Strategies to address diabetic kidney disease burden in Mexico: a narrative review by the Mexican College of Nephrologists.

Chronic kidney disease (CKD) is a growing global public health challenge worldwide. In Mexico, CKD prevalence is alarmingly high and remains a leading cause of morbidity and mortality. Diabetic kidney disease (DKD), a severe complication of diabetes, is a leading determinant of CKD. The escalating diabetes prevalence and the complex regional landscape in Mexico underscore the pressing need for tailored strategies to reduce the burden of CKD. This narrative review, endorsed by the Mexican College of Nephrologists, aims to provide a brief overview and specific strategies for healthcare providers regarding preventing, screening, and treating CKD in patients living with diabetes in all care settings. The key topics covered in this review include the main cardiometabolic contributors of DKD (overweight/obesity, hyperglycemia, arterial hypertension, and dyslipidemia), the identification of kidney-related damage markers, and the benefit of novel pharmacological approaches based on Sodium-Glucose Co-Transporter-2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA). We also address the potential use of novel therapies based on Mineralocorticoid Receptor Antagonists (MRAs) and their future implications. Emphasizing the importance of multidisciplinary treatment, this narrative review aims to promote strategies that may be useful to alleviate the burden of DKD and its associated complications. It underscores the critical role of healthcare providers and advocates for collaborative efforts to enhance the quality of life for millions of patients affected by DKD.

Socioeconomic disparities and the genomic landscape of gastric cancer.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.

Predicting Alzheimer's disease CSF core biomarkers: a multimodal Machine Learning approach.

Introduction: Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Current core cerebrospinal fluid (CSF) AD biomarkers, widely employed for diagnosis, require a lumbar puncture to be performed, making them impractical as screening tools. Considering the role of sleep disturbances in AD, recent research suggests quantitative sleep electroencephalography features as potential non-invasive biomarkers of AD pathology. However, quantitative analysis of comprehensive polysomnography (PSG) signals remains relatively understudied. PSG is a non-invasive test enabling qualitative and quantitative analysis of a wide range of parameters, offering additional insights alongside other biomarkers. Machine Learning (ML) gained interest for its ability to discern intricate patterns within complex datasets, offering promise in AD neuropathology detection. Therefore, this study aims to evaluate the effectiveness of a multimodal ML approach in predicting core AD CSF biomarkers. Methods: Mild-moderate AD patients were prospectively recruited for PSG, followed by testing of CSF and blood samples for biomarkers. PSG signals underwent preprocessing to extract non-linear, time domain and frequency domain statistics quantitative features. Multiple ML algorithms were trained using four subsets of input features: clinical variables (CLINVAR), conventional PSG parameters (SLEEPVAR), quantitative PSG signal features (PSGVAR) and a combination of all subsets (ALL). Cross-validation techniques were employed to evaluate model performance and ensure generalizability. Regression models were developed to determine the most effective variable combinations for explaining variance in the biomarkers. Results: On 49 subjects, Gradient Boosting Regressors achieved the best results in estimating biomarkers levels, using different loss functions for each biomarker: least absolute deviation (LAD) for the Aß42, least squares (LS) for p-tau and Huber for t-tau. The ALL subset demonstrated the lowest training errors for all three biomarkers, albeit with varying test performance. Specifically, the SLEEPVAR subset yielded the best test performance in predicting Aß42, while the ALL subset most accurately predicted p-tau and t-tau due to the lowest test errors. Conclusions: Multimodal ML can help predict the outcome of CSF biomarkers in early AD by utilizing non-invasive and economically feasible variables. The integration of computational models into medical practice offers a promising tool for the screening of patients at risk of AD, potentially guiding clinical decisions.

An efficient inducible model for the control of gene expression in renin cells.

Fate mapping and genetic manipulation of renin cells have relied on either non-inducible Cre lines that can introduce developmental effects of gene deletion or BAC transgene-based inducible models that may be prone to spurious and/or ectopic gene expression. To circumvent these problems, we generated an inducible mouse model in which CreERT2 is under the control of the endogenous Akr1b7 gene, an independent marker of renin cells that is expressed in a few extrarenal tissues. We confirmed the proper expression of Cre using Akr1b7CreERT2/+;R26RmTmG/+ mice in which Akr1b7+/renin+ cells become GFP+ upon tamoxifen administration. In embryos and neonates, GFP was found in Juxtaglomerular cells, along the arterioles, and in the mesangium, and in adults, GFP was present mainly in Juxtaglomerular cells. In mice treated with captopril and a low salt diet to induce recruitment of renin cells, GFP extended along the afferent arterioles and in the mesangium. We generated Akr1b7CreERT2/+;Ren1cFl/-;R26RmTmG/+ mice to conditionally delete renin in adult mice and found a marked reduction in kidney renin mRNA and protein, and mean arterial pressure in mutant animals. When subjected to a homeostatic threat, mutant mice were unable to recruit renin+ cells. Most importantly, these mice developed concentric vascular hypertrophy ruling out potential developmental effects on the vasculature due to the lack of renin. We conclude that Akr1b7CreERT2 mice constitute an excellent model for the fate mapping of renin cells and for the spatial and temporal control of gene expression in renin cells.

Variability in the Timing of Respiratory Syncytial Virus Epidemics in Guatemala, 2008-2018.

BACKGROUND: The description of local seasonality patterns in respiratory syncytial virus (RSV) incidence is important to guide the timing of administration of RSV immunization products. METHODS: We characterized RSV seasonality in Guatemala using the moving epidemic method (MEM) with absolute counts of RSV-associated acute respiratory infections (ARI) from hospital surveillance in Santa Rosa and Quetzaltenango departments of Guatemala. RESULTS: From Week 17 of 2008 through Week 16 of 2018, 8487 ARI cases tested positive for RSV by rRT-PCR. Season onsets varied up to 5 months; early seasons starting in late May to early August and finishing in September to November were most common, but late seasons starting in October to November and finishing in March to April were also observed. Both epidemic patterns had similar durations ranging from 4 to 6 months. Epidemic thresholds (the levels of virus activity that signal the onset and end of a seasonal epidemic) calculated prospectively using previous seasons' data captured between 70% and 99% of annual RSV detections. Onset weeks differed by 2-10 weeks, and offset weeks differed by 2-16 weeks between the two surveillance sites. CONCLUSIONS: Variability in the timing of seasonal RSV epidemics in Guatemala demonstrates the difficulty in precisely predicting the timing of seasonal RSV epidemics based on onset weeks from past seasons and suggests that maximal reduction in RSV disease burden would be achieved through year-round vaccination and immunoprophylaxis administration to at-risk infants.

Molecular characterization of Pseudomonas aeruginosa from diabetic foot infections in Tunisia.

Background. Pseudomonas aeruginosa is an invasive organism that frequently causes severe tissue damage in diabetic foot ulcers.Gap statement. The characterisation of P. aeruginosa strains isolated from diabetic foot infections has not been carried out in Tunisia.Purpose. The aim was to determine the prevalence of P. aeruginosa isolated from patients with diabetic foot infections (DFIs) in Tunisia and to characterize their resistance, virulence and molecular typing.Methods. Patients with DFIs admitted to the diabetes department of the International Hospital Centre of Tunisia, from September 2019 to April 2021, were included in this prospective study. P. aeruginosa were obtained from the wound swabs, aspiration and soft tissue biopsies during routine clinical care and were confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing, serotyping, integron and OprD characterization, virulence, biofilm production, pigment quantification, elastase activity and molecular typing were analysed in all recovered P. aeruginosa isolates by phenotypic tests, specific PCRs, sequencing, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing.Results. Sixteen P. aeruginosa isolates (16.3 %) were recovered from 98 samples of 78 diabetic patients and were classified into 6 serotypes (O:11 the most frequent), 11 different PFGE patterns and 10 sequence types (three of them new ones). The high-risk clone ST235 was found in two isolates. The highest resistance percentages were observed to netilmicin (69 %) and cefepime (43.8 %). Four multidrug-resistant (MDR) isolates (25 %) were detected, three of them being carbapenem-resistant. The ST235-MDR strain harboured the In51 class 1 integron (intI1 +aadA6+orfD+qacED1-sul1). According to the detection of 14 genes involved in virulence or quorum sensing, 5 virulotypes were observed, including 5 exoU-positive, 9 exoS-positive and 2 exoU/exoS-positive strains. The lasR gene was truncated by ISPpu21 insertion sequence in one isolate, and a deletion of 64 bp in the rhlR gene was detected in the ST235-MDR strain. Low biofilm, pyoverdine and elastase production were detected in all P. aeruginosa; however, the lasR-truncated strain showed a chronic infection phenotype characterized by loss of serotype-specific antigenicity, high production of phenazines and high biofilm formation.Conclusions. Our study demonstrated for the first time the prevalence and the molecular characterization of P. aeruginosa strains from DFIs in Tunisia, showing a high genetic diversity, moderate antimicrobial resistance, but a high number of virulence-related traits, highlighting their pathological importance.

The Structural Biology of Catalase Evolution.

Catalases are essential enzymes for removal of hydrogen peroxide, enabling aerobic and anaerobic metabolism in an oxygenated atmosphere. Monofunctional heme catalases, catalase-peroxidases, and manganese catalases, evolved independently more than two billion years ago, constituting a classic example of convergent evolution. Herein, the diversity of catalase sequences is analyzed through sequence similarity networks, providing the context for sequence distribution of major catalase families, and showing that many divergent catalase families remain to be experimentally studied.

Selenium supplementation via modulation of selenoproteins ameliorates binge drinking-induced oxidative, energetic, metabolic, and endocrine imbalance in adolescent rats' skeletal muscle.

Adolescence is characterized by increased vulnerability to addiction and ethanol (EtOH) toxicity, particularly through binge drinking (BD), a favored acute EtOH-ingestion pattern among teenagers. BD, highly pro-oxidant, induces oxidative stress (OS), affecting skeletal muscle (SKM), where selenium (Se), an antioxidant element and catalytic center of selenoproteins, is stored, among other tissues. Investigating the effects of Se supplementation on SKM after BD exposure holds therapeutic promise. For this, we randomised 32 adolescent Wistar rats into 4 groups, exposed or not to intermittent i.p. BD [BD and control (C)] (3 g EtOH per kg per day), and supplemented with selenite [BDSe and CSe] (0.4 ppm). In SKM, we examined the oxidative balance, energy status (AMPK, SIRT-1), protein turnover (IRS-1, Akt1, mTOR, IGF-1, NF-κB p65, MAFbx, ULK1, pelF2α), serum myokines (myostatin, IL-6, FGF21, irisin, BDNF, IL-15, fractalkine, FSTL-1, FABP-3), and selenoproteins (GPx1, GPx4, SelM, SelP). In the pancreas, we studied the oxidative balance and SIRT-1 expression. Selenite supplementation mitigated BD-induced OS by enhancing the expression of selenoproteins, which restored oxidative balance, notably stimulating protein synthesis and normalizing the myokine profile, leading to improved SKM mass growth and metabolism, and reduced inflammation and apoptosis (caspase-3). Selenite restoration of SelP's receptor LRP1 expression, reduced by BD, outlines the crucial role of SKM in the SelP cycle, linking Se levels to SKM development. Furthermore, Se attenuated pancreatic OS, preserving insulin secretion. Se supplementation shows potential for alleviating SKM damage from BD, with additional beneficial endocrine effects on the pancreas, adipose tissue, liver, heart and brain that position it as a broad-spectrum treatment for adolescent alcohol consumption, preventing metabolic diseases in adulthood.

Stroke Mimicking Symptoms and Consequences of Alcohol Intoxication: A Case Report.

A 41-year-old Black male with a history of hypertension was involved in a car accident, after which he exhibited symptoms such as slow and incoherent speech, unstable gait, dizziness, drowsiness, slow thinking, and loss of strength in his limbs. Despite multiple negative alcohol tests, his symptoms mimicked those of acute alcohol intoxication. Upon presentation to the emergency room, physical examination and brain imaging revealed a right anterior thalamic ischemic infarction. He was discharged completely recovered after two days without sequelae. This case underscores the importance of considering stroke as a differential diagnosis in patients presenting with symptoms similar to alcohol intoxication, particularly in hypertensive individuals.

Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State.

BACKGROUND: Renin-expressing cells are myoendocrine cells crucial for the maintenance of homeostasis. Renin is regulated by cAMP, p300 (histone acetyltransferase p300)/CBP (CREB-binding protein), and Brd4 (bromodomain-containing protein 4) proteins and associated pathways. However, the specific regulatory changes that occur following inhibition of these pathways are not clear. METHODS: We treated As4.1 cells (tumoral cells derived from mouse juxtaglomerular cells that constitutively express renin) with 3 inhibitors that target different factors required for renin transcription: H-89-dihydrochloride, PKA (protein kinase A) inhibitor; JQ1, Brd4 bromodomain inhibitor; and A-485, p300/CBP inhibitor. We performed ATAC-seq, single-cell RNA sequencing, CUT&Tag, and chromatin immunoprecipitation sequencing for H3K27ac and p300 binding on biological replicates of treated and control As4.1 cells. RESULTS: In response to each inhibitor, Ren1 expression was significantly reduced and reversible upon washout. Chromatin accessibility at the Ren1 locus did not markedly change but was globally reduced at distal elements. Inhibition of PKA led to significant reductions in H3K27ac and p300 binding specifically within the Ren1 super-enhancer region. Further, we identified enriched TF (transcription factor) motifs shared across each inhibitory treatment. Finally, we identified a set of 9 genes with putative roles across each of the 3 renin regulatory pathways and observed that each displayed differentially accessible chromatin, gene expression, H3K27ac, and p300 binding at their respective loci. CONCLUSIONS: Inhibition of renin expression in cells that constitutively synthesize and release renin is regulated by an epigenetic switch from an active to poised state associated with decreased cell-cell communication and an epithelial-mesenchymal transition. This work highlights and helps define the factors necessary for renin cells to alternate between myoendocrine and contractile phenotypes.

Nutritional Strategies for Optimizing Health, Sports Performance, and Recovery for Female Athletes and Other Physically Active Women: A Systematic Review.

CONTEXT: Despite the progress toward gender equality in events like the Olympic Games and other institutionalized competitions, and the rising number of women engaging in physical exercise programs, scientific studies focused on establishing specific nutritional recommendations for female athletes and other physically active women are scarce. OBJECTIVE: This systematic review aimed to compile the scientific evidence available for addressing the question "What dietary strategies, including dietary and supplementation approaches, can improve sports performance, recovery, and health status in female athletes and other physically active women?" DATA SOURCES: The Pubmed, Web of Science, and Scopus databases were searched. DATA EXTRACTION: The review process involved a comprehensive search strategy using keywords connected by Boolean connectors. Data extracted from the selected studies included information on the number of participants and their characteristics related to sport practice, age, and menstrual function. DATA ANALYSIS: A total of 71 studies were included in this review: 17 focused on the analysis of dietary manipulation, and 54 focused on the effects of dietary supplementation. The total sample size was 1654 participants (32.5% categorized as competitive athletes, 30.7% as highly/moderately trained, and 37.2% as physically active/recreational athletes). The risk of bias was considered moderate, mainly for reasons such as a lack of access to the study protocol, insufficient description of how the hormonal phase during the menstrual cycle was controlled for, inadequate dietary control during the intervention, or a lack of blinding of the researchers. CONCLUSION: Diets with high carbohydrate (CHO) content enhance performance in activities that induce muscle glycogen depletion. In addition, pre-exercise meals with a high glycemic index or rich in CHOs increase CHO metabolism. Ingestion of 5-6 protein meals interspersed throughout the day, with each intake exceeding 25 g of protein favors anabolism of muscle proteins. Dietary supplements taken to enhance performance, such as caffeine, nitric oxide precursors, ß-alanine, and certain sport foods supplements (such as CHOs, proteins, or their combination, and micronutrients in cases of nutritional deficiencies), may positively influence sports performance and/or the health status of female athletes and other physically active women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD480674.

Deformity correction from the convexity of the curve in neuromuscular scoliosis.

Background: "Convex Pedicle Screw Technique" reduces the theoretical risk of neurovascular injury. Our aim is to evaluate the efficacy of this technique in patients with neuromuscular scoliosis (NMS). Methods: Retrospective study of 12 patients who underwent a Convex Pedicle Screw Technique and were diagnosed with NMS. Patients who had undergone previous spinal surgery were excluded. The minimum follow-up required was 24 months. Demographic data, intraoperative data, neurovascular complications and neurophysiological events requiring implant repositioning, as well as pre- and postoperative radiological variables were collected. Results: Twelve patients diagnosed with NMS underwent surgery. The median operative time was 217 minutes. Mean blood loss was 3.8±1.1 g/dL hemoglobin (Hb). The median postoperative stay was 8.8±4 days. A reduction of the Cobb angle in primary curve of 49.1% (from 52.8°±18° to 26.5°±12.6°; P<0.001) and in secondary curve of 25.2% (from 27.8°±18.9° to 18.3°±13.3°; P=0.10) was achieved. Coronal balance improved by 69.4% (7.5±46.2 vs. 2.3±20.9 mm; P=0.72) and sagittal balance by 75% (from -14.1±71.8 vs. -3.5±48.6 mm; P=0.50). There were no neurovascular complications. There were no intraoperative neurophysiological events requiring implant repositioning, nor during reduction maneuvers. No infections were reported. Conclusions: The correction of the deformity from convexity in NMS achieves similar results to other techniques, and a very low complication rate.

Assessment of the Biodegradability and Compostability of Finished Leathers: Analysis Using Spectroscopy and Thermal Methods.

In this study, the biodegradation properties of leather treated with various finishing chemicals were evaluated in order to enhance the sustainability of leather processing. We applied advanced analytical techniques, including FT-IR, thermogravimetric analysis (TGA), and solid-state NMR spectroscopy. Leather samples treated with different polymers, resins, bio-based materials, and traditional finishing agents were subjected to a composting process under controlled conditions to measure their biodegradability. The findings revealed that bio-based polyurethane finishes and acrylic wax exhibited biodegradability, while traditional chemical finishes like isocyanate and nitrocellulose lacquer showed moderate biodegradation levels. The results indicated significant differences in the biodegradation rates and the impact on plant germination and growth. Some materials, such as black pigment, nitrocellulose lacquer and wax, were beneficial for plant growth, while others, such as polyurethane materials, had adverse effects. These results support the use of eco-friendly finishes to reduce the environmental footprint of leather production. Overall, this study underscores the importance of selecting sustainable finishing chemicals to promote eco-friendly leather-manufacturing practices.

Quality improvement collaborative for improving patient care delivery in Argentine public health sector intensive care units.

BACKGROUND: The demand for healthcare services during the COVID-19 pandemic was excessive for less-resourced settings, with intensive care units (ICUs) taking the heaviest toll. OBJECTIVE: The aim was to achieve adequate personal protective equipment (PPE) use in 90% of patient encounters, to reach 90% compliance with objectives of patient flow (OPF) and to provide emotional support tools to 90% of healthcare workers (HCWs). METHODS: We conducted a quasi-experimental study with an interrupted time-series design in 14 ICUs in Argentina. We randomly selected adult critically ill patients admitted from July 2020 to July 2021 and active HCWs in the same period. We implemented a quality improvement collaborative (QIC) with a baseline phase (BP) and an intervention phase (IP). The QIC included learning sessions, periods of action and improvement cycles (plan-do-study-act) virtually coached by experts via platform web-based activities. The main study outcomes encompassed the following elements: proper utilisation of PPE, compliance with nine specific OPF using daily goal sheets through direct observations and utilisation of a web-based tool for tracking emotional well-being among HCWs. RESULTS: We collected 7341 observations of PPE use (977 in BP and 6364 in IP) with an improvement in adequate use from 58.4% to 71.9% (RR 1.2, 95% CI 1.17 to 1.29, p<0.001). We observed 7428 patient encounters to evaluate compliance with 9 OPF (879 in BP and 6549 in IP) with an improvement in compliance from 53.9% to 67% (RR 1.24, 95% CI 1.17 to 1.32, p<0.001). The results showed that HCWs did not use the support tool for self-mental health evaluation as much as expected. CONCLUSION: A QIC was effective in improving healthcare processes and adequate PPE use, even in the context of a pandemic, indicating the possibility of expanding QIC networks nationwide to improve overall healthcare delivery. The limited reception of emotional support tools requires further analyses.

Physical activity levels and sedentary behaviour according to sex, age, BMI, academic year, and country among medical students in Latin America.

Physical inactivity represents a global challenge in public health, being the second most significant factor contributing to mortality. In Latin America, the prevalence of physical inactivity and sedentary behaviour is notable, affecting medical students as well, who play a crucial role as behavioural role models for the population. This study addresses the prevalence of physical activity and sedentary behaviour among medical students in Latin America during the year 2023. A total of 864 participants from 12 institutions across eight countries were surveyed using the Global Physical Activity Questionnaire. Significant variations in physical activity and sedentary behaviour were observed according to sex, age, body mass index, academic year, and country. Notably, Costa Rica exhibited the highest levels of moderate physical activity in leisure time (90 min/day). Strength training was more common among men (60 min/day) and in Argentina (60 min/day). Sedentary behaviour was higher in women (420 min/day) and during the first academic year (485 min/day). Uruguay stood out with high levels of sedentary behaviour (600 min/day). Correlations indicated positive moderate associations between academic year and moderate leisure-time PA (r:0,128, p:0,007). In conclusion, there are associations between the level of physical activity and sedentary behaviour with the variables studied in this research, with the main findings being that the female sex has more time spent in sedentary behaviour (minutes/day) and less time spent in strength training (minutes/day). Additionally, there are higher levels of sedentary behaviour in the early years of medical study compared to the later years of the program.

Comorbidities in Hispanic/Latino Veterans with epilepsy.

BACKGROUND: Hispanic/Latino people with epilepsy may be at a differential risk of medical and psychiatric comorbidities given genetic, environmental, sociocultural, and quality of care factors. In people with epilepsy, comorbidities are especially crucial to investigate given the well-known impact on quality of life and risk of adverse outcomes. Yet, Hispanic/Latino Veterans with Epilepsy (HL-VWE) remain an understudied population. The present nationwide population study sought to investigate medical and psychiatric comorbidities in this group. METHODS: Data from the Veterans Health Administration (VHA) Corporate Data Warehouse administrative data were used to identify 56,556 VWE (5.7 % HL-VWE) using a one-year cross-sectional analysis of ICD codes. Elixhauser Comorbidity Index scores and psychiatric diagnoses were calculated based on ICD-9/ICD-10-CM diagnoses using a lookback period. Comparisons were made between HL-VWE and non-HL-VWE using chi-squared and student t-tests. Regression analyses were then performed to examine group differences while accounting for age. RESULTS: HL-VWE had higher probability of being diagnosed with several psychiatric conditions when accounting for age, including depression (OR 1.21, 95 % CI 1.13-1.31) and schizophrenia (OR 1.56, 95 % CI 1.31-1.84). There were no significant differences in medical comorbidities between the HL-VWE and non-HL-VWE groups. CONCLUSIONS: We present results from the largest known study of HL people with epilepsy examining their psychiatric and medical comorbidities and one of the first to specifically study HL-VWE. Compared to non-HL-VWE, the Hispanic/Latino group had comparable medical comorbidity, but higher rates of multiple psychiatric conditions. Results indicate a need for increased screening and interventions in this population to reduce psychiatric disease burden.

Ataxia-telangiectasia in Latin America: clinical features, immunodeficiency, and mortality in a multicenter study.

Ataxia-telangiectasia (AT) is a rare genetic disorder leading to neurological defects, telangiectasias, and immunodeficiency. We aimed to study the clinical and immunological features of Latin American patients with AT and analyze factors associated with mortality. Referral centers from 9 Latin American countries participated in this retrospective cohort study, and 218 patients were included. Median (IQR) ages at symptom onset and diagnosis were 1.0 (1.0-2.0)  and 5.0 (3.0-8.0) years, respectively. Most patients presented recurrent airway infections, which was significantly associated with IgA deficiency. IgA deficiency was observed in 60.8% of patients and IgG deficiency in 28.6%. T- and B-lymphopenias were also present in most cases. Mean survival was 24.2 years, and Kaplan-Meier 20-year-survival rate was 52.6%, with higher mortality associated with female gender and low IgG levels. These findings suggest that immunologic status should be investigated in all patients with AT.

Lower plasma melatonin levels in non-hypoxic premature newborns associated with neonatal pain.

We analyzed plasma melatonin levels in different groups of preterm newborns without hypoxia and their relationship with several perinatal variables like gestational age or neonatal pain. Prospective cohort study of preterm newborns (PTNB) without perinatal hypoxia, Apgar > 6 at 5 min, and oxygen needs on the third day of life. We compared melatonin levels at day 3 of life in different groups of non-hypoxic preterm infants (Student's t-tests, Mann-Whitney U, and chi2) and analyzed the relationship of melatonin with GA, birth weight, neonatal pain (Premature Infant Pain Profile (PIPP) scale), caffeine treatment, parenteral nutrition, or the development of free radical diseases (correlation study, linear regression) and factors associated with moderate/intense pain and free radical diseases (logistic regression analysis). Sixty-one preterm infants with gestational age (GA) of 30.7 ± 2.0 weeks with no oxygen requirements at day 3 of life were studied with plasma melatonin levels of 33.8 ± 12.01 pg/ml. Preterm infants weighing < 1250 g at birth had lower plasma melatonin levels (p = 0.05). Preterm infants with moderate or severe pain (PPIPP > 5) have lower melatonin levels (p = 0.01), and being preterm with PIPP > 5 is associated with lower plasma melatonin levels (p = 0.03). Being very preterm (GA < 32 GS), having low weight for gestational age (LWGA), receiving caffeine treatment, or requiring parenteral nutrition did not modify melatonin levels in non-hypoxic preterm infants (p = NS). Melatonin on day 3 of life in non-hypoxic preterm infants is not associated with later development of free radical diseases (BPD, sepsis, ROP, HIV, NEC). CONCLUSION: We observed that preterm infants with moderate to severe pain have lower melatonin levels. These findings are relevant because they reinforce the findings of other authors that melatonin supplementation decreases pain and oxidative stress in painful procedures in premature infants. Further studies are needed to evaluate whether melatonin could be used as an analgesic in painful procedures in preterm infants. TRIAL REGISTRATION: Trial registration was not required since this was an observational study. WHAT IS KNOWN: • Melatonin is a potent antioxidant and free radical scavenger in newborns under stress conditions: hypoxia, acidosis, hypotension, painful procedures, or parenteral nutrition. • Pain stimulates the production of melatonin. • Various studies conclude that melatonin administration decreases pain during the neonatal period. WHAT IS NEW: • Non-hypoxic preterm infants with moderate to severe pain (PIPP>5) have lower levels of melatonin. • Administration of caffeine and treatment with parenteral nutrition do not modify melatonin levels in non-hypoxic preterm infants.