Revisiting the impact of Health at Every Size® interventions on health and cardiometabolic related outcomes: An updated systematic review with meta-analysis.

AIMS: To (1) synthesise evidence from Health at Every Size® interventions on physical and psychological health in people with overweight and obesity and (2) report between-group differences within interventions evaluating the impact of Health at Every Size® interventions on health and health-related outcomes. METHODS: Six databases (Medline, Embase, Cochrane, PsychInfo, CINAHL, and Scopus) were searched from inception until November 2022. Included studies were conducted in adults with overweight or obesity, used Health at Every Size®-based interventions compared with control interventions and reported dietary, physical and/or psychological outcomes, including diet quality, anthropometry, or quality of life. Data on between-group differences were extracted. Risk of bias was assessed using ROB2. Random-effects meta-analyses were undertaken for outcomes with at least three studies reporting the same or comparable data. RESULTS: From 128 studies identified, 19 full-text articles (10 unique studies, 6 published since 2017), were included. Meta-analysis found a significant reduction for susceptibility to hunger in Health at Every Size® intervention groups relative to controls (p = 0.005), with no significant difference (p > 0.05) between Health at Every Size® interventions and control groups for anthropometric, psychological or cardiometabolic outcomes (total cholesterol, HDL cholesterol, triglycerides, systolic or diastolic blood pressure). CONCLUSION: Health at Every Size® interventions had similar results compared with weight-based interventions on anthropometric outcomes and cardiometabolic outcomes. Health at Every Size® interventions had a significant benefit for reducing susceptibility to hunger. The decision to use a Health at Every Size®-based intervention should be personalised to individual needs. Further research in more diverse populations is required using standardised outcome measures to facilitate future meta-analyses.

Benefits of applying hourly resolution in the assessment of the climate aptitude to manage tourist activities in arid regions.

The availability of reliable information on local climatic-tourism conditions is a growing need due to the influence it exerts on the quality of the organizational strategy of tourist destination's, and travel experience. Evaluations of the tourism potential of the climate have been carried out on a daily or monthly resolution, thus limiting the collection of detailed information that makes it possible to fine-tune tourism management and operational decision-making on an intraday scale. This research is the first case study to analyse the climatic suitability for nature tourism, using the weather types method at hourly resolution. The study applies to arid tourist destinations in Isfahan province (Iran). The detailed resolution has made it possible to identify the time slots favourable to the development of nature tourism in those periods of the year recognized as critical in the daily resolution analyses. In the same way, the hourly resolution has also identified critical bands in those periods indicated as favourable in the evaluations to daily resolution. The hourly resolution provides detailed information that can allow tourists and also tourism managers to establish intraday adaptation strategies that make it possible to develop the activity even in places with extreme climates.

The fatal contribution of serine protease-related genetic variants to COVID-19 outcomes.

Introduction: Serine proteases play a critical role during SARS-CoV-2 infection. Therefore, polymorphisms of transmembrane protease serine 2 (TMPRSS2) and serpine family E member 1 (SERPINE1) could help to elucidate the contribution of variability to COVID-19 outcomes. Methods: To evaluate the genetic variants of the genes previously associated with COVID-19 outcomes, we performed a cross-sectional study in which 1536 SARS-CoV-2-positive participants were enrolled. TMPRSS2 (rs2070788, rs75603675, rs12329760) and SERPINE1 (rs2227631, rs2227667, rs2070682, rs2227692) were genotyped using the Open Array Platform. The association of polymorphisms with disease outcomes was determined by logistic regression analysis adjusted for covariates (age, sex, hypertension, type 2 diabetes, and obesity). Results: According to our codominant model, the GA genotype of rs2227667 (OR=0.55; 95% CI = 0.36-0.84; p=0.006) and the AG genotype of rs2227667 (OR=0.59; 95% CI = 0.38-0.91; p=0.02) of SERPINE1 played a protective role against disease. However, the rs2227692 T allele and TT genotype SERPINE1 (OR=1.45; 95% CI = 1.11-1.91; p=0.006; OR=2.08; 95% CI = 1.22-3.57; p=0.007; respectively) were associated with a decreased risk of death. Similarly, the rs75603675 AA genotype TMPRSS2 had an OR of 1.97 (95% CI = 1.07-3.6; p=0.03) for deceased patients. Finally, the rs2227692 T allele SERPINE1 was associated with increased D-dimer levels (OR=1.24; 95% CI = 1.03-1.48; p=0.02). Discussion: Our data suggest that the rs75603675 TMPRSS2 and rs2227692 SERPINE1 polymorphisms are associated with a poor outcome. Additionally, rs2227692 SERPINE1 could participate in hypercoagulable conditions in critical COVID-19 patients, and this genetic variant could contribute to the identification of new pharmacological targets and treatment strategies to block the inhibition of TMPRSS2 entry into SARS-CoV-2.

Phenotypic and genotypic antimicrobial resistance of Listeria spp. in Spain.

Listeriosis is a zoonotic disease caused by Listeria monocytogenes and Listeria ivanovii. The genus Listeria currently includes 27 recognized species and is found throughout the environment. The number of systematic studies on antimicrobial resistance in L. monocytogenes isolates from domestic farms using antimicrobial substances is limited. Importantly, dairy ruminant farms are reservoir of hypervirulent lineage I L. monocytogenes isolates, previously associated with human clinical cases. Considering that the classes of antibiotics used in food-producing domestic animals are frequently the same or closely related to those used in human medicine, studies about the impact of antibiotic use on the acquisition of antibiotic resistance in Listeria spp. in domestic animal farms are, therefore, of high importance. Here, susceptibility to 25 antibiotics was determined. Eighty-one animal-related, 35 food and 21 human pathogenic Listeria spp. isolates and 114 animal-related non-pathogenic Listeria spp. isolates were tested. Whole genome sequencing data was used for molecular characterization. Regarding L. monocytogenes, 2 strains from the clinical-associated linage I showed resistance to erythromycin, both related to dairy ruminants. Acquired resistance to one antibiotic was exhibited in 1.5% of L. monocytogenes isolates compared with 14% of non-pathogenic Listeria spp. isolates. Resistance to tetracycline (7.9%), doxycycline (7.9%), penicillin (4.4%), and ampicillin (4.4%) were the most frequently observed in non-pathogenic Listeria spp. While resistance to two or more antibiotics (5.6%) was most common in Listeria spp., isolates, resistance to one antibiotic was also observed (1.6%). The present results show that non-pathogenic Listeria spp. harbour antimicrobial resistance genes.

Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL) / Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis

Introducción y objetivos: La amiloidosis cardiaca (AC) es una patología asociada a un elevado número de ingresos hospitalarios. Dada la escasa información disponible al respecto, planteamos un análisis de la incidencia y las causas de hospitalización en esta enfermedad.Material y métodosSe evaluaron 143 pacientes (128 por transtiretina [AC-ATTR] y 15 por cadenas ligeras [AC-AL]) incluidos en el Registro de Amiloidosis Cardiaca de Galicia (AMIGAL), recogiendo todas sus hospitalizaciones.ResultadosDurante un seguimiento mediano de 959 días se produjeron 179 hospitalizaciones no programadas (tasa de incidencia [TI] 512,6 ingresos hospitalarios por 1.000 pacientes-año), siendo las más habituales las de causa cardiovascular (n=109, TI 312,2). El motivo individual de ingreso hospitalario más frecuente fue la insuficiencia cardiaca (IC) (n=87, TI 249,2).La AC-AL se asoció con una TI de hospitalizaciones no programadas más elevada que la AC-ATTR (TI 781 vs. 483,2; HR 1,62; p=0,029) a expensas de las de causa no cardiovascular (TI 376 vs. 181,2; HR 2,07; p=0,027). La supervivencia libre de hospitalización no programada al año y a los tres años en la AC-AL fue menor que en la AC-ATTR (46,7 y 20,0% vs. 73,4 y 35,2%, respectivamente; p=0,021). (AU)

Introduction and objetives: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease.Material and methodsOne hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations.ResultsDuring a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2).AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). (AU)

Controlling Coxiella burnetii in naturally infected sheep, goats and cows, and public health implications: a scoping review.

Q fever is a worldwide zoonotic disease which domestic ruminants are the main source of infection for humans. This scoping review summarizes the control measures currently available to reduce Coxiella burnetii (Cb) infection in naturally infected sheep, goat and cattle herds. A total of 28 articles were included in the review. A lack of methodological standardization was noted in the articles analyzed. The results indicated that long-term vaccination in cows reduces bacterial excretion in milk and environmental contamination. In small ruminants, the results of vaccination in terms of efficacy are variable. In goats, there is a reduction in bacterial excretion, unlike in sheep, where a long-term vaccination program is necessary to reduce bacterial excretion. Moreover, the high persistence of viable Cb in the environment means that control measures for sheep are needed for several years. The use of antibiotics as a control measure in cows and sheep was not found to reduce excretion. However, the combination of vaccination with antibiotic therapy appears to have positive effects in small ruminants in terms of controlling outbreaks of Q fever. Hygiene and biosecurity measures are the basic means for controlling Cb infection on ruminant farms and ensuring public health.

Spanish-French leech trade and its consequences: From the increase in medical demand to resource depletion and technical innovation.

This article studies the impact caused by the success and dissemination of Broussais' theories on the use of leeches as a medical supply on Spanish-French trade relations, as well as its consequences for the Spanish market between 1821 and the 1860s. Analysing the documents produced by the different public administrations, together with newspaper and archival sources in both Spain and France and the literature and legislation of that period, allows us to understand the evolution of this trade and the heavy impact it had on the autochthonous population of this animal resource. The article reveals how, at the beginning of the 1820s, leeches became an important medical supply and how the demand for them increased significantly. This gave rise to a trade relation between Spain and France that led to the overexploitation of the resource, the issuing of regulations on the matter, and the search for technological solutions to increase the production of leeches.

Assessing the complementary information from an increased number of biologically relevant features in liquid biopsy-derived RNA-Seq data.

Liquid biopsy-derived RNA sequencing (lbRNA-seq) exhibits significant promise for clinic-oriented cancer diagnostics due to its non-invasiveness and ease of repeatability. Despite substantial advancements, obstacles like technical artefacts and process standardisation impede seamless clinical integration. Alongside addressing technical aspects such as normalising fluctuating low-input material and establishing a standardised clinical workflow, the lack of result validation using independent datasets remains a critical factor contributing to the often low reproducibility of liquid biopsy-detected biomarkers. Considering the outlined drawbacks, our objective was to establish a workflow/methodology characterised by: 1. Harness the rich diversity of biological features accessible through lbRNA-seq data, encompassing a holistic range of molecular and functional attributes. These components are seamlessly integrated via a Machine Learning-based Ensemble Classification framework, enabling a unified and comprehensive analysis of the intricate information encoded within the data. 2. Implementing and rigorously benchmarking intra-sample normalisation methods to heighten their relevance within clinical settings. 3. Thoroughly assessing its efficacy across independent test sets to ascertain its robustness and potential utility. Using ten datasets from several studies comprising three different sources of biological material, we first show that while the best-performing normalisation methods depend strongly on the dataset and coupled Machine Learning method, the rather simple Counts Per Million method is generally very robust, showing comparable performance to cross-sample methods. Subsequently, we demonstrate that the innovative biofeature types introduced in this study, such as the Fraction of Canonical Transcript, harbour complementary information. Consequently, their inclusion consistently enhances prediction power compared to models relying solely on gene expression-based biofeatures. Finally, we demonstrate that the workflow is robust on completely independent datasets, generally from different labs and/or different protocols. Taken together, the workflow presented here outperforms generally employed methods in prediction accuracy and may hold potential for clinical diagnostics application due to its specific design.

Management of Vertebral Fragility Fracture in Older People: Recommendations from a Spanish Consensus of Experts.

Vertebral fragility fractures (VFF) pose a challenge for appropriate care. The aim of this study was to develop consensus recommendations for the management of VFF in older people from a multidisciplinary approach. Specialists in osteoporosis belonging to different scientific societies reviewed the main clinical practice guidelines published in Spain in 2014. Thirty-five recommendations for the management of VFF were evaluated by seven experts using an anonymous survey. Consensus was defined as 80% of responses of 8 (agree) and 9 (strongly agree) on a Likert scale. Consensus was achieved in 22 recommendations (62.8%). The experts agreed on the need for anamnesis, clinical assessment, and laboratory tests, including erythrocyte sedimentation rate, proteinography, and the assessment of levels of calcium, vitamin D, alkaline phosphatase, and thyroid-stimulating hormone. Optional tests, such as bone turnover markers (BTMs), magnetic resonance imaging, bone scintigraphy, or using a fracture risk assessment tool (FRAX®), did not achieve an agreed consensus. Also, there was consensus regarding the administration of calcium/vitamin D supplements, the withdrawal of toxic habits, and personalized physical exercise. Participants agreed on the administration of teriparatide for 24 months and then a switch to denosumab or bisphosphonates in patients at high risk of fracture. Specialists in osteoporosis, primary care physicians, and geriatricians should be involved in the follow-up of patients with VFF. Although there was multidisciplinary agreement on diagnostic tests and non-pharmacological and pharmacological treatment in frail older people, therapeutic objectives should be individualized for every patient. In addition to the specific recommendations, close collaboration between the geriatrician and the primary care physician is essential for the optimal chronic management of frail patients with fragility fractures.

Novel B cell subsets as potential biomarkers in Idiopathic Inflammatory Myopathies: insights into disease pathogenesis and disease activity.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double negative subsets, as well as an expansion of the naïve compartment relative to healthy controls, that contribute to defining disease-associated B cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathies onset or development.

[Incidence and causes of hospitalization in patients with transthyretin (ATTR-CA) and light chain (AL-CA) cardiac amyloidosis]. / Incidencia y causas de hospitalización en pacientes con amiloidosis cardiaca por transtiretina (AC-ATTR) y por cadenas ligeras (AC-AL).

INTRODUCTION AND OBJETIVES: Cardiac amyloidosis (CA) is a disorder associated with high number of hospital admissions. Given the scarce information available, we propose an analysis of the incidence and causes of hospitalization in this disease. MATERIAL AND METHODS: One hundred and forty-three patients [128 by transthyretin (ATTR-CA) and 15 by light chains (AL-CA)] included in Registro de Amiloidosis Cardiaca de Galicia (AMIGAL) were evaluated, including all hospitalizations. RESULTS: During a median follow-up of 959 days there were 179 unscheduled hospitalizations [incidence rate (IR) 512.6 admissions per 1000 patients-year], most common due to cardiovascular reasons (n=109, IR 312.2). Most frequent individual cause of hospitalization was heart failure (n=87, TI 249.2). AL-CA was associated with a higher IR of unscheduled hospitalizations than ATTR-CA (IR 781 vs. 483.2; HR 1.62; p=0,029) due to non-cardiovascular admissions (IR 376 vs. 181.2; HR 2.07; p=0.027). Unscheduled admission-free survival at 1 and 3 years in AL-CA was inferior than in ATTR-CA (46.7% and 20.0% vs. 73.4% and 35.2%, respectively; p=0.021). CONCLUSIONS: CA was associated with high incidence of hospitalizations, being heart failure the most frequent individual cause; unscheduled admission-free survival in AL-CA was lower than in ATTR-CA due mostly to non-cardiovascular admissions.

In Vitro Interaction between Mycoplasma agalactiae and Small Ruminants' Endogenous Bacterial Strains of Enterococcus spp. and Coagulase-Negative Staphylococcus.

Recently, an antimicrobial effect on Mycoplasma agalactiae (Ma), the main etiological agent of contagious agalactia (CA), was reported in vitro with strains of Enterococcus spp. from ovine and caprine milk. The aim of this work was to evaluate the interaction of Ma with the same Enterococcus spp. isolated from other anatomical locations (vagina) and other bacterial populations present in milk, such as coagulase-negative staphylococci (CNS). The vaginal Enterococcus strains and the raw milk CNS were isolated from sheep and goats. Experimental in vitro conditions were prepared to assess the growth of Ma with and without the presence of these strains. The selected vaginal strains were identified as Enterococcus (E.) hirae and E. mundtii, and the strains of CNS were identified as Staphylococcus petrasii. Different interactions of Ma with ovine and caprine wild vaginal strains of Enterococcus and dairy strains of CNS are described for the first time: Ma can grow exponentially during 15 h with the selected strains, although with certain strains, its optimal growth can be negatively affected (p < 0.05). The colonization and/or excretion of Ma could, therefore, be influenced by certain endogenous bacterial strains. Our results increase the knowledge about possible bacterial ecology dynamics surrounding CA.

Longitudinal changes in the functional connectivity of individuals at risk of Alzheimer's disease.

First-degree relatives of Alzheimer's disease patients constitute a key population in the search for early markers. Our group identified functional connectivity differences between cognitively unimpaired individuals with and without a family history. In this unprecedented follow-up study, we examine whether family history is associated with a longitudinal increase in the functional connectivity of those regions. Moreover, this is the first work to correlate electrophysiological measures with plasma p-tau231 levels, a known pathology marker, to interpret the nature of the change. We evaluated 69 cognitively unimpaired individuals with a family history of Alzheimer's disease and 28 without, at two different time points, approximately 3 years apart, including resting state magnetoencephalography recordings and plasma p-tau231 determinations. Functional connectivity changes in both precunei and left anterior cingulate cortex in the high-alpha band were studied using non-parametric cluster-based permutation tests. Connectivity values were correlated with p-tau231 levels. Three clusters emerged in individuals with family history, exhibiting a longitudinal increase of connectivity. Notably, the clusters for both precunei bore a striking resemblance to those found in previous cross-sectional studies. The connectivity values at follow-up and the change in connectivity in the left precuneus cluster showed significant positive correlations with p-tau231. This study consolidates the use of electrophysiology, in combination with plasma biomarkers, to monitor healthy individuals at risk of Alzheimer's disease and emphasizes the value of combining noninvasive markers to understand the underlying mechanisms and track disease progression. This could facilitate the design of more effective intervention strategies and accurate progression assessment tools.

Effect of an algorithm for automatic placing of standardised test order sets on low-value appointments and attendance rates at four Spanish teaching hospitals: an interrupted time series analysis.

OBJECTIVE: Reducing backlogs for elective care is a priority for healthcare systems. We conducted an interrupted time series analysis demonstrating the effect of an algorithm for placing automatic test order sets prior to first specialist appointment on avoidable follow-up appointments and attendance rates. DESIGN: Interrupted time series analysis. SETTING: 4 academic hospitals from Madrid, Spain. PARTICIPANTS: Patients referred from primary care attending 10 033 470 outpatient appointments from 16 clinical specialties during a 6-year period (1 January 2018 to 30 June 2023). INTERVENTION: An algorithm using natural language processing was launched in May 2021. Test order sets developed for 257 presenting complaints from 16 clinical specialties were placed automatically before first specialist appointments to increase rates of diagnosis and initiation of treatment with discharge back to primary care. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes included rate of diagnosis and discharge to primary care and follow-up to first appointment index. The secondary outcome was trend in 'did not attend' rates. RESULTS: Since May 2021, a total of 1 175 814 automatic test orders have been placed. Significant changes in trend of diagnosis and discharge to primary care at first appointment (p=0.005, 95% CI 0.5 to 2.9) and 'did not attend' rates (p=0.006, 95% CI -0.1 to -0.8) and an estimated attributable reduction of 11 306 avoidable follow-up appointments per month were observed. CONCLUSION: An algorithm for placing automatic standardised test order sets can reduce low-value follow-up appointments by allowing specialists to confirm diagnoses and initiate treatment at first appointment, also leading to early discharge to primary care and a reduction in 'did not attend' rates. This initiative points to an improved process for outpatient diagnosis and treatment, delivering healthcare more effectively and efficiently.

Abdominal ultrasound features and reference values in healthy guinea pigs (Cavia porcellus).

BACKGROUND: This study aimed to determine the ultrasonographic features and reference values of the abdominal anatomy in guinea pigs. METHODS: A complete abdominal ultrasonographic examination was performed in 20 adults and 20 young guinea pigs. The thickness of the wall of the gallbladder, stomach, duodenum, caecum, colon and urinary bladder (UB) was measured. Also, the adrenal glands (AGs) (width of the cranial and caudal poles, length), kidneys (length, width, height), ovaries (length, width), testes (length, width), uterus (width) and seminal glands (width) and the thickness of the spleen and pancreas were measured. All the measurements were compared between age groups and sexes. RESULTS: The liver, gallbladder, gastrointestinal tract, pancreas, spleen, kidneys, UB, AGs and great vessels were clearly visualised in all the guinea pigs. No significant statistical differences were found between the sexes, but there were statistically significant differences in the size of the kidneys, AGs, pancreas, spleen and reproductive organs between age groups. No significant differences in the wall thickness of the digestive system, gallbladder and UB were observed between groups. LIMITATIONS: The main limitation of this study is the lack of gross anatomical or histological correlation. CONCLUSIONS: The results of this study support the use of ultrasonography as a diagnostic tool in guinea pigs and provide reference values for the abdominal organs of this species.

Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus.

OBJECTIVE: To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. METHODS: We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2 K (SLEDAI 2 K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann-Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2 K on the mentioned parameters, we applied a generalized mixed linear model. RESULTS: Twenty-three patients (88.4%) were women. The SLEDAI 2 K was higher at baseline 8 (6-14) in comparison to that at follow-up (6 (4-8), P = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2 K was the main factor influencing these functional innate immune parameters. CONCLUSION: Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.

Corrigendum: Understanding the effects of cortical gyrification in tACS: insights from experiments and computational models.

[This corrects the article DOI: 10.3389/fnins.2023.1223950.].

Spectroscopy of a mesospheric ghost reveals iron emissions.

Mesospheric Green emissions from excited Oxygen in Sprite Tops (ghosts) are infrequent and faint greenish transient luminous events that remain for hundreds of milliseconds on top of certain energetic sprites. The main hypothesis to explain this glow persistence is the long lifetime of excited atomic oxygen at 557.73 nm, a well-known emission line in aurora and airglow. However, due to the lack of spectroscopic campaigns to analyse such events to date, the species involved in the process can not yet be identified. Here we report observational results showing the temporal evolution of a ghost spectrum between 500 nm and 600 nm. Besides weak -but certain- traces of excited atomic oxygen, our results show four main contributors related to the slow decay of the glow: atomic iron and nickel, molecular nitrogen and ionic molecular oxygen. Additionally, we are able to identify traces of atomic sodium, and ionic silicon, these observations being consistent with previous direct measurements of density profiles of meteoric metals in the mesosphere and lower thermosphere. This finding calls for an upgrade of current air plasma kinetic understanding under the influence of transient luminous events.

Broadening the clinical spectrum: molecular mechanisms and new phenotypes of ANO3-dystonia.

Anoctamin 3 (ANO3) belongs to a family of transmembrane proteins that form phospholipid scramblases and ion channels. A large number of ANO3 variants were identified as the cause of craniocervical dystonia, but the underlying pathogenic mechanisms remain obscure. It was suggested that ANO3 variants may dysregulate intracellular Ca2+ signalling, as variants in other Ca2+ regulating proteins like hippocalcin were also identified as a cause of dystonia. In this study, we conducted a comprehensive evaluation of the clinical, radiological, and molecular characteristics of four individuals from four families who carried heterozygous variants in ANO3. The median age at follow-up was 6.6 years (ranging from 3.8 to 8.7 years). Three individuals presented with hypotonia and motor developmental delay. Two patients exhibited generalized progressive dystonia, while one patient presented with paroxysmal dystonia. Additionally, another patient exhibited early dyskinetic encephalopathy. One patient underwent bipallidal deep brain stimulation (DBS) and showed a mild but noteworthy response, while another patient is currently being considered for DBS treatment. Neuroimaging analysis of brain MRI studies did not reveal any specific abnormalities. The molecular spectrum included two novel ANO3 variants (V561L and S116L) and two previously reported ANO3 variants (A599D and S651N). As anoctamins are suggested to affect intracellular Ca2+ signals, we compared Ca2+ signalling and activation of ion channels in cells expressing wild type ANO3 and cells expressing ANO variants. Novel V561L and S116L variants were compared with previously reported A599D and S651N variants and with wtANO3 expressed in fibroblasts isolated from patients or when overexpressed in HEK293 cells. We identified ANO3 as a Ca2+-activated phospholipid scramblase that also conducts ions. Impaired Ca2+ signalling and compromised activation of Ca2+ dependent K+ channels were detected in cells expressing ANO3 variants. In the brain striatal cells of affected patients, impaired activation of KCa3.1 channels due to compromised Ca2+ signals may lead to depolarized membrane voltage and neuronal hyperexcitability and may also lead to reduced cellular viability, as shown in the present study. In conclusion, our study reveals the association between ANO3 variants and paroxysmal dystonia, representing the first reported link between these variants and this specific dystonic phenotype. We demonstrate that ANO3 functions as a Ca2+-activated phospholipid scramblase and ion channel; cells expressing ANO3 variants exhibit impaired Ca2+ signalling and compromised activation of Ca2+-dependent K+ channels. These findings provide a mechanism for the observed clinical manifestations and highlight the importance of ANO3 for neuronal excitability and cellular viability.