T cell activation regulates CD6 alternative splicing by transcription dynamics and SRSF1

The T cell-surface glycoprotein CD6 is a modulator of cellular responses and has been implicated in several autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and psoriasis. During Ag presentation, CD6 is targeted to the immunological synapse in a ligand binding-dependent manner, in which CD6 domain 3 directly contacts CD166, expressed on the APC. T cell activation results in the induction of CD6?d3, an alternatively spliced isoform that lacks the ligand-binding domain and thus no longer localizes at the immunological synapse. In this study, we investigated the molecular mechanisms regulating the expression of CD6?d3 upon human primary T cell activation. Using chromatin immunoprecipitation, we observed an increase in RNA polymerase II occupancy along the CD6 gene and augmented CD6 transcription. We showed that activation leads to transcription-related chromatin modifications, revealed by higher CD6 acetylation levels. Modulation of chromatin conformation using a histone deacetylase inhibitor that increases transcription rate causes an increase of exon 5 skipping. We further showed that the splicing factor SRSF1 binds to a regulatory element in CD6 intron 4, activating exon 5 splicing and promoting exon 5 inclusion. Concomitant with T cell activation-induced exon 5 skipping, we observed a downregulation of SRSF1. Using RNA immunoprecipitation, we showed that in activated T cells, SRSF1 recruitment to the CD6 transcript is impaired by increased chromatin acetylation levels. We propose that upon T cell activation, SRSF1 becomes limiting, and its function in CD6 exon 5 splicing is countered by an increase in CD6 transcription, dependent on chromatin acetylation. Copyright © 2014 by The American Association of Immunologists, Inc.This work was supported by the European Regional Development Fund, Programa Operacional Ciencia, Tecnologia e Inovacao 2010 (POCI and POCTI 2010), and the Fundacao para a Ciencia e Tecnologia (PTDC/SAU-GMG/116621/2010, PTDC/BEX-BCM/0468/2012, PTDC/IMI-IMU/0158/2012)

"Detachment of the carinal hook following endobronchial intubation with a double lumen tube"

<p>Abstract</p> <p>Background</p> <p>Carinal hooks increases difficulty at endotracheal intubation. Amputation of the carinal hook during passage and malpositioning of the tube to the hook are some of the potential problems related with left-sided Carlens double lumen tube (DLT). This article reports an amputation of the hook during a difficult selective intubation and aimed at calling the attention to complications associated with DLTs and the importance of fiberoptic bronchoscopy.</p> <p>Case presentation</p> <p>A 68 year-old woman was scheduled for right-sided thoracotomy in whom blind DLT insertion was performed. Narrowed trachea causes difficulty in rotating the DLT 90° counter-clockwise. After carinal hook was noticed upon visual inspection of the DLT, fiberoptic bronchoscopy was used to remove the missing part (with the use of forceps) from the right mainstem bronchus.</p> <p>Conclusion</p> <p>Insertion of DLTs with carinal hook is associated with technical problems and potentially life-threatening hazards have discouraged their use. Fiberoptic evaluation and repositioning solves most of the problems. Although amputation of the carinal hook has not been previously reported, clinicians should be alert. This case report emphasizes the utility of the fiberoptic bronchoscopy in the operating theatre for placement, positioning and inspection of the carinal hook DLT.</p

Actinobacteria and Cyanobacteria Diversity in Terrestrial Antarctic Microenvironments Evaluated by Culture-Dependent and Independent Methods

Bacterial diversity from McMurdo Dry Valleys in Antarctica, the coldest desert on earth, has become more easily assessed with the development of High Throughput Sequencing (HTS) techniques. However, some of the diversity remains inaccessible by the power of sequencing. In this study, we combine cultivation and HTS techniques to survey actinobacteria and cyanobacteria diversity along different soil and endolithic micro-environments of Victoria Valley in McMurdo Dry Valleys. Our results demonstrate that the Dry Valleys actinobacteria and cyanobacteria distribution is driven by environmental forces, in particular the effect of water availability and endolithic environments clearly conditioned the distribution of those communities. Data derived from HTS show that the percentage of cyanobacteria decreases from about 20% in the sample closest to the water source to negligible values on the last three samples of the transect with less water availability. Inversely, actinobacteria relative abundance increases from about 20% in wet soils to over 50% in the driest samples. Over 30% of the total HTS data set was composed of actinobacterial strains, mainly distributed by 5 families: Sporichthyaceae, Euzebyaceae, Patulibacteraceae, Nocardioidaceae, and Rubrobacteraceae. However, the 11 actinobacterial strains isolated in this study, belonged to Micrococcaceae and Dermacoccaceae families that were underrepresented in the HTS data set. A total of 10 cyanobacterial strains from the order Synechococcales were also isolated, distributed by 4 different genera (Nodosilinea, Leptolyngbya, Pectolyngbya, and Acaryochloris-like). In agreement with the cultivation results, Leptolyngbya was identified as dominant genus in the HTS data set. Acaryochloris-like cyanobacteria were found exclusively in the endolithic sample and represented 44% of the total 16S rRNA sequences, although despite our efforts we were not able to properly isolate any strain from this Acaryochloris-related group. The importance of combining cultivation and sequencing techniques is highlighted, as we have shown that culture-dependent methods employed in this study were able to retrieve actinobacteria and cyanobacteria taxa that were not detected in HTS data set, suggesting that the combination of both strategies can be usefull to recover both abundant and rare members of the communities

The effect of polymer/plasticiser ratio in film forming solutions on the properties of chitosan films

In this work physical-chemical properties of chitosan/ glycerol film forming solutions (FFS) and the resulting films were analysed. Solutions were prepared using different concentrations of plasticising agent (glycerol) and chitosan. Films were produced by solvent casting and equilibrated in a controlled atmosphere. FFS water activity and rheological behaviour were determined. Films water content, solubility, water vapour and oxygen permeabilities, thickness, and mechanical and thermal properties were determined. Fourier transform infrared (FTIR) spectroscopy was also used to study the chitosan/glycerol interactions. Results demonstrate that FFS chitosan concentration influenced solutions consistency coefficient and this was related with differences in films water retention and structure. Plasticiser addition led to an increase in films moisture content, solubility and water vapour permeability, water affinity and structural changes. Films thermo-mechanical properties are significantly affected by both chitosan and glycerol addition. FTIR experiments confirm these results. This work highlights the importance of glycerol and water plasticisation in films properties.This work was supported by National Funds from FCT - Fundacao para a Ciencia e a Tecnologia, through project PEst-OE/EQB/LA0016/2011.Authors Joana F. Fundo, Andrea C. Galvis-Sanchez and Mafalda A. C. Quintas acknowledge FCT for research grants SFRH/ BD / 62176 / 2009, SFRH/BPD/37890/2007 and SFRH / BPD / 41715 / 2007, respectively

Serological screening in a large-scale municipal survey in Cascais, Portugal, during the first waves of the COVID-19 pandemic: lessons for future pandemic preparedness efforts

BackgroundSerological surveys for SARS-CoV-2 were used early in the COVID-19 pandemic to assess epidemiological scenarios. In the municipality of Cascais (Portugal), serological testing combined with a comprehensive socio-demographic, clinical and behavioral questionnaire was offered to residents between May 2020 and beginning of 2021. In this study, we analyze the factors associated with adherence to this municipal initiative, as well as the sociodemographic profile and chronic diseases clinical correlates associated to seropositivity. We aim to contribute with relevant information for future pandemic preparedness efforts.MethodsThis was a cross-sectional study with non-probabilistic sampling. Citizens residing in Cascais Municipality went voluntarily to blood collection centers to participate in the serological survey. The proportion of participants, stratified by socio-demographic variables, was compared to the census proportions to identify the groups with lower levels of adherence to the survey. Univariate and multivariate logistic regression were used to identify socio-demographic, clinical and behavioral factors associated with seropositivity.ResultsFrom May 2020 to February 2021, 19,608 participants (9.2% of the residents of Cascais) were included in the study. Based on the comparison to census data, groups with lower adherence to this survey were men, the youngest and the oldest age groups, individuals with lower levels of education and unemployed/inactive. Significant predictors of a reactive (positive) serological test were younger age, being employed or a student, and living in larger households. Individuals with chronic diseases generally showed lower seroprevalence.ConclusionThe groups with low adherence to this voluntary study, as well as the socio-economic contexts identified as more at risk of viral transmission, may be targeted in future pandemic situations. We also found that the individuals with chronic diseases, perceiving higher risk of serious illness, adopted protective behaviors that limited infection rates, revealing that health education on preventive measures was effective for these patients

MAMMALS IN PORTUGAL : A data set of terrestrial, volant, and marine mammal occurrences in P ortugal

Mammals are threatened worldwide, with 26% of all species being includedin the IUCN threatened categories. This overall pattern is primarily associatedwith habitat loss or degradation, and human persecution for terrestrial mam-mals, and pollution, open net fishing, climate change, and prey depletion formarine mammals. Mammals play a key role in maintaining ecosystems func-tionality and resilience, and therefore information on their distribution is cru-cial to delineate and support conservation actions. MAMMALS INPORTUGAL is a publicly available data set compiling unpublishedgeoreferenced occurrence records of 92 terrestrial, volant, and marine mam-mals in mainland Portugal and archipelagos of the Azores and Madeira thatincludes 105,026 data entries between 1873 and 2021 (72% of the data occur-ring in 2000 and 2021). The methods used to collect the data were: live obser-vations/captures (43%), sign surveys (35%), camera trapping (16%),bioacoustics surveys (4%) and radiotracking, and inquiries that represent lessthan 1% of the records. The data set includes 13 types of records: (1) burrowsjsoil moundsjtunnel, (2) capture, (3) colony, (4) dead animaljhairjskullsjjaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8),observation in shelters, (9) photo trappingjvideo, (10) predators dietjpelletsjpine cones/nuts, (11) scatjtrackjditch, (12) telemetry and (13) vocalizationjecholocation. The spatial uncertainty of most records ranges between 0 and100 m (76%). Rodentia (n=31,573) has the highest number of records followedby Chiroptera (n=18,857), Carnivora (n=18,594), Lagomorpha (n=17,496),Cetartiodactyla (n=11,568) and Eulipotyphla (n=7008). The data setincludes records of species classified by the IUCN as threatened(e.g.,Oryctolagus cuniculus[n=12,159],Monachus monachus[n=1,512],andLynx pardinus[n=197]). We believe that this data set may stimulate thepublication of other European countries data sets that would certainly contrib-ute to ecology and conservation-related research, and therefore assisting onthe development of more accurate and tailored conservation managementstrategies for each species. There are no copyright restrictions; please cite thisdata paper when the data are used in publications.info:eu-repo/semantics/publishedVersio

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Mammals in Portugal: a data set of terrestrial, volant, and marine mammal occurrences in Portugal

Mammals are threatened worldwide, with ~26% of all species being included in the IUCN threatened categories. This overall pattern is primarily associated with habitat loss or degradation, and human persecution for terrestrial mammals, and pollution, open net fishing, climate change, and prey depletion for marine mammals. Mammals play a key role in maintaining ecosystems functionality and resilience, and therefore information on their distribution is crucial to delineate and support conservation actions. MAMMALS IN PORTUGAL is a publicly available data set compiling unpublished georeferenced occurrence records of 92 terrestrial, volant, and marine mammals in mainland Portugal and archipelagos of the Azores and Madeira that includes 105,026 data entries between 1873 and 2021 (72% of the data occurring in 2000 and 2021). The methods used to collect the data were: live observations/captures (43%), sign surveys (35%), camera trapping (16%), bioacoustics surveys (4%) and radiotracking, and inquiries that represent less than 1% of the records. The data set includes 13 types of records: (1) burrows | soil mounds | tunnel, (2) capture, (3) colony, (4) dead animal | hair | skulls | jaws, (5) genetic confirmation, (6) inquiries, (7) observation of live animal (8), observation in shelters, (9) photo trapping | video, (10) predators diet | pellets | pine cones/nuts, (11) scat | track | ditch, (12) telemetry and (13) vocalization | echolocation. The spatial uncertainty of most records ranges between 0 and 100 m (76%). Rodentia (n =31,573) has the highest number of records followed by Chiroptera (n = 18,857), Carnivora (n = 18,594), Lagomorpha (n = 17,496), Cetartiodactyla (n = 11,568) and Eulipotyphla (n = 7008). The data set includes records of species classified by the IUCN as threatened (e.g., Oryctolagus cuniculus [n = 12,159], Monachus monachus [n = 1,512], and Lynx pardinus [n = 197]). We believe that this data set may stimulate the publication of other European countries data sets that would certainly contribute to ecology and conservation-related research, and therefore assisting on the development of more accurate and tailored conservation management strategies for each species. There are no copyright restrictions; please cite this data paper when the data are used in publications

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Potentially inappropriate medications with risk of cardiovascular adverse events in the elderly : A systematic review of tools addressing inappropriate prescribing

WHAT IS KNOWN AND OBJECTIVE: In the last decades, many lists have been developed to screen for inappropriate prescribing. However, information on which potentially inappropriate medications (PIMs) could increase the cardiovascular risk in the elderly is not objectively presented. This review aimed to identify and quantify those PIMs by extracting information from published PIM-lists. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), a systematic review of PIM-lists was conducted. The search strategy was run in PubMed, MEDLINE and Google Scholar (1991-09/2017). All PIMs described in those lists were extracted and stratified by their potential cardiovascular risk (including major adverse cardiovascular events-MACE). The number of times each PIM was reported on those lists was also assessed. RESULTS AND DISCUSSION: We identified 724 papers, and 24 were retained. From those, a total of 17 PIMs to be avoided by the elderly and 21 drug-disease interactions were retrieved. The reporting of PIMs with risk of cardiovascular adverse events was 15.3%, whereas the reporting of those with MACE risk was 7.2%. PIMs most frequently described were tricyclic antidepressants (TCAs; 12/24), centrally acting antiadrenergic agents (11/24), NSAIDs (7/24), antiarrhythmics (Class I and III; 6/24), peripherally acting antiadrenergic agents (6/24) and antithrombotic agents (5/24). Most frequently described PIMs with MACE risk were NSAIDs (7/24), antiarrhythmics (Class I and III) (7/24), selective calcium channel blockers with vascular effects (6/24) and antipsychotics (4/24). WHAT IS NEW AND CONCLUSION: Data suggest that PIM-lists focus mainly on common adverse events and often poorly describe the potential consequence for MACE occurrence. This systematic review could help healthcare professionals in the identification and deprescribing of these medicines in older patients with high cardiovascular risk during medication review