Erratum: Altered gene expression linked to germline dysfunction following exposure to DEET.

[This corrects the article DOI: 10.1016/j.isci.2023.108699.].

Loop diuretic down-titration at discharge in patients hospitalized for acute heart failure.

AIMS: The current literature provides limited guidance on the best diuretic strategy post-hospitalization for acute heart failure (AHF). It is postulated that the efficacy and safety of the outpatient diuretic regimen may be significantly influenced by the degree of fluid overload (FO) encountered during hospitalization. We hypothesize that in patients with more pronounced FO, reducing their regular oral diuretic dosage might be associated with an elevated risk of unfavourable clinical outcomes. METHODS AND RESULTS: It was a retrospective observational study of 410 patients hospitalized for AHF in which the dose of furosemide at admission and discharge was collected. Patients were categorized across diuretic dose status into two groups: (i) the down-titration group and (ii) the stable/up-titration group. FO status was evaluated by a clinical congestion score and circulating biomarkers. The endpoint of interest was the composite of time to all-cause death and/or heart failure readmission. A multivariable Cox proportional hazard regression model was constructed to analyse the endpoints. The median age was 86 (78-92) years, 256 (62%) were women, and 80% had heart failure with preserved ejection fraction. After multivariate adjustment, the down-titration furosemide equivalent dose remained not associated with the risk of the combined endpoint in the whole sample (hazard ratio 1.34, 95% confidence interval 0.86-2.06, P = 0.184). The risk of the combination of death and/or worsening heart failure associated with the diuretic strategy at discharge was significantly influenced by FO status, including clinical congestion scores and circulating proxies of FO like BNP and cancer antigen 125. CONCLUSIONS: In patients hospitalized for AHF, furosemide down-titration does not imply an increased risk of mortality and/or heart failure readmission. However, FO status modifies the effect of down-titration on the outcome. In patients with severe congestion or residual congestion at discharge, down-titration was associated with an increased risk of mortality and/or heart failure readmission.

Electrochemical bioplatform to manage alpha-gal syndrome by tracking the carbohydrate allergen in meat.

This work presents the first bioplatform described to date for the determination of galactose-α-1,3-galactose (α-Gal), a non-primate mammalian oligosaccharide responsible for almost all cases of red meat allergy. The bioplatform is based on the implementation of an indirect competitive immunoassay and enzymatic labeling with the enzyme horseradish peroxidase (HRP) built on the surface of magnetic microparticles (MBs) and amperometric transduction on screen-printed carbon electrodes (SPCEs) using the H2O2/hydroquinone (HQ) system. The target α-Gal competed with biotinylated α-Gal immobilized on the surface of neutravidin-modified MBs for the limited immunorecognition sites of a detection antibody enzymatically labeled with an HRP-conjugated secondary antibody. The resulting magnetic immunoconjugates were trapped on the surface of the SPCE working electrode and amperometric transduction was performed, providing a cathodic current variation inversely proportional to the concentration of α-Gal in the analyzed sample. The developed biotool was optimized, characterized and applied with satisfactory results to the determination of the target allergen in different samples of raw and processed meats.

[Health consequences of violence against women by the couple]. / Consecuencias para la salud de la violencia contra la mujer por la pareja.

Intimate partner violence against women (IPV) has devastating effects on the healthcare and well-being of women and their children. Physical, psychological, and social consequences, a worse perception of their own health, and loss of quality of life are well-documented, while aftereffects persist in time even after the end of abuse. Psychological consequences of abuse last longer and are more serious. IPV also affects sons and daughters, disabled people, family, and the attacker himself. Many health problems, both physical and mental, that lead women to go to healthcare services in search of help have an origin in the violence they experience. Treatment of the symptoms without awareness of its relation to such violence favours medicalization, iatrogenesis, and chronification. Psychological violence poses a threat that is invisible, subtle, cumulative, and difficult to detect; it is, however, the most destructive.

Altered gene expression linked to germline dysfunction following exposure to DEET.

N,N-diethyl-meta-toluamide (DEET) is a commonly used synthetic insect repellent. Although the neurological effects of DEET have been widely investigated, its effects on the germline are less understood. Here, we show that exposure of the nematode Caenorhabditis elegans, which is highly predictive of mammalian reprotoxicity, resulting in internal DEET levels within the range detected in human biological samples, causes activation of p53/CEP-1-dependent germ cell apoptosis, altered meiotic recombination, chromosome abnormalities, and missegregation. RNA-sequencing analysis links DEET-induced alterations in the expression of genes related to redox processes and chromatin structure to reduced mitochondrial function, impaired DNA double-strand break repair progression, and defects during early embryogenesis. We propose that Caenorhabditis elegans exposure to DEET interferes with gene expression, leading to increased oxidative stress and altered chromatin structure, resulting in germline effects that pose a risk to reproductive health.

Exploring the influence of baseline rheumatoid factor levels on TNF inhibitor retention rate in patients with rheumatoid arthritis: a multicentre and retrospective study.

OBJECTIVE: To assess whether the retention rate of certolizumab pegol (CZP) was longer than that of other tumour necrosis factor inhibitors (TNFi) based on baseline rheumatoid factor (RF) levels. METHODS: Longitudinal, retrospective and multicentre study including patients with RA who were treated with any TNFi (monoclonal antibodies (mAB), etanercept (ETA) or CZP). Log-rank test and Cox regressions were conducted to evaluate the retention rate in the three groups according to the level of RF, with the third quartile of the baseline levels used as cut-off: <200 (

Systematic Evaluation of Protein-Small Molecule Hybrids on the Yeast Surface.

Protein-small molecule hybrids are structures that have the potential to combine the inhibitory properties of small molecules and the specificities of binding proteins. However, achieving such synergies is a substantial engineering challenge with fundamental principles yet to be elucidated. Recent work has demonstrated the power of the yeast display-based discovery of hybrids using a combination of fibronectin-binding domains and thiol-mediated conjugations to introduce small-molecule warheads. Here, we systematically study the effects of expanding the chemical diversity of these hybrids on the yeast surface by investigating a combinatorial set of fibronectins, noncanonical amino acid (ncAA) substitutions, and small-molecule pharmacophores. Our results show that previously discovered thiol-fibronectin hybrids are generally tolerant of a range of ncAA substitutions and retain binding functions to carbonic anhydrases following click chemistry-mediated assembly of hybrids with diverse linker structures. Most surprisingly, we identified several cases where replacement of a potent acetazolamide warhead with a substantially weaker benzenesulfonamide warhead still resulted in the assembly of multiple functional hybrids. In addition to these unexpected findings, we expanded the throughput of our system by validating a 96-well plate-based format to produce yeast-displayed hybrid conjugates in parallel. These efficient explorations of hybrid chemical diversity demonstrate that there are abundant opportunities to expand the functions of protein-small molecule hybrids and elucidate principles that dictate their efficient discovery and design.

"Who Takes Care of Carers?": Experiences of Intensive Care Unit Nurses in the Acute Phase of the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic caused an international health emergency situation where nursing took on a fundamental role. The high number of patients in hospital ICUs led to a shift in nurses' working conditions and workload. Objective: The objective of this study was to describe the experiences of nurses who worked in ICUs during the acute phase of the COVID-19 pandemic. Methodology: A qualitative, descriptive study was carried out, with the participation of 21 nurses who worked in the ICU during the pandemic. Data collection took place between May and July 2021 through 21 in-depth interviews. Results: Three main themes emerged: (1) COVID-19 in ICUs: nurses on the frontline. (2) United against adversity: teamwork. (3) New optics of critical care and the nursing profession. COVID-19 was perceived with harshness, and the lack of knowledge about the virus generated confusion, anxiety and fear due to the risk of transmission to family members and relatives. The pandemic marked a shift in the management of human, material and economic resources. Novice nurses learned critical care at an accelerated pace, with significant physical and psychological strain. Expert nurses carried the burden of training new nurses. Although there were tense situations, experiencing these adverse situations as a team led to feelings of increased belonging, togetherness and professional bonding for nurses. While the participants noted an increase in motivation to continue in their profession, they also had a feeling of not having been cared for as they deserve by healthcare institutions.

El papel de la enfermería en la polifarmacia de las personas mayores / The role of nursing in polypharmacy of elderly people

Introducción: La población española se encuentra cada vez más envejecida, lo que favorece el aumento de la asistencia sanitaria, propiciando así la aparición de la polimedicación, que repercute de forma evidente en la calidad de vida del paciente. Enfermería, dada su cercanía al paciente, es la clave para implantar medidas de evaluación y prevención de la polifarmacia. Objetivos: Describir con exactitud la repercusión de la polifarmacia en las personas mayores y enunciar las intervenciones que tiene que realizar enfermería para controlar dicha polifarmacia. Metodología: Se realiza una revisión bibliográfica en las bases de datos LILACS, PubMed, ProQuest y Cochrane Library. Resultados: Se obtuvo un total de 711 artículos, de los cuales 16 fueron incluidos en el análisis. Conclusión: La polifarmacia en ancianos mayores de 65 años se asocia con la pérdida de calidad de vida, la disminución de la capacidad funcional y la fragilidad. Estas consecuencias incrementan las comorbilidades y la mortalidad. En este contexto, la enfermería desempeña un rol clave mediante intervenciones educativas y conductuales, incluyendo evaluaciones regulares para detectar y abordar efectos adversos.(AU)

Introduction: The Spanish population is increasingly aging, which favors the increase in health care, favoring the appearance of polypharmacy, clearly affecting the quality of life of the patient. Nursing, given its closeness to the patient, is the key to implementing measures for the evaluation and prevention of polypharmacy. Objectives: To accurately describe the repercussion of polypharmacy in the elderly and state the nursing interventions to control said polypharmacy. Methodology: A bibliographic review was carried out in the LILACS, PubMed, ProQuest and Cochrane Library databases. Results: A total of 711 articles were obtained, of which 16 were included in the analysis. Conclusion: Polypharmacy in elderly people over 65 years of age is associated with loss of quality of life, decreased functional capacity and frailty. These consequences increase comorbidities and mortality. In this context, nursing plays a key role through educational and behavioral interventions, including regular evaluations, to detect and address adverse effects.(AU)

The scaffold nucleoporins SAR1 and SAR3 are essential for proper meiotic progression in Arabidopsis thaliana.

Nuclear Pore Complexes (NPCs) are embedded in the nuclear envelope (NE), regulating macromolecule transport and physically interacting with chromatin. The NE undergoes dramatic breakdown and reformation during plant cell division. In addition, this structure has a specific meiotic function, anchoring and positioning telomeres to facilitate the pairing of homologous chromosomes. To elucidate a possible function of the structural components of the NPCs in meiosis, we have characterized several Arabidopsis lines with mutations in genes encoding nucleoporins belonging to the outer ring complex. Plants defective for either SUPPRESSOR OF AUXIN RESISTANCE1 (SAR1, also called NUP160) or SAR3 (NUP96) present condensation abnormalities and SPO11-dependent chromosome fragmentation in a fraction of meiocytes, which is increased in the double mutant sar1 sar3. We also observed these meiotic defects in mutants deficient in the outer ring complex protein HOS1, but not in mutants affected in other components of this complex. Furthermore, our findings may suggest defects in the structure of NPCs in sar1 and a potential link between the meiotic role of this nucleoporin and a component of the RUBylation pathway. These results provide the first insights in plants into the role of nucleoporins in meiotic chromosome behavior.

Recurring renal lithiasis due to Dent's disease.

Dent's disease is a rare cause of hypercalciuria and recurring urolithiasis. Patients with this disease have elevated bone resorption due to the presence of parathormone (PTH) in the urine. We describe the case of a 21-year-old male with hypercalciuria, elevated bone resorption and recurring bilateral urolithiasis that achieves radiological and clinical stability with percutaneous nephrolithotomy (PNL) and medical treatment with hydrochlorothiazide, potassium-citrate and phytate.

Case Report: A Presentation of Early-Onset Immune-Mediated Bullous Pemphigoid in a Patient with Urothelial Cancer.

Cutaneous immune-related adverse events (cirAEs) are the most common side effects of immune checkpoint inhibitor (ICI) therapy (30-50% for all grades). The vast majority of them are low or mild and can be treated without ICI interruption. Autoimmune blistering disorders, such as immune-mediated bullous pemphigoid (IBP), are rare (<1%) but potentially serious conditions that must be early detected. The onset generally occurs within the first months of the treatment, and it appears to be more common with antiprogrammed death-1 or antiprogrammed ligand 1 (anti-PD1/PDL1) than with anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4). We present a case of a three-day severe IBP onset after receiving the first cycle of atezolizumab. This exceptional early presentation could suggest the presence of some predisposing condition and demonstrates the need to better understand predictive toxicity-related biomarkers in candidate patients for immunotherapy.

Comprehensive proteomics and meta-analysis of COVID-19 host response.

COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community.

Electrochemical biotool for the dual determination of epithelial mucins associated to prognosis and minimal residual disease in colorectal cancer.

This work reports a dual immunoplatform for the simultaneous detection of two epithelial glycoproteins of the mucin family, mucin 1 (MUC1) and mucin 16 (MUC16), whose expression is related to adverse prognosis and minimal residual disease (MRD) in colorectal cancer (CRC). The developed immunoplatform involves functionalised magnetic microparticles (MBs), a set of specific antibody pairs (a capture antibody, cAb, and a biotinylated detector antibody b-dAb labelled with a streptavidin-horseradish peroxidase, Strep-HRP, polymer) for each target protein and amperometric detection at dual screen-printed carbon electrodes (SPdCEs) using the hydroquinone (HQ)/horseradish peroxidase (HRP)/H2O2 system. This dual immunoplatform allows, under the optimised experimental conditions, to achieve LOD values of 50 and 1.81 pg mL-1 (or mU mL-1) for MUC1 and MUC16, respectively, and adequate selectivity for the determination of the two targets in the clinic. The developed immunoplatform was employed to analyse CRC cell protein extracts (1.0 µg/determination) with different metastatic potential providing results in agreement with those obtained by blotting technologies but using affordable and applicable point-of-care instruments. This new biotool also emerges competitive in state-of-the-art electrochemical immunoplatforms seeking a compromise among simplicity, reduction of test time and analytical characteristics.

Usefulness of urinary potassium to creatinine ratio to predict diuretic response in patients with acute heart failure and preserved ejection fraction.

BACKGROUND: Patients with acute heart failure (AHF) require intensification in the diuretic strategy. However, the optimal diuretic strategy remains unclear. In this work, we aimed to evaluate the role of urinary potassium to creatinine ratio (K/Cr) to predict diuretic and natriuretic response to thiazide or mineralocorticoid receptor antagonists (MRAs) in a cohort of patients with AHF and preserved ejection fraction (AHF-pEF). HYPOTHESIS: Patients with a high urinary K/Cr ratio will have a better diuretic and natriuretic response with spironolactone versus chlorthalidone. METHODS: This is a study of 44 patients with AHF-pEF with suboptimal loop diuretic response. The primary endpoint was the baseline K/Cr associated with natriuretic and diuretic effect of chlorthalidone versus spironolactone at 24 and 72 h. Mixed linear regression models were used to analyze the endpoints. Estimates were reported as least squares mean with their respective 95% confidence interval (CIs). RESULTS: The median age of the study population was 85 years (82.5-88.5), and 30 (68.2%) were women. The inferential multivariate analysis suggested a greater natriuretic and diuretic effect of chlorthalidone across K/Cr levels. In the upper category, chlorthalidone translated into a statistically increase in natriuresis at 24 and 72 h. Chlorthalidone versus spironolactone showed ∆uNa of 25.7 mmol/L at 24 h (95% CI = -3.7 to 55.4, p = .098) and ∆uNa of 24.8 mmol/L at 72 h (95% CI = -4 to 53.6, p = .0106). The omnibus p value is .027. Multivariate analyses revealed a significant increase in 72 h cumulative diuresis irrespective of K/Cr status in those on chlorthalidone. CONCLUSIONS: In patients with AHF-pEF and suboptimal diuretic response, diuresis and natriuresis are higher with the administration of chlorthalidone over spironolactone. These data don't support the hypothesis that the K/Cr ratio can help guide the choice of thiazide diuretic versus MRA in AHF-pEF patients on loop diuretic.

Differential effects of sleep on brain structure and metabolism at the preclinical stages of AD.

INTRODUCTION: Poor sleep quality is associated with cognitive outcomes in Alzheimer's disease (AD). We analyzed the associations between self-reported sleep quality and brain structure and function in cognitively unimpaired (CU) individuals. METHODS: CU adults (N = 339) underwent structural magnetic resonance imaging, lumbar puncture, and the Pittsburgh Sleep Quality Index (PSQI) questionnaire. A subset (N = 295) performed [18F] fluorodeoxyglucose positron emission tomography scans. Voxel-wise associations with gray matter volumes (GMv) and cerebral glucose metabolism (CMRGlu) were performed including interactions with cerebrospinal fluid (CSF) AD biomarkers status. RESULTS: Poorer sleep quality was associated with lower GMv and CMRGlu in the orbitofrontal and cingulate cortices independently of AD pathology. Self-reported sleep quality interacted with altered core AD CSF biomarkers in brain areas known to be affected in preclinical AD stages. DISCUSSION: Poor sleep quality may impact brain structure and function independently from AD pathology. Alternatively, AD-related neurodegeneration in areas involved in sleep-wake regulation may induce or worsen sleep disturbances. Highlights Poor sleep impacts brain structure and function independent of Alzheimer's disease (AD) pathology. Poor sleep exacerbates brain changes observed in preclinical AD. Sleep is an appealing therapeutic strategy for preventing AD.

Levels and sources of hydrocarbons in the Patos Lagoon estuary and Cassino Beach mud bank (South Atlantic, Brazil): evidence of transference between environments.

This study assessed the concentrations and sources of natural and anthropogenic aliphatic (AHs) and polycyclic aromatic hydrocarbons (PAHs) in superficial sediments collected along the Patos Lagoon estuary and in sediment cores obtained from the Cassino Beach mud bank. Levels and distribution of n-alkanes indicate terrestrial sources, overlapping with a low amount of petrogenic hydrocarbons (heavy oils). Unresolved complex mixture (UCM) was observed in all samples. On the other hand, the distribution of PAHs in the sediments showed a predominance of pyrolytic over petrogenic sources. In general, hydrocarbons (HCs) contamination in the Patos Lagoon estuary and its adjacent coastal area can be considered low, except for sites near urban or industrial effluents, where moderate to high levels of contamination were found. Concentrations of hydrocarbons were homogeneous throughout the sediment cores, suggesting that mixing processes may have occurred along the layers or that HCs inputs to the mud banks were uniform during the studied deposition period. In addition, the levels and profile of HCs in the coastal sediments were similar to those observed in the estuary. Moreover, the frequent remobilization of sediments from the mud bank towards Cassino beach does not seem to pose any threats to the local biota or beach users since the levels of contamination were relatively low and below the threshold limits of sediment quality guidelines.

Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia.

BACKGROUND: COVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features. METHODS: We measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients. RESULTS: We identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers. CONCLUSIONS: This study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.