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Background: Basal cell carcinomas (BCCs) are the most common cancers worldwide. Although most BCCs are amenable to local treatment, there are limited therapeutic options for surgically unresectable locally advanced and metastatic BCCs. Activation of the sonic hedgehog signalling pathway plays a significant role in the development of most BCCs. Hedgehog pathway inhibitors (HPIs) can be used to inhibit this pathway. Efficacy and safety data on HPI use in Australia is scarce. Objectives: This study aims to present the effectiveness and safety of HPI at a tertiary dermatology referral centre. Methods: We conducted a retrospective analysis of the clinical charts of all patients with BCC treated with an HPI at a tertiary Dermatology referral centre in New South Wales, Australia from 1 January 2016 to 1 July 2023. Results: Twenty‐three patients with BCCs were treated with an HPI; 11 locally advanced, 8 multiple, 3 basal cell naevus syndrome and 1 metastatic. All patients were of Caucasian background, with a median age of 56. Across 41 treatment cycles, the median treatment duration was 4 months. The overall response rate (ORR) was 20/23 (87%) and complete response (CR) rate was 9/23 (39%); patients treated with sonidegib achieved an ORR of 11/12 (92%) and CR of 4/12 (33%), and vismodegib‐treated patients achieved an ORR of 9/11 (82%) and CR of 5/11 (45%). Patients who responded to HPI treatment also responded to a subsequent HPI rechallenge. Common treatment emergent adverse events (TEAEs) included muscle spasms, dysgeusia and alopecia. Dysgeusia was more frequent with vismodegib than sonidegib (p = 0.0001). There was no evidence to suggest a difference in other TEAEs between the two HPIs. Four treatment cycles were stopped due to grade 3 muscle spasm. Conclusions: In our cohort of 23 patients being treated with HPI, the ORR was 87% and CR was 39%. All patients who experienced TEAEs and had a drug holiday successfully responded to HPI rechallenge. TEAEs, particularly muscle spasms, are common reasons for treatment cessation. Clinicians should implement strategies to mitigate TEAE to improve drug survivability. [ABSTRACT FROM AUTHOR]

Introduction: The Positive and Negative Syndrome Scale (PANSS) has been used as a universal instrument for clinical assessment of psychopathology in schizophrenia. Different studies have analyzed the factorial structure of this scale and have suggested a five-factor model: positive, negative, excited, depressive, and cognitive/disorganized factors. Two of the most used models are the Marder´s solution and the Wallwork´s one. Objectives: The aim of this work was to study the correlations of the two cognitive factors (Marder and Wallwork) with a cognitive assessment performed with a standard cognitive battery, in a sample of patients with first psychotic episode of schizophrenia. Methods: Seventy four patients with first psychotic episode of schizophrenia (26.9, SD:7.8 years old; 70.3% male) were included. The cognitive assessment was performed with the MATRICS Consensus Cognitive Battery (MCCB). The MCCB present seven cognitive domains: Speed of processing, Working memory, Attention/Vigilance, Verbal Learning, Visual Learning, Reasoning and Problem Solving, and Social cognition). Pearson correlations were performed between MCCB scores and Marder´s PANSS cognitive factor (P2, N5, G5, G10, G11, G13, G15) and Wallwork´s one (P2, N5, G11). Results: Correlation between MCCB scores and cognitive factors of Marder and Wallwork can be seen in the table. Marder´s cognitive factor Wallwork´s cognitive factor Speed of processing r = -0.461; p<0.001 r = -0.455; p<0.001 Attention/Vigilance r = -0.414; p<0.001 r = -0.415; p<0.001 Working memory r = -0.449; p<0.001 r = -0.468; p<0.001 Verbal Learning r = -0.511; p<0.001 r = -0.405; p<0.001 Visual Learning r = -0.252; p=0.024 r = -0.254; p=0.029 Reasoning and Problem Solving r = -0.244; p=0.036 r = -0.272; p=0.019 Social cognition r = -0.268; p=0.024 r = -0.202; p=0.091 Conclusions: Both PANSS cognition factors show a moderate correlations with Speed of processing, Working memory, Attention/Vigilance and Verbal Learning assessed by MCCB. More discrete correlations were found with Visual Learning, Reasoning and Problem Solving, and with Social cognition (in fact, non-significant correlation with Wallwork´s cognitive factor was found). Acknowledgements. This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project PI19/00766 and co-funded by the European Union. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

This article discusses a study conducted to understand the cardiovascular remodeling and function in fetuses with tetralogy of Fallot (ToF) using echocardiography. The study included 63 ToF fetuses and 66 healthy fetuses as controls. The results showed that ToF fetuses had lower cardiac sphericity index with biventricular hypertrophy, prolonged filling time fractions, and increased cardiac index. Additionally, there were associations between certain echocardiographic parameters and postnatal outcomes. The study concludes that further research is needed to correlate these findings with postnatal echocardiography. [Extracted from the article]

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Barbara Badanta,1,&ast; Isabel Álvarez-Pérez,2 Patricia Bonilla Sierra,3 María González-Cano-Caballero,4,&ast; Giancarlo Lucchetti,5 Rocío de Diego-Cordero1,&ast; 1Department of Nursing; Faculty of Nursing, Physiotherapy and Podiatry, University of Seville, Seville, Spain; 2Faculty of Nursing, Physiotherapy and Podiatry. University of Seville, Seville, Spain; 3Department of Health Sciences, Universidad Técnica Particular de Loja (UTPL), Loja, Ecuador; 4Department of Nursing; Faculty of Health Sciences, University of Granada, Granada, Spain; 5Department of Medicine; School of Medicine, Universidade Federal de Juiz de Fora, Juiz de Fora, Brazil&ast;These authors contributed equally to this workCorrespondence: María González-Cano-Caballero, Department of Nursing, Faculty of Health Sciences, University of Granada, Av. de la Ilustración, 60, Granada, 18071, Spain, Email mariagcc@ugr.esAbstract: This study aims to investigate the current evidence for the use of complementary and alternative medicine (CAM) in fibromyalgia (FM). A systematic review was conducted searching for PubMed, Scopus, CINAHL, PsycInfo, and Web of Science databases. Randomized controlled trials published up to December 2023 in peer-reviewed journals were included. Methodological quality was assessed by the Quality Assessment of Controlled Intervention Studies tool. A total of 216 articles were identified and 15 constituted the final sample. The type of CAM most used was traditional Chinese medicine (60%), and the most common instrument used was the Fibromyalgia Impact Questionnaire (60%). Our review was grouped into four themes based on the origin of the therapies: 1) Traditional Chinese Medicine; 2) Japanese natural harmonization (eg, Reiki); 3) Ayurvedic Medicine; and 4) Other non-drug therapies. Our systematic review showed that there is a wide range of CAMs used to treat FM. Most of the clinical trials have shown significant results for the effectiveness of these interventions in both physical and mental health outcomes of FM as compared to control groups. However, the heterogeneity of the interventions and outcomes warrants further studies on this topic.Keywords: complementary therapies, fibromyalgia treatment, nonpharmacological interventions, traditional medicine

Objective: To evaluate the impact of a medical-pharmaceutical intervention strategy on patients exposed to azathioprine-allopurinol (AZA-ALO) interaction in the Community of Madrid (CM)., Material/methods: Multicentre retrospective observational study. We reviewed the database generated after an intervention carried out in the healthcare context in which Primary Care Pharmacists (PCP) review the treatment of patients with safety risks and, when there are incidents, they contact (by telephone and/or e-mail) their Family Physicians (FP) for possible resolution., Study Population: CM patients with an active clinical history in Primary Care who have been dispensed both medications (AZA-ALO) in the period April-June 2022 according to prescription billing data from the National Health System (NHS). Main variable: suppression or dose adjustment of either of the two drugs., Results: Forty-nine patients were analysed. Mean age: 65.65±11.67 years. Males; 77.6%. 8,834 patients withdrew azathioprine (28,724 packs) and 89,297 withdrew allopurinol (141,188 packs) from pharmacies, with a very low prevalence of patients at risk (<1%). The prescription was modified in 32 patients (65.31%-IC95%: 51.98%-78.63%), with allopurinol being discontinued in 65.62% and, with regard to azathioprine, the dose was reduced by 18.75% and discontinued in 9.37%. Analytical alterations compatible with adverse effects due to the interaction were recorded in 28 patients (57.1%-IC95%: 43.29%-71%), including anaemia (39.3%) and leukopenia/neutropenia (25%)., Conclusions: Coordinated intervention between pharmacists and physicians was effective, resulting in prescription modification in a significant percentage of patients, which reduced the risk of toxicity., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: There is a significant prevalence of chronic spontaneous urticaria (CSU) in children across the globe. Some children with CSU do not achieve disease control with first-line antihistamine treatment and may need anti-IgE therapy with omalizumab. Recently, several novel treatment options, including dupilumab and BTK inhibitors, showed promising results in the treatment of antihistamine-refractory CSU in adults. However, information regarding their use in pediatric CSU is scarce, and most data is extrapolated from adult studies., Areas Covered: The review highlights the evidence on the use of mAbs and small-molecule inhibitors in pediatric CSU and aims to bridge the knowledge gaps and highlight unmet needs., Expert Opinion: Omalizumab is approved for allergic asthma patients aged ≥6 years, and some experience with omalizumab in children with CSU at this age has been published. However, approximately 5-10% of pediatric CSU patients may show insufficient response to omalizumab, necessitating other therapies. The available information on the off-label use of biologics other than omalizumab in children is limited to case reports. No data is available for other new therapies.

Postoperative pain management is challenging. We used mice with a transverse laparotomy to study tactile allodynia measured by the von Frey test, pain at rest measured by facial pain expressions detected by an artificial intelligence algorithm, and movement-induced pain measured by reductions in exploratory activity. The standard analgesics morphine and ibuprofen induced distinct patterns of outcome-dependent effects. Whereas morphine was more effective in reversing pain at rest compared to tactile allodynia, it was unable to alter movement-induced pain. Ibuprofen showed comparable effects across the three outcomes. Administered together, the compounds induced synergistic effects in the three aspects of postoperative pain, mirroring the known advantages of multimodal analgesia used in clinical practice. We explored the impact of neuroimmune interactions using a neutrophil depletion strategy. This reversed pain at rest and movement-induced pain, but did not alter cutaneous sensitivity. Non-peptidergic (IB4+) and peptidergic (CGRP+) nociceptors are segregated neuronal populations in the mouse. We tested the effects of gefapixant, an antitussive drug targeting non-peptidergic nociceptors through P2X3 antagonism, and olcegepant, an antimigraine drug acting as a CGRP antagonist. Both compounds reversed tactile allodynia, while only gefapixant reversed pain at rest, and none of them reversed movement-induced pain. In conclusion, tactile allodynia, pain at rest, and movement-induced pain after surgery have different pharmacological profiles, and none of the three aspects of postoperative pain can predict the effects of a given intervention on the other two. Combining these measures provides a more realistic view of postoperative pain and has the potential to benefit analgesic development., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

B cells rapidly adapt their endocytic pathway to promote the uptake and processing of extracellular antigens recognized through the B-cell receptor (BCR). The mechanisms coupling changes in endomembrane trafficking to the capacity of B cells to screen for antigens within lymphoid tissues remain unaddressed. We investigated the role of SNX5, a member of the sorting nexin family, which interacts with endocytic membranes to regulate vesicular trafficking and macropinocytosis. Our results show that in steady state, B cells form SNX5-rich protrusions at the plasma membrane, which dissipate upon interaction with soluble antigens, whereas B cells activated with immobilized antigens accumulate SNX5 at the immune synapse where it regulates actin-dependent spreading responses. B cells silenced for SNX5 exhibit enlarged lysosomes, which are not recruited to the synaptic membrane, decreasing their capacity to extract immobilized antigens. Overall, our findings reveal that SNX5 is critical for actin-dependent plasma membrane remodeling in B cells involved in antigen screening and immune synapse formation, as well as endolysosomal trafficking required to promote antigen extraction and presentation., (© 2024 Cabrera-Reyes et al.)

Introduction: Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear., Methods: We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination., Results: We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion., Discussion: Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Donadeu, Gomez-Olles, Casanova, Torija, Lopez-Meseguer, Boada-Pérez, Kervella, Crespo, Carrera-Muñoz, Campos-Varela, Castells, Cortese, Esperalba, Fernández-Naval, Quintero, Muñoz, Agüero, Gonzalez-Costello, Lladó, Favà, Cañas, del Mar de la Hoz-Caballero, Meneghini, Torres, Juvé, Hafkamp, Vila, Robles, Buzón, Toapanta, Zúñiga, Monforte, Saez-Giménez, Len, Arcos, Miret, Ariceta, Pardo, Martínez, Moreso and Bestard.)

Background: Escherichia coli (E. coli) is one of the main bacteria associated with preterm premature rupture of membranes by increasing pro-matrix metalloproteinase 9 (proMMP-9) and degradation of type IV collagen in human feto-maternal interface (HFMi). proMMP-9 is regulated by progesterone (P4) but it is unclear whether P4 inhibits proMMP in human maternal decidual (MDec). This study aimed to determine a role of P4 on proMMP-2 and - 9 and type IV collagen induced by E. coli infection in MDec., Methods: Nine HFMi were mounted in a Transwell system. MDec was stimulated with P4 or E. coli for 3-, 6-, or 24-hours. proMMP-2, -9 and type IV collagen were assessed., Results: Gelatin zymography revealed an increase in proMMP-9 after 3, 6, and 24 h of stimulating MDec with E. coli. Using immunofluorescence, it was confirmed the increase in the HFMi tissue and a reduction on the amount of type IV collagen leading to the separation of fetal amniochorion and MDEc. The degradative activity of proMMP-9 was reduced by 20% by coincubation with P4., Conclusions: P4 modulates the activity of proMMP-9 induced by E. coli stimulation but it was unable to completely reverse the degradation of type IV collagen in human MDec tissue., (© 2024. The Author(s).)

Background: Chagas disease (CD), a Neglected Tropical Disease caused by Trypanosoma cruzi , affects millions of people in Latin America and the southern US and spreads worldwide. CD results from close interactions between humans, animals, and vectors, influenced by sociodemographic factors and housing materials., Methods: This study aimed to evaluate how these factors, along with seasonal changes, affect the distribution of CD vectors in an endemic community near Puebla, Mexico, using a cross-sectional survey. A total of 383 people from this area, known for the presence of major vectors such as Triatoma barberi and Triatoma pallidipennis , were surveyed., Results: As a result of the survey, it was found that only 27.4% of respondents knew about CD, and 83.3% owned potential reservoir pets; additionally, the quality of the wall, roof, and floor significantly influenced vector sightings, while the seasonal pattern showed less of an association. Chi-square tests confirmed these associations between vector sightings and housing materials ( p < 0.001); vector sightings versus seasonal patterns showed less of an association ( p = 0.04), and land use changes did not show an association ( p = 0.27)., Conclusions: Construction materials play an important role in the sighting of triatomines in homes, so important actions should be taken to improve homes. However, further experimental or longitudinal studies are needed to establish causality.

The discovery and development of electrocochleography (ECochG) in animal models has been fundamental for its implementation in clinical audiology and neurotology. In our laboratory, the use of round-window ECochG recordings in chinchillas has allowed a better understanding of auditory efferent functioning. In previous works, we gave evidence of the corticofugal modulation of auditory-nerve and cochlear responses during visual attention and working memory. However, whether these cognitive top-down mechanisms to the most peripheral structures of the auditory pathway are also active during audiovisual crossmodal stimulation is unknown. Here, we introduce a new technique, wireless ECochG to record compound-action potentials of the auditory nerve (CAP), cochlear microphonics (CM), and round-window noise (RWN) in awake chinchillas during a paradigm of crossmodal (visual and auditory) stimulation. We compared ECochG data obtained from four awake chinchillas recorded with a wireless ECochG system with wired ECochG recordings from six anesthetized animals. Although ECochG experiments with the wireless system had a lower signal-to-noise ratio than wired recordings, their quality was sufficient to compare ECochG potentials in awake crossmodal conditions. We found non-significant differences in CAP and CM amplitudes in response to audiovisual stimulation compared to auditory stimulation alone (clicks and tones). On the other hand, spontaneous auditory-nerve activity (RWN) was modulated by visual crossmodal stimulation, suggesting that visual crossmodal simulation can modulate spontaneous but not evoked auditory-nerve activity. However, given the limited sample of 10 animals (4 wireless and 6 wired), these results should be interpreted cautiously. Future experiments are required to substantiate these conclusions. In addition, we introduce the use of wireless ECochG in animal models as a useful tool for translational research., (Copyright © 2024. Published by Elsevier B.V.)

To explore preoperative and operative risk factors for red blood cell (RBC) transfusion requirements during liver transplantation (LT) and up to 24 h afterwards. We evaluated the associations between risk factors and units of RBC transfused in 176 LT patients using a log-binomial regression model. Relative risk was adjusted for age, sex, and the model for end-stage liver disease score (MELD) (adjustment 1) and baseline hemoglobin concentration (adjustment 2). Forty-six patients (26.14%) did not receive transfusion. Grafts from cardiac-death donors were used in 32.61% and 31.54% of non-transfused and transfused patients, respectively. The transfused group required more reoperation for bleeding (P = 0.035), longer mechanical ventilation after LT (P < 0.001), and longer ICU length of stay (P < 0.001). MELD and hemoglobin concentrations determined RBC requirements. For each unit of increase in the MELD score, 2% more RBC units were transfused, and non-transfusion was 0.83-fold less likely. For each 10-g/L higher hemoglobin concentration at baseline, 16% less RBC transfused, and non-transfusion was 1.95-fold more likely. Ascites was associated with 26% more RBC transfusions. With an increase of 2 mm from the baseline in the A10FIBTEM measurement of maximum clot firmness, non-transfusion was 1.14-fold more likely. A 10-min longer cold ischemia time was associated with 1% more RBC units transfused, and the presence of post-reperfusion syndrome with 45% more RBC units. We conclude that preoperative correction of anemia should be included in LT. An intervention to prevent severe hypotension and fibrinolysis during graft reperfusion should be explored.Trial register: European Clinical Trials Database (EudraCT 2018-002,510-13) and ClinicalTrials.gov (NCT01539057)., (© 2024. The Author(s).)

Introduction: The increase in risky sexual behaviors among adolescent students has sparked alarm and has become an area of research interest. As adolescents prioritize confidentiality and accessibility, digital interventions are becoming increasingly relevant in sex education. We therefore posed the following research question: Are digital application interventions effective to prevent risky sexual behaviors in school adolescents?, Design: A systematic peer review was conducted between January and December 2023 in five databases (PubMed, Web of Science, Scopus, EMBASE, and PsycINFO) without restricting for language or year of publication., Method: We included randomized control trials or quasi-experimental studies that measured the effectiveness of interventions targeting young people aged 10-19 years or their parents and developed in a school setting. Interventions aimed at young people with intellectual disabilities, learning difficulties, or any disease requiring a specific intervention were excluded., Results: The search ultimately yielded 27 studies covering a total of 18 digital interventions that demonstrated positive effects, not maintained over time, on knowledge, attitudes, and behaviors, although the latter to a lesser extent., Discussion: We have found very interesting digital interventions with effects, among others, on knowledge, attitudes, and contraceptive use in adolescents. In general, digital interventions have positive effects on knowledge and attitudes, but it is more difficult to modify behaviors with strictly digital interventions or combined with complementary face-to-face sessions or group class activities., Conclusion: We thus believe that digital interventions are adequate to reduce adolescent sexual risk behaviors, and our systematic review facilitates the implementation of these interventions by sharing existing digital interventions that have had positive effects, as well as the main characteristics a digital intervention should possess to reduce sexually risky behaviors in adolescents., Clinical Relevance: Digital interventions with adolescents improve sexual behaviors and can be a valuable resource in education on this topic due to their accessibility and confidentiality, two key points for young people., (© 2024 The Author(s). Journal of Nursing Scholarship published by Wiley Periodicals LLC on behalf of Sigma Theta Tau International.)

Percutaneous liver procedures are frequently performed in patients with abnormal coagulation tests. Current guidelines suggest prophylactic transfusion is not mandatory in all patients with liver disease or cirrhosis, depending on the risk of bleeding. This study aims to describe the incidence and risk of major bleeding after percutaneous liver procedure in patients with and without cirrhosis. This retrospective study includes patients who underwent percutaneous liver biopsy and radiofrequency and microwave ablation of liver lesions at 3 centers in Spain. A transfusion protocol was considered for platelet counts <50,000 and/or international normalized ratio >1.5. The primary outcome was major bleeding. A total of 1797 patients were included in the study, with 316 having cirrhosis (18%) and 1481 without cirrhosis (82%). Among the patients with cirrhosis, 80 were classified as Child A, and percutaneous liver biopsy was the most frequent procedure (86%). Fourteen patients (0.8%) experienced major bleeding, with 0.4% occurring in radiofrequency and microwave ablation and 0.8% in percutaneous liver biopsy. Bleeding occurred in 0.6% of patients with cirrhosis compared to 0.8% in those without ( p = ns). No clinical or procedural variables were associated with bleeding. Twenty-five patients (1.4%) had an international normalized ratio >1.5, and 22 patients (1.2%) had a platelet count <50,000. Only 24% (6/25) of patients with an international normalized ratio >1.5 were transfused with fresh frozen plasma, and 72% (16/22) of those with platelet counts <50,000 received platelet transfusion. Patients with cirrhosis were more frequently transfused (5.9% vs. 1.5%). None of the patients who met the criteria for transfusion experienced major bleeding, regardless of whether they received a transfusion, and none of the patients who had a major bleeding episode met the transfusion criteria. In this cohort, major bleeding after percutaneous liver procedure occurred in <1% of patients, making it a low-risk procedure for patients with and without cirrhosis. Although not uniformly adopted, the current transfusion protocol still led to unnecessary blood product administration., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Objective: We aimed to anlayse the relationship between anti-Xa activity below range and thomboembolic events., Design: Single center prospective observational longitudinal cohort study (February-November 2021)., Setting: Patients admitted to the ICU of a University Hospital., Participants: Patients with severe COVID-19 pneumoniae., Interventions: Enoxaparin was used for prophylactic and therapeutic anticoagulation. Enoxaparin dosing and dose adjustment were based on anti-Xa activity according to the hospital protocol., Main Variables of Interest: Target: thomboembolic events., Predictors: demographics, pharmacotherapy, anti-Xa measurements, clinical data, and laboratory results. Logistic regression was used to identify independent risk factors for thomboembolic events., Results: Data were available for 896 serum anti-Xa measurements from 228 subjects. Overall, 71.9% were male, with a median age of 62. Most patients needed invasive mechanical ventilation (87.7%) and mortality was 24.1%. A total of 28.9% new thomboembolic events were diagnosed. There were 27.1% anti-Xa measesurements below range. When multivariable logistic regression analysis was performed anti-Xa activity below range (RR, 4.2; p = 0.000), C-reactive protein (25 mg/L increase) (RR, 1.14; p = 0.005) and D-dimer (1000 ng/L increase) (RR, 1.06; p = 0.002) were the independent factors related to new thomboembolic events in patients with severe COVID-19., Conclusions: Anti-Xa activity below range, C-reactive protein and D-dimer were the independent factors related to thomboembolic events in patients with severe COVID-19. Purposely designed clinical trials should be carried out to confirm the benefit of an anti-Xa monitoring., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Fibrous dysplasia (FD) is a mosaic non-inheritable genetic disorder of the skeleton in which normal bone is replaced by structurally unsound fibro-osseous tissue. There is no curative treatment for FD, partly because its pathophysiology is not yet fully known. We present a simple mathematical model of the disease incorporating its basic known biology, to gain insight on the dynamics of the involved bone-cell populations, and shed light on its pathophysiology. We develop an analytical study of the model and study its basic properties. The existence and stability of steady states are studied, an analysis of sensitivity on the model parameters is done, and different numerical simulations provide findings in agreement with the analytical results. We discuss the model dynamics match with known facts on the disease, and how some open questions could be addressed using the model., (© 2024. The Author(s), under exclusive licence to the Society for Mathematical Biology.)

Several in vivo studies have shown that systemic inflammation, mimicked by LPS, triggers an inflammatory response in the CNS, driven by microglia, characterized by an increase in inflammatory cytokines and associated sickness behavior. However, most studies induce relatively high systemic inflammation, not directly compared with the more common low-grade inflammatory events experienced in humans during the life course. Using mice, we investigated the effects of low-grade systemic inflammation during an otherwise healthy early life, and how this may precondition the onset and severity of Alzheimer's disease (AD)-like pathology. Our results indicate that low-grade systemic inflammation induces sub-threshold brain inflammation and promotes microglial proliferation driven by the CSF1R pathway, contrary to the effects caused by high systemic inflammation. In addition, repeated systemic challenges with low-grade LPS induce disease-associated microglia. Finally, using an inducible model of AD-like pathology (Line 102 mice), we observed that preconditioning with repeated doses of low-grade systemic inflammation, prior to APP induction, promotes a detrimental effect later in life, leading to an increase in Aβ accumulation and disease-associated microglia. These results support the notion that episodic low-grade systemic inflammation has the potential to influence the onset and severity of age-related neurological disorders, such as AD., (© 2024 The Authors. GLIA published by Wiley Periodicals LLC.)

The American Association of Nurse Anesthesiology (AANA) Practice Committee, in collaboration with AANA Professional Practice staff, advisory panels, and subject matter experts, annually applies a standardized evidence-based process to review, evaluate, and revise clinical resource documents found in the Professional Practice Manual for the CRNA (Certified Registered Nurse Anesthetist) and on the AANA website. This article highlights several revised and newly developed documents, which include topics such as diversity, equity, and inclusion, anesthesia and analgesia for obstetric patients, and safe injection guidelines., (Copyright © by the American Association of Nurse Anesthetists.)

Antimicrobial resistance (AMR) poses a critical threat to global health and development, with environmental factors-particularly in urban areas-contributing significantly to the spread of antibiotic resistance genes (ARGs). However, most research to date has been conducted at a local level, leaving significant gaps in our understanding of the global status of antibiotic resistance in urban environments. To address this issue, we thoroughly analyzed a total of 86,213 ARGs detected within 4,728 metagenome samples, which were collected by the MetaSUB International Consortium involving diverse urban environments in 60 cities of 27 countries, utilizing a deep-learning based methodology. Our findings demonstrated the strong geographical specificity of urban environmental resistome, and their correlation with various local socioeconomic and medical conditions. We also identified distinctive evolutionary patterns of ARG-related biosynthetic gene clusters (BGCs) across different countries, and discovered that the urban environment represents a rich source of novel antibiotics. Our study provides a comprehensive overview of the global urban environmental resistome, and fills a significant gap in our knowledge of large-scale urban antibiotic resistome analysis., (© 2024. Science China Press.)

Endothelial cells (ECs) are highly glycolytic, but whether they generate glycolytic intermediates via gluconeogenesis (GNG) in glucose-deprived conditions remains unknown. Here, we report that glucose-deprived ECs upregulate the GNG enzyme PCK2 and rely on a PCK2-dependent truncated GNG, whereby lactate and glutamine are used for the synthesis of lower glycolytic intermediates that enter the serine and glycerophospholipid biosynthesis pathways, which can play key roles in redox homeostasis and phospholipid synthesis, respectively. Unexpectedly, however, even in normal glucose conditions, and independent of its enzymatic activity, PCK2 silencing perturbs proteostasis, beyond its traditional GNG role. Indeed, PCK2-silenced ECs have an impaired unfolded protein response, leading to accumulation of misfolded proteins, which due to defective proteasomes and impaired autophagy, results in the accumulation of protein aggregates in lysosomes and EC demise. Ultimately, loss of PCK2 in ECs impaired vessel sprouting. This study identifies a role for PCK2 in proteostasis beyond GNG., (© 2024. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects various mammalian species, with farmed minks experiencing the highest number of outbreaks. In Spain, we analyzed 67 whole genome sequences and eight spike sequences from 18 outbreaks, identifying four distinct lineages: B.1, B.1.177, B.1.1.7, and AY.98.1. The potential risk of transmission to humans raises crucial questions about mutation accumulation and its impact on viral fitness. Sequencing revealed numerous not-lineage-defining mutations, suggesting a cumulative mutation process during the outbreaks. We observed that the outbreaks were predominantly associated with different groups of mutations rather than specific lineages. This clustering pattern by the outbreaks could be attributed to the rapid accumulation of mutations, particularly in the ORF1a polyprotein and in the spike protein. Notably, the mutations G37E in NSP9, a potential host marker, and S486L in NSP13 were detected. Spike protein mutations may enhance SARS-CoV-2 adaptability by influencing trimer stability and binding to mink receptors. These findings provide valuable insights into mink coronavirus genetics, highlighting both host markers and viral transmission dynamics within communities.

Eggs and embryo manipulation is an important biotechnological challenge to enable positioning, entrapment, and selection of reproductive cells to advance into a new era of nature-like assisted reproductive technologies. Oviductin (OVGP1) is an abundant protein in the oviduct that binds reversibly to the zona pellucida, an extracellular matrix that surrounds eggs and embryos. Here, the study reports a new method coupling OVGP1 to magnetic nanoparticles (NP) forming a complex (NPOv). NPOv specifically surrounds eggs and embryos in a reversible manner. Eggs/embryos bound to NPOv can be moved or retained when subjected to a magnetic force, and interestingly only mature-competent eggs are attracted. This procedure is compatible with normal development following gametes function, in vitro fertilization, embryo development and resulting in the birth of healthy offspring. The results provide in vitro proof-of-concept that eggs and embryos can be precisely guided in the absence of physical contact by the use of magnets., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The effects of parity and somatic cell count in milk (SCC) threshold on the udder morphology, milkability traits, and milk composition was evaluated in 41 Canarian goats in mid-lactation. The animals were divided according to parity (1st, 2nd, and 3rd), and a SCC threshold of 2000 × 10 3 cells/mL in milk was set to evaluate the effect of this factor on the different measured parameters. Results showed that primiparous goats had the udder smaller and less distended than multiparous goats, but no differences were detected on milk flow parameters. Furthermore, SCC and total bacterial count (TBC) tended to be higher when the parity increased. On the other hand, goats with SCC ≤ 2000 × 10 3 had higher cistern-floor distance (CF) and lower TBC values compared with those goats with a count above the predetermined threshold. The results suggest that a reduction in SCC can be achieved by a selection of udder morphological traits. Moreover, milk flow parameters do not seem to be a tool to determine the udder health status in Canarian goats, but long-term studies are needed to verify it.

Protein-based materials have emerged as promising candidates for proton-conducting biomaterials. Therefore, drawing inspiration from the amino acid composition of prion-like domains, we designed short self-assembling peptides incorporating the (X-Tyr) motif, with X representing Asn, Gly and Ser, which form fibrillar structures capable of conducting protons. In this study, we conducted an analysis of the conductivity capacity of these fibers, with a focus on temperature and frequency dependence of conductivity. The loss tangent curves data and the electrode polarization model with the Debye approximation were employed to calculate transport properties, including conductivity, diffusivity, and density of charge carriers. Results revealed the prion-like fibers can transport protons more efficiently than biomaterials and other synthetic proton conducting materials, and that a significant increase in conductivity is observed with fibrillar orientations. The temperature dependence of conductivity of the peptides, measured in wet conditions, showed conductivities following the trend σ (NY7) < σ (GY7) < σ (SY7), in all the range of temperatures studied. The Arrhenius behavior, and the activation energy associated with conductivity followed the trend: E act (SY7) = 8.2 ± 0.6 kJ mol -1 < E act (GY7) < 13 ± 5 kJ mol -1 < E act (NY7) = 31 ± 7 kJ mol -1 , in different range of temperatures depending of the peptide. Furthermore, the diffusion coefficient correlated with increasing temperature in GY7 and SY7 fibers for temperatures compress between 20 °C and 80 °C, while NY7 only below 60 °C. However, it is noteworthy that the diffusivity observed in the SY7 peptide is lower, compared to GY7 and NY7 presumably due to its enlarged length. This observation can be attributed to two factors: firstly, the higher conductivity values observed in SY7 compared to GY7 and NY7, and secondly, to the value of relation observed of cations present in the peptide SY7 compared with GY7 and NY7, which in turn is dependent on temperature. In light of these findings, we envision our prion-inspired nanofibers as highly efficient proton-conducting natural biopolymers that are both biocompatible and biodegradable. These properties provide the opportunity for the development of next-generation bioelectrical interfaces and protonic devices., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Background: This study compares the severity of SARS-CoV-2 infections caused by Alpha, Delta or Omicron variants in periods of co-circulation in Spain, and estimates the variant-specific association of vaccination with severe disease., Methods: SARS-CoV-2 infections notified to the national epidemiological surveillance network with information on genetic variant and vaccination status were considered cases if they required hospitalisation or controls otherwise. Alpha and Delta were compared during June-July 2021; and Delta and Omicron during December 2021-January 2022. Adjusted odds ratios (aOR) were estimated using logistic regression, comparing variant and vaccination status between cases and controls., Results: We included 5,345 Alpha and 11,974 Delta infections in June-July and 5,272 Delta and 10,578 Omicron in December-January. Unvaccinated cases of Alpha (aOR: 0.57; 95% CI: 0.46-0.69) or Omicron (0.28; 0.21-0.36) had lower probability of hospitalisation vs. Delta. Complete vaccination reduced hospitalisation, similarly for Alpha (0.16; 0.13-0.21) and Delta (June-July: 0.16; 0.14-0.19; December-January: 0.36; 0.30-0.44) but lower from Omicron (0.63; 0.53-0.75) and individuals aged 65+ years., Conclusion: Results indicate higher intrinsic severity of the Delta variant, compared with Alpha or Omicron, with smaller differences among vaccinated individuals. Nevertheless, vaccination was associated to reduced hospitalisation in all groups., (Copyright © 2022 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Family centered developmental care (FCDC) are a philosophy of care in the neonatal care units (NICU), based on the control of sensory stimulation the adequate position and of newborn and the family involvement of cares. Nursing staff are the main providers of this care. Sanitary measure to control of the COVID-19, such as the use of masks, isolation of positive cases and capacity limit, conditioned the implementation of FCDC., Objectives: To understand the meaning of the experience of the nursing staff of a neonatal intensive care unit (NICU) on the implementation of the FCDC, under the sanitary measures imposed for the containment of COVID-19., Methods: A qualitative study was conducted from the descriptive phenomenological paradigm in which NICU nurses were recruited. The qualitative data collection was carried out through open-ended and semi-structured interviews. These were analyzed respectively through a preliminary narrative analysis and a thematic analysis of the informant nurses' narratives and discourses., Results: Three open-ended and 7 semi-structured interviews were conducted from which three main topics emerged: 1) changes in the FCDC derived from the sanitary restrictions implemented for the containment of COVID-19; 2) changes in interpersonal relationships in the context of a pandemic, and 3) transition to normality., Conclusions: The nurses of NICU perceived changes in the implementation of the FCDC due to the containment of COVID-19, that modified the relationship with the parents of NB, accelerating their training as caregivers, and involved the implementation of new measures such as video calls., (Copyright © 2023 The Authors. Published by Elsevier España S.L.U. All rights reserved.)

Adipose tissue has recently been recognized as an important endocrine organ that plays a crucial role in energy metabolism and in the immune response in many metabolic tissues. With this regard, emerging evidence indicates that an important crosstalk exists between the adipose tissue and the brain. However, the contribution of adipose tissue to the development of age-related diseases, including Alzheimer's disease, remains poorly defined. New studies suggest that the adipose tissue modulates brain function through a range of endogenous biologically active factors known as adipokines, which can cross the blood-brain barrier to reach the target areas in the brain or to regulate the function of the blood-brain barrier. In this review, we discuss the effects of several adipokines on the physiology of the blood-brain barrier, their contribution to the development of Alzheimer's disease and their therapeutic potential. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc., (© 2023 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

The experience of menstruation is often associated with negative connotations and gender stereotypes, which results in making it invisible. This research aimed to explore the perceptions, beliefs, and knowledge of young Spanish women regarding the menstrual cycle and menstruation and their impact on their lives. The study delves into their understanding, menstrual management practices, the types of menstrual products employed, and their experiences related to menstrual health. Qualitative methodology was used with discussion groups as a data collection technique. The participants comprised 45 young Spanish women, aged between 18 and 23, hailing from both rural and urban areas. The majority were university students, with some engaged in part-time work, and one participant working full-time. While many experienced menstrual pain ranging from mild to debilitating, a normalization of this pain often led them to forego seeking specialist assistance. Disposable menstrual products (DMPs) are the most used by participants, despite limited awareness of their absorption capacity. Regarding reusable menstrual products (RMPs), menstrual cup users emphasized comfort but expressed a need for proper training. Negative menstruation experiences could evoke fear and difficulties, underscoring the importance of providing comprehensive menstrual health education encompassing both theoretical and practical components.