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Mitral valve (MV) surgery has traditionally been performed by conventional sternotomy (CS), but more recently minimally invasive surgery (MIS) has become another treatment option. The aim of this study is to compare short- and long-term results of MV surgery after CS and MIS.

This study was a retrospective propensity-matched analysis of MV operations between January 2005 and December 2015.

Among 1357 patients, 496 underwent CS and 861 MIS. Matching resulted in 422 patients per group. The procedure time was longer with MIS than CS (192 vs. 185min; p = 0.002) as was cardiopulmonary bypass time (133 vs. 101min; p < 0.001) and X-clamp time (80 vs. 71min; p < 0.001). 'Short-term' successful valve repair was higher with MIS (96.0% vs. 76.0%, p < 0.001). Length of hospital stay was shorter in MIS than CS patients (10 vs. 11days; p = 0.001). There was no difference in the overall 30-day mortality rate. Cardiovascular death was lower after MIS (1.2%) compared with CS (3.8%; OR 0.30; 95%CI 0.11-0.84). The difference did not remain significant after adjustment for procedural differences (aOR 0.40; 95%CI 0.13-1.25). Pacemaker was required less often after MIS (3.3%) than CS (11.2%; aOR 0.31; 95%CI 0.16-0.61), and acute renal failure was less common (2.1% vs. 11.9%; aOR 0.22; 95%CI 0.10-0.48). There were no significant differences with respect to rates of stroke, myocardial infarction or repeat MV surgery. The 7-year survival rate was significantly better after MIS (88.5%) than CS (74.8%; aHR 0.44, 95%CI 0.31-0.64).

This study demonstrates that good results for MV surgery can be obtained with MIS, achieving a high MV repair rate, low peri-procedural morbidity and mortality, and improved long-term survival.

This study demonstrates that good results for MV surgery can be obtained with MIS, achieving a high MV repair rate, low peri-procedural morbidity and mortality, and improved long-term survival.

The sequence content of the 3' UTRs of many mRNA transcripts is regulated through alternative polyadenylation (APA). The study of this process using RNAseq data, though, has been historically challenging.

To combat this problem, we developed LABRAT, an APA isoform quantification method. LABRAT takes advantage of newly developed transcriptome quantification techniques to accurately determine relative APA site usage and how it varies across conditions. Using LABRAT, we found consistent relationships between gene-distal APA and subcellular RNA localization in multiple cell types. We also observed connections between transcription speed and APA site choice as well as tumor-specific transcriptome-wide shifts in APA isoform abundance in hundreds of patient-derived tumor samples that were associated with patient prognosis. We investigated the effects of APA on transcript expression and found a weak overall relationship, although many individual genes showed strong correlations between relative APA isoform abundance and overall gene expression. We interrogated the roles of 191 RNA-binding proteins in the regulation of APA isoforms, finding that dozens promote broad, directional shifts in relative APA isoform abundance both in vitro and in patient-derived samples. Finally, we find that APA site shifts in the two classes of APA, tandem UTRs and alternative last exons, are strongly correlated across many contexts, suggesting that they are coregulated.

We conclude that LABRAT has the ability to accurately quantify APA isoform ratios from RNAseq data across a variety of sample types. Further, LABRAT is able to derive biologically meaningful insights that connect APA isoform regulation to cellular and molecular phenotypes.

We conclude that LABRAT has the ability to accurately quantify APA isoform ratios from RNAseq data across a variety of sample types. Further, LABRAT is able to derive biologically meaningful insights that connect APA isoform regulation to cellular and molecular phenotypes.

The unexpected outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 49 million cases and an estimated 2,000,000 associated deaths worldwide. In Germany, there are currently more than 2,000,000 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases including 51,800 deaths. However, regional differences also became apparent and with the second wave of infections, the detailed characterization of COVID-19 patients is crucial to early diagnosis and disruption of chains of infections.

Handing out detailed questionnaires to all individuals tested for COVID-19, we evaluated the clinical characteristics of negative and positive tested individuals. Expression of symptoms, symptom duration and association between predictor variables (i.e. age, gender) and a binary outcome (olfactory and gustatory dysfunction) were assessed.

Overall, the most common symptoms among individuals who tested positive for SARS-CoV-2 were fatigue, headache, and cough. Olfactory and gustatory dysfunction were also reported by many SARS-CoV-2 negative individuals, more than 20% of SARS-CoV-2 negative tested individuals in our study reported olfactory and gustatory dysfunction. Independent of SARS-CoV-2 status, more females displayed symptoms of gustatory (29.8%, p = 0.0041) and olfactory dysfunction (22.9%, p = 0.0174) compared to men.

Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.

Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.

Understanding behavioral factors associated with low health literacy (HL) is relevant for health care providers to better support their patients' health and adherence to preventive treatment. In this study, we aim to study associations between low HL and socio-demographic characteristics, medication-related perceptions and experience, as well as general psychological factors among patients aged 50-80 years.

We used across-sectional survey design based on a representative group of 6,871 Danish citizens aged 50-80 years returning a web-based questionnaire with socio-demographic data added from a national registry. Chi-square tests were conducted to analyze associations between low HL and daily use of medication and self-rated health. Chi-square tests and binary logistic regression were conducted for analyzing data from respondents using prescribed medicines daily (N = 4,091).

Respondents with low HL were more often on daily medications (19 % [777/4,091] vs. 16 % [436/2,775]; P < 0.001) and were more likely to have poorer self-rated health (P < 0.001). Among patients on daily medications, low HL was significantly higher among men and those with lower educational attainment and lower family income. selleck kinase inhibitor Low HL was independently and positively associated with perceptions that taking prescribed medicines daily is difficult and time-consuming, with forgetting to take prescribed medicines, and with lower satisfaction with life and poor self-assessed health.

Our study provides information that patients aged 50-80 years with low HL are challenged on their adherence to treatment plans which is not only related to traditional sociodemographic factors but also on perceptions related to taking medication per se.

Our study provides information that patients aged 50-80 years with low HL are challenged on their adherence to treatment plans which is not only related to traditional sociodemographic factors but also on perceptions related to taking medication per se.

Dementia is one of the most critical challenges of our time. According to the Dementia Statistics Hub, only about 66 % of all UK residents with dementia were diagnosed in 2017-2018. Yet, there are reservations about the early diagnosis of dementia-related diseases. As a result, the UK National Screening Committee does not recommend systematic population screening of dementia, although case-finding strategies are still applied for high-risk groups.

This study added additional evidence of the effectiveness of the National Dementia Strategy and increased numbers of diagnosis of dementia on the younger cohorts of the older people, using the intrinsic estimator age-period-cohort (APC) models and the English Longitudinal Study of Ageing data.

Age effects show that diagnosis increases in volume only among those aged 75 and above, suggesting that many of those aged below 75 might not be diagnosed in time. Period effects show that although there was an initial increase due to the new policy implementation, the trend stalled in later years, indicating that the increase might not have been even across the period when controlled for age and cohort. The study also shows that cohort effects indicate lower prevalence in younger cohorts controlled for age and period effects.

Although more research in diverse contexts is warranted, this study cautions against the abandonment of timely diagnosis, increased screening and case-finding, and shows some effectiveness of prevention strategies on the national level.

Although more research in diverse contexts is warranted, this study cautions against the abandonment of timely diagnosis, increased screening and case-finding, and shows some effectiveness of prevention strategies on the national level.

Phenotypic and functional heterogeneity of macrophages is known to be the main reason for their ability to regulate inflammation and promote tumorigenesis. Mesenchymal stem cells (MSCs) are one of the principal cells commonly found in the tumor stromal niche, with capability of macrophage phenotypic switching. The objective of this study was to evaluate the role of C-X-C motif chemokine ligand 12 (CXCL12) produced by marrow-derived MSCs in the phenotypic and functional pattern of bone marrow-derived macrophages (BMDMs).

First, the CRISPR/Cas9 system was used for the CXCL12 gene knock-out in MSCs. Then, coculture systems were used to investigate the role of MSCs

and MSCs

in determination of macrophage phenotype. To further analyze the role of the MSC-derived CXCL12 niche, cocultures of 4T1 mammary tumor cells and macrophages primed with MSCs

or MSCs

as well as in-vivo limiting dilution assays were performed.

Our results revealed that the expression of IL-4, IL-10, TGF-β and CD206 as M2 markers was significantly increased in macrophages co-cultured with MSCs

, whereas the expression of IL-6, TNF-α and iNOS was conversely decreased. The number and size of multicellular tumor spheroids were remarkably higher when 4T1 cells were cocultured with MSC

-induced M2 macrophages. We also found that the occurrence of tumors was significantly higher in coinjection of 4T1 cells with MSC

-primed macrophages. Tumor initiating cells were significantly decreased after coinjection of 4T1 cells with macrophages pretreated with MSCs

.

In conclusion, our findings shed new light on the role of MSC-derived CXCL12 in macrophage phenotypic switching to M2, affecting their function in tumorigenesis.

In conclusion, our findings shed new light on the role of MSC-derived CXCL12 in macrophage phenotypic switching to M2, affecting their function in tumorigenesis.

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