PURPOSE: This study provides an insight on the extent of muscular variability at the suprascapular notch and elaborates on its anatomical interference in suprascapular nerve arthroscopic decompression procedures. METHODS: The suprascapular notch was dissected and its muscular topography was observed in 115 cadaveric specimens. High resolution imaging of the suprascapular notch was captured by a handheld digital microscope (Q-scope). The supraspinatus and subscapularis muscles were traced as they course at the suprascapular notch vicinity. The omohyoid muscle attachment onto the suprascapular ligament was measured. A scoping review and meta-analysis were done to investigate the observed rare muscular variants. RESULTS: In 3.48%, the suprascapular notch anterior surface was fully covered by the subscapularis muscle. The omohyoid muscle inserted onto the suprascapular ligament in 31.25% and extended up to 3/4th of the suprascapular ligament length in 2.61%. Two rare variant muscles were encountered: subclavius posticus muscle and a newly reported "coracoscapularis muscle". CONCLUSIONS: Four categories of muscles with topographical relationship to the suprascapular notch and its arthroscopic feasibility have been classified: (1) constant muscles not intervening with the suprascapular notch space - supraspinatus muscle; (2) constant muscles with variable positions that can intervene with the suprascapular notch space - subscapularis muscle; (3) constant muscles with variable positions that can intervene with the surgical approach - omohyoid muscle; (4) variable muscles intervening with the suprascapular notch space and surgical approach - subclavius posticus and coracoscapularis muscles. This study elucidates the necessity to assess/secure the omohyoid muscle attachment onto the suprascapular ligament in suprascapular nerve decompression ligamentectomy. LEVEL OF EVIDENCE: V Basic Science Research.

• MeSH
• Anatomic Variation * MeSH
• Arthroscopy * methods   MeSH
• Decompression, Surgical methods   MeSH
• Muscle, Skeletal * innervation   anatomy & histology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Scapula innervation   anatomy & histology   MeSH
• Cadaver * MeSH
• Shoulder Joint innervation   surgery   anatomy & histology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Feasibility Studies MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Bacteria have evolved structured RNAs that can associate with RNA polymerase (RNAP). Two of them have been known so far-6S RNA and Ms1 RNA but it is unclear if any other types of RNAs binding to RNAP exist in bacteria. To identify all RNAs interacting with RNAP and the primary σ factors, we have established and performed native RIP-seq in Bacillus subtilis, Corynebacterium glutamicum, Streptomyces coelicolor, Mycobacterium smegmatis and the pathogenic Mycobacterium tuberculosis. Besides known 6S RNAs in B. subtilis and Ms1 in M. smegmatis, we detected MTS2823, a homologue of Ms1, on RNAP in M. tuberculosis. In C. glutamicum, we discovered novel types of structured RNAs that associate with RNAP. Furthermore, we identified other species-specific RNAs including full-length mRNAs, revealing a previously unknown landscape of RNAs interacting with the bacterial transcription machinery.

• MeSH
• Bacillus subtilis genetics   metabolism   MeSH
• Bacterial Proteins * metabolism   genetics   MeSH
• RNA, Bacterial * metabolism   genetics   MeSH
• Corynebacterium glutamicum genetics   metabolism   MeSH
• DNA-Directed RNA Polymerases * metabolism   genetics   MeSH
• Transcription, Genetic MeSH
• Nucleic Acid Conformation MeSH
• Mycobacterium smegmatis genetics   metabolism   enzymology   MeSH
• Mycobacterium tuberculosis genetics   metabolism   MeSH
• RNA, Untranslated MeSH
• Gene Expression Regulation, Bacterial MeSH
• Sigma Factor * metabolism   genetics   MeSH
• Streptomyces coelicolor genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Reconstruction of right ventricular outflow tract in patients with congenital heart disease in various age groups remains a controversial issue. Currently, a little is known about the fate of secondary and subsequent conduit. The aim of the study was to determine risk factors of conduit failure, evaluate long-term conduit survival, find out which type of conduit should be preferred in case of reoperations. We performed a retrospective analysis of a total of 249 records of valved conduit secondary and subsequent replacement in right ventricular outflow tract in 197 patients. Median follow-up was 5.7 years. The study endpoints were defined as conduit explants; balloon dilatation of the graft (excluding balloon dilatation of left/right pulmonary artery), transcatheter pulmonary valve implantation; heart transplantation or death of the patient. There were total of 21 deaths (11% mortality) among 197 patients during the follow-up, 2 patients underwent heart transplant, in 23 implanted conduits pulmonary angioplasty or/including transcatheter pulmonary valve implantation was afterwards performed due to graft failure, conduit had to be explanted in 46 cases. After 28 years follow-up, freedom from graft failure after 5 years was 77%, 48% after 10 years and 21% after 15 years. Reoperative right ventricular outflow tract reconstruction demonstrates good mid-term and acceptable long-term outcomes regardless of the type of conduit implanted. Worse long-term graft survival of secondary and further conduits is associated with younger age of the recipient at implantation, small size of the conduit, younger age of donor and male donor in case of allograft implantation.

• MeSH
• Infant MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Reoperation MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Heart Ventricles surgery   MeSH
• Heart Defects, Congenital * surgery   MeSH
• Treatment Outcome MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

• MeSH
• Cystic Fibrosis * MeSH
• Precision Medicine MeSH
• Colforsin pharmacology   MeSH
• Humans MeSH
• Mutation MeSH
• Cystic Fibrosis Transmembrane Conductance Regulator genetics   MeSH
• Intestinal Mucosa MeSH
• Check Tag
• Humans MeSH
• Publication type
• Letter MeSH

Úvod: Studie se zabývala vztahem mezi subjektivní klasifikací New York Heart Association (NYHA) a objektivní zátěžovou kapacitou (měřenou pomocí vrcholového příjmu kyslíku [VO2peak]) u pacientů se srdečním selháním a dále tím, zda je tento vztah ovlivněn adherencí k medikaci. Metody: Byly analyzovány údaje 170 pacientů se srdečním selháním z registru Level-CHF. Adherence byla hodnocena pomocí testování koncentrace léků v séru. Objektivní zátěžová kapacita byla hodnocena pomocí spiroergometrie na bicyklovém ergometru. Výsledky: Hodnota objektivní maximální spotřeby kyslíku často převyšovala odpovídající subjektivní třídu NYHA se 46% shodou, rozdíly se projevovaly zejména na krajních koncích spektra. Byly zaznamenány drobné odchylky v subjektivním hodnocení třídy NYHA v souvislosti s adherencí k medikaci, ale nebyly pozorovány žádné podstatné rozdíly. Závěr: Výsledek upozorňuje na rozdíly mezi subjektivním a objektivním hodnocením funkční kapacity u pacientů se srdečním selháním. To by mělo vést k většímu využívání objektivních měření při klinickém rozhodování na základě funkční kapacity a k využívání přímo měřených hodnot VO2peak nad subjektivní třídou NYHA. Dodržování medikace významně nezměnilo subjektivně-objektivní trendy NYHA

Introduction: This study investigated the relationship between the subjective New York Heart Association (NYHA) class and objective exercise capacity (VO2peak) in patients with heart failure and whether it is influenced by medication adherence. Methods: Data from 170 heart failure patients in the Level-CHF register were analysed, and adherence was assessed by serum drug level testing. Objective exercise capacity was assessed by cardiopulmonary exercise testing using a bicycle ergometer. Results: Objective VO2peak frequently exceeded the subjective NYHA class with 46% concordance, especially at the extreme ends of the spectrum. Minor differences in subjective NYHA class in relation to medication adherence were noted, but no substantial disparity was observed. Conclusion: These findings highlight the discrepancies between subjective and objective assessments of functional capacity in patients with heart failure. This calls for a greater use of objective measurements in clinical decision-making based on functional capacity and for preference of direct VO2peak values over subjective NYHA categories. Medication adherence did not significantly alter the subjective-objective NYHA trends.

• Keywords
• NYHA,
• MeSH
• Medication Adherence MeSH
• Humans MeSH
• Oxygen Consumption drug effects   MeSH
• Heart Failure * physiopathology   prevention & control   MeSH
• Exercise Test methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Clinical Study MeSH
• Research Support, Non-U.S. Gov't MeSH

Superior efficacy of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) over tezacaftor/ivacaftor (TEZ/IVA) in people with cystic fibrosis (CF) and Phe508del/Phe508del genotype was shown in clinical trials. We utilized intestinal organoid approach to compare in vitro responses to these 2 CFTR modulator drug combinations and to check potential inter-individual variability in therapeutic response to the triple combination. Organoids from 17 subjects with Phe508del/Phe508del were screened with forskolin induced swelling assay. Significantly larger swelling, when exposed to ELX/TEZ/IVA as compared to TEZ/IVA, was observed in 16 of them. However, 1 sample showed no additional effect of ELX. The finding of unique CFTR variants in this sample indicates that genetic traits other than CF-causing CFTR mutation are worth exploring as they may have an impact on the definitive modulator drug response.

• MeSH
• Chloride Channel Agonists pharmacology   therapeutic use   MeSH
• Aminophenols pharmacology   therapeutic use   MeSH
• Benzodioxoles pharmacology   therapeutic use   MeSH
• Quinolones MeSH
• Cystic Fibrosis * drug therapy   genetics   MeSH
• Drug Combinations MeSH
• Indoles MeSH
• Humans MeSH
• Mutation MeSH
• Organoids * MeSH
• Cystic Fibrosis Transmembrane Conductance Regulator genetics   MeSH
• Pyrazoles MeSH
• Pyridines MeSH
• Pyrrolidines MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVE: To externally validate various prognostic models and scoring rules for predicting short term mortality in patients admitted to hospital for covid-19. DESIGN: Two stage individual participant data meta-analysis. SETTING: Secondary and tertiary care. PARTICIPANTS: 46 914 patients across 18 countries, admitted to a hospital with polymerase chain reaction confirmed covid-19 from November 2019 to April 2021. DATA SOURCES: Multiple (clustered) cohorts in Brazil, Belgium, China, Czech Republic, Egypt, France, Iran, Israel, Italy, Mexico, Netherlands, Portugal, Russia, Saudi Arabia, Spain, Sweden, United Kingdom, and United States previously identified by a living systematic review of covid-19 prediction models published in The BMJ, and through PROSPERO, reference checking, and expert knowledge. MODEL SELECTION AND ELIGIBILITY CRITERIA: Prognostic models identified by the living systematic review and through contacting experts. A priori models were excluded that had a high risk of bias in the participant domain of PROBAST (prediction model study risk of bias assessment tool) or for which the applicability was deemed poor. METHODS: Eight prognostic models with diverse predictors were identified and validated. A two stage individual participant data meta-analysis was performed of the estimated model concordance (C) statistic, calibration slope, calibration-in-the-large, and observed to expected ratio (O:E) across the included clusters. MAIN OUTCOME MEASURES: 30 day mortality or in-hospital mortality. RESULTS: Datasets included 27 clusters from 18 different countries and contained data on 46 914patients. The pooled estimates ranged from 0.67 to 0.80 (C statistic), 0.22 to 1.22 (calibration slope), and 0.18 to 2.59 (O:E ratio) and were prone to substantial between study heterogeneity. The 4C Mortality Score by Knight et al (pooled C statistic 0.80, 95% confidence interval 0.75 to 0.84, 95% prediction interval 0.72 to 0.86) and clinical model by Wang et al (0.77, 0.73 to 0.80, 0.63 to 0.87) had the highest discriminative ability. On average, 29% fewer deaths were observed than predicted by the 4C Mortality Score (pooled O:E 0.71, 95% confidence interval 0.45 to 1.11, 95% prediction interval 0.21 to 2.39), 35% fewer than predicted by the Wang clinical model (0.65, 0.52 to 0.82, 0.23 to 1.89), and 4% fewer than predicted by Xie et al's model (0.96, 0.59 to 1.55, 0.21 to 4.28). CONCLUSION: The prognostic value of the included models varied greatly between the data sources. Although the Knight 4C Mortality Score and Wang clinical model appeared most promising, recalibration (intercept and slope updates) is needed before implementation in routine care.

• MeSH
• Data Analysis MeSH
• COVID-19 * MeSH
• Humans MeSH
• Hospital Mortality MeSH
• Prognosis MeSH
• Models, Statistical * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH

Acetylcholine is an important modulator of striatal activity, and it is vital to controlling striatal-dependent behaviors, including motor and cognitive functions. Despite this significance, the mechanisms determining how acetylcholine impacts striatal signaling are still not fully understood. In particular, little is known about the role of nAChRs expressed by striatal interneurons. In the present study, we used FISH to determine which neuronal types express the most prevalent beta2 nicotinic subunit in the mouse striatum. Our data support a common view that nAChR expression is mostly restricted to striatal interneurons. Surprisingly though, cholinergic interneurons were identified as a population with the highest expression of beta2 nicotinic subunit. To investigate the functional significance of beta2-containing nAChRs in striatal interneurons, we deleted them by injecting the AAV-Cre vector into the striatum of beta2-flox/flox male mice. The deletion led to alterations in several behavioral domains, namely, to an increased anxiety-like behavior, decrease in sociability ratio, deficit in discrimination learning, and increased amphetamine-induced hyperlocomotion and c-Fos expression in mice with beta2 deletion. Further colocalization analysis showed that the increased c-Fos expression was present in both medium spiny neurons and presumed striatal interneurons. The present study concludes that, despite being relatively rare, beta2-containing nAChRs are primarily expressed in striatal neurons by cholinergic interneurons and play a significant role in behavior.SIGNIFICANCE STATEMENT A large variety of nAChRs are expressed in the striatum, a brain region that is crucial in the control of behavior. The complexity of receptors with different functions is hindering our understanding of mechanisms through which striatal acetylcholine modulates behavior. We focused on the role of a small population of beta2-containing nAChRs. We identified neuronal types expressing these receptors and determined their impact in the control of explorative behavior, anxiety-like behavior, learning, and sensitivity to stimulants. Additional experiments showed that these alterations were associated with an overall increased activity of striatal neurons. Thus, the small population of nicotinic receptors represents an interesting target for a modulation of response to stimulant drugs and other striatal-based behavior.

• MeSH
• Acetylcholine metabolism   MeSH
• Cholinergic Agents pharmacology   MeSH
• Corpus Striatum metabolism   MeSH
• Interneurons metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Receptors, Nicotinic * metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Inflammatory bowel diseases (IBD) are chronic disorders of the gastrointestinal tract that have been linked to microbiome dysbiosis and immune system dysregulation. We investigated the longitudinal effect of anti-TNF therapy on gut microbiota composition and specific immune response to commensals in IBD patients. The study included 52 patients tracked over 38 weeks of therapy and 37 healthy controls (HC). To characterize the diversity and composition of the gut microbiota, we used amplicon sequencing of the V3V4 region of 16S rRNA for the bacterial community and of the ITS1 region for the fungal community. We measured total antibody levels as well as specific antibodies against assorted gut commensals by ELISA. We found diversity differences between HC, Crohn's disease, and ulcerative colitis patients. The bacterial community of patients with IBD was more similar to HC at the study endpoint, suggesting a beneficial shift in the microbiome in response to treatment. We identified factors such as disease severity, localization, and surgical intervention that significantly contribute to the observed changes in the gut bacteriome. Furthermore, we revealed increased IgM levels against specific gut commensals after anti-TNF treatment. In summary, this study, with its longitudinal design, brings insights into the course of anti-TNF therapy in patients with IBD and correlates the bacterial diversity with disease severity in patients with ulcerative colitis (UC).

• MeSH
• Biodiversity MeSH
• Adult MeSH
• Feces microbiology   MeSH
• Fungi genetics   MeSH
• Inflammatory Bowel Diseases blood   drug therapy   microbiology   surgery   MeSH
• Tumor Necrosis Factor Inhibitors therapeutic use   MeSH
• Interleukin-17 metabolism   MeSH
• Leukocytes, Mononuclear metabolism   MeSH
• Humans MeSH
• Metagenomics MeSH
• Antibodies blood   MeSH
• RNA, Ribosomal, 16S genetics   MeSH
• Gastrointestinal Microbiome * genetics   MeSH
• Case-Control Studies MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

We collected a multi-centric retrospective dataset of patients (N = 213) who were admitted to ten hospitals in Czech Republic and tested positive for SARS-CoV-2 during the early phases of the pandemic in March-October 2020. The dataset contains baseline patient characteristics, breathing support required, pharmacological treatment received and multiple markers on daily resolution. Patients in the dataset were treated with hydroxychloroquine (N = 108), azithromycin (N = 72), favipiravir (N = 9), convalescent plasma (N = 7), dexamethasone (N = 4) and remdesivir (N = 3), often in combination. To explore association between treatments and patient outcomes we performed multiverse analysis, observing how the conclusions change between defensible choices of statistical model, predictors included in the model and other analytical degrees of freedom. Weak evidence to constrain the potential efficacy of azithromycin and favipiravir can be extracted from the data. Additionally, we performed external validation of several proposed prognostic models for Covid-19 severity showing that they mostly perform unsatisfactorily on our dataset.

• MeSH
• COVID-19 epidemiology   pathology   therapy   MeSH
• Adult MeSH
• COVID-19 Drug Treatment MeSH
• Hospitalization * MeSH
• Middle Aged MeSH
• Humans MeSH
• Disease Progression * MeSH
• Aged MeSH
• Models, Statistical MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH