Real-world effectiveness and safety of bimekizumab for hidradenitis suppurativa: An ambispective observational study.

In this original research, we present the results in terms of effectiveness and safety of bimekizumab for hidradenitis suppurativa in real clinical practice. Results indicated significant improvement in all activity scores and patient-reported outcomes at week 16, including a notable decrease in mean IHS4 from 27.1 to 15.6 (p < 0.001), HS-PGA from 5.1 to 3.2 (p < 0.001), VAS pain from 8.3 to 4.7 (p < 0.001) and DLQI from 21.6 to 12.6 (p < 0.001). Bimekizumab, administered every 2 or 4 weeks, was well-tolerated with no discontinuations and no new safety concerns identified. These findings corroborate the drug's effectiveness and favourable safety profile observed in phase 3 clinical trials, supporting its use in real-world clinical practice for treating HS.

Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.

Machine learning regression algorithms to predict emissions from steam boilers.

Currently, the modeling of complex chemical-physical processes is drastically influencing industrial development. Therefore, the analysis and study of the combustion process of the boilers using machine learning (ML) techniques are vital to increase the efficiency with which this equipment operates and reduce the pollution load they contribute to the environment. This work aims to predict the emissions of CO, CO2, NOx, and the temperature of the exhaust gases of industrial boilers from real data. Different ML algorithms for regression analysis are discussed. The following are input variables: ambient temperature, working pressure, steam production, and the type of fuel used in around 20 industrial boilers. Each boiler's emission data was collected using a TESTO 350 Combustion Gas Analyzer. The modeling, with a machine learning approach using the Gradient Boosting Regression algorithm, showed better performance in the predictions made on the test data, outperforming all other models studied. It was achieved with predicted values showing a mean absolute error of 0.51 and a coefficient of determination of 99.80%. Different regression models (DNN, MLR, RFR, GBR) were compared to select the most optimal. Compared to models based on Linear Regression, the DNN model has better prediction performance. The proposed model provides a new method to predict CO2, CO, NOx emissions, and exhaust gas outlet temperature.

Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial.

Importance: Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. It is unknown whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. Objective: To compare anticoagulation vs antiplatelet therapy for secondary stroke prevention in patients with cryptogenic stroke and evidence of atrial cardiopathy. Design, Setting, and Participants: Multicenter, double-blind, phase 3 randomized clinical trial of 1015 participants with cryptogenic stroke and evidence of atrial cardiopathy, defined as P-wave terminal force greater than 5000 µV × ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250 pg/mL, or left atrial diameter index of 3 cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomization. Enrollment and follow-up occurred from February 1, 2018, through February 28, 2023, at 185 sites in the National Institutes of Health StrokeNet and the Canadian Stroke Consortium. Interventions: Apixaban, 5 mg or 2.5 mg, twice daily (n = 507) vs aspirin, 81 mg, once daily (n = 508). Main Outcomes and Measures: The primary efficacy outcome in a time-to-event analysis was recurrent stroke. All participants, including those diagnosed with atrial fibrillation after randomization, were analyzed according to the groups to which they were randomized. The primary safety outcomes were symptomatic intracranial hemorrhage and other major hemorrhage. Results: With 1015 of the target 1100 participants enrolled and mean follow-up of 1.8 years, the trial was stopped for futility after a planned interim analysis. The mean (SD) age of participants was 68.0 (11.0) years, 54.3% were female, and 87.5% completed the full duration of follow-up. Recurrent stroke occurred in 40 patients in the apixaban group (annualized rate, 4.4%) and 40 patients in the aspirin group (annualized rate, 4.4%) (hazard ratio, 1.00 [95% CI, 0.64-1.55]). Symptomatic intracranial hemorrhage occurred in 0 patients taking apixaban and 7 patients taking aspirin (annualized rate, 1.1%). Other major hemorrhages occurred in 5 patients taking apixaban (annualized rate, 0.7%) and 5 patients taking aspirin (annualized rate, 0.8%) (hazard ratio, 1.02 [95% CI, 0.29-3.52]). Conclusions and Relevance: In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. Trial Registration: ClinicalTrials.gov Identifier: NCT03192215.

Pathways of depressive symptoms to self-harm and suicide warning signs during COVID-19 pandemic: The role of anxiety and related distress, dysfunction and somatization.

BACKGROUND: Early in the COVID-19 pandemic, concern about widespread waves of depression and suicide emerged worldwide. Clarity on the relationship between mental health symptoms and warning signs of current self-harm or suicide thoughts and behaviors (ShSTB) in Mexican adults could be useful for designing effective public health policies and preventive strategies during health emergencies. OBJECTIVE: The present study uses a path model to explore the relationship between depressive symptoms, anxiety, and related distress, dysfunction, and somatization with ShSTB warning signs in Mexican adults during the COVID-19 pandemic. The study also describes the relative risks of these mental health variables for men and women, and for those who were seeking psychological care versus those who were not. METHOD: The study was conducted with 18,449 Mexicans (M = 33 years, SD = 11.00, range = 18-59), including 12,188 women (66.10 %) and 2706 (14.67 %) who were seeking psychological care. A web-based application included two multidimensional screening scales to evaluate depression, anxiety and somatic symptoms and related distress/dysfunction, as well as past and current ShSTB. Based on the participants' sex, the entire sample was randomly divided into two sub-samples to compare and replicate the Confirmatory Factor Analysis (CFA) results, getting evidence of the multidimensionality of the scales. With the two sub-samples, we also tested the nested models from a structural equation model (SEM) to suggest a relationship between mental health and self-harm/suicide variables. FINDINGS: Our findings suggest that 31 % of participants were at risk for depression, 42.30 % for anxiety, 38.30 % for Marked Distress, Dysfunction and Somatization (MDDS), 33.30 % for at least one ShSTB, and 4.20 % for Previous Self Harm Thoughts and Behaviors (PShTB) during the COVID-19 pandemic. A greater percentage of women and participants seeking psychological care showed high levels of mental health symptoms, PShTB, MDDS, and ShSTB. The path model suggested a direct influence of PShTB and MDDS on ShSTB. Depression symptoms lead to ShSTB in three possible ways: through PShTB, PShTB affecting MDDS, and generalized anxiety affecting MDDS. DISCUSSION AND OUTLOOK: The pandemic was accompanied by a high prevalence of depression-anxiety, marked distress, dysfunction and somatization and self-harm/suicide thoughts and behaviors. The findings of this study suggest evidence over the well-known association between depression and anxiety, and between depression, previous self-harm thoughts and behaviors, and self-harm/suicide. The evidence suggests to distinguish when participants were suffering from MDDS and anxious depression from those only suffering from depression. The methodological conditions of the study suggest a comprehensive model of ShSTB prevention. Findings also suggest the need to care for Mexicans with depressive symptoms and PShTB as well as those suffering from anxious depression with MDDS to prevent suicide, by implementing effective public health policies and preventive strategies to reduce the mental health gap during health emergencies. LIMITATIONS: This research was a cross-sectional study, suggesting that future analyses should focus on the evaluation of its consistency with confirmed diagnoses of mental health disorders, self-harm/suicide risks, and the effect of remote psychological help to address these problems.

Development and content validity of EVAD: A novel tool for evaluating and classifying the severity of adverse events for psychotherapeutic clinical trials.

OBJECTIVE: Develop and obtain content validity of a new tool for Evaluating and Classifying the Severity of Adverse Events for Psychotherapeutic Clinical Trials (EVAD). METHOD: Study of the development process of EVAD in four stages: (1) identify the domain and concept definition through a literature review, (2) instrument design, (3) expert judgment of the EVAD items through Gwent's concordance coefficient, and (4) applicability. RESULTS: In the absence of a consistent conceptual framework of adverse events in psychotherapeutic clinical trials, we have developed a framework and defined it. We have designed EVAD items and their complementary tool for rating adverse events. Content validation by expert judges resulted in CVR = 1.0 for each item and CVI = 0.79 in sufficiency, 0.76 in clarity, 0.91 in coherence and 0.95 in relevance for all items (p < 0.001). Final version of EVAD were applied to three participants for 7 weeks. Overall EVAD seems to be clear and meaningful for participants. CONCLUSIONS: EVAD is a semistructured interview based on a consistent conceptual framework, and proven content validity following the most important guidelines described in the literature. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03878186.

Dynamic shifts in primary metabolism across fruit development stages in Capsicum chinense (cv. Habanero).

The development of fleshy fruits involves changes in size and mass, followed by cell differentiation, which is associated with anatomical and histological changes. Parallel to these changes, metabolic alterations lead to the production of osmolytes and energy that modify cell turgor pressure, thereby promoting cell expansion and fruit growth. Detailed information is known about these processes in climacteric fruits (e.g. tomato); however, the regulation of metabolism and its association with anatomical changes in non-climacteric fruit development are poorly understood. In this study, we used detailed anatomical and histological analyses to define three developmental phases of chili pepper (Capsicum chinense cv. Habanero): cell division, cell expansion, and ripening. We showed that each was marked by distinct metabolic profiles, underpinning the switches in energy metabolism to support cellular processes. Interestingly, mitochondrial activity was high in the early stages of development and declined over time, with a modest increase in O2 consumption by pericarp tissues at the beginning of the ripening stage. This respiratory-like burst was associated with the degradation of starch and malate, which are the sources of energy and carbon required for other processes associated with fruit maturation.

Analyzing self-assembled spindle dynamics in fission yeast meiosis using in vivo fluorescence imaging.

Chromosome segregation in female meiosis in many metazoans is mediated by acentrosomal spindles. The analysis of the dynamics of self-assembled spindles is a challenge due to the low availability of oocytes. Here, we present a protocol for analyzing self-assembled spindle dynamics in fission yeast meiosis using in vivo fluorescence imaging. We describe steps for starter culture preparation, meiosis induction, and sample preparation. We then detail procedures for acquisition and analysis of images of self-assembled spindles. For complete details on the use and execution of this protocol, please refer to Pineda-Santaella and Fernández-Álvarez (2019)1 and Pineda-Santaella et al. (2021).2.

A study on the strength and durability characteristics of fiber-reinforced recycled aggregate concrete modified with supplementary cementitious material.

Recycled aggregate (RA) made from waste concrete is an environmentally friendly alternative to natural aggregate (NA) for concrete manufacturing. However, compared to NA concrete, concrete produced with recycled aggregates has poor characteristics. Supplementary cementitious materials (SCMs) can be used to enhance the poor properties of recycled aggregate concrete (RAC). Silica fume and fly ash are commonly used SCMs in the World, but their high usage led to a shortage of silica fume and fly ash. Still, the deficiency of these materials in large parts of the world is a challenge that requires exploring alternative feedstock materials for the construction industry in the coming years. Wheat straw ash (WSA) is an agricultural waste product that could be used as an alternative SCM due to its pozzolanic behavior to enhance the properties of RAC. In addition, concrete is brittle and needs reinforcement, for which polypropylene fibers (PPFs) can be used. The current research examines the mechanical characteristics of fiber-reinforced RAC, including compressive strength, splitting tensile strength, and ductility performance. Durability indicators, such as chloride diffusion, chloride penetration, acid resistance, and water absorption test, were also assessed. The results showed that concrete samples with 10% WSA, 50% RA and 1.5% PPFs had the highest compressive and splitting tensile strength, 60.2 MPa and 7.25 MPa, respectively, representing increases of 24.75% and 30.65%, as compared to plain samples at 56 days. In these samples, water absorption was reduced by 13% due to the finer WSA particles resulting in the lowest reduction in strength and mass recorded when exposing concrete samples to acidic media. The statistical analysis also validated that irrespective of WSA and PPFs, the concrete with 0% RA had the highest performance in strength and durability behavior. The study showed that WSA and PPFs might be employed in tandem to offset the poor behavior of RA, enhance the bond between fibers and concrete, and improve the mechanical strength and durability performance of RAC, thus demonstrating its suitability as a sustainable and economical construction material.

Physiological and metabolic changes in response to Boron levels are mediated by ethylene affecting tomato fruit yield.

Boron (B) is an essential nutrient for the plant, and its stress (both deficiency and toxicity) are major problems that affect crop production. Ethylene metabolism (both signaling and production) is important to plants' differently responding to nutrient availability. To better understand the connections between B and ethylene, here we investigate the function of ethylene in the responses of tomato (Solanum lycopersicum) plants to B stress (deficiency, 0 µM and toxicity, 640 µM), using ethylene related mutants, namely nonripening (nor), ripening-inhibitor (rin), never ripe (Nr), and epinastic (Epi). Our results show that B stress does not necessarily inhibit plant growth, but both B stress and ethylene signaling severely affected physiological parameters, such as photosynthesis, stomatal conductance, and chlorophyll a fluorescence. Under B toxicity, visible symptoms of toxicity appeared in the roots and margins of the older leaves through necrosis, caused by the accumulation of B which stimulated ethylene biosynthesis in the shoots. Both nor and rin (ethylene signaling) mutants presented similar responses, being these genotypes more sensitive and displaying several morphophysiological alterations, including fruit productivity reductions, in response to the B toxicity conditions. Therefore, our results suggest that physiological and metabolic changes in response to B fluctuations are likely mediated by ethylene signaling.

Morbidity and mortality of elderly patients with pancreaticobiliary disease according to age and comprehensive geriatric assessment: A prospective observational study.

BACKGROUND: This study was designed to analyze the influence of age and comprehensive geriatric evaluation on clinical results of pancreaticobiliary disease management in elderly patients. METHODS: A prospective observational study has been undertaken, including 140 elderly patients (over 75 years) with benign pancreaticobiliary disease. Patients were divided according to age in the following groups: group 1: 75-79 years old; group 2: 80-84 years old; group 3: 85 years and older. They underwent a comprehensive geriatric assessment with different scales: Barthel Index, Pfeiffer Index, Charlson Index, and Fragility scale, at admission and had been follow-up 90 days after hospital discharge to analyze its influence on morbidity and mortality. RESULTS: Overall, 140 patients have been included (group 1=51; group 2=43 and group 3=46). Most of them, 52 cases (37.8%), had acute cholecystitis, followed by 29 cases of acute cholangitis (20.2%) and acute pancreatitis with 25 cases (17.9%). Significant differences has been observed on complications in different age groups (p=0.033). Especially in patients with a Barthel Index result ≤60, which suggests that these less functional patients had more severe complications after their treatment (p=0.037). The mortality rate was 7.1% (10 patients). CONCLUSIONS: No significant differences were found between age, morbidity and mortality in elderly patients with pancreaticobiliary disease. Comprehensive geriatric scales showed some utility in their association with specific complications.

To the bone: Prevalence and correlates of depression and anxiety among orthopedic residents in Mexico.

OBJECTIVE: The present study examined among orthopedic residents the relationship between the presence of depressive or anxious symptoms and the degree of perfectionism, perceived work-related distress, and involvement in the care of patient(s) who died. METHOD: A cross-sectional online survey based on self-reported measures was used to collect the data from October 2019 to April 2021. RESULTS: The sample consisted of 642 orthopedic residents (50.6% response rate; 70.9% male; average age 29.8 years old). A total of 12.5 and 18.4% reported depressive or anxious symptoms, respectively. On a scale of 0-100, the mean score of perceived work-related distress was 51.9. A third (33.6%) reported being involved in the care of patient(s) who had died. Higher levels of perceived work-related distress and higher scores on the indecision of action/perfectionism dimension were associated with depressive and anxious symptoms. Being involved in the care of patient(s) who had died was associated with having anxious symptoms (OR = 1.79; 95%CI = 1.18-2.72). CONCLUSIONS: These results highlight the need for the systematic monitoring of the mental health status of orthopedic residents in Mexico, particularly those who report a high level of work-related distress or perfectionism or who have recently experienced the death of a patient.

Comparison between Colistin and Polymyxin B in the Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus Complex.

Polymyxins are still widely used for the treatment of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa bloodstream infections (BSIs). This study seeks to evaluate the impact of polymyxin B versus colistin on mortality and nephrotoxicity in BSI caused by these bacteria. We conducted a retrospective cohort study from 2014 to 2021 in Porto Alegre, Brazil. We included patients aged ≥18 years and excluded patients with polymicrobial infection or treatment for ≤48 h. The 30-day mortality was the primary outcome evaluated through Cox regression. We included 259 patients with BSI episodes: 78.8% caused by A. baumannii and 21.2% caused by P. aeruginosa. Polymyxin B did not impact mortality compared to colistin (adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI), 0.52-1.30; p = 0.40 (when adjusted for COVID-19 comorbidity, p = 0.05), Pitt bacteremia score, p < 0.01; Charlson comorbidity index, p < 0.001; time to start active antimicrobial therapy, p = 0.02). Results were maintained in the subgroups of BSI caused by A. baumannii (aHR, 0.92; 95% CI, 0.55-1.54; p = 0.74), P. aeruginosa (aHR, 0.47; 95% CI, 0.17-1.32; p = 0.15) and critical care patients (aHR, 0.77; 95% CI, 0.47-1.26; p = 0.30). Treatment with polymyxin B or colistin did not impact 30-day mortality in patients with carbapenem-resistant A. baumannii or P. aeruginosa BSI.

Interpersonal and Intimate Violence in Mexican Youth: Drug Use, Depression, Anxiety, and Stress during the COVID-19 Pandemic.

The COVID-19 pandemic may have increased interpersonal and intimate violence, harmful use of alcohol and other drugs (AODs), and mental health problems. This study uses a valid path model to describe relationships between these conditions of young Mexicans during the second year of the pandemic. A sample of 7420 Mexicans ages 18 to 24-two-thirds of whom are women-completed the Life Events Checklist, the Alcohol, Smoking, and Substance Involvement Screening Test, the Major Depressive Episode Checklist, the Generalized Anxiety Scale, and the Post-traumatic Stress Disorder (PTSD) Checklist. Young Mexicans reported higher rates of victimization and perpetration of interpersonal and intimate violence and mental health symptomatology than those noted pre- and in the first year of the pandemic. The harmful use of AOD rates were similar to those reported by adolescents before. The findings suggest asymmetric victimization and perpetration of intimate violence by gender (with women at a higher risk). More men than women have engaged in the harmful use of AODs (except for sedatives, which more women abuse). More women than men were at risk of all mental health conditions. The path model indicates that being a victim of intimate violence predicts the harmful use of tobacco, alcohol, cocaine, and sedatives, depression, anxiety, and specific PTSD symptoms (such as re-experimentation and avoidance symptoms). Being a victim of interpersonal violence resulted in severe PTSD symptoms (including avoidance, negative alterations in cognition-mood, and hyperarousal signs). The harmful use of sedatives predicted depressive symptoms. Men's victimizing intimate violence model contrasted with that of women, which included being the victim of interpersonal violence and severe PTSD symptoms. The high school youth model had three paths: victimizing intimate violence, victimizing interpersonal abuse, and sedative use, which predicted depression. Our findings could serve as the basis for future studies exploring the mechanisms that predict violence to develop cost-effective preventive programs and public policies and to address mental health conditions during community emergencies.

Autosomal dominant polycystic kidney disease in young adults.

Background: The clinical manifestations of autosomal dominant polycystic kidney disease (ADPKD) usually appear in adulthood, however pediatric series report a high morbidity. The objective of the study was to analyze the clinical characteristics of ADPKD in young adults. Methods: Family history, hypertension, albuminuria, estimated glomerular filtration rate (eGFR) and imaging tests were examined in 346 young adults (18-30 years old) out of 2521 patients in the Spanish ADPKD registry (REPQRAD). A literature review searched for reports on hypertension in series with more than 50 young (age <30 years) ADPKD patients. Results: The mean age of this young adult cohort was 25.24 (SD 3.72) years. The mean age at diagnosis of hypertension was 21.15 (SD 4.62) years, while in the overall REPQRAD population was aged 37.6 years. The prevalence of hypertension was 28.03% and increased with age (18-24 years, 16.8%; 25-30 years, 36.8%). Although prevalence was lower in women than in men, the age at onset of hypertension (21 years) was similar in both sexes. Mean eGFR was 108 (SD 21) mL/min/1.73 m2, 38.0% had liver cysts and 3.45% of those studied had intracranial aneurysms. In multivariate analyses, hematuria episodes and kidney length were independent predictors of hypertension (area under the curve 0.75). The prevalence of hypertension in 22 pediatric cohorts was 20%-40%, but no literature reports on hypertension in young ADPKD adults were found. Conclusions: Young adults present non-negligible ADPKD-related morbidity. This supports the need for a thorough assessment of young adults at risk of ADPKD that allows early diagnosis and treatment of hypertension.