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Antipsychotics improve the positive symptoms of schizophrenia. However, little is known about the extent of antidepressive effects of antipsychotics and their correlation with effects on other symptom domains in schizophrenia. The aim was to investigate whether antidepressive effects of antipsychotics have a significant correlation with the effects on specific symptom domains of schizophrenia.

Electronic databases were searched to identify eligible studies that reported antidepressive effects of antipsychotics for the treatment of adult patients with schizophrenia in double-blind, randomized placebo-controlled trials (RCTs). Mean change from baseline in depressive symptoms was meta-analyzed, and the correlation with the effects on other symptom domains was examined through meta-regression analysis.

Thirty-five RCTs (13 890 patients) were included in this meta-analysis. Overall, antipsychotics showed greater efficacy than placebo in reducing depressive symptoms, with small to medium effect sizes (standared for improvement in negative symptoms.

CRD42019133015.
CRD42019133015.Citrobacter freundii is a significant cause of human infections, responsible for food poisoning, diarrhea and urinary tract infections. We previously identified a highly cytotoxic and adhesive C. freundii strain CF74 expressing a type VI secretion system (T6SS). In this study, we show that in mice-derived macrophages, C. freundii CF74 activated the NLRP3 inflammasomes in a T6SS-dependent manner. The C. freundii T6SS activated the inflammasomes mainly through caspase-1 and mediated pyroptosis of macrophages by releasing the cleaved gasdermin-N domain. The CF74 T6SS was required for flagellin-induced interleukin (IL)-1β release by macrophages. We further show that the T6SS tail component and effector, Hcp-2, was necessary and sufficient to trigger NLRP3 inflammasome activation. In vivo, the T6SS played a key role in mediating IL-1β secretion and the survival of mice during C. freundii infection in mice. These findings provide novel insights into the role of T6SS in the pathogenesis of C. freundii.
Bloodstream infections (BSI) are associated with significant short-term mortality. There are many different scoring systems for assessing the severity of BSI.

We studied CURB65, CRB65, qSOFA, SIRS and NEWS and assessed how effective they were at predicting 30-day mortality across three separate BSI cohorts.

A retrospective analysis was performed on three established BSI cohorts 1) All cause BSI, 2) Escherichia coli and 3) Streptococcus pneumoniae.

The performance characteristics (sensitivity, specificity, positive predictive value, negative predictive value and area under receiver operating curve [AUROC]) for the prediction of 30-day mortality was calculated for the 5 scores using clinically relevant cut-offs.

528 patients were included All cause BSI-148, Escherichia coli - 191, and Streptococcus pneumoniae-189. Overall, thirty-day mortality was 22%. In predicting mortality, the AUROC for CURB65 and CRB65 were superior compared to qSOFA, SIRS and NEWS in the all cause BSI (0.72, 0.70, 0.66, 0.51, 0.53) and E.coli cohorts (0.81, 0.76, 0.73, 0.55, 0.71). In the pneumococcal cohort, CURB65, CRB65, qSOFA and NEWS were broadly equal (0.63, 0.65, 0.66, 0.62), but all were superior to SIRS (0.57). CURB65, CRB65 and qSOFA had considerably higher accuracy than SIRS or NEWS across all cohorts.

CURB65 was superior to other scores in predicting thirty-day mortality in the E.coli and all cause BSI cohorts. TP0903 Further research is required to assess the potential of broadening the application of CURB65 beyond pneumonia.
CURB65 was superior to other scores in predicting thirty-day mortality in the E.coli and all cause BSI cohorts. Further research is required to assess the potential of broadening the application of CURB65 beyond pneumonia.Lichen-forming fungi are known to produce a large number of secondary metabolites. Some metabolites are deposited in the cortical layer of the lichen thallus where they exert important ecological functions, such as UV filtering. The fact that closely related lineages of lichen-forming fungi can differ in cortical chemistry suggests that natural product biosynthesis in lichens can evolve independent from phylogenetic constraints. Usnic acid is one of the major cortical pigments in lichens. Here we used a comparative genomic approach on 46 lichen-forming fungal species of the Lecanoromycetes to elucidate the biosynthetic gene content and evolution of the gene cluster putatively responsible for the biosynthesis of usnic acid. Whole-genome sequences were gathered from taxa belonging to different orders and families of Lecanoromycetes, where Parmeliaceae is the most well-represented taxon, and analyzed with a variety of genomic tools. The highest number of biosynthetic gene clusters was found in Evernia prunastri,nomic adaptations to the evolutionary success of these lichen-forming fungal species and sets a baseline for further exploration of biosynthetic gene content and its evolutionary significance.Introgression events and population admixture occurred among Sus species across the Eurasian mainland in the Middle Pleistocene, which reflects the local adaption of different populations and contributes to evolutionary novelty. Previous findings on these population introgressions were largely based on extensive genome-wide single-nucleotide polymorphism information, ignoring structural variants (SVs) as an important alternative resource of genetic variations. Here, we profiled the genome-wide SVs and explored the formation of pattern-related SVs, indicating that PRE1-SS is a recently active subfamily that was strongly associated with introgression events in multiple Asian and European pig populations. As reflected by the three different combination haplotypes from two specific patterns and known phylogenetic relationships in Eurasian boars, we identified the Asian Northern wild pigs as having experienced introgression from European wild boars around 0.5-0.2 Ma and having received latitude-related selection. During further exploration of the influence of pattern-related SVs on gene functions, we found substantial sequence changes in 199 intron regions of 54 genes and 3 exon regions of 3 genes (HDX, TRO, and SMIM1), implying that the pattern-related SVs were highly related to positive selection and adaption of pigs. Our findings revealed novel introgression events in Eurasian wild boars, providing a timeline of population admixture and divergence across the Eurasian mainland in the Middle Pleistocene.
Although frailty has been associated with atypical manifestations of infections, little is known about COVID-19 presentations in hospitalized frail patients. We aimed to investigate the association between age, frailty, and clinical characteristics of COVID-19 in hospitalized middle-aged and older adults.

Longitudinal observational study comprising 711 patients aged ≥50 years consecutively admitted to a university hospital dedicated to COVID-19 severe cases, between March and May 2020. We reviewed electronic medical records to collect data on demographics, comorbidities, COVID-19 signs/symptoms, and laboratory findings on admission. We defined frailty using the Clinical Frailty Scale (CFS = 1-9; frail ≥5). We also documented in-hospital mortality. We used logistic regressions to explore associations between age, frailty, and COVID-19 signs/symptoms; and between typical symptoms (fever, cough, dyspnea) and mortality.

Participants had a mean age of 66 ± 11 years, and 43% were female. link2 Overall, 25% were frail, and 37% died. The most common COVID-19 presentations were dyspnea (79%), cough (74%), and fever (62%), but patients aged ≥65 years were less likely to have a co-occurrence of typical symptoms, both in the absence (OR = 0.56; 95% CI = 0.39-0.79) and in the presence of frailty (OR = 0.52; 95% CI = 0.34-0.81). In contrast, older age and frailty were associated with unspecific presentations, including functional decline, acute mental change, and hypotension. After adjusting for age, sex, and frailty, reporting fever was associated with lower odds of mortality (OR = 0.70; 95% CI = 0.50-0.97).

Atypical COVID-19 presentations are common in frail and older hospitalized patients. Providers should be aware of unspecific disease manifestations during the management and follow-up of this population.
Atypical COVID-19 presentations are common in frail and older hospitalized patients. Providers should be aware of unspecific disease manifestations during the management and follow-up of this population.c-Met hyperactivity has been observed in numerous neoplasms. Several researchers have shown that the abnormal activation of c-Met is mainly caused by transcriptional activation. However, the molecular mechanism behind this transcriptional regulation is poorly understood. Here, we suggest that Smad3 negatively regulates the expression and activation of c-Met via a transcriptional mechanism. We explore the molecular mechanisms that underlie Smad3-induced c-Met transcription inhibition. We found in contrast to the high expression of c-Met, Smad3 showed low protein and mRNA levels. Smad3 and c-Met expression was inconsistent between lung cancer tissues and cell lines. We also found that Smad3 overexpression suppresses whereas Smad3 knockdown significantly promotes EMT and production of the angiogenic factors VEGF, CTGF and COX-2 through the ERK1/2 pathway. In addition, Smad3 overexpression decreases whereas Smad3 knockdown significantly increases protein and mRNA levels of invasion related β-catenin and FAK through the PI3K/Akt pathway. link3 Furthermore, using the ChIP analysis method, we demonstrate that a transcriptional regulatory complex consisting of HDAC1, Smad3 and mSin3A binds to the promoter of the c-Met gene. By either silencing endogenous mSin3A expression with siRNA or by pretreating cells with a specific HDAC1 inhibitor (MS-275), Smad3-induced transcriptional suppression of c-Met could be effectively attenuated. These results demonstrate that Smad3-induced inhibition of c-Met transcription depends on of a functional transcriptional regulatory complex that includes Smad3, mSin3A and HDAC1 at the c-Met promoter. Collectively, our findings reveal a new regulatory mechanism of c-Met signaling, and suggest a potential molecular target for the development of anticancer drugs.
To date, scientific literature has not as yet come up with any review showing the diagnostic tests used for functional assessment of the foot and leg.

A literature review was conducted of electronic databases (MEDLINE, PEDro, DOAJ, BioMed Central, PLOS, and Centre for Reviews and Dissemination at the University of York) up to December 8, 2018. The biomechanical tests, which have adequate supportive literature, were divided into qualitative tests that provide a dichotomy/trichotomy-type answer to clinical diagnostic questions; semiquantitative tests that provide numerical data to clinical diagnostic questions; and quantitative tests that record continuous numerical data (in analogue or digital form).

These tests produce a useful functional evaluation model of the foot and leg for different purposes evaluation of lower limb deficits or abnormalities in healthy patients and in athletes (in sports or other physical activities); assessment of tissue stress syndromes caused by pathomechanics; evaluation of lower limb deficits or abnormalities in rheumatic disease and diabetic foot patients; and to determine the appropriate functional or semifunctional foot orthotic therapy and therapeutic path used in gait rehabilitation.
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