Plasma levels of Complement components C5 and C9 are associated with thrombin generation.

BACKGROUND: The thrombin generation assay (TGA) evaluates the potential of plasma to generate thrombin over time, providing a global picture of an individual's hemostatic balance. OBJECTIVES: This study aimed to identify novel biological determinants of thrombin generation using a multi-omics approach. METHODS: Associations between TGA parameters and plasma levels of 377 antibodies targeting 236 candidate proteins for cardiovascular risk were tested using multiple linear regression analysis in 770 individuals with venous thrombosis from the MARTHA study. Proteins associated with at least three TGA parameters were selected for validation in an independent population of 536 healthy individuals (EFS-AM). Proteins with strongest associations in both groups underwent additional genetic analyses and in vitro experiments. RESULTS: Eighteen proteins were associated (p<1.33x10-4) with at least three TGA parameters in MARTHA, among which 13 demonstrated a similar pattern of associations in EFS-AM. Complement proteins C5 and C9 had the strongest associations in both groups. Ex vivo supplementation of platelet-poor plasma with purified C9 protein had a significant dose-dependent effect on TGA parameters. No effect was observed with purified C5. Several single nucleotide polymorphisms associated with C5 and C9 plasma levels were identified, with the strongest association for the C5 missense variant rs17611, which was associated with a decrease in C5 levels, ETP and Peak in MARTHA. No association of this variant with TGA parameters was observed in EFS-AM. CONCLUSIONS: This study identified complement proteins C5 and C9 as potential determinants of thrombin generation. Further studies are warranted to establish causality and elucidate the underlying mechanisms.

Combined PIK3CA and SOX2 Gene Amplification Predicts Laryngeal Cancer Risk beyond Histopathological Grading.

The PIK3CA and SOX2 genes map at 3q26, a chromosomal region frequently amplified in head and neck cancers, which is associated with poor prognosis. This study explores the clinical significance of PIK3CA and SOX2 gene amplification in early tumorigenesis. Gene copy number was analyzed by real-time PCR in 62 laryngeal precancerous lesions and correlated with histopathological grading and laryngeal cancer risk. Amplification of the SOX2 and PIK3CA genes was frequently detected in 19 (31%) and 32 (52%) laryngeal dysplasias, respectively, and co-amplification in 18 (29%) cases. The PIK3CA and SOX2 amplifications were predominant in high-grade dysplasias and significantly associated with laryngeal cancer risk beyond histological criteria. Multivariable Cox analysis further revealed PIK3CA gene amplification as an independent predictor of laryngeal cancer development. Interestingly, combined PIK3CA and SOX2 amplification allowed us to distinguish three cancer risk subgroups, and PIK3CA and SOX2 co-amplification was found the strongest predictor by ROC analysis. Our data demonstrate the clinical relevance of PIK3CA and SOX2 amplification in early laryngeal tumorigenesis. Remarkably, PIK3CA amplification was found to be an independent cancer predictor. Furthermore, combined PIK3CA and SOX2 amplification is emerging as a valuable and easy-to-implement tool for cancer risk assessment in patients with laryngeal precancerous lesions beyond current WHO histological grading.

Equity in out-of-pocket health expenditure: Evidence from a health insurance program reform in Mexico.

Background: The fragmentation of health systems in low- and middle-income countries (LMICs) deepens health inequities and shifts the economic burden of health care to families via out-of-pocket spending (OOPHE). This problem has been addressed by introducing public health insurance programs for poor people; however, there is a lack of knowledge about how equitable these programs are. We aimed to analyse the long-term effects of the Seguro Popular (SP) voluntary health insurance program, recently phased out and replaced by the Health Institute for Welfare (Instituto de Salud para el Bienestar (INSABI)), on OOPHE equity in the poor Mexican population. Methods: We conducted a pooled cross-sectional analysis using eleven waves of the National Household Income and Expenditure Survey (2002-2020). We identified the effect of SP by selecting households without social security (with SP or without health insurance (n = 169 766)) and matched them by propensity score to reduce bias in the decision to enrol in SP. We estimated horizontal and vertical equity metrics and assessed their evolution across subpopulations. Results: The program's entry years (2003-2010) show a positive redistributive effect associated with a focalised stage of the program, while oversaturation could have diluted these effects during 2010-2014, with adverse results in terms of vertical equity and re-ranking among insured families. SP is more horizontally inequitable than for those uninsured. Within SP, the redistributive effect could improve up to 13% if all families with similar expenditures were spending equal OOPHE and horizontal equity was eliminated. Regarding vertical equity, SP outperforms the insured population with middle-range coverage some years after the implementation, but this progress disappears. Conclusions: To achieve universal health coverage, health authorities need to create and execute financial protection mechanisms that effectively address structural inequalities. This involves implementing a more comprehensive risk-pooling mechanism that makes social insurance sustainable in the long-run by increasing the social-economic influx of resources. It is essential to monitor oversaturation and financial sustainability to achieve optimal results. The replacement of the SP with INSABI highlights the complexity of maintaining a social insurance program where the ideology of different governments can influence the program structure, regulation, financing, and even its existence.

Inequitable Financial Protection in Health for Indigenous Populations: the Mexican Case.

BACKGROUND: There is an important gap in the literature concerning the level, inequality, and evolution of financial protection for indigenous (IH) and non-indigenous (NIH) households in low- and middle-income countries. This paper offers an assessment of the level, socioeconomic inequality and middle-term trends of catastrophic (CHE), impoverishing (IHE), and excessive (EHE) health expenditures in Mexican IHs and NIHs during the period 2008-2020. METHODS: We conducted a pooled cross-sectional analysis using the last seven waves of the National Household Income and Expenditure Survey (n = 315,829 households). We assessed socioeconomic inequality in CHE, IHE, and EHE by estimating their Wagstaff concentration indices according to indigenous status. We adjusted the CHE, IHE, and EHE by estimating a maximum-likelihood two-stage probit model with robust standard errors. RESULTS: We observed that, during the period analyzed, CHE, IHE, and EHE were concentrated in the poorest IHs. CHE decreased from 5.4% vs. 4.7% in 2008 to 3.4% vs. 2.9% in 2014 in IHs and NIHs, respectively, and converged at 2008 levels towards 2020. IHE remained unchanged from 2008 to 2014 (1.6% for IHs vs. 1.0% for NIHs) and increased by 40% in IHs and NIHs during 2016-2020. EHE plunged in 2014 (4.6% in IHs vs. 3.8% in NIHs), then rose, and remained unchanged during 2016-2020 (6.7% in IHs and 5.6% in NIHs). CONCLUSION: In pursuit of universal health coverage, health authorities should formulate and implement effective financial protection mechanisms to address structural inequalities, especially forms of discrimination including racialization, that vulnerable social groups such as indigenous peoples have systematically faced. Doing so would contribute to closing the persistent ethnic gaps in health.

Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy.

Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success of immune checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, the limited overall responses and lack of reliable predictive biomarkers of patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects the compelling need of unveiling novel targets for immunotherapy that allow to expand the spectrum of ICB-based strategies to achieve optimal therapeutic efficacy and benefit for cancer patients. This review thoroughly dissects current molecular and functional knowledge of BTLA/HVEM axis and the future perspectives to become a target for cancer immunotherapy. BTLA/HVEM dysregulation is commonly found and linked to poor prognosis in solid and hematological malignancies. Moreover, circulating BTLA has been revealed as a blood-based predictive biomarker of immunotherapy response in various cancers. On this basis, BTLA/HVEM axis emerges as a novel promising target for cancer immunotherapy. This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.

First report of Fusarium clavum causing garlic bulb rot in Mexico.

In Mexico, the main states for garlic (Allium sativum L.) production are Zacatecas, Guanajuato, and Puebla. In the 2020 crop season, garlic cultivation encompassed 6,794 ha, yielding 85,505 tons (SIAP, 2021). In February 2020, 35 garlic samples showing basal rot symptoms were collected from the garlic-growing regions in the states of Zacatecas and Aguascalientes in the municipalities of San Antonio Tepezala 22°13'13.5''N, 102°15'55.3''W, Rincón de Romos 22°17'44.9''N, 102°13'06.8''W, and Calera 22°58'39.4''N and 102°41'29.9W, respectively. The sampling carried out was random sampling by conglomerates, dividing each field in groups with plants that showed similar symptoms. The infected plants were stunted in growth, with reddish dying leaves. The stalks and bulbs were soft, and their root system was poorly developed. The collected samples were placed in polyethylene bags and taken to laboratory. The roots and bulbs of 35 plants were cleaned, portions of the diseased tissue was cut into 0.5 cm pieces and disinfected in 1% sodium hypochlorite for 3 minutes. The samples were rinsed twice with sterile distilled water and dried on sterile paper towels. The tissues were cultured on Potato Dextrose Agar (PDA) medium and incubated in the dark at 25°C. Seven days after incubation, pure cultures were obtained using monoconidial cultures technique on Spezieller Nährstoffmmarmer agar (SNA) and subcultured on carnation leaf agar (CLA). Ten isolates were obtained that grew slowly, showing a white coloration, then turning yellow with abundant aerial mycelia. Microscopic traits of 30 characterized spores included slender macroconidia that were curved dorsiventrally, tapering towards both ends, with five to seven thin septa, measuring 36.4-56.6 µm × 4.0-4.9 µm in size and chlamydospores that were abundant, globose to oval, subhyaline and terminal or intercalary in chains measuring 8.8-4.5 µm in diameter. Microconidia, were single-celled, hyaline, nonseptate, and ovoid. The morphological traits matched the description of Fusarium clavum (Xia et al. 2019). To confirm the strain's identity, DNA was extracted from six monoconidial cultures and used as template to amplify translation elongation factor (TEF) gene 1α, RNA polymerase largest subunit (RPB1), and RNA polymerase second largest subunit (RPB2) (O'Donnell et al. 2010). The products were sequenced and deposited in GenBank as ON209360, OM640008 and OM640009, the homology analysis using BLASTn was similar to F. clavum with 99.46%, 99.49% and 98.82% respectively with E VALUE 0.0 in all cases with access numbers OP48709, HM347171 and OP486686. Koch postulate was performed to confirm the pathogenicity of the six isolates. Variegated garlic cloves were planted after being disinfected with sodium hypochlorite at 3% w/v in 2-kg pots under the greenhouse conditions. When the garlic plants developed 4 or 5 true leaves, their basal stalks were inoculated by pouring uniformly with 1 mL of a spore suspension at 108 conidia/mL prepared from 1-week-old colonies (Lai et al. 2020). Twenty-four plants were inoculated with six isolates (four plants per isolate), and four control plants were treated with sterile distilled water. Symptoms appeared 20 days post-inoculation. The leaves were reddish, and the stalks were soft. The leaves eventually developed foliar dieback disease symptoms, their root system showed brown lesions and rot, and all water-inoculated controls remained asymptomatic. Isolations were made on the diseased plants, and the inoculated pathogen was recovered and confirmed morphologically and molecularly by DNA extraction and PCR reactions. Koch's postulate was repeated twice, obtaining the same results. To our best knowledge, this is the first report of F. clavum infecting Allium sativum L. in Mexico. bulb rot caused by F. clavum is a severe threat to garlic cultivation, and identification of this pathogen is important for effective disease management and control.

Resultados a corto y medio plazo de la reparación transcatéter de la válvula tricúspide: revisión sistemática y metanálisis de estudios observacionales / Early and mid-term outcomes of transcatheter tricuspid valve repair: systematic review and meta-analysis of observational studies

Introducción y objetivos La insuficiencia tricuspídea (IT) se asocia con un peor pronóstico si no se corrige. Se han publicado recientemente numerosos estudios sobre reparación transcatéter de la válvula tricúspide (RTT) Métodos Se llevó a cabo una revisión sistemática de estudios que publican datos clínicos de pacientes con IT significativa sometidos a RTT. Se evaluaron objetivos clínicos y ecocardiográficos a corto y medio plazo. Las razones de riesgo (RR) y las diferencias de medias (DM) se obtuvieron de la comparación de datos previos y posteriores a la intervención. Se hizo también un análisis de sensibilidad según el abordaje principal (reparación borde a borde frente a anuloplastia) Resultados Se incluyeron 19 estudios (todos observacionales o ensayos de un solo grupo) con un total de 991 pacientes sometidos a RTT sola. Las tasas de mortalidad e ictus a 30 días fueron del 2,8 y el 0,2% respectivamente. El análisis agrupado de efectos aleatorios mostró una reducción significativa de IT (RR=0,33; IC95%, 0,26-0,42; p <0,001), vena contracta (DM, 5,9mm; IC95%, 4-7,9; p <0,001), diámetro telediastólico del ventrículo derecho (DM, 3,5mm; IC95%, 2,5-4,5; p <0,001) y clase funcional de la NYHA 3 o 4 (RR=0,32; IC95%, 0,27-0,37; p <0,001) a los 30 días. Las complicaciones hemorrágicas y la IT residual al menos grave fueron numéricamente superiores en el grupo de anuloplastia percutánea en comparación con el grupo de reparación borde a borde (hemorragias, el 13,3 y el 2,8%; IT residual, el 40,4 y el 27,9%) Conclusiones En los 991 pacientes que formaron parte de la experiencia inicial de RTT, tras la intervención se observó una reducción estadísticamente significativa del grado de IT grave o peor, una mala clase funcional (NYHA 3-4), la anchura de la vena contracta y el diámetro telediastólico del ventrículo derecho. Hasta ahora, el abordaje con reparación borde a borde parece tener un mejor perfil de seguridad (AU)

Introduction and objectives Severe tricuspid regurgitation (TR) is associated with poor prognosis when left untreated, and a growing number of studies on transcatheter tricuspid valve repair (TTVr) have been published over the last few months. Methods We performed a comprehensive systematic review of published literature providing clinical data on TTVr for patients with significant TR. Early and mid-term clinical and echocardiographic outcomes were evaluated. Risk ratios (RR) or mean differences (MD) were obtained when comparing pre- and postprocedural data. A sensitivity analysis was also performed according to the main approach for repair (edge-to-edge vs annuloplasty). Results A total of 19 studies (all observational or single-arm trials) and 991 patients who underwent isolated TTVr were included. Thirty-day mortality and stroke rates were 2.8% and 0.2%, respectively. Pooled random-effects resulted in a significant reduction of ≥ severe TR (RR, 0.33; 95%CI, 0.26-0.42; P<.001), vena contracta width (MD, 5.9mm; 95%CI, 4-7.9; P <.001), right ventricular end-diastolic diameter (MD, 3.5mm; 95%CI, 2.5-4.5; P <.001), and New York Heart Association (NYHA) class III or IV at last follow-up (RR, 0.32; 95%CI, 0.27-0.37; P <.001). Bleeding complications and residual ≥ severe TR were numerically higher in the annuloplasty-like group compared with edge-to-edge repair (13.3% vs 3.8% for bleeding and 40.4% vs 27.9% for residual severe TR). Conclusions Among 991 patients comprising the early experience for several TTVr devices, there was a statistically significant reduction in ≥ severe TR, NYHA class III-IV, vena contracta width and right ventricular end-diastolic diameter after TTVr. Thus far, the edge-to-edge approach seems to be associated with a better safety profile (AU)

Targeting oncogenic functions of miR-301a in head and neck squamous cell carcinoma by PI3K/PTEN and MEK/ERK pathways.

Treatment of head and neck squamous cell carcinomas (HNSCC), the sixth most frequent cancer worldwide, remains challenging. miRNA dysregulation is closely linked to tumorigenesis and tumor progression, thus emerging as suitable targets for cancer treatment. Transcriptomic analysis of TCGA HNSCC dataset revealed that miR-301a expression levels significantly increased in primary tumors, as compared to patient-matched normal tissue. This prompted us to investigate its pathobiological role and potential as new therapeutic target using different preclinical HNSCC models. miR-301a overexpression in HNSCC-derived cell lines led to enhanced proliferation and invasion, whereas miR-301 inhibition reduced these effects. In vivo validation was performed using an orthotopic mouse model. Results concordantly showed that the mitotic counts, the percentage of infiltration depth and Ki67 proliferative index were significantly augmented in the subgroup of mice harboring miR-301a-overexpressing tumors. Further mechanistic characterization revealed PI3K/PTEN/AKT and MEK/ERK pathways as central signaling nodes responsible for mediating the oncogenic activity of miR-301a observed in HNSCC cells. Notably, pharmacological disruption of PI3K and ERK signals with BYL-719 and PD98059, respectively, was effective to completely revert/abolish miR-301a-promoted tumor cell growth and invasion. Altogether, these findings demonstrate that miR-301a dysregulation plays an oncogenic role in HNSCC, thus emerging as a candidate therapeutic target for this disease. Importantly, available PI3K and ERK inhibitors emerge as promising anti-tumor agents to effectively target miR-301a-mediated signal circuit hampering growth-promoting and pro-invasive functions.

The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma.

The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas.

Blood Coagulation and Beyond: Position Paper from the Fourth Maastricht Consensus Conference on Thrombosis.

The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited.

The influence of meaningful activities in the quality of life and functional autonomy of adults with intellectual disability: A prospective study during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic might negatively impact the quality of life and functional autonomy of Spanish adults with intellectual disability, and meaningful activities could prevent this negative progression. METHODS: This is a prospective cohort study in Spanish adults with intellectual disability during the COVID-19 pandemic. Quality of life, functional autonomy and functional independence were measured. The meaningful activities studied were structured-leisure, community self-management, and occupational and physical activities. RESULTS: Seventy-three participants were included in the study. Quality of life and functional autonomy significantly deteriorated during the COVID-19 pandemic (all p > .001). Greater participation in community self-management activities before COVID-19 was associated with less detriment to quality of life (ß = -.312; p = .008), while greater participation in occupational and physical activities was associated with less detriment to the performance of instrumental activities (ß = -.317; p = .016; and ß = -.285; p = .030, respectively). CONCLUSION: People with intellectual disability living in residential homes experienced a decrease in their quality of life and functional autonomy during the COVID-19 pandemic. Their involvement in community self-management activities and physical and occupational activities before the pandemic had preventive effects on the detriment to the quality of life and functional autonomy.

Remote ophthalmology with a smartphone adapter handled by nurses for the diagnosis of eye posterior pole pathologies during the COVID-19 pandemic.

INTRODUCTION: The use of smartphones to provide specialist ophthalmology services is becoming a more commonly used method to support patients with eye pathologies. During the COVID-19 pandemic, demand for telehealth services such as tele-ophthalmology, is increasing rapidly. METHODS: In 2019, the agreement between diagnostic tests was investigated by comparing the diagnostic performance for eye posterior pole pathologies of the images obtained by a smartphone coupled to a medical device known as open retinoscope (OR), handled by a nurse and subsequently assessed by an ophthalmologist versus the images obtained by an ophthalmologist using a slit lamp associated to a 76 diopter indirect ophthalmic lens (Volk Super FieldVR ) (SL-IOL) at the outpatient department of a hospital. The OR used in this study worked with a 28 diopter indirect lens. RESULTS: An examination of 151 dilated eyes (79 adult patients, mean age of 66.7 years, 59.5% women) was conducted. Sensitivity was 98.9%, specificity was 89.8%, the positive predictive value was 93.8% and the negative predictive value was 98.2%. The kappa index between both tests was 0.90 (95% CI: 0.83-0.97) in basic diagnosis, 0.81 (95% CI: 0.74-0.89) in syndromic diagnosis (13 categories) and 0.70 (95% CI: 0.62-0.77) in advanced diagnosis (23 categories). DISCUSSION: Images obtained by a nurse using a smartphone coupled to the OR and subsequently assessed by an ophthalmologist showed a high diagnostic performance for eye posterior pole pathologies, which could pave the way for remote ophthalmology systems for this patient group.

Early and mid-term outcomes of transcatheter tricuspid valve repair: systematic review and meta-analysis of observational studies.

INTRODUCTION AND OBJECTIVES: Severe tricuspid regurgitation (TR) is associated with poor prognosis when left untreated, and a growing number of studies on transcatheter tricuspid valve repair (TTVr) have been published over the last few months. METHODS: We performed a comprehensive systematic review of published literature providing clinical data on TTVr for patients with significant TR. Early and mid-term clinical and echocardiographic outcomes were evaluated. Risk ratios (RR) or mean differences (MD) were obtained when comparing pre- and postprocedural data. A sensitivity analysis was also performed according to the main approach for repair (edge-to-edge vs annuloplasty). RESULTS: A total of 19 studies (all observational or single-arm trials) and 991 patients who underwent isolated TTVr were included. Thirty-day mortality and stroke rates were 2.8% and 0.2%, respectively. Pooled random-effects resulted in a significant reduction of ≥ severe TR (RR, 0.33; 95%CI, 0.26-0.42; P < .001), vena contracta width (MD, 5.9mm; 95%CI, 4-7.9; P <.001), right ventricular end-diastolic diameter (MD, 3.5mm; 95%CI, 2.5-4.5; P <.001), and New York Heart Association (NYHA) class III or IV at last follow-up (RR, 0.32; 95%CI, 0.27-0.37; P <.001). Bleeding complications and residual ≥ severe TR were numerically higher in the annuloplasty-like group compared with edge-to-edge repair (13.3% vs 3.8% for bleeding and 40.4% vs 27.9% for residual severe TR). CONCLUSIONS: Among 991 patients comprising the early experience for several TTVr devices, there was a statistically significant reduction in ≥ severe TR, NYHA class III-IV, vena contracta width and right ventricular end-diastolic diameter after TTVr. Thus far, the edge-to-edge approach seems to be associated with a better safety profile.

Association of the Surgical Technique With the Structural Valve Deterioration of a Bioprosthesis: A Prospective Cohort Study.

The Trifecta aortic valve is a prosthesis with externally mounted leaflets and a stent which may be deformed during implant. Our aim was to know if the use of the holder as a protection device during the knotting has an impact on the incidence of structural valve deterioration (SVD) or endocarditis. Prospective cohort study where all patients who underwent aortic valve replacement with a Trifecta aortic valve between 2013 and 2018 were included. The use of the holder as a protection device was collected in a database. Propensity-score matched methods were used and analyses were based on competing events. Death without SVD or prosthesis replacement not due to SVD was considered competing events. 782 patients were included, 352 pairs after the matching. Rates of SVD at 5 and 8 years were 5.8% (95% CI 3.5-8.7) and 13.6% (95% CI 9.2-18.9) in the group without holder and 2.3% (95% CI 1-4.5) and 7% (95% CI 4.2-10.8) in the group with holder; sHR = 0.49 (95% CI 0.27-0.86; P = 0.015). The risk of endocarditis at 8 years was 4.8% (95% CI 2.8-7.4) in the group without holder and 2.3% (95% CI 1.1-4.3) in the group with holder, sHR = 0.49 (95% CI 0.21-1.15, P = 0.1). The use of holder as a protection device during the knotting of the Trifecta aortic valve is associated with less risk of SVD.

Do People Care about the Origin of Wildlife? The Role of Social Stereotypes on Public Preference for Exotic Animals.

People's attitudes to animals are becoming increasingly important for the success of invasive species management. We asked college students from Argentina to fill a questionnaire that included a question about their favorite free-living animal. A total of 159 responses were obtained. Native species were significantly less preferred than non-native species. We tested if these preferences were associated with animal stereotypes. The stereotype hypothesis predicts that animals from the contemptible stereotype (invertebrate, rodents, and reptiles) should be the least preferred taxa, and animals from the protective stereotype (pets, horses, and primates) should be the most preferred taxa; animals from the subordination (lagomorphs and birds) and threatening-awe stereotype (large carnivores) should show intermediate preferences. The first prediction was supported. However, students showed significant preference for non-native taxa included in the threatening-awe stereotype. We proposed that people prefer large carnivores (stereotypically strong, intelligent, and beautiful animals) when they are exotic, because they did not represent a risk.

Free time, gender and the pandemic: An exploration of children's daily routines in the times of COVID-19 in Chile.

This article discusses the differentiation by gender displayed by children between 8 and 12 years old on how they used their free time during the COVID-19 pandemic in Chile. This study had a qualitative approach, where 43 in-depth interviews were conducted with children from three different regions of the country, using participatory photo-elicitation as the central tool. The main results of the study show a configuration of free time based on gender stereotypes, showing that boys are the ones who most adhere to such stereotypes, triggering a crisis in the identity construction of masculinities during childhood. The study also suggests that socioeconomic and territorial differences between children configures different experiences of the use of free time.

The cytoplasmic microtubule array in Neurospora crassa depends on microtubule-organizing centers at spindle pole bodies and microtubule +end-depending pseudo-MTOCs at septa.

γ-Tubulin ring complexes (γ-TuRC) mediate nucleation and anchorage of microtubules (MTs) to microtubule organizing centers (MTOCs). In fungi, the spindle pole body (SPB) is the functional equivalent of the centrosome, which is the main MTOC. In addition, non-centrosomal MTOCs (ncMTOCs) contribute to MT formation in some fungi like Schizosaccharomyces pombe and Aspergillus nidulans. In A. nidulans, MTOCs are anchored at septa (sMTOC) and share components of the outer plaque of the SPB. Here we show that the Neurospora crassa SPB is embedded in the nuclear envelope, with the γ-TuRC targeting proteins PCP-1Pcp1/PcpA located at the inner plaque and APS-2Mto1/ApsB located at the outer plaque of the SPB. PCP-1 was a specific component of nuclear MTOCs, while APS-2 was also present at the septal pore. Although γ-tubulin was only detected at the nucleus, spontaneous MT nucleation occurred in the apical and subapical cytoplasm during recovery from benomyl-induced MT depolymerization experiments. There was no evidence for MT nucleation at septa. However, without benomyl treatment MT plus-ends were organized in the septal pore through MTB-3EB1. Those septal MT plus ends polymerized MTs from septa in interphase cells Thus we conclude that the SPB is the only MT nucleation site in N. crassa, but the septal pore aids the MT network arrangement through the anchorage of the MT plus-ends through a pseudo-MTOC.

Effective access to health care in Mexico.

OBJECTIVES: This paper assesses the impact of effective access on out-of-pocket health payments and catastrophic health expenditure. Effective access cannot be attained unless both health services and financial risk protection are accessible, affordable, and acceptable. Therefore, it represents a key determinant in the transition from fragmented health systems to universal coverage that many low- and middle-income countries face. METHODS: We use a definition of effective access as the utilization of health insurance when available. We conducted a cross-sectional analysis using the 2018 Mexican National Health Survey (ENSANUT) at the household level. The analysis is performed in two stages. The first stage is a multinomial analysis that captures the factor associated with choosing effective access against the alternative of paying privately. The second stage consists of an impact analysis regarding the decision of not choosing effective access in terms of out-of-pocket (OOP) health payments and catastrophic health expenditures (CHE). The analysis corrects for both the decision to buy insurance and the decision to pay for health care. RESULTS: We found that, on average, not choosing effective access increases OOP health payments by around 2300 pesos annually. Medicine payments are the most common factor in this increase. Nevertheless, outpatient and medicines health care are the main drivers of the increase in OOP health payments in all insurance beneficiaries. Not having effective access increases the probability of CHE health expenditures by 2.7 p.p. for the case of Social Security Insurance and 4.0 p.p. for Social Government insurance. Household enrolled in Prospera program for the poor are more likely to choose effective access while having household heads with more education and assets value does the opposite. Diabetes illnesses are associated with a higher probability of effective access. CONCLUSION: Improving effective access is a middle step that cannot be disregarded when seeking universal coverage because OOP health payments and catastrophic outcomes are direct consequences. Public insurance in general, has around 50% effective access which remains a challenge in terms of health services utilization and health public policy design, calling for the need of better coordination across insurance types and pooling mechanisms to increase sustainability of needed health services.

Mujeres ocupando autorías preferenciales de artículos en la revista EMERGENCIAS: análisis de la última década / Women occupying preferential authorship positions for articles in the journal Emergencias: an analysis of authorship during the last decade

Objetivos. Analizar la desigualdad de género en la producción científica de la revista EMERGENCIAS en la última década. Método. Estudio longitudinal retrospectivo que revisó los números publicados entre enero de 2011 y diciembre de 2020. Se analizaron el número de autores, género, tipo y año de publicación y autoría preferencial (primera autoría, autoría de correspondencia o última autoría). La participación de la mujer se calculó en base a valores porcentuales y se analizó la tendencia existente a lo largo de los años. Resultados. Se recogieron 1.240 artículos con un número total de 5.213 firmantes, 1.889 de ellos (36,2%) mujeres. En 384 (31%) artículos, una mujer asumió la primera autoría, en 352 (28,4%) fue autora para correspondencia y en 358 (28,9%) la última autora. A lo largo de la década, se identificó una tendencia creciente en los que una mujer fue primera autora en los artículos originales o metanálisis (p = 0,047). En los editoriales, revisiones, cartas científicas o comunicaciones breves, cartas al editor y otros no existió una tendencia creciente significativa en las autorías preferenciales. Conclusión. La participación de autoras en la producción científica de la revista EMERGENCIAS ha aumentado en la última década. No obstante, comparado con la de hombres, sigue existiendo una menor participación. (AU)

Objective. To analyze gender disparity in scientific productivity reflected by the authorship of articles in the journal Emergencias over the past decade. Methods. Retrospective longitudinal study. We included articles in all issues published between January 2011 and December 2020, analyzing the number of authors, their gender, article type, year of publication, and preferential authorship credit (first author, corresponding author, and last author positioning). The percentages of women named in each position were calculated, and the trend over time was analyzed. Results. A total of 1240 articles signed by 5213 authors were collected; a woman was named in 1889 of the cases (36.2%). A woman was the first author of 384 articles (31%), the corresponding author of 352 (28.4%), and the last author of 358 (28.9%). The number of female authors of original research articles or meta-analyses tended to increase over time (P = .047), but no statistically significant gender trends were observed in the authorship of editorials, narrative reviews, scientific letters or short communications, letters to the editor, or any other publication category. Conclusions. The publication of articles by women in Emergencias has increased over the past decade. However, women continue to author fewer articles than men. (AU)