A Macroscopic Interpretation of the Correlation between Electrical Percolation and Mechanical Properties of Poly-(Ethylene Vinyl Acetate)/Zn Composites.

Elastic composites were prepared using a procedure involving hot plates and zinc powder that was directly dispersed into an EVA matrix. The correlation between the zinc content and the conductive properties of the material was studied via impedance spectroscopy, the thermal properties of the material were studied via differential calorimetry and the mechanical properties of the composites were studied via tensile strength curves, representing an important advancement in the characterization of this type of composite material. The composites' tensile strength and elongation at break decrease with the addition of filler since zinc particles act as stress-concentrating centres, while the composites' hardness and Young's modulus increase because of an increase in the stiffness of the material. The AC perturbation across the EVA/Zn composites was characterized using an RC parallel equivalent circuit that allowed us to easily measure their resistivity (ρp) and permittivity (εp). The dependence of these electrical magnitudes on the zinc content is correlated with their mechanical properties across the characteristic time constant τp = ρp·Îµp of this equivalent circuit. The dependence of the mechanical and electrical magnitudes on the zinc content is consistent with the formation of percolation clusters. The addition of graphite particles increases their potential performance. Three possible mechanisms for the electrical transport of the ac-perturbation across the EVA/Zn composites have been identified. Chemical corrosion in acid media causes the loss of zinc surface particles, but their bulk physical properties practically remain constant.

Valorization of Crab Shells as Potential Sorbent Materials for CO2 Capture.

This study delves into the potential advantage of utilizing crab shells as sustainable solid adsorbents for CO2 capture, offering an environmentally friendly alternative to conventional porous adsorbents, such as zeolites, silicas, metal-organic frameworks (MOFs), and porous carbons. The investigation focuses on crab shell waste, which exhibits inherent natural porosity and N-bearing groups, making them promising candidates for CO2 physisorption and chemisorption applications. Selective deproteinization and demineralization treatments were used to enhance textural properties while preserving the natural porous structure of the crab shells. The impact of deproteinization and demineralization treatments on CO2 adsorption and speciation at the atomic scale, via solid-state NMR, and correlated findings with textural properties and biomass composition were investigated. The best-performing sample exhibits a surface area of 36 m2/g and a CO2 adsorption capacity of 0.31 mmol/g at 1 bar and 298 K, representing gains of ∼3.5 and 2, respectively, compared to the pristine crab shell. These results underline the potential of fishing industry wastes as a cost-effective, renewable, and eco-friendly source to produce functional porous adsorbents.

Transverse colon volvulus in a young patient with wandering liver.

We present the case of a 26-year-old male patient with no history of interest who consulted the emergency department due to occlusive symptoms. Urgent CT showed the presence of a transverse colonic volvulus in the context of a heterotopic liver, located in the left hypochondrium. There were no clinical or radiological signs of perforation or ischemia, so urgent endoscopic decompression was performed with subsequent elective surgery with a favorable resolution of the condition. Transverse colonic volvulus is rare (<1%) and wandering liver is an exceptional predisposing factor, with less than a hundred published cases. In these patients, endoscopic decompression carries a risk of perforation with high recurrence rates, and surgical treatment should be considered. However, in this case, in the absence of severity criteria, decompressive colonoscopy was considered an urgent treatment and subsequent elective surgery with favorable results.

Overview and Recent Advances in Hyphenated Electrochemical Techniques for the Characterization of Electroactive Materials.

A hyphenated electrochemical technique consists of the combination of the coupling of an electrochemical technique with a non-electrochemical technique, such as spectroscopical and optical techniques, electrogravimetric techniques, and electromechanical techniques, among others. This review highlights the development of the use of this kind of technique to appreciate the useful information which can be extracted for the characterization of electroactive materials. The use of time derivatives and the acquisition of simultaneous signals from different techniques allow extra information from the crossed derivative functions in the dc-regime to be obtained. This strategy has also been effectively used in the ac-regime, reaching valuable information about the kinetics of the electrochemical processes taking place. Among others, molar masses of exchanged species or apparent molar absorptivities at different wavelengths have been estimated, increasing the knowledge of the mechanisms for different electrode processes.

Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility.

BACKGROUND: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. OBJECTIVES: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. MATERIALS AND METHODS: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. RESULTS: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. CONCLUSIONS: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.

A real-world evidence study of nabiximols in multiple sclerosis patients with resistant spasticity: Analysis in relation to the newly described 'spasticity-plus syndrome'.

BACKGROUND AND PURPOSE: Nabiximols is a therapeutic option for patients with multiple sclerosis (MS) spasticity whose symptoms are poorly controlled by conventional oral first-line medications. This study aimed to assess the relationship between changes in spasticity severity (measured on the 0-10 numeric rating scale [NRS]) and the presence of associated symptoms in patients treated with nabiximols, and to investigate the presence of the newly described 'spasticity-plus syndrome'. METHODS: We analyzed real-world data from the Italian Medicines Agency e-Registry on 1138 patients with MS spasticity who began treatment with nabiximols. Evaluation time points were baseline, 4 weeks, and 3, 6, 12 and 18 months after treatment start. RESULTS: Common symptoms associated with MS spasticity in this cohort were pain (38.4% at baseline), sleep disturbances (32.7%), and spasms/cramps (28.5%). Pain was frequently clustered with sleep disturbances (57.2% of pain cases) and spasms/cramps (43.9%). Approximately one-third of patients with data at all evaluation time points maintained treatment at 18 months. Nabiximols reduced the baseline mean spasticity 0-10 NRS score by 24.6% at Week 4, and by 33.9% at 18 months in treatment continuers. Nabiximols resolved a range of MS spasticity-associated symptoms at Week 4, and after 18 months in treatment continuers. CONCLUSION: This real-world analysis supports the concept of a spasticity-plus syndrome and suggests that nabiximols can favorably impact a range of spasticity-associated symptoms.

Dermatofibrosarcoma protuberans of the upper eyelid treated with surface mould high-dose-rate brachytherapy.

Dermatofibrosarcoma protuberans (DFSP) is a rare spindle cell tumor, comprising less than 0.1% of all malignant neoplasms. The trunk is the most commonly affected area, followed by the extremities and the head and neck. Of the latter cases, involvement of the periorbital area has been infrequently reported. Surgery is the cornerstone of treatment but is associated with a high rate of recurrence if margins remain close or positive. This rate has been shown to be considerably decreased by the use of adjuvant radiotherapy. However, most reported cases utilize external beam radiation therapy (EBRT ) in the treatment of DFSP, including those with primary periorbital locations. We report a case of a 40-year-old male, presenting with a small nodule on the right upper eyelid, diagnosed as DFSP with positive margins post-surgery and treated with adjuvant customized surface mould high-dose-rate (HDR) brachytherapy in a low-resource setting.

Early Detection of Atrial Fibrillation in Community Pharmacies-CRIFAFARMA Study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia to appear in clinical practice. People with AF have 5 times the risk of stroke compared to the general population. OBJECTIVE: This study aimed to determine the prevalence of AF in people over the age of 50 without known AF, who presented to a community pharmacy to check their cardiovascular risk factors, to identify risk factors associated with AF, and to assess the risk of stroke in people who screened positive for AF. METHODS: A multicenter observational descriptive study of a screening program took place from May to December 2016. A blood pressure monitor (Microlife Watch BP Home) was used to screen for AF, and the CHA2DS2-VASc questionnaire was used to assess stroke risk. RESULTS: The study included 452 adults over the age of 50. The CRIFAFARMA study detected a prevalence of AF of 9.1%. Risk factors for AF were: age of 75 years or older (P = .024), lack of physical activity (P = .043), diabetes (P < .001), dyslipidemia (P = .003), and history of cardiovascular disease (P = .003). Diabetes (OR 2.79, P = .005) and dyslipidemia (OR 2.16, P = .031) had a combined explanatory capacity in the multivariable logistic regression model adjusted for age. 85% were at high risk of stroke according to the CHA2DS2-VASc scale. CONCLUSIONS: AF was detected in more than 9% of the included population. Factors associated with AF were advanced age, lack of physical activity, diabetes, dyslipidemia, and history of cardiovascular disease, with diabetes and dyslipidemia standing out as the factors with independent explanatory capacity.

Mortality Trends Related to Bladder Cancer in Spain, 1999-2018.

Bladder cancer (BC) is an important cause of premature mortality (PM, <75 years). Spain has one of the highest BC mortality rates in Europe. The objective of this study was to analyse BC mortality trends between 1999 and 2018 in Spain. The study was based on data from the National Institute of Statistics (Instituto Nacional de Estadística-INE). Age-adjusted mortality rates (AAMRs) were calculated by sex and age group. A trend analysis was performed using Joinpoint regression models and years of potential life lost (YPLL). Mortality in men resulting from BC decreased in all age groups studied. This was not observed in women, for whom mortality only decreased in the ≥75 age group. Deaths due to BC occurred prematurely in 38.6% of men and in 23.8% of women, which indicated a greater impact on YPLL in men compared to women. Over the last 20 years, there has been a significant decrease in BC mortality rate, except in women under 75 years of age. Despite this temporal trend of decreasing mortality, BC continues to have a significant impact on YPLL, mainly in men. Given this context, it is important to direct more resources towards prevention and early diagnosis strategies to correct this situation.

Impact of a clinical pathway on cardiovascular risk in patients with diabetes.

OBJECTIVES: Clinical pathways (CPs) are interventions that target the way clinical practice guidelines are applied. They can be implemented in different diseases, including diabetes. In this study we evaluated the impact of the implementation of a CP in the control of cardiovascular risk factors and the occurrence of new events in patients with type 2 diabetes. METHODS: A pre- and post-intervention population-based study in a Spanish region, conducted in 2014-2016. Variables before and after the intervention were: screening; good control of diabetes, dyslipidemia and hypertension; hypoglycemia and hyperglycemic decompensation; obesity; cardiovascular events; diabetic ketoacidosis; hyperglycemic and hypoglycemic coma. Proportional differences and parameters of clinical relevance (absolute and relative risk reduction, relative risk and number needed to treat) were calculated. RESULTS: The CP achieved an improvement in all outcomes, reducing events and increasing control of different cardiovascular parameters. The greatest improvement was in metabolic control (HbA1c) (37.1% in younger patients and 34.0% in older patients) and screening (5.4%). Indicators of clinical relevance showed that the CP was able to improve metabolic control of diabetes with little effort and great benefit. CONCLUSION: The CP was of considerable benefit to metabolic control as well as control of dyslipidemia and obesity. Screening for diabetes also benefitted. The CP decreased the incidence of events, especially of angina pectoris.

A new fastening system for temporary pacing with active-fixation leads: effectiveness and safety.

AIMS: Temporary cardiac pacing with active-fixation leads (TPAFL) using a reusable permanent pacemaker generator has been shown to be safer than lead systems without fixation. However, TPAFL requires the off-label use of pacemaker leads and generators. We designed a fastening system to ensure the safety and efficacy of the procedure: the KronoSafe System®. To demonstrate the safety and effectiveness of the KronoSafe System® for temporary pacing in a series of patients receiving TPAFL. METHODS AND RESULTS: A prospective cohort of 20 patients undergoing TPAFL between August 2019 and June 2020 was recruited in a Spanish region. The temporary pacemaker was implanted through jugular access and secured with the KronoSafe System®. R-wave detection, lead impedance, and capture threshold were assessed every 48 h. Complications associated with the procedure or occurring during TPAFL were recorded. There were no complications associated with temporary pacing, and the therapy was effective in all cases. TPAFL was used for a mean of 7.6 days (maximum 25 days), and 84.56% of the time in a cardiology ward. CONCLUSION: TPAFL secured using the KronoSafe system® provides safe and stable cardiac stimulation for patients requiring temporary cardiac pacing.

Influence of Pharmaceutical Copayment on Emergency Hospital Admissions: A 1978-2018 Time Series Analysis in Spain.

No studies have evaluated the influence of pharmaceutical copayment on hospital admission rates using time series analysis. Therefore, we aimed to analyze the relationship between hospital admission rates and the influence of the introduction of a pharmaceutical copayment system (PCS). In July 2012, a PCS was implemented in Spain, and we designed a time series analysis (1978-2018) to assess its impact on emergency hospital admissions. Hospital admission rates were estimated between 1978 and 2018 each month using the Hospital Morbidity Survey in Spain (the number of urgent hospital admissions per 100,000 inhabitants). This was conducted for men, women and both and for all-cause, cardiovascular and respiratory hospital discharges. Life expectancy was obtained from the National Institute of Statistics. The copayment variable took a value of 0 before its implementation (pre-PCS: January 1978-June 2012) and 1 after that (post-PCS: July 2012-December 2018). ARIMA (Autoregressive Integrated Moving Average) (2,0,0)(1,0,0) models were estimated with two predictors (life expectancy and copayment implementation). Pharmaceutical copayment did not influence hospital admission rates (with p-values between 0.448 and 0.925) and there was even a reduction in the rates for most of the analyses performed. In conclusion, the PCS did not influence hospital admission rates. More studies are needed to design health policies that strike a balance between the amount contributed by the taxpayer and hospital admission rates.

Midkine Interaction with Chondroitin Sulfate Model Synthetic Tetrasaccharides and Their Mimetics: The Role of Aromatic Interactions.

Midkine (MK) is a neurotrophic factor that participates in the embryonic central nervous system (CNS) development and neural stem cell regulation, interacting with sulfated glycosaminoglycans (GAGs). Chondroitin sulfate (CS) is the natural ligand in the CNS. In this work, we describe the interactions between a library of synthetic models of CS-types and mimics. We did a structural study of this library by NMR and MD (Molecular Dynamics), concluding that the basic shape is controlled by similar geometry of the glycosidic linkages. Their 3D structures are a helix with four residues per turn, almost linear. We have studied the tetrasaccharide-midkine complexes by ligand observed NMR techniques and concluded that the shape of the ligands does not change upon binding. The ligand orientation into the complex is very variable. It is placed inside the central cavity of MK formed by the two structured beta-sheets domains linked by an intrinsically disordered region (IDR). Docking analysis confirmed the participation of aromatics residues from MK completed with electrostatic interactions. Finally, we test the biological activity by increasing the MK expression using CS tetrasaccharides and their capacity in enhancing the growth stimulation effect of MK in NIH3T3 cells.

Management of Truncal Acne With Oral Sarecycline: Pooled Results from Two Phase-3 Clinical Trials.

BACKGROUND: Acne vulgaris is a common skin disease that affects the face, chest, and back. While truncal acne is present in at least 50% of patients, clinical studies have focused predominantly on facial acne.1,2 Few treatments to date have been evaluated for truncal acne. Sarecycline is a narrow-spectrum, third-generation, tetracycline-class oral drug approved for the treatment of acne. Pivotal phase-3 studies show that sarecycline is safe, well-tolerated, and effective treatment for moderate to severe acne vulgaris. METHOD: Pooled analysis was performed for truncal acne results with sarecycline from the two phase 3 studies. Investigator Global Assessment (IGA) success was evaluated at weeks 3, 6, 9, and 12. RESULTS: Chest IGA success rate were significantly greater with sarecycline versus placebo at weeks 3 (11.84% vs 7.71%, respectively; P=0.0192), 6 (18.81% vs 14.03%, respectively; P=0.0390), and 12 (33.42% vs 20.77%, respectively; P<0.0001). Back IGA success rate was also significantly greater with sarecycline versus placebo group at weeks 3 (12.13% vs 7.04%, respectively; P=0.0023), 6 (18.42% vs 14.34%, respectively; P=0.0412), 9 (29.05% vs 19.88%, respectively; P=0.0004) and 12 (33.07% vs 21.91%, respectively; P<0.0001)Conclusion: Sarecycline efficacy for truncal acne was observed within 3 weeks after treatment, supporting sarecycline as an optimal choice for oral treatment of moderate to severe truncal acne. J Drugs Dermatol. 2021;20(6):634-640. doi:10.36849/JDD.6204.

Impact of Anal Fissure on Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness: A Case-Control Study.

INTRODUCTION: Scientific literature on determining patterns of personality traits in patients with anal fissure is limited. OBJECTIVES: To determine whether certain common psychological traits are associated with anal fissure. METHODS: A case-control study was carried out in Spain in 2016-2017. Patients with acute or chronic idiopathic anal fissure (n = 35) and controls (n = 32) were recruited. The main outcome measures were those defined in the NEO-FFI questionnaire, validated in Spain, which was administered to all the participants. This questionnaire evaluates the following traits: neuroticism, extraversion, openness, agreeableness, and conscientiousness. RESULTS: Three significant traits were noted: (1) greater neuroticism in the cases (OR 1.19, 95% CI 1.08-1.32, p < 0.001, AUC 0.77), (2) greater openness to experience in the controls (OR 0.90, 95% CI 0.83-0.98, p = 0.015, AUC 0.69), and (3) greater conscientiousness in the controls (OR 0.91, 95% CI 0.83-1.00, p = 0.049, AUC 0.69). CONCLUSIONS: The cases mainly presented higher levels of neuroticism and lower levels of openness to experience and conscientiousness. Further studies are needed to corroborate our results.

Factors Associated with Non-Adherence to Drugs in Patients with Chronic Diseases Who Go to Pharmacies in Spain.

BACKGROUND: Pharmacological non-adherence in chronic diseases is 40-65%. No predictive profile of non-adherence exists in patients with multiple chronic diseases. Our study aimed to quantify the prevalence of non-adherence to pharmacological treatment and its associated factors in patients who visit pharmacies in Spain. METHODS: This observational cross-sectional study included patients with one or more chronic diseases. The variables analyzed were demographics, diseases involved, self-medication, information about disease, and lifestyle. The main variable was adherence using the Morisky-Green test. A total of 132 pharmacies collaborated, providing 6327 patients representing all Spain regions (April-December 2016). Bivariate and multivariate analyses were performed and the area under the receiver operating characteristic (ROC) curve was calculated. RESULTS: Non-adherence was 48.4% (95% confidence interval (CI): 47.2-49.7%). The variables that reached significance in the multivariate model were: difficulty in taking medication, self-medication, desire for more information, smoking, lower physical activity, younger age and number of chronic treatments. Discrimination was satisfactory (area under the ROC curve = 70%). Our study found that 50% patients was non-adherent and we obtained a profile of variables associated with therapeutic non-adherence. CONCLUSIONS: It is cause for concern that in patients with multiple diseases and taking multiple medications, there is an association between non-adherence, self-medication and worse lifestyle.

A Systematic Review of Clinical Trials Assessing Sexuality in Hysterectomized Patients.

In hysterectomized patients, even though there is still controversy, evidence indicates that in the short term, the vaginal approach shows benefits over the laparoscopic approach, as it is less invasive, faster and less costly. However, the quality of sexual life has not been systematically reviewed in terms of the approach adopted. Through a systematic review, we analyzed (CRD42020158465 in PROSPERO) the impact of hysterectomy on sexual quality and whether there are differences according to the surgical procedure (abdominal or vaginal) for noncancer patients. MEDLINE (through PubMed), Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and Scopus were reviewed to find randomized clinical trials assessing sexuality in noncancer patients undergoing total hysterectomy, comparing vaginal and abdominal (laparoscopic and/or open) surgery. Three studies that assessed the issue under study were finally included. Two of these had a low risk of bias (Cochrane risk of bias tool); one was unclear. There was significant variability in how sexuality was measured, with no differences between the two approaches considered in the review. In conclusion, no evidence was found to support one procedure (abdominal or vaginal) over another for non-oncological hysterectomized patients regarding benefits in terms of sexuality.

Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort.

BACKGROUND: Severe spermatogenic failure (SpF) represents the most extreme manifestation of male infertility, as it decreases drastically the semen quality leading to either severe oligospermia (SO, <5 million spermatozoa/mL semen) or non-obstructive azoospermia (NOA, complete lack of spermatozoa in the ejaculate without obstructive causes). OBJECTIVES: The main objective of the present study is to analyze in the Iberian population the effect of 6 single-nucleotide polymorphisms (SNPs) previously associated with NOA in Han Chinese through genome-wide association studies (GWAS) and to establish their possible functional relevance in the development of specific SpF patterns. MATERIALS AND METHODS: We genotyped 674 Iberian infertile men (including 480 NOA and 194 SO patients) and 1058 matched unaffected controls for the GWAS-associated variants PRMT6-rs12097821, PEX10-rs2477686, CDC42BPA-rs3000811, IL17A-rs13206743, ABLIM1-rs7099208, and SOX5-rs10842262. Their association with SpF, SO, NOA, and different NOA phenotypes was evaluated by logistic regression models, and their functional relevance was defined by comprehensive interrogation of public resources. RESULTS: ABLIM1-rs7099208 was associated with SpF under both additive (OR = 0.86, p = 0.036) and dominant models (OR = 0.78, p = 0.026). The CDC42BPA-rs3000811 minor allele frequency was significantly increased in the subgroup of NOA patients showing maturation arrest (MA) of germ cells compared to the remaining NOA cases under the recessive model (OR = 4.45, p = 0.044). The PEX10-rs2477686 SNP was associated with a negative testicular sperm extraction (TESE) outcome under the additive model (OR = 1.32, p = 0.034). The analysis of functional annotations suggested that these variants affect the testis-specific expression of nearby genes and that lincRNA may play a role in SpF. CONCLUSIONS: Our data support the association of three previously reported NOA risk variants in Asians (ABLIM1-rs7099208, CDC42BPA-rs3000811, and PEX10-rs2477686) with different manifestations of SpF in Iberians of European descent, likely by influencing gene expression and lincRNA deregulation.

The Sumo proteome of proliferating and neuronal-differentiating cells reveals Utf1 among key Sumo targets involved in neurogenesis.

Post-translational modification by covalent attachment of the Small ubiquitin-like modifier (Sumo) polypeptide regulates a multitude of processes in vertebrates. Despite demonstrated roles of Sumo in the development and function of the nervous system, the identification of key factors displaying a sumoylation-dependent activity during neurogenesis remains elusive. Through a SILAC (stable isotope labeling by/with amino acids in cell culture)-based proteomic approach, we have identified the Sumo proteome of the model cell line P19 under proliferation and neuronal differentiation conditions. More than 300 proteins were identified as putative Sumo targets differentially associated with one or the other condition. A group of proteins of interest were validated and investigated in functional studies. Among these, Utf1 was revealed as a new Sumo target. Gain-of-function experiments demonstrated marked differences between the effects on neurogenesis of overexpressing wild-type and sumoylation mutant versions of the selected proteins. While sumoylation of Prox1, Sall4a, Trim24, and Utf1 was associated with a positive effect on neurogenesis in P19 cells, sumoylation of Kctd15 was associated with a negative effect. Prox1, Sall4a, and Kctd15 were further analyzed in the vertebrate neural tube of living embryos, with similar results. Finally, a detailed analysis of Utf1 showed the sumoylation dependence of Utf1 function in controlling the expression of bivalent genes. Interestingly, this effect seems to rely on two mechanisms: sumoylation modulates binding of Utf1 to the chromatin and mediates recruitment of the messenger RNA-decapping enzyme Dcp1a through a conserved SIM (Sumo-interacting motif). Altogether, our results indicate that the combined sumoylation status of key proteins determines the proper progress of neurogenesis.

A critical appraisal of the prognostic predictive models for patients with sepsis: Which model can be applied in clinical practice?

BACKGROUND: Sepsis is associated with high mortality and predictive models can help in clinical decision-making. The objective of this study was to carry out a systematic review of these models. METHODS: In 2019, we conducted a systematic review in MEDLINE and EMBASE (CDR42018111121:PROSPERO) of articles that developed predictive models for mortality in septic patients (inclusion criteria). We followed the CHARMS recommendations (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies), extracting the information from its 11 domains (Source of data, Participants, etc). We determined the risk of bias and applicability (participants, outcome, predictors and analysis) through PROBAST (Prediction model Risk Of Bias ASsessment Tool). RESULTS: A total of 14 studies were included. In the CHARMS extraction, the models found showed great variability in its 11 domains. Regarding the PROBAST checklist, only one article had an unclear risk of bias as it did not indicate how missing data were handled while the others all had a high risk of bias. This was mainly due to the statistical analysis (inadequate sample size, handling of continuous predictors, missing data and selection of predictors), since 13 studies had a high risk of bias. Applicability was satisfactory in six articles. Most of the models integrate predictors from routine clinical practice. Discrimination and calibration were assessed for almost all the models, with the area under the ROC curve ranging from 0.59 to 0.955 and no lack of calibration. Only three models were externally validated and their maximum discrimination values in the derivation were from 0.712 and 0.84. One of them (Osborn) had undergone multiple validation studies. DISCUSSION: Despite most of the studies showing a high risk of bias, we very cautiously recommend applying the Osborn model, as this has been externally validated various times.