Search

Introduction: This study aims to estimate the validity and reliability of sound transmission tests using a tuning fork and stethoscope compared with the usual clinical procedures for the diagnosis of developmental dysplasia of the hip in newborns from the state of Guanajuato, Mexico., Methodology: This is a cross-sectional study of newborns at the Guanajuato General Hospital of the Institute of Public Health from Guanajuato. The population under study comprised newborns born from April to May 2023. All parents of newborns were invited to participate. The Ortolani, Barlow, Peter-Baden, and sound transmission tests were performed with a tuning fork and stethoscope three times by two observers. Ultrasonography using the Graf technique was also applied to both hips. We evaluated the validity and repeatability of clinical procedures and sound transmission tests against ultrasonography as the gold standard. We calculated sensitivity, specificity, and predictive values for validity and Cohen's kappa for repeatability., Results: The sample consisted of 100 newborns (56% male and 44% female); 65% born by vaginal delivery. Sound transmission test results for sensitivity, specificity, the positive predictive value, and the negative predictive value were 87.88%, 95.81%, 80%, and 97.53%, respectively. The intra-observer kappa was 0.89 (95% CI = 0.80-0.97) and the inter-observer kappa was 0.85 (95% CI = 0.73-0.97). The validity and repeatability of the Ortolani, Barlow, and Peter-Baden tests were low compared with the sound transmission test., Conclusion: The sound transmission test using a tuning fork and stethoscope is helpful for the diagnosis of developmental dysplasia of the hip., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Padilla-Raygoza, Plascencia-Roldán, Morales-Reyes, Patiño-Gutiérrez, Girón-Soto, Meza-Galván, Anguiano-Canchola, Luna Santillana, Torres-Hernández and Flores-Vargas.)

The drift characteristics of valence change memory (VCM) devices have been analyzed through both experimental analysis and 3D kinetic Monte Carlo (kMC) simulations. By simulating six distinct low-resistance states (LRS) over a 24-hour period at room temperature, we aim to assess the device temporal stability and retention. Our results demonstrate the feasibility of multi-level operation and reveal insights into the conductive filament (CF) dynamics. The cumulative distribution functions (CDFs) of read-out currents measured at different time intervals provide a comprehensive view of the device performance for the different conductance levels. These findings not only enhance the understanding of VCM device switching behaviour but also allow the development of strategies for improving retention, thereby advancing the development of reliable nonvolatile resistive switching memory technologies.

Background: Intensive care to facilitate organ donation (ICOD) involves the initiation or continuation of intensive care for patients with devastating brain injury for donation purposes. In the Spanish system, relatives undergo an early interview to request consent for this procedure. If they consent, a waiting time is agreed upon in the expectation that death by neurological criteria occurs and donation after brain death takes place. Otherwise, relatives can decide on donation after circulatory determination of death or withdrawal of life support. This study analyzes how Spanish transplant coordinators interact with relatives in early interviews and follow-ups on potential donation pathways., Methods: Semistructured interviews were conducted with a random stratified sample of 23 Spanish transplant coordination teams to explore strategies, practices, and perceptions of ICOD consent requests. The interviews were recorded, transcribed, and analyzed using content analysis., Results: Previous coordination with other units and information retrieval regarding patient and relatives' situations is crucial. The development of early interviews includes an introduction to the family, identification of decision makers, empathizing with relatives and offering condolences, reaffirming the fatal prognosis, explaining the possibility of donating based on the patient's will, confirming the family's understanding and resolving doubts, and ensuring comfort and assessing family needs., Conclusions: Approaching families to obtain ICOD consent is a regular practice for Spanish coordination teams. It involves a highly professional and diversified set of strategies based on establishing a support relationship for relatives. Our study provides strategies that serve as a reference for obtaining ICOD consent from families in other settings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Wild ungulates are expanding in range and number worldwide leading to an urgent need to manage their populations to minimize conflicts and promote coexistence with humans. In the metropolitan area of Barcelona (MAB), wild boar is the main wildlife species causing a nuisance, from traffic accidents to health risks. Selective harvesting of specific sex and age classes and reducing anthropogenic food resources would be the most efficient approach to dealing with overpopulation. Nonetheless, there is a gap in knowledge regarding the age and sex selectivity of the capture methods currently applied in the MAB for wild boar population control. Thus, this study aimed to evaluate the performance and age and sex bias of different hunting and capture methods and the seasonal patterns in their performance (number of captured individuals per event). From February 2014 to August 2022, 1454 wild boars were captured in the MAB using drop net, teleanaesthesia, cage traps, night stalks, and drive hunting. We applied generalized linear models (GLM) to compare the performance of these methods for the total number of wild boars, the wild boars belonging to each age category (i.e., adult, yearling, and juvenile), and for each season. The studied capture methods showed age-class bias and sex bias in adults (>2 years). Drive hunting and drop net removed mainly adult females and yearlings (1-2 years), with drive hunting having the highest performance for adult males. Instead, cage traps and drop net were the best methods to capture juveniles (<1 year). Overall, global performance was higher in summer, decreasingly followed by autumn and spring, winter being the worst performing season. Wildlife managers and researchers should consider the different performance and sex and age bias of each hunting and capture method, as well as the associated public cost, to improve efficiency and achieve the best results in wild boar population management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Chromosome pairing constitutes an important level of genome organization, yet the mechanisms that regulate pairing in somatic cells and the impact on 3D chromatin organization are still poorly understood. Here, we address these questions in Drosophila, an organism with robust somatic pairing. In Drosophila, pairing preferentially occurs at loci consisting of numerous architectural protein binding sites (APBSs), suggesting a role of architectural proteins (APs) in pairing regulation. Amongst these, the anti-pairing function of the condensin II subunit CAP-H2 is well established. However, the factors that regulate CAP-H2 localization and action at APBSs remain largely unknown. Here, we identify two factors that control CAP-H2 occupancy at APBSs and, therefore, regulate pairing. We show that Z4, interacts with CAP-H2 and is required for its localization at APBSs. We also show that hyperosmotic cellular stress induces fast and reversible unpairing in a Z4/CAP-H2 dependent manner. Moreover, by combining the opposite effects of Z4 depletion and osmostress, we show that pairing correlates with the strength of intrachromosomal 3D interactions, such as active (A) compartment interactions, intragenic gene-loops, and polycomb (Pc)-mediated chromatin loops. Altogether, our results reveal new players in CAP-H2-mediated pairing regulation and the intimate interplay between inter-chromosomal and intra-chromosomal 3D interactions., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

A new statistical analysis is presented to assess cycle-to-cycle variability in resistive memories. This method employs two-dimensional (2D) distributions of parameters to analyse both set and reset voltages and currents, coupled with a 2D coefficient of variation (CV). This 2D methodology significantly enhances the analysis, providing a more thorough and comprehensive understanding of the data compared to conventional one-dimensional methods. Resistive switching (RS) data from two different technologies based on hafnium oxide are used in the variability study. The 2D CV allows a more compact assessment of technology suitability for applications such as non-volatile memories, neuromorphic computing and random number generation circuits.

Chromatin-associated RNAs (cRNAs) are a poorly characterized fraction of cellular RNAs that co-purify with chromatin. Their full complexity and the mechanisms regulating their packaging and chromatin association remain poorly understood. Here, we address these questions in Drosophila. We find that cRNAs constitute a heterogeneous group of RNA species that is abundant in heterochromatic transcripts. We show that heterochromatic cRNAs interact with the heterogeneous nuclear ribonucleoproteins (hnRNP) hrp36/hrp48 and that depletion of linker histone dH1 impairs this interaction. dH1 depletion induces the accumulation of RNA::DNA hybrids (R-loops) in heterochromatin and, as a consequence, increases retention of heterochromatic cRNAs. These effects correlate with increased RNA polymerase II (RNAPII) occupancy at heterochromatin. Notably, impairing cRNA assembly by depletion of hrp36/hrp48 mimics heterochromatic R-loop accumulation induced by dH1 depletion. We also show that dH1 depletion alters nucleosome organization, increasing accessibility of heterochromatin. Altogether, these perturbations facilitate annealing of cRNAs to the DNA template, enhancing R-loop formation and cRNA retention at heterochromatin., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A 3D simulation of conductive nanofilaments (CNFs) in multilayer hexagonal-BN memristors is performed. To do so, a simulation tool based on circuit breakers is developed including for the first time a 3D resistive network. The circuit breakers employed can be modeled with two, three and four resistance states; in addition, a series resistance and a module to account for quantum effects, by means of the quantum point contact model, are also included. Finally, to describe real dielectric situations, regions with a high defect density are modeled with a great variety of geometrical shapes to consider their influence in the resistive switching (RS) process. The simulator has been tuned with measurements of h-BN memristive devices, fabricated with chemical-vapour-deposition grown h-BN layers, which were electrically and physically characterized. We show the formation of CNFs that produce filamentary charge conduction in our devices. Moreover, the simulation tool is employed to describe partial filament rupture in reset processes and show the low dependence of the set voltage on the device area, which is seen experimentally.

Objective: We present a solitary fibrous tumor (SFT) of the abdominal wall treated laparoscopically., Method: We will discuss the clinicopathologic characteristics and will present a review of the literature., Results: SFTs are rare neoplasms of mesenchymal origin. Its location in the abdominal wall is extremely rare. To the best of our knowledge, only 20 cases have currently been described in the literature., Conclusions: Complete surgical resection is the main therapy for all cases. A laparoscopic approach is safe. Clinical-radiological follow-up must be carried out due to its uncertain behavior, and perioperative treatment may be necessary in high-risk patients., (Copyright: © 2024 Permanyer.)

Background and Aims: The Organic Law Regulating Euthanasia (LORE, for its initials in Spanish) came into force in June 2021. This study aims to examine knowledge of the LORE among physicians licensed in Spain as well as their involvement with and the impact of the law., Methods: This work is a descriptive, cross-sectional study conducted by means of a survey. Information was gathered through a self-administered questionnaire., Results: The survey was answered by 1446 physicians licensed in Spain. The samples' demographic characteristics were as follows: 54.7% were women, the mean age was 52 ± 14 years, and 66.0% worked in a hospital. Catalonia was the autonomous community with the most participants (44.6%). Regarding specialties, anesthesiology and resuscitation had the highest number of participants (21.9%), followed by family and community medicine (18.5%). The LORE was known in detail by 24.3% of physicians, 58.0% had a positive opinion of it, and 31.1% had direct experience with the euthanasia procedure. Practitioners working in the hospital setting perceived the law more favorably compared to those in the primary care setting (62.3% vs. 47.3%, p < 0.01)., Conclusions: Most doctors did not have in-depth knowledge of the LORE, although a majority supported its existence, particularly those in hospital medicine. Most physicians who viewed the LORE negatively were male, older, and worked in primary care. A minority of physicians considered registering as conscientious objectors., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

A preliminary exploration of the physiology and morphology of the zebrafish embryo (ZFE) during the late-blastula and early-gastrula stages through its electrical properties was performed, applying the electrorotation (ROT) technique. This method, based on induced polarizability at the interfaces, was combined with an analytical spherical shell model to obtain the best fit of empirical data and the desired information, providing a means of understanding the role of different membranes. Suspended in two solutions of low conductivity, the major compartments of the ZFE were electrically characterized, considering morphological data from both observed records and data from the literature. Membrane integrity was also analyzed for dead embryos. The low permeability and relatively high permittivity obtained for the chorion probably reflected both its structural characteristics and external conditions. Reasonable values were derived for perivitelline fluid according to the influx of water that occurs after the fertilization of the oocyte. The so-called yolk membrane, which comprises three different and contiguous layers at the epiboly stage, showed atypical electrical values of the membrane, as did the yolk core with a relatively low permittivity. The internal morphological complexity of the embryo itself could be addressed in future studies by developing an accurate geometric model.

Background: Bacillus cereus is associated with milk, dairy product, and dairy farm contamination. The aim of this study was to characterize strains of B. cereus in the small-scale artisanal cheese production chain in southwestern Mexico., Methods: 130 samples were collected. B. cereus isolation was performed on Mannitol Egg Yolk Polymyxin (MYP) agar. Genotyping, enterotoxigenic profile, and determination of genes involved in the formation of B. cereus biofilm were performed by PCR. An antimicrobial susceptibility test was made by broth microdilution assay. The phylogenetic analysis was performed by amplification and sequencing of 16s rRNA., Results: B. cereus sensu lato was isolated and molecularly identified in 16 samples and B. cereus sensu stricto ( B. cereus ) was the most frequently isolated and identified species (81.25%). Of all the isolated B. cereus sensu lato strains, 93.75% presented at least one gene for some diarrheagenic toxins, 87.5% formed biofilms, and 18.75% were amylolytic. All B. cereus sensu lato strains were resistant to beta-lactams and folate inhibitors. A close phylogenetic relationship between isolates was found between the cheese isolates and the air isolates., Conclusions: Strains of B. cereus sensu lato were found in small-scale artisanal cheeses on a farm in southwestern Mexico.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population., Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases., Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism., Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term., Funding: None., Competing Interests: EAV, AS, CB, RM, KH, AGS, GR, MJS, and PBR are employees of Janssen Research and Development LLC and shareholders of Johnson & Johnson (J&J) stock. Many data partners (including JMR, JMRA, MAM, MdW, LHJ, GB, PRR) on this project have received funding from the Innovative Medicines Initiative (IMI) 2 Joint Undertaking (JU) under grant agreement No 806968. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The funding source had no role in writing the manuscript or the decision to submit it for publication. Odysseus Data Services, where SvS is employed, is a beneficiary of the mentioned IMI 2 JU project. DPA has received support from the EMA and Innovative Medicines Initiative. DPA's research group has received grant support from Amgen, Chesi-Taylor, Novartis, GSK, UCB Biopharma and J&J. DPA's department has received advisory/consultancy fees from AstraZeneca, Amgen, Astellas, J&J, and UCB Biopharma. DPA's department has received fees for speaker services from Amgen and UCB Biopharma. DPA's has other financial or non-financial interests in Janssen, on behalf of the IMI-funded EHDEN and European Medical Information Framework (EMIF) consortiums, and Synapse Management Partners have supported training programmes organised by DPA's department that was open for external participants. TDS received financial support from the Institute de Salud Carlos Ill (ISCIII; Miguel Servet 2021: CP21/00023) which is co-funded by the European Union. The funding source had no role in writing the manuscript or the decision to submit it for publication. PRR, MdW, LHJ work for a research group who received/receives unconditional research grants from Chiesi, Amgen, UCB, J&J, European Medicines Agency (EMA), and IMI. GH provided funding for use of the CUIMC database and the OHDSI infrastructure. GH received support through a grant to Columbia University (NIH R01 LM006910). MAS receives grants from the US Department of Veterans Affairs within the scope of this work, and grants and contracts from the US National Institutes of Health, US Food & Drug Administration, and Janssen Research & Development outside the scope of this work. EPM receives salary support from the Department of Medicine at University of Calgary. EPM receives consulting fees from Janssen Research & Development for work that is outside the scope of the current study. FM's main employment is for Heliant d.o.o, an EHR provider in Serbia. JDP received salary support through the Universidad de Norte. DJD and ZC are full-time employees of CPRD, which provides contract research services for government and related healthcare authorities, and the pharmaceutical industry, including Janssen. FN holds some AstraZeneca shares and was employed there until 2019. RV, AJB, AP2, LD, and CH received partial funding for this work by the University of California Health System and its Center for Data-Driven Insights and Innovation. MGK received support for the manuscript via institutional (internal funding) only. AJB's research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor’s Office of Planning and Research, California Institute for Regenerative Medicine, L’Oréal, and Progenity. AJB receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. AJB is a co-founder and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, Merck, and Roche. AJB has received honoraria and travel reimbursement for invited talks from J&J, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, many academic institutions, medical or disease specific foundations and associations, and health systems. AJB is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, Vet24seven, and several other non-health related companies and mutual funds. DRM has grants or contracts from Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). FB has a leadership or fiduciary role as the program chair of j-ISBA., (© 2023 The Author(s).)

COVID-19 lockdown measures have impacted the environment with both positive and negative effects. However, how human populations have perceived such changes in the natural environment and how they may have changed their daily habits have not been yet thoroughly evaluated. The objectives of this work were to investigate (1) the social perception of the environmental changes produced by the COVID-19 pandemic lockdown and the derived change in habits in relation to i) waste management, energy saving, and sustainable consumption, ii) mobility, iii) social inequalities, iv) generation of noise, v) utilization of natural spaces, and, vi) human population perception towards the future, and (2) the associations of these potential new habits with various socio-demographic variables. First, a SWOT analysis identified strengths (S), weaknesses (W), opportunities (O), and threats (T) generated by the pandemic lockdown measures. Second, a survey based on the aspects of the SWOT was administered among 2370 adults from 37 countries during the period from February to September 2021. We found that the short-term positive impacts on the natural environment were generally well recognized. In contrast, longer-term negative effects arise, but they were often not reported by the survey participants, such as greater production of plastic waste derived from health safety measures, and the increase in e-commerce use, which can displace small storefront businesses. We were able to capture a mismatch between perceptions and the reported data related to visits to natural areas, and generation of waste. We found that age and country of residence were major contributors in shaping the survey participants ´answers, which highlights the importance of government management strategies to address current and future environmental problems. Enhanced positive perceptions of the environment and ecosystems, combined with the understanding that livelihood sustainability, needs to be prioritized and would reinforce environmental protection policies to create greener cities. Moreover, new sustainable jobs in combination with more sustainable human habits represent an opportunity to reinforce environmental policy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis., Summary Background Data: Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended., Methods: Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded., Results: A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas., Conclusions: Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Diabetes is a frequent comorbidity in cancer patients, since they share common risk factors. In cancer, the concurrence of cachexia represents a poor prognostic factor, which is aggravated by poor nutritional status. Clinically, cancer cachexia manifests as a significant reduction in body weight, accompanied by changes in body composition and alterations in the balance of the biological system, and causes progressive dysfunction. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) with cancer cachexia.

Introduction: Type 2 diabetes mellitus is a highly prevalent disease worldwide, generating an increasing clinical and economic burden due to its micro- and macrovascular complications. Frequently, people with diabetes are hospitalized for various pathologies. These patients generally have higher risk of complications, prolonged hospitalizations and mortality. An additional factor that worsens the prognosis in these patients is the concurrence of malnutrition, especially in elderly people. All this makes the management of these patients challenging and requires a specific nutritional approach, whose purpose is to cover the nutritional requirements while always maintaining glycemic control. The purpose of this work is to provide, based on the evidence available in the literature and clinical experience, consensus recommendations by eighteen experts in Endocrinology and Nutrition on the nutritional approach of hospitalized patients with diabetes/ hyperglycemia and compare the optimal management, based on these recommendations with bedside usual care according to a panel of Spanish doctors surveyed about their daily clinical practice. This first article of this extraordinary issue of the journal Nutrición Hospitalaria describes the methodology of the study and the results obtained regarding common issues for all pathologies.

Introduction: People with diabetes are at high risk of requiring surgical intervention throughout their lives, and of perioperative complications in case of poor metabolic control. Hospitalization represents a stressful event that, together with other factors associated with diagnostic and therapeutic procedures, leads to a deterioration in the nutritional status of the patients. An association between poor nutritional status and adverse outcomes in surgical patients has been observed. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) in the perioperative setting.

Introduction: Exhaustive bibliographc research in PubMed/Medline.

Introduction: Heart failure (HF) is one of the leading causes of morbidity and mortality among older people, making it a major public health problem. Cardiovascular diseases in general, and HF in particular, are common comorbidities in people with type 2 diabetes (DM2). The concurrence of DM2 and HF is associated with more severe clinical symptoms and signs, and poorer quality of life and prognosis. Furthermore, due to the hypercatabolic state and nutrient absorption disorders, malnutrition is present in many HF cases. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) with HF.

Introduction: Sarcopenia is a multidimensional condition that negatively affects muscle mass, muscle strength, and physical performance. The prevalence of sarcopenia in people with diabetes is much higher than that of the general population, especially in individuals with poor nutritional status. Both sarcopenia and malnutrition are conditions amenable to intervention to improve clinical prognosis. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) with sarcopenia.

Introduction: The yearly incidence of hip fracture is very high, which generates significant healthcare and socioeconomic burden. These fractures can occur at any age, but the vast majority occur in people over 65 years of age and predominantly in women, due to the increased risk of menopause-associated osteoporosis. Type 2 diabetes mellitus (DM2), apart from altering glucose, lipid and protein metabolisms, also causes a deregulation of calcium, phosphorus and magnesium and dysfunction in bone metabolism. The prevalence of malnutrition in patients with hip fracture is also high, due to their advanced age, and the acute injury itself provokes catabolic and inflammatory responses that result in disease-related malnutrition and sarcopenia, which aggravates the patient's clinical condition. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) with hip fracture.

Introduction: Liver cirrhosis is a progressive and chronic disease of the liver, of diverse etiology, which is frequently associated with glucose intolerance and in some cases concurs with type 2 diabetes (DM2). DM2 is associated with adverse outcomes in patients with cirrhosis, including a higher rate of hospitalizations, a higher prevalence of hepatocellular carcinoma, and an increased risk of mortality. Malnutrition is another frequent complication of cirrhosis, the prevalence of which increases with the degree of liver dysfunction, worsening the prognosis. This article describes the results of the expert consensus and the responses of the panelists on the nutritional management in routine clinical practice of patients with diabetes/hyperglycemia hospitalized (non-critically ill) with liver cirrhosis.

Background & Aims: COVID-19 patients present a high hospitalization rate with a high mortality risk for those requiring intensive care. When these patients have other comorbid conditions and older age, the risk for severe disease and poor outcomes after ICU admission are increased. The present work aims to describe the preliminary results of the ongoing NUTRICOVID study about the nutritional and functional status and the quality of life of adult COVID-19 survivors after ICU discharge, emphasizing the in-hospital and discharge situation of this population., Methods: A multicenter, ambispective, observational cohort study was conducted in 16 public hospitals of the Community of Madrid with COVID-19 survivors who were admitted to the ICU during the first outbreak. Preliminary results of this study include data retrospectively collected. Malnutrition and sarcopenia were screened at discharge using MUST and SARC-F; the use of healthcare resources was measured as the length of hospital stay and requirement of respiratory support and tracheostomy during hospitalization; other study variables were the need for medical nutrition therapy (MNT); and patients' functional status (Barthel index) and health-related quality of life (EQ-5D-5L)., Results: A total of 176 patients were included in this preliminary analysis. Most patients were male and older than 60 years, who suffered an average (SD) weight loss of 16.6% (8.3%) during the hospital stay, with a median length of stay of 53 (27-89.5) days and a median ICU stay of 24.5 (11-43.5) days. At discharge, 83.5% and 86.9% of the patients were at risk of malnutrition and sarcopenia, respectively, but only 38% were prescribed MNT. In addition, more than 70% of patients had significant impairment of their mobility and to conduct their usual activities at hospital discharge., Conclusions: This preliminary analysis evidences the high nutritional and functional impairment of COVID-19 survivors at hospital discharge and highlights the need for guidelines and systematic protocols, together with appropriate rehabilitation programs, to optimize the nutritional management of these patients after discharge., Competing Interests: Conflict of interest Dr. C.C. reports personal fees from Takeda, personal fees from Fresenius Kabi, personal fees from Baxter, personal fees from Nutricia, personal fees from Persan Farma, outside the submitted work. The rest of the authors declare no conflict of interest related to this article. The authors declare that the funding provider was not involved in analyzing and dissemination of the study results, and that no conflict of interest exists with this organization., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate short-term mortality in people transferred from aged care homes for treatment in a hospital emergency department (ED) and to analyze factors associated with mortality., Material and Methods: Multicenter study of a random sample of retrospective data of patients treated in 5 EDs in Catalonia in 2017. The patients were over the age of 65 years and lived in residential care facilities. In addition to short-term mortality (in the ED or within 30 days of discharge), we analyzed sociodemographic characteristics, prior functional and cognitive status, multimorbidity, triage level on arrival, length of stay in the ED, and hospital admission. Odds ratios (ORs) for factors associated with short-term mortality were calculated by multivariate regression analysis., Results: A total of 2444 ED admissions were analyzed. The patients' mean (SD) age was 85.9 (7.1) years, and 67.7% .were women. Short-term mortality (in 15.5%) was associated with age >90 years (OR, 1.50; 95% CI, 1.5-1.95 years), a Charlson index >2 (OR, 1.47; 95% CI, 1.14-1.90), and dependency assessed as moderate (OR, 1.50; 95% CI, 1.03- 2.20) or severe (OR, 2.56; 95% CI, 1.84-3.55). Other associated factors were a higher level of urgency on triage, duration of ED stay, and hospital admission., Conclusion: Aged residents with the characteristics associated with short-term mortality could benefit from interventions for potentially avoiding unnecessary transfers to an ED, and from the implementation of comprehensive geriatric care within the ED. This could be useful to support good quality of care at the end of life.

Background: A huge amount of clinical data is generated daily and it is usually filed in clinical reports as natural language. Data extraction and further analysis requires reading and manual review of each report, which is a time consuming process. With the aim to test folksonomy to quickly obtain and analyze the information contained in media reports we set up this study., Methods and Objectives: We have used folksonomy to quickly obtain and analyze data from 1631 discharge clinical reports from the Nephrology Department of Hospital del Mar, without the need to create a structured database., Results: After posing some questions related to daily clinical practice (hypoglycaemic drugs used in diabetic patients, antihypertensive drugs and the use of renin angiotensin blockers during hospitalization in the nephrology department and data related to emotional environment of patients with chronic kidney disease) this tool has allowed the conversion of unstructured information in natural language into a structured pool of data for its further analysis., Conclusions: Folksonomy allows the conversion of the information contained in clinical reports as natural language into a pool of structured data which can be further easily analyzed without the need for the classical manual review of the reports., (Copyright © 2021 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Altered skeletal development in Down syndrome (DS) results in a brachycephalic skull, flattened face, shorter mandibular ramus, shorter limbs, and reduced bone mineral density (BMD). Our previous study showed that low doses of green tea extract enriched in epigallocatechin-3-gallate (GTE-EGCG), administered continuously from embryonic day 9 to postnatal day 29, reduced facial dysmorphologies in the Ts65Dn (TS) mouse model of DS, but high doses could exacerbate them. Here, we extended the analyses to other skeletal structures and systematically evaluated the effects of high and low doses of GTE-EGCG treatment over postnatal development in wild-type (WT) and TS mice using in vivo µCT and geometric morphometrics. TS mice developed shorter and wider faces, skulls, and mandibles, together with shorter and narrower humerus and scapula, and reduced BMD dynamically over time. Besides facial morphology, GTE-EGCG did not rescue any other skeletal phenotype in TS treated mice. In WT mice, GTE-EGCG significantly altered the shape of the skull and mandible, reduced the length and width of the long bones, and lowered the BMD. The disparate effects of GTE-EGCG depended on the dose, developmental timepoint, and anatomical structure analyzed, emphasizing the complex nature of DS and the need to further investigate the simultaneous effects of GTE-EGCG supplementation.

Background: A cancer diagnosis is a source of psychological and emotional stress, which are often maintained for sustained periods of time that may lead to depressive disorders. Depression is one of the most common psychological conditions in patients with cancer. According to the Global Cancer Observatory, breast and colorectal cancers are the most prevalent cancers in both sexes and across all age groups in Spain., Objective: This study aimed to compare the prevalence of depression in patients before and after the diagnosis of breast or colorectal cancer, as well as to assess the usefulness of the analysis of free-text clinical notes in 2 languages (Spanish or Catalan) for detecting depression in combination with encoded diagnoses., Methods: We carried out an analysis of the electronic health records from a general hospital by considering the different sources of clinical information related to depression in patients with breast and colorectal cancer. This analysis included ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) diagnosis codes and unstructured information extracted by mining free-text clinical notes via natural language processing tools based on Systematized Nomenclature of Medicine Clinical Terms that mentions symptoms and drugs used for the treatment of depression., Results: We observed that the percentage of patients diagnosed with depressive disorders significantly increased after cancer diagnosis in the 2 types of cancer considered-breast and colorectal cancers. We managed to identify a higher number of patients with depression by mining free-text clinical notes than the group selected exclusively on ICD-9-CM codes, increasing the number of patients diagnosed with depression by 34.8% (441/1269). In addition, the number of patients with depression who received chemotherapy was higher than those who did not receive this treatment, with significant differences (P<.001)., Conclusions: This study provides new clinical evidence of the depression-cancer comorbidity and supports the use of natural language processing for extracting and analyzing free-text clinical notes from electronic health records, contributing to the identification of additional clinical data that complements those provided by coded data to improve the management of these patients., (©Angela Leis, David Casadevall, Joan Albanell, Margarita Posso, Francesc Macià, Xavier Castells, Juan Manuel Ramírez-Anguita, Jordi Martínez Roldán, Laura I Furlong, Ferran Sanz, Francesco Ronzano, Miguel A Mayer. Originally published in JMIR Cancer (https://cancer.jmir.org), 11.07.2022.)

The importance of hybridization and introgression is well documented in the evolution of plants but, in insects, their role is not fully understood. Given the fact that insects are the most diverse group of organisms, assessing the impact of reticulation events on their evolution may be key to comprehend the emergence of such remarkable diversity. Here, we used an insect model, the Spialia butterflies, to gather genomic evidence of hybridization as a promoter of novel diversity. By using double-digest RADseq (ddRADseq), we explored the phylogenetic relationships between Spialia orbifer, S. rosae and S. sertorius, and documented two independent events of interspecific gene flow. Our data support that the Iberian endemism S. rosae probably received genetic material from S. orbifer in both mitochondrial and nuclear DNA, which could have contributed to a shift in the ecological preferences of S. rosae. We also show that admixture between S. sertorius and S. orbifer probably occurred in Italy. As a result, the admixed Sicilian populations of S. orbifer are differentiated from the rest of populations both genetically and morphologically, and display signatures of reproductive character displacement in the male genitalia. Additionally, our analyses indicated that genetic material from S. orbifer is present in S. sertorius along the Italian Peninsula. Our findings add to the view that hybridization is a pervasive phenomenon in nature and in butterflies in particular, with important consequences for evolution due to the emergence of novel phenotypes., (© 2022 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p < .001), ischemic type biliary lesions (OR 0.112, 95% CI 0.042-0.299, p < .001), graft loss (HR 0.371, 95% CI 0.267-0.516, p < .001), and patient death (HR 0.540, 95% CI 0.373-0.781, p = .001). Cold ischemia time (HR 1.004, 95% CI 1.001-1.007, p = .021) and re-transplantation indication (HR 9.552, 95% CI 3.519-25.930, p < .001) were significant independent predictors for graft loss among cDCD livers with A-NRP. While use of A-NRP helps overcome traditional limitations in cDCD liver transplantation, opportunity for improvement remains for cases with prolonged cold ischemia and/or technically complex recipients, indicating a potential role for complimentary ex situ perfusion preservation techniques., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: Routinely collected real world data (RWD) have great utility in aiding the novel coronavirus disease (COVID-19) pandemic response. Here we present the international Observational Health Data Sciences and Informatics (OHDSI) Characterizing Health Associated Risks and Your Baseline Disease In SARS-COV-2 (CHARYBDIS) framework for standardisation and analysis of COVID-19 RWD., Patients and Methods: We conducted a descriptive retrospective database study using a federated network of data partners in the United States, Europe (the Netherlands, Spain, the UK, Germany, France and Italy) and Asia (South Korea and China). The study protocol and analytical package were released on 11th June 2020 and are iteratively updated via GitHub. We identified three non-mutually exclusive cohorts of 4,537,153 individuals with a clinical COVID-19 diagnosis or positive test , 886,193 hospitalized with COVID-19 , and 113,627 hospitalized with COVID-19 requiring intensive services ., Results: We aggregated over 22,000 unique characteristics describing patients with COVID-19. All comorbidities, symptoms, medications, and outcomes are described by cohort in aggregate counts and are readily available online. Globally, we observed similarities in the USA and Europe: more women diagnosed than men but more men hospitalized than women, most diagnosed cases between 25 and 60 years of age versus most hospitalized cases between 60 and 80 years of age. South Korea differed with more women than men hospitalized. Common comorbidities included type 2 diabetes, hypertension, chronic kidney disease and heart disease. Common presenting symptoms were dyspnea, cough and fever. Symptom data availability was more common in hospitalized cohorts than diagnosed., Conclusion: We constructed a global, multi-centre view to describe trends in COVID-19 progression, management and evolution over time. By characterising baseline variability in patients and geography, our work provides critical context that may otherwise be misconstrued as data quality issues. This is important as we perform studies on adverse events of special interest in COVID-19 vaccine surveillance., Competing Interests: Ms. Kostka was an employee of IQVIA during the conduct of this study and received grant funding from the NIH NCATS National COVID Cohort Collaborative and the Bill and Melinda Gates Foundation. Mr. Sena is an employee and holds stock at Janssen Research & Development, a Johnson and Johnson family of companies. Dr. Golozar reports personal fees from Regeneron Pharmaceuticals, outside the submitted work. She is a full-time employee at Regeneron Pharmaceuticals. This work was not conducted at Regeneron Pharmaceuticals. Dr. Nyberg was an employee of AstraZeneca until 2019 and hold some shares. Dr. Wilcox reports grants from Bill and Melinda Gates Foundation, grants from National Institute of Health, during the conduct of the study. Mr. Andryc is an employee of Janssen Research & Development, a subsidiary of Johnson & Johnson. Dr. Reich is an employee of IQVIA. Dr. Blacketer reports she is an employee and holds stock at Janssen Research & Development, a Johnson and Johnson family of companies. Dr. Morales is supported by a Wellcome Trust Clinical Research Development Fellowship (Grant 214588/Z/18/Z) and reports grants from Chief Scientist Office (CSO), grants from Health Data Research UK (HDR-UK), grants from National Institute of Health Research (NIHR), outside the submitted work. Mr. DeFalco reports he is an employee and holds stock at Janssen Research & Development, a Johnson and Johnson family of companies. Mr. Thomas reports grants from Bill and Melinda Gates Foundation (INV-016910), grants from National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002369 to his institution, during the conduct of the study. Dr Jiang Bian reports grants from NIH/NIEHS (R21ES032762), during the conduct of the study. Dr. Posada reports grants from National Library of Medicine, during the conduct of the study. Dr. Natarajan reports grants from US NIH, during the conduct of the study. Dr. Matheny reports grants from US NIH, grants from US VA HSR&D, during the conduct of the study. Dr. Weiskopf reports personal fees from Merck, during the conduct of the study and outside the submitted work. Dr. Shah reports grants from National Library of Medicine, during the conduct of the study. Dr. Park reports grants from Ministry of Trade, Industry & Energy, Republic of Korea, grants from Ministry of Health & Welfare, Republic of Korea, grants from Bill & Melinda Gates Foundation, during the conduct of the study. Mr Robert Schuff reports grants from Gates Foundation, grants from NIH-NCATS, during the conduct of the study. Ms. Seager is an employee of IQVIA. Dr. DuVall reports grants from Anolinx, LLC, Astellas Pharma, Inc, AstraZeneca Pharmaceuticals LP, Boehringer Ingelheim International GmbH, Celgene Corporation, Eli Lilly and Company, Genentech Inc., Genomic Health, Inc., Gilead Sciences Inc., GlaxoSmithKline PLC, Innocrin Pharmaceuticals Inc., Janssen Pharmaceuticals, Inc., Kantar Health, Myriad Genetic Laboratories, Inc., Novartis International AG, and Parexel International Corporation through the University of Utah or Western Institute for Veteran Research outside the submitted work. Dr. Fortin is an employee of Janssen R&D, a subsidiary of Johnson and Johnson. Dr. Subbian reports grants from State of Arizona; Arizona Board of Regents, during the conduct of the study; grants from National Science Foundation (grant# 1838745), grants from Agency for Healthcare Research and Quality, grants from National Institutes of Health, outside the submitted work. Dr. Rijnbeek reports grants from Innovative Medicines Initiative, Janssen Research and Development, during the conduct of the study. He also works for a research institute which receives/received unconditional research grants from Yamanouchi, Pfizer-Boehringer Ingelheim, GSK, Amgen, UCB, Novartis, Astra-Zeneca, Chiesi, Janssen Research and Development, none of which relate to the content of this work. Dr. Hripcsak reports grants from US NIH and Janssen Research. Dr. Ryan is an employee of Janssen Research and Development and shareholder of Johnson & Johnson. Dr. Suchard reports grants from US National Institutes of Health, Department of Veterans Affairs, during the conduct of the study; grants and/or personal fees from IQVIA, Janssen Research and Development, US Food and Drug Administration, and Private Health Management, outside the submitted work. Dr. Prieto-Alhambra reports grants, non-financial support, speaker/consultancy services and/or advisory board membership from AMGEN, UCB Biopharma, and Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programmes organised by DPA’s Department and open for external participants. The views expressed are those of the authors and do not necessarily represent the views or policy of the Department of Veterans Affairs or the United States Government. No other relationships or activities that could appear to have influenced the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Kostka et al.)

Objective: The objective of the study is to assess and quantify the effect of the appearance of synchronous contralateral axillary on breast cancer survival. Breast cancer with contralateral axillary metastases (CAM) is classified as a metastatic disease. There are few cases reported and a lack of evidence of the significance of CAM when synchronous appearance with a primary tumor and no other site of disease., Methods: A systematic review following PRISMA guidelines to evaluate the prognosis of patients with synchronous CAM without other metastatic diseases comparing with metastatic disease is conducted through a search in PubMed, Embase, Clinical Key, and Cochrane Library databases. We present one case. The median age, follow-up, clinico-pathological characteristics, status of lymph nodes, treatments, and outcomes are analyzed., Results: A total of 23 articles (10 case reports and 13 case series) with a total 68 patients, including our case. Median age was 48 years old. Median follow-up was 27 months. Overall survival of the series was 71.4%. Twenty-one of 49 patients reported (36.2%) were alive without disease, fourteen (28.6%) were alive with disease while the rest fourteen (28.6%) died. Inflammatory presentation and ipsilateral axilla status were related to overall survival., Conclusions: Synchronous CAM in breast cancer show better outcomes in terms of overall survival than other metastatic diseases. The absence of comparative studies may not allow definitive conclusions, meanwhile, together with other authors we suggest treatment with curative intention. More studies may lead to consider a modification of TNM system., (© 2021. The Japanese Breast Cancer Society.)

Introduction: Surgical stress predisposes patients to have immune dysfunction and an increased risk of infection. Malnourished surgical patients have higher postoperative morbidity and mortality rates, higher readmission rates, and higher hospital costs. The use of an immunomodulatory formula is associated in the ESPEN guidelines with a reduction in wound healing problems, suture failure, and infectious and global complications. Several authors have suggested that, since most clinical trials evaluating the efficacy of immunonutrition have been carried out in a traditional perioperative setting, it would be interesting to investigate its efficacy in a more controlled setting, such as in the ERAS (Enhanced Recovery after Surgery) protocol. The objective of this work was: a) to define the role that immunonutrition should play in ERAS protocols based on the best scientific evidence available; b) to analyze the difficulties that continue to exist in real-life clinical practice to screen the nutritional risk of patients; c) to make a proposal of algorithms adapted to the characteristics of our environment regarding the screening, assessment, and nutritional treatment of surgical patients in fast-track surgery.

Reproductive character displacement occurs when competition for successful breeding imposes a divergent selection on the interacting species, causing a divergence of reproductive traits. Here, we show that a disputed butterfly taxon is actually a case of male wing colour shift, apparently produced by reproductive character displacement. Using double digest restriction-site associated DNA sequencing and mitochondrial DNA sequencing we studied four butterfly taxa of the subgenus Cupido (Lepidoptera: Lycaenidae): Cupido minimus and the taxon carswelli, both characterized by brown males and females, plus C. lorquinii and C. osiris, both with blue males and brown females. Unexpectedly, taxa carswelli and C. lorquinii were close to indistinguishable based on our genomic and mitochondrial data, despite displaying strikingly different male coloration. In addition, we report and analysed a brown male within the C. lorquinii range, which demonstrates that the brown morph occurs at very low frequency in C. lorquinii. Such evidence strongly suggests that carswelli is conspecific with C. lorquinii and represents populations with a fixed male brown colour morph. Considering that these brown populations occur in sympatry with or very close to the blue C. osiris, and that the blue C. lorquinii populations never do, we propose that the taxon carswelli could have lost the blue colour due to reproductive character displacement with C. osiris. Since male colour is important for conspecific recognition during courtship, we hypothesize that the observed colour shift may eventually trigger incipient speciation between blue and brown populations. Male colour seems to be an evolutionarily labile character in the Polyommatinae, and the mechanism described here might be at work in the wide diversification of this subfamily of butterflies., (© 2020 John Wiley & Sons Ltd.)

Objective: In 2007, the Ministry of Health (MoH) in Mexico implemented a multidisciplinary health-care model (MHC) for patients with type-2 diabetes (T2D), which has proven more effective in controlling this condition than the conventional health-care model (CHC)., Research Design and Methods: We compared the cost-effectiveness of the MHC vs. the CHC for patients with T2D using a quasi-experimental, retrospective design. Epidemiologic and cost data were obtained from a randomly selected sample of health-care units, using medical records as well as patient- and facility-level data. We modelled the cost-effectiveness of the MHC at one, 10 and 20 years using a simulation model., Results: The average cumulative costs per patient at 20 years were US$4,225 for the MHC and US$4,399 for the CHC. With a willingness to pay one gross domestic product (GDP) per capita per quality-adjusted life year (QALY) (US$8,910), the incremental net benefits per patient were US$1,450 and US$3,737 at 10 and 20 years, respectively. The MHC was cost-effective from the third year onward; however, increasing coverage to 500 patients per year rendered it cost-effective at year one., Conclusions: The MHC is cost-effective at 10 and 20 years. Cost-effectiveness can be achieved in the short term by increasing MHC coverage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The ischemic and primary vascular injury of the brainstem (BS) can determine, among other serious conditions, the brain death (BD) of the individual. We present 2 cases of individuals with primary ischemic vascular disease of the BS who evolved to BD and were donors of solid organs and tissues. In both cases, the clinical examination was positive for the diagnosis of BD, and transcranial Doppler did not confirm the pattern of cerebral circulatory arrest that accompanies BD. The magnetic resonance angiography performed on 1 patient confirmed the lesion etiology and the presence of vascular obstruction. Both patients were real and effective organ and tissue donors. In these cases, we suggest not to resort to transcranial Doppler as an auxiliary diagnostic test., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Objectives: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1., Material and Methods: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide., Recommendations: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives., Conclusion: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up., (Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Tools for actively targeted DNA demethylation are required to increase our knowledge about regulation and specific functions of this important epigenetic modification. DNA demethylation in mammals involves TET-mediated oxidation of 5-methylcytosine (5-meC), which may promote its replication-dependent dilution and/or active removal through base excision repair (BER). However, it is still unclear whether oxidized derivatives of 5-meC are simply DNA demethylation intermediates or rather epigenetic marks on their own. Unlike animals, plants have evolved enzymes that directly excise 5-meC without previous modification. In this work, we have fused the catalytic domain of Arabidopsis ROS1 5-meC DNA glycosylase to a CRISPR-associated null-nuclease (dCas9) and analyzed its capacity for targeted reactivation of methylation-silenced genes, in comparison to other dCas9-effectors. We found that dCas9-ROS1, but not dCas9-TET1, is able to reactivate methylation-silenced genes and induce partial demethylation in a replication-independent manner. We also found that reactivation induced by dCas9-ROS1, as well as that achieved by two different CRISPR-based chromatin effectors (dCas9-VP160 and dCas9-p300), generally decreases with methylation density. Our results suggest that plant 5-meC DNA glycosylases are a valuable addition to the CRISPR-based toolbox for epigenetic editing., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Targeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), particularly in NOTCH1-mutated patients. We provide first evidence that the Notch ligand DLL4 is a potent stimulator of Notch signaling in NOTCH1-mutated CLL cells while increases cell proliferation. Importantly, DLL4 is expressed in histiocytes from the lymph node, both in NOTCH1-mutated and -unmutated cases. We also show that the DLL4-induced activation of the Notch signaling pathway can be efficiently blocked with the specific anti-Notch1 antibody OMP-52M51. Accordingly, OMP-52M51 also reverses Notch-induced MYC, CCND1, and NPM1 gene expression as well as cell proliferation in NOTCH1-mutated CLL cells. In addition, DLL4 stimulation triggers the expression of protumor target genes, such as CXCR4, NRARP, and VEGFA, together with an increase in cell migration and angiogenesis. All these events can be antagonized by OMP-52M51. Collectively, our results emphasize the role of DLL4 stimulation in NOTCH1-mutated CLL and confirm the specific therapeutic targeting of Notch1 as a promising approach for this group of poor prognosis CLL patients.

Objectives: The IMPACT trial has compared the benefit in the reduction of moderate/severe exacerbations of single inhaler triple therapy (SITT) with fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus dual therapy with FF/VI (ICS/LABA) and UMEC/VI (LAMA/LABA) in the treatment of patients with chronic obstructive disease (COPD). This study performs a subgroup analysis of the cohort from Spain in the IMPACT study., Materials and Methods: In IMPACT, a 52-week randomized, double-blind, parallel-group, multicenter study ( N  = 10,355), patients ⩾40 years of age with COPD and ⩾1 moderate/severe exacerbations in the previous year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg or UMEC/VI 62.5/25 µg administered via the Ellipta inhaler. Here, we present a subgroup analysis of the 499 patients from Spain, included in the intent-to-treat (ITT) population in the study. Endpoint assessed included exposure-adjusted rate of moderate and severe exacerbations., Results: In the Spain cohort, the exposure-adjusted rate of on-treatment moderate/severe COPD exacerbations per year for FF/UMEC/VI was 1.31 versus 1.43 and 1.57 for FF/VI and UMEC/VI, respectively. No new adverse events were identified. The results are consistent with those observed in the overall ITT study population., Conclusion: In the Spain cohort of the IMPACT study, patients receiving triple therapy with FF/UMEC/VI had a lower exposure-adjusted rate of exacerbations compared with FF/VI and UMEC/VI, similar to the overall population. Study Title: A Phase III, 52 Week, Randomized, Double-blind, 3-arm Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Triple Combination FF/UMEC/VI With the Fixed Dose Dual Combinations of FF/VI and UMEC/VI, All Administered Once-daily in the Morning Via a Dry Powder Inhaler in Subjects With Chronic Obstructive Pulmonary Disease URL : https://www.clinicaltrialsregister.eu/ctr-search/search?query=CTT116855/ https://clinicaltrials.gov/ct2/show/NCT02164513 Registration number : GSK (CTT116855/NCT02164513). The reviews of this paper are available via the supplemental material section.

Background and Objectives: Steinert's disease or myotonic dystrophy type 1 (MD1), (OMIM 160900), is the most prevalent myopathy in adults. It is a multisystemic disorder with dysfunction of virtually all organs and tissues and a great phenotypical variability, which implies that it has to be addressed by different specialities with experience in the disease. The knowledge of the disease and its management has changed dramatically in recent years. This guide tries to establish recommendations for the diagnosis, prognosis, follow-up and treatment of the complications of MD1., Material and Methods: Consensus guide developed through a multidisciplinary approach with a systematic literature review. Neurologists, pulmonologists, cardiologists, endocrinologists, neuropaediatricians and geneticists have participated in the guide., Recommendations: The genetic diagnosis should quantify the number of CTG repetitions. MD1 patients need cardiac and respiratory lifetime follow-up. Before any surgery under general anaesthesia, a respiratory evaluation must be done. Dysphagia must be screened periodically. Genetic counselling must be offered to patients and relatives., Conclusion: MD1 is a multisystemic disease that requires specialised multidisciplinary follow-up., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Hyponatremia is the most prevalent electrolyte disorder in Intensive Care Units. It is associated with an increase in morbidity, mortality and hospital stay. The majority of the published studies are observational, retrospective and do not include critical patients; hence it is difficult to draw definitive conclusions. Moreover, the lack of clinical evidence has led to important dissimilarities in the recommendations coming from different scientific societies. Finally, etiopathogenic mechanisms leading to hyponatremia in the critical care patient are complex and often combined, and an intensive analysis is clearly needed. A study was therefore made to review all clinical aspects about hyponatremia management in the critical care setting. The aim was to develop a Spanish nationwide algorithm to standardize hyponatremia diagnosis and treatment in the critical care patient., (Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

Background: Patient satisfaction with remote patient monitoring (RPM) of implantable cardioverter defibrillators (ICDs) seems to be high, yet knowledge on long-term patient experiences is limited. The European REMOTE-CIED study explored patients' experiences with RPM, examined patient's preferences for ICD follow-up, and identified determinants of patient's preferences in the first 2 years postimplantation., Methods: European heart failure patients (N = 300; median age = 66 years [interquartile range (IQR) = 59-73], and 22% female) with a first-time ICD received a Boston Scientific LATITUDE RPM system (Marlborough, MA, USA) and had scheduled in-clinic follow-ups once a year. Patients completed questionnaires at 1-2 weeks and also at 3, 6, 12, and 24 months postimplantation and clinical data were obtained from their medical records. Patient evaluation data were analyzed descriptively, and Student's t-tests/Man-Whitney U tests or Chi-square tests/Fisher's exact tests were performed to examine determinants of patient preferences., Results: At 2 years postimplantation, the median patient satisfaction score with the RPM system was 9 out of 10 (IQR = 8-10), despite 53% of the patients experiencing issues (eg, failure to transmit data). Of the 221 patients who reported their follow-up preferences, 43% preferred RPM and 19% preferred in-clinic follow-up. Patients with a preference for RPM were more likely to be higher educated (P = 0.04), employed (P = 0.04), and equipped with a new LATITUDE model (P = 0.04), but less likely to suffer from chronic obstructive pulmonary disease (P = 0.009)., Conclusion: In general, patients were highly satisfied with RPM, but a subgroup preferred in-clinic follow-up. Therefore, physicians should include patients' concerns and preferences in the decision-making process, to tailor device follow-up to individual patients' needs and preferences., (© 2018 The Authors. Pacing and Clinical Electrophysiology Published by Wiley Periodicals, Inc.)

Embryo biopsy for fetal sexing has clinical application, but few reports are available of its use within an active embryo transfer program. We evaluated results on biopsy of 459 embryos over one breeding season. There were no significant differences in pregnancy rate between biopsied and non-biopsied embryos (72% vs 73%) or for biopsied embryos recovered at the centre (73%) compared with those shipped overnight (72%). However, the pregnancy rate decreased significantly in shipped embryos biopsied ≥20h after collection. Overall, 86% of biopsies provided a sex diagnosis. The likelihood of a positive genomic (g) DNA result was significantly higher for biopsies from large blastocysts (96%) than from smaller embryos (70-85%). In total, 38% of biopsies were positive for Y chromosome DNA (Y-DNA) and were diagnosed as male. Subsequently, 95% of Y-DNA-positive embryos were confirmed as male and 78% of Y-DNA-negative embryos were confirmed as female. The accuracy of prediction of female (Y-DNA negative) was significantly higher when the biopsy sample was probed for Y-DNA only compared with probing for both gDNA and Y-DNA. We estimate that by transferring only Y-DNA-negative embryos, 3% of potential female pregnancies may have been lost, and production of male pregnancies was reduced by 72%.

Background: The use of new mobile technologies in the health and social welfare sectors is already a reality. The ICT Social Health Foundation, in accordance with the technology strategy of the Catalan government's Ministry of Health and its Ministry of Labour, Social Affairs and Families, is leading an initiative to create a public library of apps for its AppSalut Site., Objective: The objective of this paper is to present an account of the design of the project, with a global perspective, applied to the Catalan ecosystem, which can be divided into 3 areas: the framework governing the recommendation and prescription of apps, the subset of interoperability for mobile environments, and the data storage infrastructure., Methods: The security and credibility of the apps included in the catalog is ensured by submitting them to an accreditation process in the public domain that provides users with the guarantee that they are fit for purpose and trustworthy for the management and care of their health, while providing health care professionals with the possibility of recommending the apps in the doctor's surgery, as well as adding the information generated by the users' mobile devices to the information systems of the various organizations concerned., Results: An examination of the abovementioned areas suggests possibilities for improvements in the future. The experience obtained from the development of this element has shown the heterogeneity of the vocabularies used, as expected, due to the lack of awareness on the part of the developers regarding the need to standardize the information generated by the app, requiring the foundation to take on the role of consultant., Conclusions: The project has evolved in keeping with changes in the technological and social paradigm and responds very satisfactorily to the needs posed to it. It can be seen as a landmark experience in mobile strategies in the fields of health and welfare of any public health system. The experience has shown itself to be feasible in organizational terms, necessary in any attempt to integrate mobile technologies into public health practice, and a global pioneer in the field., International Registered Report Identifier (irrid): RR1-10.2196/11414., (©Francesc López Seguí, Carme Pratdepàdua Bufill, Ariadna Rius Soler, Marc de San Pedro, Bernat López Truño, Agnès Aguiló Laine, Jordi Martínez Roldán, Francesc García Cuyàs. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 21.12.2018.)