Evolving trends in neuropsychological profiles of post COVID-19 condition: A 1-year follow-up in individuals with cognitive complaints.

Cognitive difficulties are reported as lasting sequelae within post COVID-19 condition. However, the chronicity of these difficulties and related factors of fatigue, mood, and perceived health have yet to be fully determined. To address this, the current longitudinal study aimed to clarify the trends of cognitive test performance and cognitive domain impairment following COVID-19 onset, and whether hospitalization influences outcomes. 57 participants who reported subjective cognitive difficulties after confirmed COVID-19 infection were assessed at baseline (~6 months post COVID-19) and follow-up (~15 months later) visits. Assessments included measures across multiple cognitive domains and self-report questionnaires of fatigue, mood, and overall health. Analyses were conducted in three stages: at the test score level (raw and adjusted scores), at the cognitive domain level, and stratified by hospitalization status during infection. Results at the test-score level indicate that cognitive performance remains relatively stable across assessments at the group level, with no significant improvements in any adjusted test scores at follow-up. Cognitive domain analyses indicate significant reductions in attention and executive functioning impairment, while memory impairment is slower to resolve. On self-report measures, there was a significant improvement in overall health ratings at follow-up. Finally, those hospitalized during infection performed worse on timed cognitive measures across visits and accounted for a larger proportion of cases with short-term and working memory impairment at follow-up. Overall, our findings indicate that cognitive difficulties persist both at test score and cognitive domain levels in many cases of post COVID-19 condition, but evidence suggests some improvement in global measures of attention, executive functioning and overall self-rated health. Furthermore, an effect of hospitalization on cognitive symptoms post COVID-19 may be more discernible over time.

Telerehabilitation: Vestibular Physiotherapy vs. Multicomponent Exercise for Functional Improvement in Older Adults: Randomized Clinical Trial.

The loss of vestibular and motor function can occur naturally with aging. Vestibular physiotherapy exercises (VE) specifically address vestibular rehabilitation to reduce imbalances and improve physical condition, like therapeutic exercise (TE). During COVID-19, technology was used with the elderly for implementation. Objective: to determine if vestibular exercises are as effective as multicomponent exercises in improving functional capacity using technological tools. Methods: A randomized clinical trial compared two intervention groups of 21 subjects with functional limitations and frailty (average age 76.11 years). The intervention involved multicomponent exercise for the control group (Vivifrail protocol) and vestibular exercises for the experimental group (Cawthorne and Cooksey exercises) for 6 weeks with five sessions per week both groups. Two professionals implemented the exercises, and participants received tailored exercise videos. Primary outcomes were gait speed, dynamic balance, and physical capacity. Results: Both groups showed significant improvements. For physical function measured by SPPB (0-12 points), the multicomponent exercise group improved by 1.97 (0.91; 3.03), p < 0.001, and the vestibular exercise group improved by 1.63 (0.65; 2.60), p = 0.002. For dynamic balance measured by the Timed Up and Go (TUG) test, the multicomponent exercise group improved by -0.88 (-1.33; -0.42), p < 0.001, and the vestibular exercise group improved by -0.79 (-1.21; -0.37), p < 0.001. There were no significant differences between groups. Finally, regarding gait speed, there were no differences in either group between pretest and post-test (p > 0.05). Conclusions: Both multicomponent exercise and vestibular exercises improve functional capacities via telerehabilitation as measured by the SPPB, although vestibular physiotherapy does not show superior outcomes compared to the control group.

Efficacy and safety of bempedoic acid in acute coronary syndrome. Design of the clinical trial ES-BempeDACS.

INTRODUCTION AND OBJECTIVES: Only about 1 out of every 3 patients with acute myocardial infarction (AMI) achieve low-density lipoprotein cholesterol (LDL-C) values <55mg/dL in the first year. The present study aims to evaluate the impact of early intensive therapy on lipid control after an AMI. METHODS: An independent, prospective, pragmatic, controlled, randomized, open-label, evaluator-blinded clinical trial (PROBE design) will analyze the efficacy and safety of an oral lipid-lowering triple therapy: high-potency statin+bempedoic acid (BA) 180mg+ezetimibe (EZ) 10mg versus current European-based guidelines (high-potency statin±EZ 10mg), in AMI patients. LDL-C will be determined within the first 48hours. Patients with LDL-C ≥ 115mg/dL (without previous statin therapy), ≥ 100mg/dL (with previous low-potency or high-potency statin therapy at submaximal dose), or ≥ 70mg/dL (with previous high-potency statin therapy at high dose) will be randomly assigned 1:1 between 24 and 72hours post-AMI to the BA/EZ combination or to statin±EZ, without BA. The primary endpoint is the proportion of patients reaching LDL-C <55mg/dL at 8 weeks after treatment. RESULTS: The results of this study will provide novel information for post-AMI LDL-C control by evaluating the usefulness of an early intensive lipid-lowering strategy based on triple oral therapy. CONCLUSIONS: Early intensive lipid-lowering triple oral therapy vs the treatment recommended by current clinical practice guidelines could facilitate the achievement of optimal LDL-C levels in the first 2 months after AMI (a high-risk period). IDENTIFICATION NUMBER: EudraCT 2021-006550-31.

Measuring spatial navigation during locomotion in children: A systematic review.

Spatial navigation allows us to move around our environment, walking being the most advanced form of human locomotion. Over the years, a range of tools has been developed to study spatial navigation in children. Aim. To describe the role of locomotion during the assessment of spatial navigation in children, providing an overview of the instruments available for assessing spatial navigation in typically developing children and those with neurodevelopmental disorders. Methods and Procedures. A systematic search was performed in six electronic databases between December 2022 and February 2023, then updated in July 2023. Cross-sectional and observational studies were included. Outcomes and results. Of the 3,385 studies screened, 47 were selected for this review. Five studies described the influence of locomotion on spatial navigation, and seven studies included locomotion as an explanatory variable in this area. Most studies focused on children from five to twelve years old, whereas only nine were centred on infants and preschoolers. Just eight assessed spatial abilities in individuals with neurodevelopmental disorders. Conclusions and implications. Children with or at risk of neurodevelopmental impairments show poorer spatial navigation skills. Having the choice to actively explore the space is more important than the way they locomote. It is necessary to have tools to assess spatial navigation during locomotion early in infancy.

Innate lymphoid cells are activated in HFRS, and their function can be modulated by hantavirus-induced type I interferons.

Hantaviruses cause the acute zoonotic diseases hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Infected patients show strong systemic inflammation and immune cell activation. NK cells are highly activated in HFRS, suggesting that also other innate lymphoid cells (ILCs) might be responding to infection. Here, we characterized peripheral ILC responses, and measured plasma levels of soluble factors and plasma viral load, in 17 Puumala virus (PUUV)-infected HFRS patients. This revealed an increased frequency of ILC2 in patients, in particular the ILC2 lineage-committed c-Kitlo ILC2 subset. Patients' ILCs showed an activated profile with increased proliferation and displayed altered expression of several homing markers. How ILCs are activated during viral infection is largely unknown. When analyzing PUUV-mediated activation of ILCs in vitro we observed that this was dependent on type I interferons, suggesting a role for type I interferons-produced in response to virus infection-in the activation of ILCs. Further, stimulation of naïve ILC2s with IFN-ß affected ILC2 cytokine responses in vitro, causing decreased IL-5 and IL-13, and increased IL-10, CXCL10, and GM-CSF secretion. These results show that ILCs are activated in HFRS patients and suggest that the classical antiviral type I IFNs are involved in shaping ILC functions.

Sex differences in formal recommendation of assets for health (social prescribing) in Aragon.

BACKGROUND: In primary health care, social prescribing is an important tool which is gaining popularity. It is being studied significantly, however there is not enough evidence about different related issues. The aim of this study is to analyse the differences by sex in the application of a social prescription protocol in Primary Care. METHODS: This is a cross-sectional study carried out with data from the Electronic Health Record between September 2018 and March 2021. Descriptive, bivariate and multivariate analyses of data from 2,109 records of Social Prescription protocol in primary health care centers located in Aragón in northern Spain (Europe) were performed using Jamovi Statistics software (version 2.3.28). The comparisons by sex were carried out using a Mann-Whitney U or chi-squared test to analyse differences. RESULTS: The protocol was used correctly 1,482 times, where it was applied more in females (74.8% female vs. 25.2% male). The median age in females was higher than males (female 72 vs. males 70; p = 0.003). There were significant differences by sex in several aspects to strengthen with the social prescribing, physical, emotional and relational skills. Most females and males regularly attended the recommended asset and there were significant differences in the group that never attended. Mean satisfaction was statistically different, with 4.74 points out of 5 for females and 4.86/5 for males (p = 0.010). It can be observed that older females in rural areas (OR = 34.15), whose social prescription acts on Emotional Skills and Relational and Social Skills (OR = 6.10-8.23), with good prior self-care and greater participant satisfaction (OR = 8.96), have greater chance of improving their health. CONCLUSIONS: Some results showed sex differences in the use and outcomes of formal asset recommendation. However, further research is needed to assess the relationship between social prescription, sex and gender and their implications.

Critically Appraised Topic on Canine Leishmaniosis: Does Treatment with Antimonials and Allopurinol Have the Same Clinical and Clinicopathological Efficacy as Treatment with Miltefosine and Allopurinol, after One Month of Treatment?

The treatment of canine leishmaniosis commonly involves meglumine antimoniate with allopurinol or miltefosine with allopurinol. This study aims to compare the clinical and clinicopathological efficacy at 28-30 days of conventional dosing regimens for both treatments using the critically appraised topic methodology. A comprehensive search across three databases (PubMed, CAB Abstracts, and Web of Science) from March 2004 to September 2023 yielded 16 relevant articles, encompassing 325 ogs treated with meglumine antimoniate and allopurinol, and 273 dogs treated with miltefosine and allopurinol. The findings indicated a significantly higher rate of complete clinical cure in the group treated with meglumine antimoniate and allopurinol. Most dogs in both groups exhibited improvement in clinicopathological alterations after one month of treatment. No significant difference was observed in the number of dogs that showed a negative Leishmania qPCR between the two groups, one month post-treatment. However, quantitative serology results were not commonly reported in the available data and therefore this aspect could not be compared.

Scan With Me: A Train-the-Trainer Program to Upskill MRI Personnel in Low- and Middle-Income Countries.

PURPOSE: Access to MRI in low- and middle-income countries (LMICs) remains among the poorest in the world. The lack of skilled MRI personnel exacerbates access gaps, reinforcing long-standing health disparities. The Scan With Me (SWiM) program aims to sustainably create a network of highly skilled MRI technologists in LMICs who will facilitate the transfer of MRI knowledge and skills to their peers and contribute to the implementation of highly valuable imaging protocols for effective clinical and research use. METHODS: The program introduces a case-based curriculum designed using a novel train-the-trainer approach, integrated with peer-collaborative learning to upskill practicing MRI technologists in LMICs. The 6-week curriculum uses the teach-try-use approach, which combines self-paced didactic lectures covering the basics of MR image acquisition (teach) with hands-on expert-guided scanning experience (try) and the implementation of protocols tailored to provide the best possible images on their infrastructures (use). Each program includes research translation skills training using an established advanced MRI technique relevant to LMICs. A pilot program focused on cardiac MRI (CMR) was conducted to assess the program's curriculum, delivery, and evaluation methods. RESULTS: Forty-three MRI technologists from 16 LMICs participated in the pilot CMR program and, over the course of the training, implemented optimized CMR protocols that reduced acquisition times while improving image quality. The training resources and scanner-specific standardized protocols are published openly for public use in an online repository. In general, at the end of the program, learners reported considerable improvements in CMR knowledge and skills. All respondents to the program evaluation survey agreed to recommend the program to their colleagues, while 87% indicated interest in returning to help train others. CONCLUSIONS: The SWiM program is the first master class in MRI acquisition for practicing imaging technologists in LMICs. The program holds the potential to help reduce disparities in MRI expertise and access. The support of the MRI community, imaging societies, and funding agencies will increase its reach and further its impact in democratizing MRI.

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

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

[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.

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.

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.

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 (

Altered gene expression linked to germline dysfunction following exposure of Caenorhabditis elegans 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.

"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.

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.

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.

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.

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.