Transient loss of Polycomb components induces an epigenetic cancer fate.

Although cancer initiation and progression are generally associated with the accumulation of somatic mutations1,2, substantial epigenomic alterations underlie many aspects of tumorigenesis and cancer susceptibility3-6, suggesting that genetic mechanisms might not be the only drivers of malignant transformation7. However, whether purely non-genetic mechanisms are sufficient to initiate tumorigenesis irrespective of mutations has been unknown. Here, we show that a transient perturbation of transcriptional silencing mediated by Polycomb group proteins is sufficient to induce an irreversible switch to a cancer cell fate in Drosophila. This is linked to the irreversible derepression of genes that can drive tumorigenesis, including members of the JAK-STAT signalling pathway and zfh1, the fly homologue of the ZEB1 oncogene, whose aberrant activation is required for Polycomb perturbation-induced tumorigenesis. These data show that a reversible depletion of Polycomb proteins can induce cancer in the absence of driver mutations, suggesting that tumours can emerge through epigenetic dysregulation leading to inheritance of altered cell fates.

DIDO is necessary for the adipogenesis that promotes diet-induced obesity.

The prevalence of overweight and obesity continues to rise in the population worldwide. Because it is an important predisposing factor for cancer, cardiovascular diseases, diabetes mellitus, and COVID-19, obesity reduces life expectancy. Adipose tissue (AT), the main fat storage organ with endocrine capacity, plays fundamental roles in systemic metabolism and obesity-related diseases. Dysfunctional AT can induce excess or reduced body fat (lipodystrophy). Dido1 is a marker gene for stemness; gene-targeting experiments compromised several functions ranging from cell division to embryonic stem cell differentiation, both in vivo and in vitro. We report that mutant mice lacking the DIDO N terminus show a lean phenotype. This consists of reduced AT and hypolipidemia, even when mice are fed a high-nutrient diet. DIDO mutation caused hypothermia due to lipoatrophy of white adipose tissue (WAT) and dermal fat thinning. Deep sequencing of the epididymal white fat (Epi WAT) transcriptome supported Dido1 control of the cellular lipid metabolic process. We found that, by controlling the expression of transcription factors such as C/EBPα or PPARγ, Dido1 is necessary for adipocyte differentiation, and that restoring their expression reestablished adipogenesis capacity in Dido1 mutants. Our model differs from other lipodystrophic mice and could constitute a new system for the development of therapeutic intervention in obesity.

Home-Based Trimodal Prehabilitation in Patients with Peritoneal Carcinomatosis Undergoing Cytoreductive Surgery: Effect on Functional Walking Capacity and Skeletal Muscle Mass.

BACKGROUND: Patients with peritoneal carcinomatosis often suffer from loss of skeletal muscle mass and require extensive surgery. Multimodal prehabilitation may improve physical status but its benefits for these specific patients remain unknown. This study aimed to evaluate the effect of prehabilitation on functional walking capacity and skeletal muscle mass, as well as its association with postoperative complications. PATIENTS AND METHODS: A prospective study of patients with peritoneal carcinomatosis following a home-based trimodal prehabilitation program was carried out. Functional walking capacity was assessed with the 6-min walk test (T6MWT), and by the appendicular skeletal muscle index (ASMI) estimated by bioelectrical impedance analysis. Data were collected at the first medical appointment and on the day before surgery. A 90-day postoperative morbidity was registered according to the Clavien-Dindo classification. RESULTS: A total of 62 patients were included in the analysis. Women were more prevalent (77.4%) and peritoneal metastasis from ovarian origin accounted for 48.4%. Clavien II-V grades occurred in 30 (57.7%) patients. After prehabilitation, functional walking capacity improved by 42.2 m (39.62-44.72 m) compared with baseline data (p < 0.001), but no improvement was observed in the ASMI (p = 0.301). Patients able to walk at least 360 m after prehabilitation suffered fewer Clavien-Dindo II-V postoperative complications (p = 0.016). A T6MWT of less than 360 m was identified as an independent risk factor in the multivariable analysis (OR 3.99; 1.01-15.79 p = 0.048). CONCLUSIONS: This home-based trimodal prehabilitation program improved functional walking capacity but not ASMI scores in patients with peritoneal metastasis before surgery. A T6MWT of less than 360 m was found to be a risk factor for postoperative complications.

In vitro models for neuropathic pain phenotypic screening in brain therapeutics.

The discovery of brain therapeutics faces a significant challenge due to the low translatability of preclinical results into clinical success. To address this gap, several efforts have been made to obtain more translatable neuronal models for phenotypic screening. These models allow the selection of active compounds without predetermined knowledge of drug targets. In this review, we present an overview of various existing models within the field, examining their strengths and limitations, particularly in the context of neuropathic pain research. We illustrate the usefulness of these models through a comparative review in three crucial areas: i) the development of novel phenotypic screening strategies specifically for neuropathic pain, ii) the validation of the models for both primary and secondary screening assays, and iii) the use of the models in target deconvolution processes.

Vitamin D and risk of developing type 2 diabetes in the SUN project: a prospective cohort study.

PURPOSE: Vitamin D deficiency has been associated with multiple chronic diseases, including metabolic disorders such as insulin resistance and type 2 diabetes (T2D). The aim of the study was to analyze the association between validated predicted serum vitamin D status and the risk of developing T2D in a large prospective cohort based on a Mediterranean population. METHODS: The SUN project is a prospective and dynamic Spanish cohort that gathers university graduates who have answered lifestyle questionnaires, including a validated Food Frequency Questionnaire. The association between predicted serum vitamin D and the risk of T2D was assessed through Cox regression models according to quartiles (Q) of predicted vitamin D at baseline. The models were adjusted for potential confounders and sensitivity analyses were performed to ensure the robustness of our findings. RESULTS: Our study included a total of 18,594 participants and after a total follow-up of 238,078 person-years (median follow-up of 13.5 years), 209 individuals were diagnosed with incident T2D. We found a significant inverse association between predicted levels of serum vitamin D and the risk of developing T2D, after adjusting for potential confounders and performing different sensitivity analyses (hazard ratio Q4 vs. Q1: 0.48, 95% CI 0.26-0.88; p for trend = 0.032). CONCLUSION: The outcomes suggest that higher levels of vitamin D at baseline may be associated with a reduced risk of developing T2D.

The African introgression of Murciano Granadina goats has a Moroccan origin and displays remarkable levels of inter-individual variability.

There is evidence that Murciano Granadina (MG), the most important caprine dairy breed in Spain, has been introgressed by African goats, but the precise geographic origin of such introgression has not been identified yet. Moreover, an accurate estimate of the magnitude of this African introgression is lacking, since current estimates are based on small numbers of sampled individuals. The aim of our work was to tackle these two issues by genotyping 500 MG goats with the Goat SNP50 BeadChip and comparing their genotypes with those of reference populations from Spain (Bermeya), France (Saanen), Morocco (Barcha, Draa, Ghazalia, Noire de Atlas, Nord, Moroccan), Egypt (Barki, Oasis, Saidi), Algeria (Arabia, Makatia, M'Zabite, Kabyle), Tunisia (Tunisian native breeds) and Sudan (Desert, Nilotic, Taggar). The population of 500 MG goats was subdivided into 10 datasets of 50 individuals to ensure that sample sizes of the target (MG) and reference populations are balanced. Performance of an unsupervised ADMIXTURE analysis demonstrated that MG goats have a North African ancestry, with an average proportion of 4.4 ± 2.3%. Next, we did a supervised ADMIXTURE analysis that revealed that the Moroccan genetic component reaches a proportion of 4.01 ± 3.9% in MG goats, while the Algerian (0.001 ± 0.001%), Egyptian (0.2 ± 0.1%), Sudanese (0.1 ± 0.1%) and Tunisian (0.3 ± 0.4%) components are present in extremely small proportions. The historical circumstances of this introgression event are currently unknown, but several plausible scenarios are outlined. Moreover, our results show considerable inter-individual heterogeneity regarding the magnitude of the Moroccan introgression of MG goats (0%- 12% depending on the MG data set under analysis). This result implies that reliable estimates about the introgression of autochthonous livestock by exotic breeds can only be obtained by extensively sampling target populations.

What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

BACKGROUND: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. METHODS: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. RESULTS: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. CONCLUSION: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

Farm management and husbandry practices associated with spontaneous humeral fractures in New Zealand dairy heifers.

AIMS: To use a farm-based survey to identify characteristics of the New Zealand dairy system associated with the risk of spontaneous humeral fracture in dairy heifers. METHODS: A questionnaire was designed and made available in print and online to collect information from dairy farmers and/or veterinarians, across New Zealand, about the management and nutrition of cows from birth to first lactation. Data were collected from July 2019 to March 2020 from farms that either had recorded (case farms) or not recorded (control farms) cases of humeral fractures in dairy heifers. RESULTS: A total of 68 completed questionnaires were returned, with 35 responses from case farms and 33 responses from control farms. Twenty-six responses (38%) were from the South Island (13 case farms and 13 control farms) and 38 responses (56%) were from the North Island (20 case farms and 18 control farms). For four questionnaires (6%) farm location was not given. Adjusting for the effect of age when calves accessed pasture, case farms had increased odds of having Holstein-Friesian Jersey crossbreed cows as the predominant breed (OR = 9.7; 95% CI = 3.1-36.0; p < 0.001). Adjusting for the effect of breed, allowing calves access to pasture a week later decreased the odds of being a case farm (OR = 0.68; 95% CI = 0.47-0.90; p = 0.006). CONCLUSIONS: Cows being Holstein-Friesian Jersey crossbreed was identified as a possible risk factor associated with spontaneous humeral fracture in dairy heifers in New Zealand. Given the small sample size, the likely multifactorial aetiology for humeral fractures, and the non-randomised survey, this risk factor, and the possible association between age at turn out and herd production with humeral fractures, all require further investigation.

Genitocrural Island Perforator Flap (GIP-Flap): An ideal surgical technique for covering uni- or bilateral vulvar loss tissue.

Vulvar loss of soft tissue leads to urinary, sexual and morphological dysfunctions. Most patients affected are comorbid making it difficult to perform a flap, which is the most appropriate way to reconstruct. Our multidisciplinary plastic and gynecologic surgery team has developed a new technique using a pedicled internal pudendal island flap. Reconstruction is reliable, quick and applicable to all patients, with a highly satisfactory final appearance.

Topical and Intralesional Therapies for Hidradenitis Suppurativa: A Systematic Literature Review. / [Artículo traducido] Tratamientos tópicos e intralesionales en hidradenitis supurativa. Una revisión sistemática de la literatura.

BACKGROUND AND OBJECTIVE: Topical and intralesional (IL) treatments may be considered the first-line therapy in patients with hidradenitis suppurativa (HS); however, the evidence supporting their use is limited. The aim of our review is to evaluate the efficacy and safety profile of topical and IL treatments in patients with HS. MATERIALS AND METHODS: We designed a systematic review of the current medical literature available following the PICO(T) method. And including all types of studies (Study type [T]) of individuals with HS of any sex, age, and ethnicity (Population [P]) who received any topical or IL treatment for HS (Intervention [I]) compared to placebo, other treatments, or no treatment at all (Comparator [C]), and reported efficacy and/or safety outcomes (Outcomes [O]). Two outcomes were defined: quality of life and the no. of patients with, at least, one adverse event. The search was conducted in the Cochrane Library, MEDLINE, and Embase databases; study selection was performed based on pre-defined criteria. The risk of bias was determined in each study. RESULTS: We obtained a total of 11,363 references, 31 of which met the inclusion criteria. These studies included 1143 patients with HS, 62% of whom were women. A total of 10, 8, 6, 2, and 5 studies, respectively, evaluated the use of photodynamic therapy (PDT), glucocorticoids, resorcinol, topical antibiotics, and other interventions. Most articles were case series (n=25), with only five randomized clinical trials (RCTs) and one cohort study. RCTs showed improvement in disease activity with topical clindamycin and botulinum toxin (BTX) vs placebo, and PDT with methylene blue (MB) niosomal vs free MB; however, intralesional triamcinolone acetonide was not superior to placebo. The risk of bias was low in three RCTs and high in two RCTs. CONCLUSION: The quality of evidence supporting the use of topical, or IL treatments is low. However, it supports the use of topical clindamycin, PDT, and BTX. Well-designed RCTs with standardized outcomes and homogeneous populations of patients and lesions are needed to support decision-making in the routine clinical practice.

Topical and Intralesional Therapies for Hidradenitis Suppurativa: A Systematic Literature Review.

BACKGROUND AND OBJECTIVE: Topical and intralesional (IL) treatments may be considered the first-line therapy in patients with hidradenitis suppurativa (HS); however, the evidence supporting their use is limited. The aim of our review is to evaluate the efficacy and safety profile of topical and IL treatments in patients with HS. MATERIALS AND METHODS: We designed a systematic review of the current medical literature available following the PICO(T) method. And including all types of studies (Study type [T]) of individuals with HS of any sex, age, and ethnicity (Population [P]) who received any topical or IL treatment for HS (Intervention [I]) compared to placebo, other treatments, or no treatment at all (Comparator [C]), and reported efficacy and/or safety outcomes (Outcomes [O]). Two outcomes were defined: quality of life and the no. of patients with, at least, one adverse event. The search was conducted in the Cochrane Library, MEDLINE, and EMBASE databases; study selection was performed based on pre-defined criteria. The risk of bias was determined in each study. RESULTS: We obtained a total of 11,363 references, 31 of which met the inclusion criteria. These studies included 1143 patients with HS, 62% of whom were women. A total of 10, 8, 6, 2, and 5 studies, respectively, evaluated the use of photodynamic therapy (PDT), glucocorticoids, resorcinol, topical antibiotics, and other interventions. Most articles were case series (n=25), with only five randomized clinical trials (RCTs) and one cohort study. RCTs showed improvement in disease activity with topical clindamycin and botulinum toxin (BTX) vs placebo, and PDT with methylene blue (MB) niosomal vs free MB; however, intralesional triamcinolone acetonide was not superior to placebo. The risk of bias was low in three RCTs and high in two RCTs. CONCLUSION: The quality of evidence supporting the use of topical, or IL treatments is low. However, it supports the use of topical clindamycin, PDT, and BTX. Well-designed RCTs with standardized outcomes and homogeneous populations of patients and lesions are needed to support decision-making in the routine clinical practice.

Efficacy and Safety of Dupilumab for the Treatment of Severe Atopic Dermatitis in Clinical Practice: A Single Center Experience.

BACKGROUND: Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. OBJECTIVE: Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. MATERIAL AND METHOD: Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. RESULTS: Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. CONCLUSION: Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.

Efficacy and Safety of Dupilumab for the Treatment of Severe Atopic Dermatitis in Clinical Practice: A Single Center Experience. / [Artículo traducido]Eficacia y seguridad de dupilumab para el tratamiento de la dermatitis atópica grave en la práctica clínica: experiencia en un centro terciario.

BACKGROUND: Dupilumab is a new targeted therapy for severe atopic dermatitis (AD) with limited real-world evidence. OBJECTIVE: Explore our experience with dupilumab for AD in clinical practice at a tertiary care center. MATERIAL AND METHOD: Unicentric observational retrospective study including adult and pediatric patients with severe AD receiving dupilumab between December 2017 and December 2021. The Eczema Area and Severity Index (EASI) score, Pruritus Numerical Rating Scale (P-NRS) and Sleep disturbance Numerical Rating Scale (S-NRS) were recovered to assess severity and response. RESULTS: Fifty-nine patients received dupilumab: 52, 48, 26 and 13 patients reached 6, 12, 24 and 36 months of treatment, respectively. The EASI-75 response rates were 94.2%, 95.8%, 92.3% and 100% at months 6, 12, 24 and 36. The EASI-90 response rates were 63.5%, 72.9%, 84.6% and 92.3% at months 6, 12, 24 and 36. The EASI <7 response rates were 92.3%, 91.7%, 88.5% and 100% at months 6, 12, 24 and 36. The P-NRS ≥4 reduction rates were 86%, 87.5%, 92.3% and 100% at months 6, 12, 24 and 36. The S-NRS ≥4 reduction rates were 82.7%, 85.4%, 100% and 100% at months 6, 12, 24 and 36. Adverse events were mild and occurred in 20.3% of patients, all of them adults. CONCLUSION: Our findings support dupilumab's favorable efficacy and tolerability profile in clinical practice. Dupilumab offers a rapid and sustained response, regardless of combined therapy. Longer follow-ups are still required to adequately assess its performance.

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

The KNee OsteoArthritis Prediction (KNOAP2020) challenge: An image analysis challenge to predict incident symptomatic radiographic knee osteoarthritis from MRI and X-ray images.

OBJECTIVES: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth. DESIGN: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC). RESULTS: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables. CONCLUSION: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation.

ART in Latin America: the Latin American Registry, 2020.

RESEARCH QUESTION: What was the utilization, effectiveness and safety of assisted reproductive technology (ART) in Latin America during 2020? DESIGN: Retrospective collection of multinational data on ART performed by 188 institutions in 16 countries. RESULTS: Overall, 87,732 initiated cycles resulted in 12,778 deliveries and 14,582 births. The major contributors were Brazil (46.0%), Mexico (17.0%) and Argentina (16.8%). However, the highest utilization (cycles/million inhabitants) was Uruguay with 558, followed by Argentina with 490 and Panama with 425 cycles/million. Globally, women aged ≥40 years increased to 34% while women ≤34 dropped to 24.7%. After removing freeze-all cycles, the delivery rate per oocyte retrieval was 14.8% for intracytoplasmic sperm injection and 15.6% for IVF. Single-embryo transfer (SET) represented 38.3% of all fresh transfers, with delivery rate per transfer of 20.0%; this increased to 32.4% for elective SET (eSET) and 34.2% for blastocyst eSET, compared with blastocyst elective double embryo transfer (eDET) of 37.9%. However, multiple births increased from 1% in eSET to 30.5% in eDET. Perinatal mortality increased from 7.7‰ in singletons to 24.4‰ in twins and 64.0‰ in triplets. Frozen embryo transfer (FET) represented 66.6% of all transfers, with a delivery rate/transfer of 29.0%, significantly higher than 23.9% after fresh transfers at all ages (P < 0.0001). Preimplantation genetic testing, reported in 8920 cycles, significantly improved delivery rate and decreased miscarriage rates at all ages (P ≤ 0.041), including oocyte donation (P = 0.002). Endometriosis was diagnosed in 28.3% of cases. The delivery rate in 5779 women after removal of peritoneal endometriosis was significantly better than tubal and endocrine factors in women aged 35-39 (P = 0.0004) and women aged ≥40 (P = 0.0353). CONCLUSIONS: Systematic collection and analysis of big data in a south-south cooperation model allow regional growth by implementing evidence-based reproductive decisions.

Wine yeast selection in the Iberian Peninsula: Saccharomyces and non-Saccharomyces as drivers of innovation in Spanish and Portuguese wine industries.

Yeast selection for the wine industry in Spain started in 1950 for the understanding of the microbial ecology, and for the selection of optimal strains to improve the performance of alcoholic fermentation and the overall wine quality. This process has been strongly developed over the last 30 years, firstly on Saccharomyces cerevisiae, and, lately, with intense activity on non-Saccharomyces. Several thousand yeast strains have been isolated, identified and tested to select those with better performance and/or specific technological properties. The present review proposes a global survey of this massive ex-situ preservation of eukaryotic microorganisms, a reservoir of biotechnological solutions for the wine sector, overviewing relevant screenings that led to the selection of strains from 12 genera and 22 species of oenological significance. In the first part, the attention goes to the selection programmes related to relevant wine-producing areas (i.e. Douro, Extremadura, Galicia, La Mancha and Uclés, Ribera del Duero, Rioja, Sherry area, and Valencia). In the second part, the focus shifted on specific non-Saccharomyces genera/species selected from different Spanish and Portuguese regions, exploited to enhance particular attributes of the wines. A fil rouge of the dissertation is the design of tailored biotechnological solutions for wines typical of given geographic areas.

Cost-effectiveness of benralizumab versus mepolizumab and dupilumab in patients with severe uncontrolled eosinophilic asthma in Spain.

OBJECTIVE: To assess the cost-effectiveness of benralizumab (benra) vs. mepolizumab (mepo) and dupilumab (dupi) for the treatment of patients with severe uncontrolled asthma from the Spanish Health System perspective. METHODS: Exacerbations avoided, quality-adjusted life years (QALYs) gained and costs in a 5-year period were estimated with a Markov model for a cohort of 1,000 patients in which, based on published evidence, 31% of the patients received biologics + oral corticosteroids (OCS) and 69% received only biologics. Efficacy data (exacerbation reduction and OCS elimination) were derived from a matching-adjusted indirect comparison. Published EQ-5D utilities per health state (biologic alone, biologic + OCS, standard of care + OCS, exacerbations, and post-exacerbations) were used for QALY estimation. Utility decrements associated with exacerbation management [-0.1 (OCS or emergency visits), -0.2 (hospitalization)] derived from the literature were applied. Costs (€, 2022) included drug acquisition (ex-factory price), administration and disease management. An expert panel (2 pneumologists and 1 pharmacist) validated all inputs. RESULTS: Benra was more effective (52.21 QALYs) than mepo (51.39 QALYs) and dupi (51.30 QALYs). Benra avoided more exacerbations (2.87 exacerbations) compared to mepo (4.70 exacerbations) and dupi (5.11 exacerbations) for the 5-year horizon. Total costs/patient were €56,093.77 (benra), €59,280.45 (mepo) and €62,991.76 (dupi), resulting in benra dominating (more QALYs with lower costs) vs. mepo and dupi. CONCLUSIONS: Benralizumab can be considered as a dominant treatment alternative vs. other biologic drugs for the treatment of uncontrolled severe eosinophilic asthma patients in Spain.

Short-term effects of tropospheric ozone and other environmental factors on emergency admissions due to pregnancy complications: A time-series analysis in the Madrid Region.

Air pollution has been linked to adverse neonatal outcomes, mainly in the case of prolonged exposures. This study focuses on the short-term effects on maternal health. We conducted a retrospective ecological time-series study in the Madrid Region covering the period 2013-2018. The independent variables were mean daily concentrations of tropospheric ozone (O3), particulate matter (PM10/PM2.5) and nitrogen dioxide (NO2), as well as noise levels. The dependent variables were daily emergency hospital admissions due to complications in pregnancy, childbirth and the puerperium. Poisson generalised linear regression models were fitted to quantify the relative and attributable risks, controlling for trend, seasonality, the autoregressive nature of the series, and a number of meteorological factors. There were 318 069 emergency hospital admissions due to obstetric complications across the 2191 days of study. Of this total: 13 164 (95%CI: 9930-16 398) admissions were attributable to exposure to O3, the only pollutant to show a statistically significant (p < 0.05) association with admissions due to hypertensive disorders; and 10 575 (95%CI: 3573-17 566) admissions were attributable to daytime noise levels, while admissions due to hyperemesis gravidarum and vomiting were related to exposure to night noise. Other pollutants which also displayed statistically significant associations were: NO2 concentrations, with admissions due to vomiting and preterm labour; PM10 concentrations, with premature rupture of membranes: and PM2.5 concentrations, with total complications. Exposure to a range of air pollutants, and ozone in particular, is associated with a higher number of emergency hospital admissions due to gestational complications. Hence, surveillance of environmental effects on maternal health should be intensified, and plans and strategies to minimise these should be drawn up.

Short-term impact of noise, other air pollutants and meteorological factors on emergency hospital mental health admissions in the Madrid region.

BACKGROUND: A number of environmental factors, such as air pollution, noise in urbanised settings and meteorological-type variables, may give rise to important effects on human health. In recent years, many studies have confirmed the relation between various mental disorders and these factors, with a possible impact on the increase in emergency hospital admissions due to these causes. The aim of this study was to analyse the impact of a range of environmental factors on daily emergency hospital admissions due to mental disorders in the Madrid Autonomous Region (MAR), across the period 2013-2018. METHODOLOGY: Longitudinal ecological time series study analysed by Generalised Linear Models with Poisson regression, with the dependent variable being daily Emergency Hospital Mental Health Admissions (EHMHA) in the MAR, and the independent variable being mean daily concentrations of chemical pollutants, noise levels and meteorological variables. RESULTS: EHMHA were related statistically significantly in the short term with diurnal noise levels. Relative risks (RRs) for total admissions due to mental disorders and self-inflicted injuries, in the case of diurnal noise was RR: 1.008 95%CI (1.003 1.013). Admissions attributable to diurnal noise account for 5.5% of total admissions across the study period. There was no association between hospital admissions and chemical air pollution. CONCLUSION: Noise is a variable that shows a statistically significant short-term association with EHMHA across all age groups in the MAR region. The results of this study may serve as a basis for drawing up public health guidelines and plans, which regard these variables as risk factors for mental disorders, especially in the case of noise, since this fundamentally depends on anthropogenic activities in highly urbanised areas with high levels of traffic density.