Surface Acoustic Wave-Driven Enhancement of Enzyme-Linked Immunosorbent Assays: ELISAW.

Enzyme-linked immunosorbent assays (ELISAs) are widely used in biology and clinical diagnosis. Relying on antigen-antibody interaction through diffusion, the standard ELISA protocol can be time-consuming, preventing its use in rapid diagnostics. We present a time-saving and more sensitive ELISA without changing the standard setup and protocol, using surface acoustic waves (SAWs) to enhance performance. Each step of the assay, from the initial antibody binding onto the walls of the well plate to the target analyte molecules' binding for detection─except, notably, for the blocking step─is improved principally via acoustic streaming-driven advection. Using SAWs, the time required for one step of an example ELISA is reduced from 60 to 15 min to achieve the same binding amount. By extending the duration of SAW exposure to 20 min, the sensitivity can be significantly improved over the 60 min, 35 °C ELISA without SAWs. It is also possible to confer beneficial improvements to bead-based ELISA by combining it with SAWs to further reduce the time required for binding to 2 min. By significantly increasing the speed of ELISA, its utility may be improved for a wide range of point-of-care diagnostics applications.

Experience with the ACURATE neo and neo2 transcatheter aortic valves in Spain. The PRECISA (PRospective Evaluation Complementing Investigation with ACURATE devices) registry.

BACKGROUND: Previous studies have documented a high rate of implantation success with the ACURATE neo2 valve, as well as a reduction in paravalvular leak (PVL) compared to its predecessor, the ACURATE neo. However, there are no studies that have reviewed and compared the long-term clinical and hemodynamic outcomes of these patients. AIMS: This study aimed to evaluate the results of the ACURATE neo transcatheter aortic valve in a real-world context, and to compare the results of the outcomes of both generations of this device (ACURATE neo and ACURATE neo2), with a specific focus on procedural success, safety, and long-term effectiveness. METHODS: A prospective study including all consecutive patients treated with the ACURATE neo device in seven hospitals was conducted (Clinical Trials Identification Number: NCT03846557). The primary endpoint consisted of a composite of adverse events, including mortality, aortic insufficiency, and other procedural complications. As the second-generation device (ACURATE neo2) replaced the ACURATE neo during the study period, hemodynamic and clinical results before admission, at 30 days, and at 1 year of follow-up were compared between the two generations. RESULTS: A total of 296 patients underwent transcatheter aortic valve implantation with the ACURATE device, with 178 patients receiving the ACURATE neo and 118 patients receiving the ACURATE neo2. In the overall population, the absence of device success occurred in 14.5%. The primary reason for the absence of device success was the presence of para-valvular regurgitation ≥ 2. There were no instances of coronary occlusions, valve embolization, annulus rupture, or procedural deaths. ACURATE neo2 was associated with a significantly higher device success rate (91.7% vs. 82%, p = 0.04), primarily due to a significantly lower rate of para-valvular regurgitation, which remained significant at 1 year. CONCLUSION: The use of ACURATE neo and neo2 transcatheter aortic valves is associated with satisfactory clinical results and an extremely low rate of complications. The ACURATE neo2 enables a significantly higher device success rate, primarily attributed to a significant reduction in the rate of PVL.

The Identified Skeletal Collection of the School of Legal Medicine: a contemporary osteological collection housed in Universidad Complutense de Madrid, Spain.

ABSTRA: Osteological collections are an important resource for the development of methods to assist in the study of skeletal remains in archeological and/or forensic contexts. The aim is to describe the current characteristics of the Identified Skeletal Collection of the School of Legal Medicine and its historical context. The Identified Skeletal Collection of the School of Legal Medicine of the Complutense University of Madrid consists of 138 male and 95 female individuals, born between 1880 and 1980 and deceased between 1970 and 2009. The minimum age of the sample is perinatal and the maximum age is 97 years. The collection is an essential tool for forensic research, given that its population characteristics can be extrapolated to those of present-day Spain. Access to this collection offers unique teaching opportunities as well as provides the information necessary to develop various lines of research.

Targeting the TWEAK-Fn14 pathway prevents dysfunction in cardiac calcium handling after acute kidney injury.

Heart and kidney have a closely interrelated pathophysiology. Acute kidney injury (AKI) is associated with significantly increased rates of cardiovascular events, a relationship defined as cardiorenal syndrome type 3 (CRS3). The underlying mechanisms that trigger heart disease remain, however, unknown, particularly concerning the clinical impact of AKI on cardiac outcomes and overall mortality. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are independently involved in the pathogenesis of both heart and kidney failure, and recent studies have proposed TWEAK as a possible therapeutic target; however, its specific role in cardiac damage associated with CRS3 remains to be clarified. Firstly, we demonstrated in a retrospective longitudinal clinical study that soluble TWEAK plasma levels were a predictive biomarker of mortality in patients with AKI. Furthermore, the exogenous application of TWEAK to native ventricular cardiomyocytes induced relevant calcium (Ca2+ ) handling alterations. Next, we investigated the role of the TWEAK-Fn14 axis in cardiomyocyte function following renal ischaemia-reperfusion (I/R) injury in mice. We observed that TWEAK-Fn14 signalling was activated in the hearts of AKI mice. Mice also showed significantly altered intra-cardiomyocyte Ca2+ handling and arrhythmogenic Ca2+ events through an impairment in sarcoplasmic reticulum Ca2+ -adenosine triphosphatase 2a pump (SERCA2a ) and ryanodine receptor (RyR2 ) function. Administration of anti-TWEAK antibody after reperfusion significantly improved alterations in Ca2+ cycling and arrhythmogenic events and prevented SERCA2a and RyR2 modifications. In conclusion, this study establishes the relevance of the TWEAK-Fn14 pathway in cardiac dysfunction linked to CRS3, both as a predictor of mortality in patients with AKI and as a Ca2+ mishandling inducer in cardiomyocytes, and highlights the cardioprotective benefits of TWEAK targeting in CRS3. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Racism as a public health issue in environmental health disparities and environmental justice: working toward solutions.

BACKGROUND: Environmental health research in the US has shown that racial and ethnic minorities and members of low-socioeconomic groups, are disproportionately burdened by harmful environmental exposures, in their homes, workplace, and neighborhood environments that impact their overall health and well-being. Systemic racism is a fundamental cause of these disproportionate exposures and associated health effects. To invigorate and inform current efforts on environmental justice and to raise awareness of environmental racism, the National Institute of Environmental Health Sciences (NIEHS) hosted a workshop where community leaders, academic researchers, and NIEHS staff shared perspectives and discussed ways to inform future work to address health disparities. OBJECTIVES: To share best practices learned and experienced in partnerships between academic researchers and communities that are addressing environmental racism across the US; and to outline critical needs and future actions for NIEHS, other federal agencies, and anyone who is interested in conducting or funding research that addresses environmental racism and advances health equity for all communities. DISCUSSION: Through this workshop with community leaders and researchers funded by NIEHS, we learned that partnerships between academics and communities hold great promise for addressing environmental racism; however, there are still profound obstacles. To overcome these barriers, translation of research into plain language and health-protective interventions is needed. Structural changes are also needed in current funding mechanisms and training programs across federal agencies. We also learned the importance of leveraging advances in technology to develop creative solutions that can protect public health.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.

Immediate Norepinephrine in Endotoxic Shock: Effects on Regional and Microcirculatory Flow.

OBJECTIVES: To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock. DESIGN: Animal experimental study. SETTING: University translational research laboratory. SUBJECTS: Fifteen Landrace pigs. INTERVENTIONS: Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance. MEASUREMENTS AND MAIN RESULTS: Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively). CONCLUSIONS: In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.

Prevalence of Chagas disease in Latin American pregnant women in Madrid, Spain: A multicentre cross-sectional study from 2011 to 2016.

OBJECTIVE: The aim of this study is to assess Trypanosoma cruzi infection prevalence among pregnant migrants living in Madrid according to the country of origin and to assess screening coverage in this at-risk population. METHODS: Retrospective multicentre cross-sectional study conducted from January 2011 to December 2016 in eight Madrid hospitals. Each hospital reviewed their microbiology data records to assess the screening coverage and serological diagnosis in all pregnant women coming from endemic areas. RESULTS: From 2011 to 2016, 149,470 deliveries were attended at the eight hospitals, and 11,048 pregnant women were screened for Chagas disease. Most cases (93.5%) were in women from Bolivia, who also showed the highest prevalence (12.4%, 95% confidence interval: 9.9-15.0). Pooled prevalence amongst the screened women was 2.9% (95% CI: 1.8-4.1). Chagas disease screening coverage varied greatly between centres, with a pooled mean coverage of 47% (95% CI: 37%-57%; 73% [95% CI: 63%-82%] for those centres with universal screening vs. 10% [95% CI: 6%-15%] for those with a selective screening approach; p < 0.001). CONCLUSION: Our study provides useful data for policy makers and epidemiologists in a non-endemic area without congenital Chagas screening programmes.

Lipoxin-mediated signaling: ALX/FPR2 interaction and beyond.

In the aftermath of tissue injury or infection, an efficient resolution mechanism is crucial to allow tissue healing and preserve appropriate organ functioning. Pro-resolving bioactive lipids prevent uncontrolled inflammation and its consequences. Among these mediators, lipoxins were the first described and their pro-resolving actions have been mainly described in immune cells. They exert their actions mostly through formyl-peptide receptor 2 (ALX/FPR2 receptor), a G-protein-coupled receptor whose biological function is tremendously complex, primarily due to its capacity to mediate variable cellular responses. Moreover, lipoxins can also interact with alternative receptors like the cytoplasmic aryl hydrocarbon receptor, the cysteinyl-leukotrienes receptors or GPR32, triggering different intracellular signaling pathways. The available information about this complex response mediated by lipoxins is addressed in this review, going over the different mechanisms used by these molecules to stop the inflammatory reaction and avoid the development of dysregulated and chronic pathologies.

White hair in alopecia areata: Clinical forms and proposed physiopathologic mechanisms.

Alopecia areata (AA) is a common form of nonscarring hair loss. It is believed to be a consequence of an immune-mediated stimulus, probably involving autoreactive T cells against antigens present in the hair follicle. The exact antigen is still unknown; however, some authors have proposed that melanogenesis-associated molecules might trigger autoimmunity. Although transient white hair regrowth is a common and well-known situation in AA, there are other types of white hair phenomena in this context, including permanent white hair regrowth, sparing of white hair in a patchy pattern, or sparing in a diffuse pattern, giving the appearance of the so-called overnight graying phenomena or canitis subita. In this review, we aim to describe the different clinical aspects of white hair in AA, as well as the proposed pathophysiologic mechanisms involved in this phenomena.

Effects of Liquid and Bar Soaps on the Skin of Brazilian Newborns: A Randomized Controlled Trial.

INTRODUCTION: Compared to adults, newborns' skin has a thinner epidermis and stratum corneum with decreased hydration levels, higher transepidermal water loss, and a pH variation between 5.5 and 7.5. These characteristics can predispose to the occurrence of dryness, infections, and dermatological conditions. Water and liquid soap with adequate formulation have shown to be beneficial and safe for newborns' skin. However, studies evaluating the effect of bar soap, products widely used in Brazil and Latin America, are unknown. Therefore, the objective of this study was to compare the effects of liquid and bar soaps on the term newborns' skin. METHODS: This randomized controlled, parallel, single-blind clinical trial was conducted at a public university hospital in São Paulo, Brazil. 100 healthy term newborns with no congenital anomalies, acute diseases, or dermatological conditions were randomized to use liquid soap (experimental group) or bar soap (control group). Skin pH, transepidermal water loss, stratum corneum hydration, sebum content, and skin condition were assessed before and after the first bath, at 48 h, 14 days, and 28 days after birth. These evaluations were performed on the forearm, abdomen, buttocks, and thigh. In addition, the mother's perception of soap use was also evaluated. RESULTS: Data of 100 newborns were analyzed by intention to treat. The rate of retention was 53%. Newborns exposed to the liquid soap presented significantly better skin acidification (p < 0.001) and significantly better stratum corneum hydration (p < 0.001) than the skin of newborns exposed to the bar soap, regardless of the area evaluated. There were no significant differences in transepidermal water loss, sebum content, dryness, erythema, or skin breakdown and the mother's perceptions of the use of the soaps. CONCLUSION: Newborns in the experimental group presented better skin acidification and stratum corneum hydration when compared to newborns in the control group.

[Screening for strongyloidiasis in Spain in the context of the SARS-CoV-2 pandemic: Results of a survey on diagnosis and treatment]. / Cribado de estrongiloidiosis en España en el contexto de la pandemia SARS-CoV-2: resultados de una encuesta sobre diagnóstico y tratamiento.

Introduction: The generalization of treatment with dexamethasone or other immunosuppressants in patients with SARS-CoV-2 infection may increase the risk of occurrence of severe forms of strongyloidiasis. A nationwide survey was conducted to better understand the diagnostic and therapeutic situation of strongyloidiasis in SARS-CoV-2 co-infected patients in Spain. Materials and methods: A survey was designed and sent to all SEIMC members during February and March 2021. Responses were exported for computer processing to Microsoft Excel 2017 and statistically processed with the free software PSPP. Results: 189 responses were received, of which 121 (64%) were selected for further processing. Eighty-four centers (69.5%) had no specific strongyloidiasis screening protocol. Forty-two centers (34.7%) had serological techniques available in their laboratories and the rest were sent to a reference laboratory. Only 22 centers (18%) screened for strongyloidiasis in SARS-CoV-2 infected patients. A total of 227 cases of strongyloidiasis were diagnosed in patients with SARS-CoV-2 infection. In four cases patients developed a massive hyperinfestation syndrome leading to the death of one patient. Conclusion: COVID-19 has highlighted the need to unify screening and treatment protocols for imported pathologies such as strongyloidiasis. Efforts to disseminate knowledge are needed to ensure that this potentially fatal disease is adequately treated in patients with the highest risk of complications, such as those with COVID-19.

Partial Genetic Deletion of Klotho Aggravates Cardiac Calcium Mishandling in Acute Kidney Injury.

Acute kidney injury (AKI) is associated with an elevated risk of cardiovascular major events and mortality. The pathophysiological mechanisms underlying the complex cardiorenal network interaction remain unresolved. It is known that the presence of AKI and its evolution are significantly associated with an alteration in the anti-aging factor klotho expression. However, it is unknown whether a klotho deficiency might aggravate cardiac damage after AKI. We examined intracellular calcium (Ca2+) handling in native ventricular isolated cardiomyocytes from wild-type (+/+) and heterozygous hypomorphic mice for the klotho gene (+/kl) in which an overdose of folic acid was administered to induce AKI. Twenty-four hours after AKI induction, cardiomyocyte contraction was decreased in mice with the partial deletion of klotho expression (heterozygous hypomorphic klotho named +/kl). This was accompanied by alterations in Ca2+ transients during systole and an impairment of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) function in +/kl mice after AKI induction. Moreover, Ca2+ spark frequency and the incidence of Ca2+ pro-arrhythmic events were greater in cardiomyocytes from heterozygous hypomorphic klotho compared to wild-type mice after AKI. A decrease in klotho expression plays a role in cardiorenal damage aggravating cardiac Ca2+ mishandling after an AKI, providing the basis for future targeted approaches directed to control klotho expression as novel therapeutic strategies to reduce the cardiac burden that affects AKI patients.

HPLC-TBARS-EVSC (high-performance liquid chromatography-thiobarbituric acid reactive substances-ex vivo stratum corneum) protocol: Selection of the subjects and approach to present the results.

OBJECTIVE: Nowadays, it is recognized the need for improved safety and efficacy protocols to evaluate the human stratum corneum (SC) and its interaction with topical and cosmetic formulations by minimally or non-invasive methodologies. The aim of our research work was to streamline the HPLC-TBARS-EVSC (high-performance liquid chromatography-thiobarbituric acid reactive substances-ex vivo stratum corneum) methodology, by exploring the results of a group of 18 subjects. METHODS: The study included nine women and nine men aged between 19 and 57 years old with phototypes from II to V. Sites in the forearm of each volunteer were randomly delimited, and the SC was collected by tape stripping. HPLC was used to quantify the MDA-TBA2 (malondialdehyde-thiobarbituric acid) adduct from the tape-stripped SC, irradiated and not by an ultraviolet (UV) simulator chamber. RESULTS: Observing the findings of our present investigation, and the statistical approach applied, the use of the ratio between the treatment site and control would be an adequate strategy to better discriminate and evaluate the results. Additionally, an optimal selection of the volunteers to respond specifically to the purpose of the ex vivo assay also can be considered advantageous. CONCLUSIONS: It seemed that in future studies focusing on the impact of SC UV-induced lipid peroxidation, determined by the HPLC-TBARS-EVSC, the most suitable subjects are females aged less than 35 years old, with phototype II.

OBJECTIF: Aujourd'hui, il est nécessaire d'améliorer les protocoles de sécurité d'emploi et d'efficacité pour évaluer le stratum corneum (SC) humain et son interaction avec les formulations topiques et cosmétiques par des méthodologies peu ou pas invasives. L'objectif de notre travail de recherche était de rationaliser la méthodologie HPLC-TBARS-SCEV, à savoir chromatographie en phase liquide à haute performance (High Performance Liquid Chromatography), substances réactives à l'acide thiobarbiturique (Thiobarbituric Acid Reactive Substances), stratum corneum ex vivo (SCEV), en explorant les résultats d'un groupe de 18 sujets. MÉTHODES: L'étude incluait 9 femmes et 9 hommes âgés de 19 à 57 ans présentant des phototypes II à V. Des sites de l'avant-bras de chaque volontaire ont été délimités de manière aléatoire, et le SC a été recueilli par « tape stripping ¼. La chromatographie en phase liquide à haute performance a été utilisée pour quantifier l'adduit MDA-TBA2 (malondialdéhyde - acide thiobarbiturique) à partir du SC recueilli par « tape stripping ¼, irradié et non irradié par une chambre de simulation à ultraviolets (UV). RÉSULTATS: En observant les résultats de notre recherche actuelle et l'approche statistique appliquée, l'utilisation du rapport entre le site traité et le site contrôle serait une stratégie adéquate pour mieux discriminer et évaluer les résultats. En outre, une sélection optimale des volontaires pour répondre spécifiquement à l'objectif du test ex vivo peut également être considérée comme bénéfique. CONCLUSIONS: Il semble que dans les études futures axées sur l'impact de la peroxydation lipidique induite par UV du SC, déterminé par la méthodologie HPLC-TBARS-SCEV, les sujets les plus appropriés sont les femmes âgées de moins de 35 ans présentant un phototype II.

Behavioural and neurochemical effects after repeated administration of N-ethylpentylone (ephylone) in mice.

N-ethyl-pentylone (NEP), also known as 'ephylone' and N-ethylnorpentylone, has been identified as one of the most recent novel psychostimulants to emerge into the illicit drug market and it has been associated with some intoxications and even fatalities. However, little is known about the consequences of its repeated consumption as well as the role of the monoaminergic system in such consequences. Thus, the aim of our study was to investigate the neurochemical profile and the behavioural effects after both acute and repeated NEP exposure. Male OF1 mice were acutely (1, 3, 10 mg/kg, i.p.) or repeatedly (1, 3, 10 mg/kg, i.p., 5 days, twice/day) exposed to NEP, and anxiety-like behaviour, aggressiveness, social interaction, depressive-like symptoms, body temperature, changes in monoaminergic enzymes and neurotransmitters levels as well as ΔFosB in striatum and prefrontal cortex (PFC) from post-mortem tissue were analysed short after drug-exposure or during drug-withdrawal. Acute administration of NEP induced anxiolytic effects but also an aggressive behaviour and social exploration deficits in mice, which persist during NEP-withdrawal. Moreover, NEP induced hyperthermia as well as depressive-like symptoms after repeated administrations that may be related to the decrease in serotonin and noradrenaline levels observed in striatum and PFC. Finally, the long-term increase in ΔFosB levels in striatum after NEP chronic exposure points to a high risk of dependence. Altogether indicates that NEP consumption induces different neurological and neuropsychiatric disorders accompanied by changes in the monoaminergic system, posing a threat to public health.

The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown. METHODS: We carried out a translational approach to study the relationship between the FGF23-Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels. RESULTS: Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K+) current (Itof), caused by the downregulation of K+ channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced Itof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes. CONCLUSION: The FGF23-Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD.

Enhancing Data Integration, Interoperability, and Reuse to Address Complex and Emerging Environmental Health Problems.

Environmental health sciences (EHS) span many diverse disciplines. Within the EHS community, the National Institute of Environmental Health Sciences Superfund Research Program (SRP) funds multidisciplinary research aimed to address pressing and complex issues on how people are exposed to hazardous substances and their related health consequences with the goal of identifying strategies to reduce exposures and protect human health. While disentangling the interrelationships that contribute to environmental exposures and their effects on human health over the course of life remains difficult, advances in data science and data sharing offer a path forward to explore data across disciplines to reveal new insights. Multidisciplinary SRP-funded teams are well-positioned to examine how to best integrate EHS data across diverse research domains to address multifaceted environmental health problems. As such, SRP supported collaborative research projects designed to foster and enhance the interoperability and reuse of diverse and complex data streams. This perspective synthesizes those experiences as a landscape view of the challenges identified while working to increase the FAIR-ness (Findable, Accessible, Interoperable, and Reusable) of EHS data and opportunities to address them.

Management of Persistent SARS-CoV-2 Infection in Patients with Follicular Lymphoma.

INTRODUCTION: There is no consensus on the management of the coronavirus disease (COVID-19) in patients with secondary immunosuppression due to either an underlying hematological disease or to the effects of immunochemotherapy (ICT). Some of them may present persistent infection with multiple relapses of COVID-19, requiring several admissions. This study evaluated the clinical characteristics and outcomes after treatment of 5 patients with follicular lymphoma (FL), previously treated with ICT, who developed several episodes of COVID-19. METHODS: We analyzed the clinical evolution and response to treatment with antiviral agent, steroids, and convalescent plasma in 5 patients with FL and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistent infection. Reverse transcriptase polymerase chain reaction tests and peripheral blood immunophenotype were performed for all patients. RESULTS: All patients required hospitalization due to pneumonia with severity criteria and were re-admitted after a median of 22 days (13-42) from the previous discharge. They all showed B-cell depletion by immunophenotyping, and no traces of immunoglobulin antibodies against SARS-CoV-2 were detected in any of the cases. The survival rate was 80%. CONCLUSION: The combination therapy evidenced clinical benefits, demonstrating its capacity to control infection in immunosuppressed FL patients treated with ICT.

Health promoting schools and COVID-19: preparing for the future.

We face an unprecedented period of history during which COVID-19 is clustered with other global conditions, such as obesity, undernutrition, an infodemic, and climate change. This syndemic (synergy of epidemics) calls for the development of children's and youth's health literacy and socioemotional skills, support for behavioural hygiene (e.g. washing hands, wearing masks), and adults' responsibility and caring. Moreover, it calls for creating conditions for healthy living and learning for all and paying extra attention to inequalities that have increased during the pandemic. Today, more than ever, there is an essential demand for schools to create environments that maintain and promote health for all. Within this commentary, we argue that whole-school approaches, such as the health promoting school, are essential to fight against the pandemic and to prepare schools for future challenges.

Neurological recovery after traumatic spinal cord injury: prognostic value of magnetic resonance.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: Assess the relationship between Magnetic Resonance (MR) image patterns and neurological recovery in patients with Traumatic Spinal Cord Injury (TSCI). SETTING: Spinal cord injury unit in Spain. METHODS: Patients admitted for acute TSCI between January 2010 and December 2018 with a MR exam performed in the acute phase were selected. Five patterns were established: normal, single-level edema, multilevel edema, hemorrhage, and spinal cord transection. Comparisons between the ASIA Injury Severity (AIS) score and Motor Index (MI) at admission and at discharge were made. RESULTS: Collected 296 patients. Normal and cord transection patterns were excluded due to the low number of cases. Single-level edema pattern was primarily observed in cases with incomplete injuries, hemorrhage pattern in complete injuries, and multilevel edema pattern at similar percentages in complete and incomplete lesions. Improvement of the AIS score was found in 40.9% of single-level edema, 20.2% of multilevel edema, and 19.0% of hemorrhage (p = 0.042) patterns. By excluding the AIS grade D from the analyses, the figures increased to 70.3%, 52.2%, and 19.4% respectively (p < 0.001). This significant relationship was confirmed by multivariate analysis, although it was not as relevant as the examination according to ASIA-ISCoS performed at admission (p = 0.005 vs p < 0.001). Mean variation of the MI was also significantly different (p < 0.001) between the three groups: 22.6 ± 21.4 for single-level edema, 16.9 ± 21.1 for multilevel edema, and 4.5 ± 8.4 for hemorrhage. CONCLUSION: MR injury patterns observed at the acute phase are associated with the possibility of improvement of the AIS score and MI.