Evoluci\uf3n de madurez en pre y postcosecha y potencialidad de almacenaje de peras packham's Triumph

Packham's Triumph pears ( Pyrus communis L.) were evaluated from four weeks before harvest for maturity and ethylene production. Firmness and soluble solids showed the highest correlations (r = -0.97 y 0.98, respectively)with days after full bloom (DDPF). Ethylene production was low (< 0.07 mg kg-1) and was not correlated with DDPF. Fruit harvested with 7.8 (E1) and 7.0 kg (E2) were stored in conventional cold air (0\ub0C) and two controlled atmosphere conditions (AC1: 2-2.5% O2 /1-1.5% CO2 and AC2: 1-1.3% O2/0.5-0.8% CO2), -1\ub0C, for six months. Changes in maturity, and ethylene production were measured (monthly) and incidence of physiological disorders was assessed (after four and six months). Additionally, the ethylene production rate (TPE) was monitored for seven days at room temperature, after each storage period. Fruit from both harvests, stored under AC1 and AC2 were firmer, greener and had lower ethylene production than those of FC. There were no significant differences in ripening between AC1 and AC2. Ethylene accumulation was exponential and occurred earlier and with higher values in FC (900 mg kg-1 maximum at the 5th month), with respect to AC (146 and 230 mg kg-1 for E1 and E2 at the end of the storage period). At room temperature, the TPE of the three storage conditions increased from the second month, but the climacteric peak was observed only in FC. After six months, fruit from FC and from both harvests developed superficial scald (17% for E1 and 20% for E2).Peras ( Pyrus communis L.) Packham's Triumph fueron evaluadas en madurez y producci\uf3n de etileno desde cuatro semanas previo a la cosecha. Firmeza y s\uf3lidos solubles obtuvieron las mayores correlaciones (r = -0,97 y 0,98, respectivamente) con d\uedas despu\ue9s de plena flor (DDPF). La producci\uf3n de etileno fue baja (<0.07 mg kg-1) y no mostr\uf3 correlaci\uf3n con DDPF. Fruta cosechada con 7,8 y 7,0 kg (E1 y E2, respectivamente) fue almacenada en fr\uedo convencional (FC: 0\ub0C) y dos condiciones de atm\uf3sfera controlada (AC1: 2- 2,5% O2/1-1,5% CO2 y AC2: 1-1,3% O2/0,5-0,8% CO2), -1\ub0C, por seis meses. Se midi\uf3 madurez, producci\uf3n de etileno (mensualmente) e incidencia de des\uf3rdenes fisiol\uf3gicos (despu\ue9s de cuatro y seis meses). Adicionalmente, se evalu\uf3 tasa de producci\uf3n de etileno (TPE) durante 7 d\uedas a temperatura ambiente, despu\ue9s de cada per\uedodo de almacenaje. Fruta de ambas cosechas, almacenada en AC1 y AC2 present\uf3 mayor firmeza, coloraci\uf3n verde de piel y menor TPE que en FC. No hubo diferencias en madurez entre AC1 y AC2. La acumulaci\uf3n de etileno fue exponencial y ocurri\uf3 m\ue1s temprano y con mayores valores en FC (m\ue1ximo de 900 mg kg-1 al 5\ub0 mes), respecto de AC (146 y 230 mg kg-1 para E1 y E2, al final del almacenaje). A temperatura ambiente, la TPE de las tres condiciones se increment\uf3 a partir del segundo mes, pero s\uf3lo se observ\uf3 el climacterio en FC. Despu\ue9s de seis meses fruta de FC y de ambas cosechas desarroll\uf3 escaldadura (17% para E1 y 20 % para E2)

Symptom severity and quality of life in the management of vulvovaginal atrophy in postmenopausal women

Objectives: To evaluate the association between treatments for vulvovaginal atrophy (VVA) and symptom frequency and severity, quality of life (QoL) and sexual functioning in postmenopausal women. Study design: Cross-sectional survey conducted in postmenopausal women aged 45\u201375 years. Data on demographic and clinical variables, as well as vaginal, vulvar and urinary symptoms were collected. The EuroQoL questionnaire (EQ5D3L), the Day-to-Day Impact of Vaginal Aging (DIVA), the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale - revised (FSDS-R) were filled out. Main outcome measures: Association between treatments for VVA and symptom frequency. Results: Women on VVA treatment presented with more severe symptoms. The sexual function score was higher in the treated women (FSFI: 15.6 vs 16.7; p=0.010), as was the score for sexual distress (FSDS-R: 9.2 vs 12.3, p < 0.0005). The systemic hormone group presented with fewer VVA symptoms, lower vaginal impact (DIVA), and better sexual function (FSFI and FSDS-R) and vaginal health. The rates of sexual distress and vulvar atrophy were higher in the non-hormonal treatment group. No significant differences were found according to treatment duration. Conclusions: Postmenopausal women with VVA receiving treatment complained of more severe symptoms than those untreated. Women on systemic treatment had fewer and milder VVA symptoms and presented with better vaginal and vulvar health than women on other treatments. Many women request effective local treatment too late, when VVA symptoms are already severe. Our data suggest that VVA treatments should ideally be initiated when symptoms commence and cause distress, rather tha

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease

Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data: an observational, multicohort, retrospective analysis

International audienceTwo acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. Methods: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. Findings: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90–0·95) in EARLI and 0·88 (0·84–0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81–0·94] vs 0·92 [0·88–0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. Funding: US National Institutes of Health and European Society of Intensive Care Medicine

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk