A mutation in F-actin polymerization factor suppresses the distal arthrogryposis type 5 PIEZO2 pathogenic variant in Caenorhabditis elegans.

The mechanosensitive PIEZO channel family has been linked to over 26 disorders and diseases. Although progress has been made in understanding these channels at the structural and functional levels, the underlying mechanisms of PIEZO-associated diseases remain elusive. In this study, we engineered four PIEZO-based disease models using CRISPR/Cas9 gene editing. We performed an unbiased chemical mutagen-based genetic suppressor screen to identify putative suppressors of a conserved gain-of-function variant pezo-1[R2405P] that in human PIEZO2 causes distal arthrogryposis type 5 (DA5; p. R2718P). Electrophysiological analyses indicate that pezo-1(R2405P) is a gain-of-function allele. Using genomic mapping and whole-genome sequencing approaches, we identified a candidate suppressor allele in the C. elegans gene gex-3. This gene is an ortholog of human NCKAP1 (NCK-associated protein 1), a subunit of the Wiskott-Aldrich syndrome protein (WASP)-verprolin homologous protein (WAVE/SCAR) complex, which regulates F-actin polymerization. Depletion of gex-3 by RNAi, or with the suppressor allele gex-3(av259[L353F]), significantly increased brood size and ovulation rate, as well as alleviating the crushed oocyte phenotype of the pezo-1(R2405P) mutant. Expression of GEX-3 in the soma is required to rescue the brood size defects in pezo-1(R2405P) animals. Actin organization and orientation were disrupted and distorted in the pezo-1 mutants. Mutation of gex-3(L353F) partially alleviated these defects. The identification of gex-3 as a suppressor of the pathogenic variant pezo-1(R2405P) suggests that the PIEZO coordinates with the cytoskeleton regulator to maintain the F-actin network and provides insight into the molecular mechanisms of DA5 and other PIEZO-associated diseases.

Caldendrin Is a Repressor of PIEZO2 Channels and Touch Sensation in Mice.

The sense of touch is crucial for cognitive, emotional, and social development and relies on mechanically activated (MA) ion channels that transduce force into an electrical signal. Despite advances in the molecular characterization of these channels, the physiological factors that control their activity are poorly understood. Here, we used behavioral assays, electrophysiological recordings, and various mouse strains (males and females analyzed separately) to investigate the role of the calmodulin-like Ca2+ sensor, caldendrin, as a key regulator of MA channels and their roles in touch sensation. In mice lacking caldendrin (Cabp1 KO), heightened responses to tactile stimuli correlate with enlarged MA currents with lower mechanical thresholds in dorsal root ganglion neurons (DRGNs). The expression pattern of caldendrin in the DRG parallels that of the major MA channel required for touch sensation, PIEZO2. In transfected cells, caldendrin interacts with and inhibits the activity of PIEZO2 in a manner that requires an alternatively spliced sequence in the N-terminal domain of caldendrin. Moreover, targeted genetic deletion of caldendrin in Piezo2-expressing DRGNs phenocopies the tactile hypersensitivity of complete Cabp1 KO mice. We conclude that caldendrin is an endogenous repressor of PIEZO2 channels and their contributions to touch sensation in DRGNs.

Analysis of sulfide signaling in rice highlights specific drought responses.

Hydrogen sulfide regulates essential plant processes, including adaptation responses to stress situations, and the best characterized mechanism of action of sulfide consists of the posttranslational modification of persulfidation. In this study, we reveal the first persulfidation proteome described in rice including 3443 different persulfidated proteins that participate in a broad range of biological processes and metabolic pathways. In addition, comparative proteomics revealed specific proteins involved in sulfide signaling during drought responses. Several proteins involved in the maintenance of cellular redox homeostasis, the TCA cycle and energy-related pathways, and ion transmembrane transport and cellular water homeostasis, highlighting the aquaporin family, showed the highest differential levels of persulfidation. We revealed that water transport activity is regulated by sulfide which correlates to an increasing level of persulfidation of aquaporins. Our findings emphasize the impact of persulfidation on total ATP levels, fatty acid composition, ROS levels, antioxidant enzymatic activities, and relative water content. Interestingly, the persulfidation role on aquaporin transport activity as an adaptation response in rice differs from the current knowledge in Arabidopsis, which emphasizes the distinct role of sulfide improving rice tolerance to drought.

Implications for driving based on the risk of seizures after ischaemic stroke.

BACKGROUND: In addition to other stroke-related deficits, the risk of seizures may impact driving ability after stroke. METHODS: We analysed data from a multicentre international cohort, including 4452 adults with acute ischaemic stroke and no prior seizures. We calculated the Chance of Occurrence of Seizure in the next Year (COSY) according to the SeLECT2.0 prognostic model. We considered COSY<20% safe for private and <2% for professional driving, aligning with commonly used cut-offs. RESULTS: Seizure risks in the next year were mainly influenced by the baseline risk-stratified according to the SeLECT2.0 score and, to a lesser extent, by the poststroke seizure-free interval (SFI). Those without acute symptomatic seizures (SeLECT2.0 0-6 points) had low COSY (0.7%-11%) immediately after stroke, not requiring an SFI. In stroke survivors with acute symptomatic seizures (SeLECT2.0 3-13 points), COSY after a 3-month SFI ranged from 2% to 92%, showing substantial interindividual variability. Stroke survivors with acute symptomatic status epilepticus (SeLECT2.0 7-13 points) had the highest risk (14%-92%). CONCLUSIONS: Personalised prognostic models, such as SeLECT2.0, may offer better guidance for poststroke driving decisions than generic SFIs. Our findings provide practical tools, including a smartphone-based or web-based application, to assess seizure risks and determine appropriate SFIs for safe driving.

Epilepsy Care in Latin America and the Caribbean: Overcoming Challenges and Embracing Opportunities.

The burden of epilepsy in the Latin America and the Caribbean (LAC) region causes a profound regional impact on the health care system and significantly contributes to the global epilepsy burden. As in many other resource-limited settings worldwide, health care professionals and patients with epilepsy in LAC countries face profound challenges due to a combination of factors, including high disease prevalence, stigmatization of epilepsy, disparities in access to care, limited resources, substantial treatment gaps, insufficient training opportunities for health care providers, and a diverse patient population with varying needs. This article presents an overview of the epidemiology of epilepsy and discusses the principal obstacles to epilepsy care and key contributors to the epilepsy diagnosis and treatment gap in the LAC region. We conclude by highlighting various initiatives across different LAC countries to improve epilepsy care in marginalized communities, listing strategies to mitigate treatment gaps and facilitate better health care access for patients with epilepsy by enhancing the epilepsy workforce.

Metabolomics of Plasma in XLH Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms.

X-linked hypophosphatemia (XLH) is a rare genetic disorder that increases fibroblast growth factor 23 (FGF23). XLH patients have an elevated risk of early-onset hypertension. The precise factors contributing to hypertension in XLH patients have yet to be identified. A multicenter cross-sectional study of adult patients diagnosed with XLH. Metabolomic analysis was performed using ultra-performance liquid chromatography (UPLC) coupled to a high-resolution mass spectrometer. Twenty subjects were included, of which nine (45%) had hypertension. The median age was 44 years. Out of the total, seven (35%) subjects had a family history of hypertension. No statistically significant differences were found between both groups for nephrocalcinosis or hyperparathyroidism. Those with hypertension exhibited significantly higher levels of creatinine (1.08 ± 0.31 mg/dL vs. 0.78 ± 0.19 mg/dL; p = 0.01) and LDL-C (133.33 ± 21.92 mg/dL vs. 107.27 ± 20.12 mg/dL, p = 0.01). A total of 106 metabolites were identified. Acetylcarnitine (p = 0.03), pyruvate p = (0.04), ethanolamine (p = 0.03), and butyric acid (p = 0.001) were significantly different between both groups. This study is the first to examine the metabolomics of hypertension in patients with XLH. We have identified significant changes in specific metabolites that shed new light on the potential mechanisms of hypertension in XLH patients. These findings could lead to new studies identifying associated biomarkers and developing new diagnostic approaches for XLH patients.

Emerging Themes in Genetics of Hypertrophic Cardiomyopathy: Current Status and Clinical Application.

Hypertrophic cardiomyopathy (HCM), defined clinically by the presence of unexplained left ventricular hypertrophy (LVH), with wall thickness ≥ 1.5 cm, is a phenotype in search of a diagnosis, which is most often a genetically determined, cardiac exclusive, or systemic disorder. Familial evaluation and genetic testing are required for definitive diagnosis. The role of genetic findings in predicting development of disease, outcomes, and increasingly to guide management is evolving with access to larger data sets. The specific mutation and sex of the patient are important determinants that ultimately are likely to guide management. The genetic/familial evaluation is influenced by the accuracy of the clinical diagnosis and the extent/expertise of the genetic laboratory. Genetic testing in a patient with unexplained LVH without systemic manifestations will yield a definite/likely pathogenetic mutation in a sarcomere (30%-50%), regulatory/functional (10%-15%) or metabolic/syndromic (< 5%) gene associated with Mendelian inheritance. The importance of oligo- and polygenic determinants, usually in the absence of Mendelian inheritance, is under investigation with important implications, particularly related to familial evaluation and definition of risk of disease development in relatives of probands. The results of genetic testing are increasingly important in management strategies related to the use of the implantable cardioverter defibrillator for prevention of sudden death, use of myosin inhibitors for refractory symptoms in patients with and without outflow tract obstruction, and-on the immediate horizon-gene therapy. This review will focus on genetic and outcome data in sarcomeric HCM, and minor causative genes with robust evidence of their association will also be considered.

Using Principles of Digital Development for a Smartphone App to Support Data Collection in Patients With Acute Myocardial Infarction and Physical Activity Intolerance: Case Study.

BACKGROUND: Advances in health have highlighted the need to implement technologies as a fundamental part of the diagnosis, treatment, and recovery of patients at risk of or with health alterations. For this purpose, digital platforms have demonstrated their applicability in the identification of care needs. Nursing is a fundamental component in the care of patients with cardiovascular disorders and plays a crucial role in diagnosing human responses to these health conditions. Consequently, the validation of nursing diagnoses through ongoing research processes has become a necessity that can significantly impact both patients and health care professionals. OBJECTIVE: We aimed to describe the process of developing a mobile app to validate the nursing diagnosis "intolerance to physical activity" in patients with acute myocardial infarction. METHODS: We describe the development and pilot-testing of a mobile system to support data collection for validating the nursing diagnosis of activity intolerance. This was a descriptive study conducted with 11 adults (aged ≥18 years) who attended a health institution for highly complex needs with a suspected diagnosis of coronary syndrome between August and September 2019 in Floridablanca, Colombia. An app for the clinical validation of activity intolerance (North American Nursing Diagnosis Association [NANDA] code 00092) in patients with acute coronary syndrome was developed in two steps: (1) operationalization of the nursing diagnosis and (2) the app development process, which included an evaluation of the initial requirements, development and digitization of the forms, and a pilot test. The agreement level between the 2 evaluating nurses was evaluated with the κ index. RESULTS: We developed a form that included sociodemographic data, hospital admission data, medical history, current pharmacological treatment, and thrombolysis in myocardial infarction risk score (TIMI-RS) and GRACE (Global Registry of Acute Coronary Events) scores. To identify the defining characteristics, we included official guidelines, physiological measurements, and scales such as the Piper fatigue scale and Borg scale. Participants in the pilot test (n=11) had an average age of 63.2 (SD 4.0) years and were 82% (9/11) men; 18% (2/11) had incomplete primary schooling. The agreement between the evaluators was approximately 80% for most of the defining characteristics. The most prevalent characteristics were exercise discomfort (10/11, 91%), weakness (7/11, 64%), dyspnea (3/11, 27%), abnormal heart rate in response to exercise (2/10, 20%), electrocardiogram abnormalities (1/10, 9%), and abnormal blood pressure in response to activity (1/10, 10%). CONCLUSIONS: We developed a mobile app for validating the diagnosis of "activity intolerance." Its use will guarantee not only optimal data collection, minimizing errors to perform validation, but will also allow the identification of individual care needs.

Implementation of a traceability system and safe manufacturing medications in a clean room. / Implantación de un sistema de trazabilidad y elaboración segura de medicamentos en la sala blanca.

OBJECTIVE: To describe the process of implementing a traceability and safe drug manufacturing system in the clean room of a Pharmacy Service to increase patient safety, in accordance with current legislation. METHODS: The process was carried out between September 2021 and July 2022. The software program integrated all the recommended stages of the manufacturing process outlined in the "Good Practices Guide for Medication Preparation in Pharmacy Services" (GBPP). The following sections were parameterized in the software program: personnel, facilities, equipment, starting materials, packaging materials, standardized work procedures, and quality controls. RESULTS: A total of 50 users, 4 elaboration areas and 113 equipments were included. 435 components were parameterized (195 raw materials and 240 pharmaceutical specialties), 54 packaging materials, 376 standardized work procedures (123 of them corresponding to sterile medicines and 253 to non-sterile medicines, of which 52 non-sterile were dangerous), in addition 17 were high risk, 327 medium risk, 32 low risk, and 13 quality controls. CONCLUSIONS: The computerization of the production process has allowed the implementation of a traceability and secure drug manufacturing system in a controlled environment in accordance with current legislation.

Persulfidome of Sweet Pepper Fruits during Ripening: The Case Study of Leucine Aminopeptidase That Is Positively Modulated by H2S.

Protein persulfidation is a thiol-based oxidative posttranslational modification (oxiPTM) that involves the modification of susceptible cysteine thiol groups present in peptides and proteins through hydrogen sulfide (H2S), thus affecting their function. Using sweet pepper (Capsicum annuum L.) fruits as a model material at different stages of ripening (immature green and ripe red), endogenous persulfidated proteins (persulfidome) were labeled using the dimedone switch method and identified using liquid chromatography and mass spectrometry analysis (LC-MS/MS). A total of 891 persulfidated proteins were found in pepper fruits, either immature green or ripe red. Among these, 370 proteins were exclusively present in green pepper, 237 proteins were exclusively present in red pepper, and 284 proteins were shared between both stages of ripening. A comparative analysis of the pepper persulfidome with that described in Arabidopsis leaves allowed the identification of 25% of common proteins. Among these proteins, glutathione reductase (GR) and leucine aminopeptidase (LAP) were selected to evaluate the effect of persulfidation using an in vitro approach. GR activity was unaffected, whereas LAP activity increased by 3-fold after persulfidation. Furthermore, this effect was reverted through treatment with dithiothreitol (DTT). To our knowledge, this is the first persulfidome described in fruits, which opens new avenues to study H2S metabolism. Additionally, the results obtained lead us to hypothesize that LAP could be involved in glutathione (GSH) recycling in pepper fruits.

[Translated article] Implementation of a traceability and safe drug preparation system in a clean room.

OBJECTIVE: To describe the process of implementing a traceability and safe manufacturing system in the clean room of a pharmacy service to increase patient safety, in accordance with current legislation. METHODS: The process was carried out between September 2021 and July 2022. The software program integrated all the recommended stages of the manufacturing process outlined in the "Good Practices Guide for Medication Preparation in Pharmacy Services" (GBPP). The following sections were parameterised in the software program: personnel, facilities, equipment, starting materials, packaging materials, standardised work procedures, and quality controls. RESULTS: A total of 50 users, 4 elaboration areas and 113 equipments were included. 435 components were parameterized (195 raw materials and 240 pharmaceutical specialties), 54 packaging materials, 376 standardised work procedures (123 of them corresponding to sterile medicines and 253 to non-sterile medicines, of which 52 non-sterile were dangerous), in addition, 17 were high risk, 327 medium risk, and 32 low risk, and 13 quality controls. CONCLUSIONS: The computerization of the production process has allowed the implementation of a traceability and secure manufacturing system in a controlled environment in accordance with current legislation.

[Evaluation of the management and follow-up of diabetic patients in the prevention of diabetic retinopathy]. / Evaluación del manejo y seguimiento de los pacientes diabéticos en la prevención de la retinopatía diabética.

OBJECTIVE: Diabetes mellitus is a chronic disease with high morbidity and mortality, affecting 537 million adults worldwide. Spain is the second European country in prevalence, with 14.8% in the population aged twenty/seventy-nine years; with 11.6 cases per 1,000 people/year. Diabetic retinopathy (DR) is the fifth cause of vision loss worldwide and the seventh cause of blindness/visual impairment among members of the National Organization of the Blind in Spain (ONCE). Early detection of DR prevents blindness in diabetics and is conditioned by glycosylated hemoglobin. The aim of this paper was to analyze the management of diabetic patients in Aljarafe region (Seville) and identify opportunities for improvement in the coordination of their follow-up between the Primary Care physician and the ophthalmologist. METHODS: A retrospective observational study (2016-2019) was carried out, with patients registered in the diabetic census of the twenty-eight municipalities of Aljarafe. The primary care and hospital health history, and telemedicine program were consulted. About statistical analysis, for qualitative variables, totals and percentages were calculated; for quantitative variables, mean and standard deviation (if normally distributed) and median and quartiles (if non-normally distributed). RESULTS: There were 17,175 diabetics registered in Aljarafe (5.7% of the population); 14,440 patients (84.1%) had some determination of hemoglobin during the period, 9,228 (63.9%) had all of them in the appropriate range. Fundoscopic control was performed on 12,040 diabetics (70.1%), and of those who did not, 346 (10.6%) had all of them out of range. There were 1,878 (10.9%) patients without fundoscopic or metabolic control, 1,019 (54.3%) were women, 1,219 (64.9%) were under sixty-five years of age, 1,019 (54.3%) had severe comorbidity. CONCLUSIONS: Most patients have adequate screening, and more than half have determinations within range. However, a significant percentage with no glycated hemoglobin within range lack fundoscopic control, and another smaller group lack fundoscopic or metabolic control, with inter-municipal variability. We propose to improve communication channels between levels.

OBJECTIVE: La diabetes mellitus es una enfermedad crónica con alta morbimortalidad que afecta a 537 millones de adultos en el mundo. España es el segundo país europeo en prevalencia, con un 14,8% en población de veinte-setenta y nueve años, con 11,6 casos por cada 1.000 personas/año. La retinopatía diabética (RD) es la quinta causa de pérdida de visión a nivel mundial y la séptima causa de ceguera/discapacidad visual entre afiliados a la Organización Nacional de Ciegos de España (ONCE). La detección precoz de RD previene la ceguera en diabéticos y está condicionada por la hemoglobina glicosilada. El objetivo de este trabajo fue analizar el manejo de los pacientes diabéticos en la comarca del Aljarafe (Sevilla) e identificar oportunidades de mejora en la coordinación de su seguimiento entre el médico de Atención Primaria y el médico oftalmólogo. METHODS: Se realizó un estudio observacional retrospectivo (2016-2019) con los pacientes registrados en el censo de diabéticos de los veintiocho municipios del Aljarafe. Se consultó la historia de salud de Atención Primaria y Hospital, así como el programa de Telemedicina. En cuanto al análisis estadístico, para variables cualitativas se calcularon totales y porcentajes; para variables cuantitativas, media y distribución estándar (si distribución normal), y la mediana y cuartiles (distribución no normal). RESULTS: Se registraron 17.175 diabéticos en el Aljarafe (5,7% de población); 14.440 pacientes (84,1%) tenían alguna determinación de hemoglobina durante el periodo, 9.228 (63,9%) las tenían todas en rango adecuado. Tenían control fundoscópico 12.040 diabéticos (70,1%), y de los que no, 346 (10,6%) tenían todas fuera de rango. Hubo 1.878 (10,9%) pacientes sin control fundoscópico ni metabólico, 1.019 (54,3%) eran mujeres, 1.219 (64,9%) menores de sesenta y cinco años, 1.019 (54,3%) con comorbilidad grave. CONCLUSIONS: La mayoría de los pacientes presentan un cribado adecuado y, más de la mitad, determinaciones en rango. Sin embargo, un porcentaje relevante con ninguna hemoglobina glicosilada en rango carecen de control fundoscópico, y otro grupo menor está sin control fundoscópico ni metabólico, con variabilidad intermunicipios. Planteamos mejorar los circuitos de comunicación entre niveles.

Detection through the use of RT-MqPCR of asymptomatic reservoirs of malaria in samples of patients from the indigenous Comarca of Guna Yala, Panama: Essential method to achieve the elimination of malaria.

BACKGROUND: Plasmodium vivax is the main causative agent of malaria in Panama. However, the prevalence of asymptomatic infections in the different endemic regions remains unknown. Understanding the epidemiological behavior of asymptomatic infections is essential for the elimination of malaria. This study aimed to determine the prevalence of asymptomatic malarial infections in one of the main endemic regions of Panama using multiplex real-time reverse transcription RT-MqPCR. METHODS: A cross-sectional study was conducted in three communities in the Guna Yala Comarca. A total of 551 thick blood smears and their respective samples on filter paper were collected from volunteers of different ages and sexes from June 20 to 25, 2016. Infections by the Plasmodium spp. were diagnosed using microscopy and RT-MqPCR. All statistical analyses were performed using the R software. RESULTS: The average prevalence of asymptomatic infections by P. vivax in the three communities detected by RT-MqPCR was 9.3%, with Ukupa having the highest prevalence (13.4%), followed by Aidirgandi (11.1%) and Irgandi (3.3%). A total of 74 samples were diagnosed as asymptomatic infections using RT-MqPCR. Light microscopy (LM) detected that 17.6% (13/74) of the asymptomatic samples and 82.4% (61/74) were diagnosed as false negatives. A 100% correlation was observed between samples diagnosed using LM and RT-MqPCR. A total of 52.7% (39/74) of the asymptomatic patients were female and 85.1% (63/74) were registered between the ages of 1 and 21 years. Factors associated with asymptomatic infection were community (aOR = 0.38 (95% CI 0.17-0.83), p < 0.001) and age aOR = 0.98 (95% CI 0.97-1.00), p < 0.05); F = 5.38; p < 0.05). CONCLUSIONS: This study provides novel evidence of the considerable prevalence of asymptomatic P. vivax infections in the endemic region of Kuna Yala, representing a new challenge that requires immediate attention from the National Malaria Program. The results of this study provide essential information for the health authorities responsible for developing new policies. Furthermore, it will allow program administrators to reorient and design effective malaria control strategies that consider asymptomatic infections as a fundamental part of malaria control and move towards fulfilling their commitment to eliminate it.

Longitudinal changes of angiogenic factors as a potential predictive tool in women with suspected preeclampsia.

OBJECTIVES: To investigate whether longitudinal changes of angiogenic factors (AF) sFlt-1, PlGF, and the sFlt-1/PlGF ratio, measured following identification of symptoms of preeclampsia (PE), could provide complementary information to the isolated measurements used in current clinical practice. STUDY DESIGN: Retrospective observational study. Sixty women with suspected PE and two AF results measured before gestational week (GW) 34 were included. Daily variation (DV) of AF was calculated from delta values and days elapsed between measurements. Through ROC analysis, the predictive performance of DV for PE-related events was estimated. Kaplan-Meier survival curves resulting from applying cutoff values were assessed. RESULTS: The sFlt-1, PlGF, and sFlt-1/PlGF ratio baseline levels showed significant differences between women without PE and women who developed early-onset PE (P < 0.001). DV of sFlt-1 and sFlt-1/PlGF ratio increased according to the severity of PE, showing significant differences in both pairs of groups compared (p < 0.001), so they were selected as potential predictors. Higher AUC values resulting from ROC analysis were 0.78 for early-onset PE, 0.88 for early-onset severe PE, 0.79 for occurrence of adverse maternal outcomes, and 0.89 for delivery before 37 GW, with sensitivity and specificity values higher than 0.71 and 0.80, respectively. The Kaplan-Meier analysis yielded significantly different curves (log-rank < 0.05), with shorter time-to-delivery as DV increased. CONCLUSION: Our results support the existence of a correlation between a progressive PlGF and sFlt-1 imbalance and a more aggressive clinical course of PE, detectable from the finding of PE symptoms. Its monitoring could be a useful predictive tool in women with suspected PE.

X-Linked hypophosphatemia. Data from a Spanish adult population cohort.

BACKGROUND: X-linked hypophosphatemia (XLH) represents the most prevalent cause of hereditary hypophosphatemia. X-linked hypophosphatemia causes an elevation of fibroblast growth factor 23 (FGF23), a hormone responsible for inducing hyperphosphaturia, and reduced active vitamin D synthesis. Challenges in diagnosis and the absence of well-defined clinical guidelines have resulted in higher rates of late diagnoses. While numerous reports focus on pediatric X-linked hypophosphatemia patients, studies in adults are limited. METHODS: Multicenter, cross-sectional, observational study of a cohort of adult patients diagnosed with X-linked hypophosphatemia. The study identified demographic, clinical, genetic, laboratory variables, treatments used, comorbidities, and complications. RESULTS: Twenty patients diagnosed with X-linked hypophosphatemia were collected. The median age at diagnosis was 11 (1-56) years and at data collection was 44 (21-68) years. Fifty percent of cases were diagnosed in adulthood. Main clinical manifestation was osteoarticular pain, in 75% of cases, and no relation to age at diagnosis, height, phosphorus, or parathyroid hormone (PTH) levels was observed (p > 0.05). Lower limb deformities were associated with reduced stature and earlier diagnosis (p < 0.05). Sixty percent of patients reported pain requiring chronic medication and no significant correlation was found with other variables. Anxiety and depression were found in an important number of patients. FGF23 levels were not related to any of the clinical variables studied (p > 0.05). DISCUSSION: This is the largest study on adult patients with X-linked hypophosphatemia in southern Europe. It may offer valuable insights into the natural progression and course of the condition in adults, which can aid in better clinical management.

Immediate and long-term electrophysiological biomarkers of antidepressant-like behavioral effects after subanesthetic ketamine and medial prefrontal cortex deep brain stimulation treatment.

Introduction: Both ketamine (KET) and medial prefrontal cortex (mPFC) deep brain stimulation (DBS) are emerging therapies for treatment-resistant depression, yet our understanding of their electrophysiological mechanisms and biomarkers is incomplete. This study investigates aperiodic and periodic spectral parameters, and the signal complexity measure sample entropy, within mPFC local field potentials (LFP) in a chronic corticosterone (CORT) depression model after ketamine and/or mPFC DBS. Methods: Male rats were intraperitoneally administered CORT or vehicle for 21 days. Over the last 7 days, animals receiving CORT were treated with mPFC DBS, KET, both, or neither; then tested across an array of behavioral tasks for 9 days. Results: We found that the depression-like behavioral and weight effects of CORT correlated with a decrease in aperiodic-adjusted theta power (5-10 Hz) and an increase in sample entropy during the administration phase, and an increase in theta peak frequency and a decrease in the aperiodic exponent once the depression-like phenotype had been induced. The remission-like behavioral effects of ketamine alone correlated with a post-treatment increase in the offset and exponent, and decrease in sample entropy, both immediately and up to eight days post-treatment. The remission-like behavioral effects of mPFC DBS alone correlated with an immediate decrease in sample entropy, an immediate and sustained increase in low gamma (20-50 Hz) peak width and aperiodic offset, and sustained improvements in cognitive function. Failure to fully induce remission-like behavior in the combinatorial treatment group correlated with a failure to suppress an increase in sample entropy immediately after treatment. Conclusion: Our findings therefore support the potential of periodic theta parameters as biomarkers of depression-severity; and periodic low gamma parameters and cognitive measures as biomarkers of mPFC DBS treatment efficacy. They also support sample entropy and the aperiodic spectral parameters as potential cross-modal biomarkers of depression severity and the therapeutic efficacy of mPFC DBS and/or ketamine. Study of these biomarkers is important as objective measures of disease severity and predictive measures of therapeutic efficacy can be used to personalize care and promote the translatability of research across studies, modalities, and species.

Influential Social Determinants of Adherence to Preventive and Health Promotion Activities during Pregnancy and the First Year of Life: Systematic Review.

Effective monitoring throughout pregnancy and the first year of life is a crucial factor in achieving lower rates of maternal and infant mortality. Currently, research on socioeconomic factors that influence the lack of adherence to preventive and control measures during pregnancy and the first year of life is limited. The objective of this review is to examine the available evidence on social determinants that influence participation in health promotion and preventive activities throughout the pregnancy journey and in infants during their first year of life. We performed a systematic review of the literature searching in the major scientific databases (PubMed, Scopus, EMBASE, WOS, and Cochrane Library) for articles from February 2017 to May 2023 containing information on health inequities that impact participation in health promotion and preventive measures from pregnancy through the first year of an infant's life. A total of 12 studies were selected; these studies were performed in ten different countries on five different continents. The selected studies cover preventive measures during maternal care, vaccination, and immunization during pregnancy and the first year of life, newborn screening, and follow-up of the first 12 months of life. The social factors associated with low adherence to health promotion activities during pregnancy and the first year of life include education, income, ethnicity, place of residence, and family characteristics. Despite the diverse geographical distribution, it is observed that there are common social factors linked to a decrease in the adherence to preventive measures during pregnancy and in the early years of life.

Hard ticks (Ixodida: Ixodidae) in the Colombian Caribbean harbor the Jingmen tick virus: an emerging arbovirus of public health concern.

BACKGROUND: Ticks are obligate hematophagous ectoparasites involved in transmitting viruses of public health importance. The objective of this work was to identify the Jingmen tick virus in hard ticks from the Colombian Caribbean, an arbovirus of importance for public health. METHODS: Ticks were collected in rural areas of Córdoba and Cesar, Colombia. Taxonomic identification of ticks was carried out, and pools of 13 individuals were formed. RNA extraction was performed. Library preparation was performed with the MGIEasy kit, and next-generation sequencing (NGS) with MGI equipment. Bioinformatic analyses and taxonomic assignments were performed using the Galaxy platform, and phylogenetic analyses were done using IQ-TREE2. RESULTS: A total of 766 ticks were collected, of which 87.33% (669/766) were Rhipicephalus microplus, 5.4% (42/766) Dermacentor nitens, 4.2% (32/766) Rhipicephalus linnaei, and 3.0% (23/766) Amblyomma dissimile. Complete and partial segments 1, 2, 3, and 4 of Jingmen tick virus (JMTV) were detected in the metatranscriptome of the species R. microplus, D. nitens, and A. dissimile. The JMTVs detected are phylogenetically related to JMTVs detected in Aedes albopictus in France, JMTVs detected in R. microplus in Trinidad and Tobago, JMTVs in R. microplus and A. variegatum in the French Antilles, and JMTVs detected in R. microplus in Colombia. Interestingly, our sequences clustered closely with JMTV detected in humans from Kosovo. CONCLUSIONS: JMTV was detected in R. microplus, D. nitens, and A. dissimile. JMTV could pose a risk to humans. Therefore, it is vital to establish epidemiological surveillance measures to better understand the possible role of JMTV in tropical diseases.

Executive summary of the consensus document for the training and development of clinical ultrasound in Internal Medicine: Recommendations from the Clinical Ultrasound Working Group of the Spanish Society of Internal Medicine (GTECO-SEMI).

INTRODUCTION: Given the increasing adoption of clinical ultrasound in medicine, it is essential to standardize its application, training, and research. OBJECTIVES AND METHODS: The purpose of this document is to provide consensus recommendations to address questions about the practice and operation of clinical ultrasound units. Nineteen experts and leaders from advanced clinical ultrasound units participated. A modified Delphi consensus method was used. RESULTS: A total of 137 consensus statements, based on evidence and expert opinion, were considered. The statements were distributed across 10 areas, and 99 recommendations achieved consensus. CONCLUSIONS: This consensus defines the most important aspects of clinical ultrasound in the field of Internal Medicine, with the aim of standardizing and promoting this healthcare advancement in its various aspects. The document has been prepared by the Clinical Ultrasound Working Group and endorsed by the Spanish Society of Internal Medicine.