWAH constituting at least 30% of the cohort were included and a quality assessment performed. Pooled estimates of key indicators were analysed using meta-analysis. RESULTS: We identified 39 studies (n = 13,918), 37 categorised as poor quality (Newcastle-Ottawa Scale). Prevalence of homelessness ranged between 30%-100% (37 studies). Eight studies provided all of the following: HCV screening, alcohol/substance use/liver fibrosis assessment and HCV treatment. No study provided interventions for alcohol use, with two providing opioid substitution treatment. Alcohol use prevalence (24 studies) was 4%-97%, being 59% (95% CI 20%-92%) in four studies that included only PWAH. Recent IDU prevalence (16 studies) was 7%-73%, being 21% (95% CI 17%-26%) in four studies that included only PWAH. HCV seroprevalence (25 studies) was 2.5% - 58%; in 13 studies that included only PWAH, this was 20% (95% CI 12%-30%). Prevalence of F4 fibrosis (nine studies) was 6%-28%, being 7% and 16% in two studies that included only PWAH. Direct acting antiviral-based intention-to-treat sustained virological response (SVR) rates (five studies) were 82%-92%, being 92% in the one study that included only PWAH. In the only two randomised controlled trials (RCT) identified, community-based interventions (mental health/peer mentor) significantly increased linkage to care (p = 0.04), HCV treatment (p = 0.005) and SVR rates (p = 0.018). CONCLUSION: The burden from alcohol/IDU and HCV, and consequently liver disease in PWAH needs addressing. RCT trials assessing community-based interventions to improve liver health in PWAH are needed.

MOLECULAR EPIDEMIOLOGY TO UNDERSTAND THE SARS-CoV-2 EMERGENCE IN THE BRAZILIAN AMAZON REGION

The COVID-19 pandemic in Brazil has demonstrated an important public health impact, as has been observed in the world. In Brazil, the Amazon Region contributed with a large number of cases of COVID-19, especially in the beginning of the circulation of SARS-CoV-2 in the country. Thus, we describe the epidemiological profile of COVID-19 and the genetic diversity of SARS-CoV-2 strains circulating in the Amazon Region. We observe an extensive spread of virus in this Brazilian site. The data on sex, age and symptoms presented by the investigated individuals were similar to what has been observed worldwide. The genomic analysis of the viruses revealed important amino acid changes, including the D614G and the I33T in Spike and ORF6 proteins, respectively. The latter found in strains originating in Brazil. The phylogenetic analyzes demonstrated the circulation of the lineages B.1 and B.1.1, whose circulation in Brazil has already been previous reported. Our data reveals molecular epidemiology of SARS-CoV-2 in the Amazon Region. These findings also reinforce the importance of continuous genomic surveillance this virus with the aim of providing accurate and updated data to understand and map the transmission network of this agent in order to subsidize operational decisions in public health.

Efficacy and tolerability of quetiapine in patients with schizophrenia switched from other antipsychotics.

OBJECTIVE The Seroquel Patient Evaluation on Changing Treatment Relative to Usual Medication (SPECTRUM) study assessed the efficacy and tolerability of quetiapine (Seroquel™) in patients with schizophrenia switched from treatments providing suboptimal outcomes. METHODS This was an international, open-label, non-comparative study, designed with titration to 400 mg/day quetiapine over 7 days, then flexible dosing (300-750 mg/day) for 11 weeks. Efficacy was assessed with the Positive and Negative Syndrome Scale (PANSS); Clinical Global Impression (CGI) Severity of Illness and Global Improvement scores; and the Calgary Depression Scale for Schizophrenia (CDSS). Clinical benefit and tolerability were also assessed. RESULTS The mean modal dose of quetiapine was 505 mg/day; 509 patients switched to quetiapine from olanzapine (13%), risperidone (11%), conventional antipsychotics (37%) and combinations of antipsychotics (28%), amongst others. Significant decreases in CGI Severity of Illness and PANSS scores and a significant improvement in CDSS score resulted from the switch (all P<0.001 versus baseline). There were significant reductions in extrapyramidal symptoms (EPS) on the Simpson-Angus Scale (SAS) and Barnes Akathisia Scale (BAS) (both P<0.001 versus baseline) and a low incidence of EPS-related adverse events (4.7%). CONCLUSION Results indicate that switching to quetiapine was clinically beneficial for patients with poor efficacy or intolerable side effects on their previous antipsychotic medication.

Tracheary element differentiation uses a novel mechanism coordinating programmed cell death and secondary cell wall synthesis

Tracheary element differentiation requires strict coordination of secondary cell wall synthesis and programmed cell death (PCD) to produce a functional cell corpse. The execution of cell death involves an influx of Ca2+ into the cell and is manifested by rapid collapse of the large hydrolytic vacuole and cessation of cytoplasmic streaming. This precise means of effecting cell death is a prerequisite for postmortem developmental events, including autolysis and chromatin degradation. A 40-kD serine protease is secreted during secondary cell wall synthesis, which may be the coordinating factor between secondary cell wall synthesis and PCD. Specific proteolysis of the extracellular matrix is necessary and sufficient to trigger Ca2+ influx, vacuole collapse, cell death, and chromatin degradation, suggesting that extracellular proteolysis plays a key regulatory role during PCD. We propose a model in which secondary cell wall synthesis and cell death are coordinated by the concomitant secretion of the 40-kD protease and secondary cell wall precursors. Subsequent cell death is triggered by a critical activity of protease or the arrival of substrate signal precursor corresponding with the completion of a functional secondary cell wall.

Dim-red-light-induced increase in polar auxin transport in cucumber seedlings. I. Development Of altered capacity, velocity, and response to inhibitors

We have developed and characterized a system to analyze light effects on auxin transport independent of photosynthetic effects. Polar transport of [3H]indole-3-acetic acid through hypocotyl segments from etiolated cucumber (Cucumis sativus L.) seedlings was increased in seedlings grown in dim-red light (DRL) (0.5 &mgr;mol m-2 s-1) relative to seedlings grown in darkness. Both transport velocity and transport intensity (export rate) were increased by at least a factor of 2. Tissue formed in DRL completely acquired the higher transport capacity within 50 h, but tissue already differentiated in darkness acquired only a partial increase in transport capacity within 50 h of DRL, indicating a developmental window for light induction of commitment to changes in auxin transport. This light-induced change probably manifests itself by alteration of function of the auxin efflux carrier, as revealed using specific transport inhibitors. Relative to dark controls, DRL-grown seedlings were differentially less sensitive to two inhibitors of polar auxin transport, N-(naphth-1-yl) phthalamic acid and 2,3,5-triiodobenzoic acid. On the basis of these data, we propose that the auxin efflux carrier is a key target of light regulation during photomorphogenesis.