Pelomyxa palustris is a giant anaerobic/microaerobic amoeba, characterized by a number of exceptional cytological and physiological features, among them the presumed absence of energy producing organelles and the presence of endosymbiotic bacteria. These endosymbionts have been previously distinguished as: a large rectangular-shaped Gram-variable rod with a central cleft; a slender Gram-negative rod; and a slender Gram-positive rod. Using DNA extracted from P. palustris cysts, we have obtained three SSU rRNA gene sequences. We have determined that these sequences are affiliated to three different prokaryotic genera: Methanosaeta (a methanogenic archaea), Syntrophorhabdus (a syntrophic Gram-negative bacteria) and Rhodococcus (an aerobic chemoorganotrophic Gram-positive bacteria). To our knowledge, it is the first time that Syntrophorhabdus has been described as an endosymbiont in association with a methanogen. Strikingly, no traces of Methanobacterium formicicum could be detected, despite this methanogen had allegedly been isolated from trophozoites of P. palustris. It seems that the host and the endosymbionts have established a multipartite syntrophic consortium resembling to some extent those found in sewage treatment plants.

• MeSH
• Archamoebae mikrobiologie   fyziologie   MeSH
• archeální RNA genetika   MeSH
• bakteriální RNA genetika   MeSH
• Deltaproteobacteria klasifikace   genetika   izolace a purifikace   fyziologie   MeSH
• fylogeneze MeSH
• Methanosarcinales klasifikace   genetika   izolace a purifikace   fyziologie   MeSH
• Rhodococcus klasifikace   genetika   izolace a purifikace   fyziologie   MeSH
• RNA ribozomální 16S genetika   MeSH
• sekvenční analýza RNA MeSH
• symbióza * MeSH
• Publikační typ
• časopisecké články MeSH

The frailty syndrome is a common clinical marker of vulnerability in older adults conducive to an overall decline in inflammatory stress responsiveness; yet little is known about the genetic risk factors for frailty in elderly. Our aim was to investigate the association between the rs2476601 polymorphism in PTPN22 gene and susceptibility to frailty in Mexican older adults. Data included 630 subjects 70 and older from The Coyoacán cohort, classified as frail, pre-frail, and non-frail following Fried's criteria. Sociodemographic and clinical characteristics were compared between groups at baseline and after a multivariate analysis. The rs2476601 polymorphism was genotyped by TaqMan genotyping assay using real-time PCR and genotype frequencies were determined for each frailty phenotype in all participants and subsets by age range. Genetic association was examined using stratified and interaction analyses adjusting for age, sex and variables selected in the multivariate analysis. Disability for day-life activities, depression and cognitive impairment were associated with the risk of pre-frailty and frailty at baseline and after adjustment. Carrying the T allele increased significantly the risk of frailty in patients 76 and older (OR 5.64, 95% CI 4.112-7.165) and decreased the risk of pre-frailty under no clinical signs of depression (OR 0.53; 95% CI 0.17-1.71). The PTPN22 polymorphism, rs2476601, could be a genetic risk factor for frailty as subject to quality of life. This is the first study analyzing such relationship in Mexican older adults. Confirming these findings requires additional association studies on wider age ranges in populations of older adults with frailty syndrome.

• MeSH
• alely MeSH
• fenotyp MeSH
• genetická predispozice k nemoci * MeSH
• genetické asociační studie * MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kohortové studie MeSH
• křehkost genetika   patofyziologie   MeSH
• křehký senior MeSH
• kvalita života MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tyrosinfosfatasa nereceptorového typu 22 genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Mexiko MeSH

• MeSH
• aplikace lokální MeSH
• dospělí MeSH
• lidé MeSH
• plicní hypertenze farmakoterapie   MeSH
• srdeční katetrizace MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

BACKGROUND: Historically, studies of adherence to airway clearance therapy in cystic fibrosis (CF) have relied on self-reporting. We compared self-reported airway clearance therapy adherence to actual usage data from home high-frequency chest wall compressions (HFCWC) vests and identified factors associated with overestimation of adherence in self-reports. METHODS: Pediatric patients who perform airway clearance therapy with a HFCWC vest were eligible to participate. Objective adherence data were obtained from the HFCWC device, which records cumulative utilization time. Two readings at least 5 weeks apart were collected. Objective adherence was recorded as a ratio of mean-to-prescribed daily use (%). Self-reported adherence data were collected with a caregiver survey at enrollment. Adherence rates were categorized as low (< 35% of prescribed), moderate (36-79% of prescribed), and high (≥ 80% of prescribed). An overestimation was present when self-reported adherence was at least one category higher than objective adherence. RESULTS: In the final sample (N = 110), mean adherence by usage data was 61%. Only 35% of subjects (n = 38) were highly adherent, and 28% (n = 31) were low adherent. In contrast, 65% of subjects (n = 72) reported high adherence and only 8% (n = 9) reported low adherence (P < .001). Nearly half of self-reports (46%) overestimated adherence. In a multiple regression analysis, overestimation was associated with multiple airway clearance therapy locations (odds ratio 7.13, 95% CI 1.16-43.72, P = .034) and prescribed daily use ≥ 60 min (odds ratio 3.85, 95% CI 1.08-13.76, P < .038). Among subjects with prescribed daily airway clearance therapy ≥ 60 min, the odds of overestimating adherence increased 3-fold (odds ratio 3.04, 95% CI 1.17-7.87, P = .02) in a lower-income (< $50,000/y) environment. CONCLUSIONS: Self-reports overestimated actual adherence to airway clearance therapy, and the overestimation increased with treatment occurring in multiple households and prescribed therapy duration. Among participants with prescribed airway clearance therapy ≥ 60 min, overestimation increased with lower income. Objective measures of adherence are needed, particularly for lower-income children and those receiving treatments in multiple locations.

• MeSH
• adherence pacienta psychologie   statistika a číselné údaje   MeSH
• časové faktory MeSH
• cystická fibróza psychologie   terapie   MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• odds ratio MeSH
• oscilace hrudní stěny přístrojové vybavení   statistika a číselné údaje   MeSH
• zajištění dýchacích cest přístrojové vybavení   psychologie   statistika a číselné údaje   MeSH
• zpráva o sobě statistika a číselné údaje   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

OBJECTIVE: The initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days). METHODS: This is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality. RESULTS: In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p<0.0001). This reduction was significantly associated with age, being higher in older adults (>75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (p<0.001). Furthermore, the pandemic was associated with a significant increase in door-to-balloon time (40 (25-70) min vs 40 (25-64) min, p=0.01) and total ischaemia time (225 (135-410) min vs 196 (120-355) min, p<0.001), which may have contributed to the higher in-hospital (6.5% vs 5.3%, p<0.001) and 30-day (8% vs 6.5%, p=0.001) mortality observed during the pandemic. CONCLUSION: Percutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatment, which may have contributed to the increased in-hospital and 30-day mortality during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

• MeSH
• čas zasáhnout při rozvinutí nemoci trendy   MeSH
• časové faktory MeSH
• COVID-19 * MeSH
• hodnocení rizik MeSH
• incidence MeSH
• infarkt myokardu s elevacemi ST úseků diagnóza   mortalita   terapie   MeSH
• kardiologové trendy   MeSH
• koronární angioplastika škodlivé účinky   mortalita   trendy   MeSH
• lékařská praxe - způsoby provádění trendy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita v nemocnicích trendy   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. METHODS: Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn's Multiple Comparison and T tests. Kaplan-Meier and log-rank tests were used to determine overall survival. RESULTS: Gal-7 was constantly downregulated in our meta-analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. CONCLUSIONS: Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks, such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.

• MeSH
• galektiny metabolismus   MeSH
• lidé MeSH
• nádorové mikroprostředí fyziologie   MeSH
• nádory děložního čípku metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH

Estimating structural connectivity from diffusion-weighted magnetic resonance imaging is a challenging task, partly due to the presence of false-positive connections and the misestimation of connection weights. Building on previous efforts, the MICCAI-CDMRI Diffusion-Simulated Connectivity (DiSCo) challenge was carried out to evaluate state-of-the-art connectivity methods using novel large-scale numerical phantoms. The diffusion signal for the phantoms was obtained from Monte Carlo simulations. The results of the challenge suggest that methods selected by the 14 teams participating in the challenge can provide high correlations between estimated and ground-truth connectivity weights, in complex numerical environments. Additionally, the methods used by the participating teams were able to accurately identify the binary connectivity of the numerical dataset. However, specific false positive and false negative connections were consistently estimated across all methods. Although the challenge dataset doesn't capture the complexity of a real brain, it provided unique data with known macrostructure and microstructure ground-truth properties to facilitate the development of connectivity estimation methods.

• MeSH
• difuzní magnetická rezonance * metody   MeSH
• fantomy radiodiagnostické MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• mozek diagnostické zobrazování   MeSH
• počítačové zpracování obrazu * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Plants and fungi use light and other signals to regulate development, growth, and metabolism. The fruiting bodies of the fungus Phycomyces blakesleeanus are single cells that react to environmental cues, including light, but the mechanisms are largely unknown [1]. The related fungus Mucor circinelloides is an opportunistic human pathogen that changes its mode of growth upon receipt of signals from the environment to facilitate pathogenesis [2]. Understanding how these organisms respond to environmental cues should provide insights into the mechanisms of sensory perception and signal transduction by a single eukaryotic cell, and their role in pathogenesis. We sequenced the genomes of P. blakesleeanus and M. circinelloides and show that they have been shaped by an extensive genome duplication or, most likely, a whole-genome duplication (WGD), which is rarely observed in fungi [3-6]. We show that the genome duplication has expanded gene families, including those involved in signal transduction, and that duplicated genes have specialized, as evidenced by differences in their regulation by light. The transcriptional response to light varies with the developmental stage and is still observed in a photoreceptor mutant of P. blakesleeanus. A phototropic mutant of P. blakesleeanus with a heterozygous mutation in the photoreceptor gene madA demonstrates that photosensor dosage is important for the magnitude of signal transduction. We conclude that the genome duplication provided the means to improve signal transduction for enhanced perception of environmental signals. Our results will help to understand the role of genome dynamics in the evolution of sensory perception in eukaryotes.

• MeSH
• duplikace genu * MeSH
• genetická transkripce účinky záření   MeSH
• genom fungální * MeSH
• molekulární evoluce * MeSH
• Mucor genetika   účinky záření   MeSH
• multigenová rodina MeSH
• percepce MeSH
• Phycomyces genetika   účinky záření   MeSH
• signální transdukce genetika   MeSH
• světlo MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19. METHODS: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality. RESULTS: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients. CONCLUSIONS: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic. TRIAL REGISTRATION NUMBER: NCT04412655.

• MeSH
• čas zasáhnout při rozvinutí nemoci trendy   MeSH
• časové faktory MeSH
• COVID-19 diagnóza   epidemiologie   mortalita   MeSH
• diabetes mellitus diagnóza   epidemiologie   mortalita   MeSH
• hypertenze epidemiologie   MeSH
• infarkt myokardu s elevacemi ST úseků mortalita   terapie   MeSH
• koronární angioplastika škodlivé účinky   mortalita   trendy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita v nemocnicích trendy   MeSH
• registrace MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Concerns have been raised on a potential interaction between renin-angiotensin system inhibitors (RASI) and the susceptibility to coronavirus disease 2019 (COVID-19). No data have been so far reported on the prognostic impact of RASI in patients suffering from ST-elevation myocardial infarction (STEMI) during COVID-19 pandemic, which was the aim of the present study. METHODS: STEMI patients treated with primary percutaneous coronary intervention (PPCI) and enrolled in the ISACS-STEMI COVID-19 registry were included in the present sub-analysis and divided according to RASI therapy at admission. RESULTS: Our population is represented by 6095 patients, of whom 3654 admitted in 2019 and 2441 in 2020. No difference in the prevalence of SARSCoV2 infection was observed according to RASI therapy at admission (2.5% vs 2.1%, p = 0.5), which was associated with a significantly lower mortality (adjusted OR [95% CI]=0.68 [0.51-0.90], P = 0.006), confirmed in the analysis restricted to 2020 (adjusted OR [95% CI]=0.5[0.33-0.74], P = 0.001). Among the 5388 patients in whom data on in-hospital medication were available, in-hospital RASI therapy was associated with a significantly lower mortality (2.1% vs 16.7%, OR [95% CI]=0.11 [0.084-0.14], p < 0.0001), confirmed after adjustment in both periods. Among the 62 SARSCoV-2 positive patients, RASI therapy, both at admission or in-hospital, showed no prognostic effect. CONCLUSIONS: This is the first study to investigate the impact of RASI therapy on the prognosis and SARSCoV2 infection of STEMI patients undergoing PPCI during the COVID-19 pandemic. Both pre-admission and in-hospital RASI were associated with lower mortality. Among SARSCoV2-positive patients, both chronic and in-hospital RASI therapy showed no impact on survival.

• MeSH
• antihypertenziva terapeutické užití   MeSH
• COVID-19 mortalita   terapie   MeSH
• farmakoterapie COVID-19 MeSH
• hospitalizace MeSH
• infarkt myokardu s elevacemi ST úseků mortalita   terapie   MeSH
• koronární angioplastika MeSH
• lidé středního věku MeSH
• lidé MeSH
• pandemie MeSH
• prognóza MeSH
• registrace MeSH
• renin-angiotensin systém MeSH
• reperfuze myokardu * MeSH
• SARS-CoV-2 * MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH