[Medical nutrition therapy in amyotrophic lateral sclerosis - Do we act or react? A case report and multidisciplinary review]. / Tratamiento médico nutricional en la esclerosis lateral amiotrófica: ¿Actuamos o reaccionamos? Un caso clínico y revisión multidisciplinar.

BACKGROUND: amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a progressive course. The current prevalence is between 3 and 6 cases/100,000. Malnutrition is closely related to patient prognosis in ALS. The implications of this conditions have been that we should recommend patient care in a multidisciplinary unit. CASE REPORT: the case presented shows the evolution of a patient with ALS. The patient was referred to different clinical departments after neurological evaluation and her nutritional, functional and respiratory status were assessed. There was no nutritional deterioration at diagnosis; however, intake was below energy-protein requirements. The clinical evolution of the patient showed a decrease in muscle mass with preservation of weight and fat mass. "Aggressive" measures to control nutritional status such as gastrostomy were rejected in the initial stages of the disease, but had to be carried out after development of dysphagia and associated malnutrition. This situation of progressive morphofunctional deterioration and the development of disease-related complications made essential the participation of different health services and professionals in its control. DICUSSION: the management of ALS in a multidisciplinary manner allows to improve the course of the disease and the quality of life of both the patients and their families. Patient follow-up is based on the adjustment and management of complications. The basis of the relationship with these patients includes maintaining an adequate communication with them and their families, and ensuring joint decision-making about their condition.

Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69 ± 10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P < .001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39 ± 0.89 pre- and 0.18 ± 0.57 postadoption (P < .001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P < .001). The mean number of visits per patient was 0.47 ± 1.11 pre- and 0.16 ± 0.51 postadoption (P < .001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

Survival analysis and gender differences in hypertrophic cardiomyopathy proband patients referred for genetic testing.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is believed to have low overall mortality rate, that could be influenced by gender, particularly among probands. We aimed to evaluate the survival rates and possible gender differences in a homogeneous cohort of HCM proband patients, referred for genetic testing, from the same geographical area, without differences in medical care access nor clinical referral pathways. METHODS: we compared the mortality rates of a cohort of consecutive HCM probands referred for genetic testing (2000-2022), from a Spanish region (xxx1) with a centralized genetic testing pathway, with its control reference population by Ederer II method. Gender differences were analyzed. RESULTS: Among the 649 HCM probands included in this study, there were significantly more men than women (61.3% vs 38.7, p < 0.05), with an earlier diagnosis (53.5 vs 61.1 years old, p < 0.05). Clinical evolution or arrhythmogenic HCM profile did no show no significant gender differences. Mean follow up was 9,8 years ±6,6 SD (9,9 ± 7 vs 9,6 ± 6,1, p = 0.59). No statistically significant differences in observed mortality, expected survival and excess mortality were found in the general HCM proband cohort. However, we found a significant excess mortality in female probands with HCM. No additional differences in analysis by genetic status were identified. CONCLUSION: Expected survival in our HCM probands did not differ from its reference population. However, despite no gender differences in phenotype severity were identified, proband HCM women did present a diagnosis delay and worse mortality outcomes.

Chromosome-Y haplogroups in Asturias (Northern Spain) and their association with severe COVID-19.

The main objective of this study was to determine whether the common Y-haplogroups were be associated with the risk of developing severe COVID-19 in Spanish male. We studied 479 patients who required hospitalization due to COVID-19 and 285 population controls from the region of Asturias (northern Spain), They were genotyped for several polymorphisms that define the common European Y-haplogroups. We compared the frequencies between patients and controls aged ≤ 65 and >65 years. There were no different haplogroup frequencies between the two age groups of controls. Haplogroup R1b was less common in patients aged ≤65 years. Haplogroup I was more common in the two patient´s groups compared to controls (p = 0.02). Haplogroup R1b was significantly more frequent among hypertensive patients, without difference between the hypertensive and normotensive controls. This suggested that R1b could increase the risk for severe COVID-19 among male with pre-existing hypertension. In conclusion, we described the Y-haplogroup structure among Asturians. We found an increased risk of severe COVID-19 among haplogroup I carriers, and a significantly higher frequency of R1b among hypertensive patients. These results indicate that Y-chromosome variants could serve as markers to define the risk of developing a severe form of COVID-19.

Deep continual learning for medical call incidents text classification under the presence of dataset shifts.

The aim of this work is to develop and evaluate a deep classifier that can effectively prioritize Emergency Medical Call Incidents (EMCI) according to their life-threatening level under the presence of dataset shifts. We utilized a dataset consisting of 1982746 independent EMCI instances obtained from the Health Services Department of the Region of Valencia (Spain), with a time span from 2009 to 2019 (excluding 2013). The dataset includes free text dispatcher observations recorded during the call, as well as a binary variable indicating whether the event was life-threatening. To evaluate the presence of dataset shifts, we examined prior probability shifts, covariate shifts, and concept shifts. Subsequently, we designed and implemented four deep Continual Learning (CL) strategies-cumulative learning, continual fine-tuning, experience replay, and synaptic intelligence-alongside three deep CL baselines-joint training, static approach, and single fine-tuning-based on DistilBERT models. Our results demonstrated evidence of prior probability shifts, covariate shifts, and concept shifts in the data. Applying CL techniques had a statistically significant (α=0.05) positive impact on both backward and forward knowledge transfer, as measured by the F1-score, compared to non-continual approaches. We can argue that the utilization of CL techniques in the context of EMCI is effective in adapting deep learning classifiers to changes in data distributions, thereby maintaining the stability of model performance over time. To our knowledge, this study represents the first exploration of a CL approach using real EMCI data.

PaCO2 Association with Outcomes of Patients with Traumatic Brain Injury at High Altitude: A Prospective Single-Center Cohort Study.

BACKGROUND: Partial pressure of carbon dioxide (PaCO2) is generally known to influence outcome in patients with traumatic brain injury (TBI) at normal altitudes. Less is known about specific relationships of PaCO2 levels and clinical outcomes at high altitudes. METHODS: This is a prospective single-center cohort of consecutive patients with TBI admitted to a trauma center located at 2600 m above sea level. An unfavorable outcome was defined as a Glasgow Outcome Scale-Extended (GOSE) score < 4 at the 6-month follow-up. RESULTS: We had a total of 81 patients with complete data, 80% (65/81) were men, and the median (interquartile range) age was 36 (25-50) years. Median Glasgow Coma Scale (GCS) score on admission was 9 (6-14); 49% (40/81) of patients had severe TBI (GCS 3-8), 32% (26/81) had moderate TBI (GCS 12-9), and 18% (15/81) had mild TBI (GCS 13-15). The median (interquartile range) Abbreviated Injury Score of the head (AISh) was 3 (2-4). The frequency of an unfavorable outcome (GOSE < 4) was 30% (25/81), the median GOSE was 4 (2-5), and the median 6-month mortality rate was 24% (20/81). Comparison between patients with favorable and unfavorable outcomes revealed that those with unfavorable outcome were older, (median age 49 [30-72] vs. 29 [22-41] years, P < 0.01), had lower admission GCS scores (6 [4-8] vs. 13 [8-15], P < 0.01), had higher AISh scores (4 [4-4] vs. 3 [2-4], P < 0.01), had higher Acute Physiology and Chronic Health disease Classification System II scores (17 [15-23] vs. 10 [6-14], P < 0.01), had higher Charlson scores (0 [0-2] vs. 0 [0-0], P < 0.01), and had higher PaCO2 levels (mean 35 ± 8 vs. 32 ± 6 mm Hg, P < 0.01). In a multivariate analysis, age (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.1-1.30, P < 0.01), AISh (OR 4.7, 95% CI 1.55-21.0, P < 0.05), and PaCO2 levels (OR 1.23, 95% CI 1.10-1.53, P < 0.05) were significantly associated with the unfavorable outcomes. When applying the same analysis to the subgroup on mechanical ventilation, AISh (OR 5.4, 95% CI 1.61-28.5, P = 0.017) and PaCO2 levels (OR 1.36, 95% CI 1.13-1.78, P = 0.015) remained significantly associated with the unfavorable outcome. CONCLUSIONS: Higher PaCO2 levels are associated with an unfavorable outcome in ventilated patients with TBI. These results underscore the importance of PaCO2 levels in patients with TBI and whether it should be adjusted for populations living at higher altitudes.

Immunoglobulin genes and severity of COVID-19.

There is tremendous interindividual and interracial variability in the outcome of SARS-CoV-2 infection, suggesting the involvement of host genetic factors. Here, we investigated whether IgG allotypes GM (γ marker) 3 and GM 17, genetic markers of IgG1, contributed to the severity of COVID-19. IgG1 plays a pivotal role in response against SARS-CoV-2 infection. We also investigated whether these GM alleles synergistically/epistatically with IGHG3 and FCGR2A alleles-which have been previously implicated in COVID-19-modulated the extent of COVID-19 severity. The study population consisted of 316 COVID-19 patients who needed treatment in the intensive care unit of Hospital Universitario Central de Asturias. All individuals were genotyped for GM 3/17, IGHG3 hinge length, and FCGR2A rs1801274 A/G polymorphisms. Among the 316 critical patients, there were 86 deaths. The risk of death among critical patients was significantly higher in subjects with GM 17 (IgG1) and short hinge length (IgG3). GM 17-carriers were at almost three-fold higher risk of death than non-carriers (p < 0.001; OR = 2.86, CI 1.58-5.16). Subjects with short hinge length of IgG3 had a two-fold higher risk of death than those with medium hinge length (p = 0.01; OR = 2.16, CI 1.19-3.90). GM 3/3 and IGHG3 (MM) genotypes were less frequent among death vs. survivors (9% vs 36%, p < 0.001) and associated with protective effect (OR = 0.18, 95% CI = 0.08-0.39). This is the first report implicating IgG1 allotypes in COVID-19-spurred death. It needs to be replicated in an independent study population.

Diversity and biogeography of South American mud turtles elucidated by multilocus DNA sequencing (Testudines: Kinosternidae).

Kinosternon is the most speciose genus of extant turtles, with 22 currently recognized species, distributed across large parts of the Americas. Most species have small distributions, but K. leucostomum and K. scorpioides range from Mexico to South America. Previous studies have found discordance between mitochondrial and nuclear phylogenies in some kinosternid groups, with the current taxonomy following the nuclear-based results. Herein, based on extended molecular, geographic, and taxonomic sampling, we explore the phylogeographic structure and taxonomic limits for K. leucostomum and the K. scorpioides group and present a fossil-calibrated nuclear time tree for Kinosternon. Our results reveal contrasting differentiation patterns for the K. scorpioides group and K. leucostomum, despite overlapping distributions. Kinosternon leucostomum shows only shallow geographic divergence, whereas the K. scorpioides group is polyphyletic with up to 10 distinct taxa, some of them undescribed. We support the elevation of K. s. albogulare and K. s. cruentatum to species level. Given the deep divergence within the genus Kinosternon, we propose the recognition of three subgenera, Kinosternon, Cryptochelys and Thyrosternum, and the abandonment of the group-based classification, at least for the K. leucostomum and K. scorpioides groups. Our results show an initial split in Kinosternon that gave rise to two main radiations, one Nearctic and one mainly Neotropical. Most speciation events in Kinosternon occurred during the Quaternary and we hypothesize that they were mediated by both climatic and geological events. Additionally, our data imply that at least three South American colonizations occurred, two in the K. leucostomum group, and one in the K. scorpioides group. Additionally, we hypothesize that discordance between mitochondrial and nuclear phylogenetic signal is due to mitochondrial capture from an extinct kinosternine lineage.

Effectiveness of a training program for the management of risky alcohol use in primary care professionals based on motivational interviewing / Eficacia de un programa de formación para el manejo del consumo de riesgo de alcohol en profesionales de atención primaria basado en la entrevista motivacional

Objective: To assess the effectiveness of a training program for Primary Care (PC) professionals developed to increase knowledge, attitudes, and skills for managing patients with risky alcohol use and in the motivational interview. Design: Multicenter, two-arm parallel, randomized, open-label controlled clinical trial. Setting: PC of the Andalusian Health Service. Participants: The study was completed by 80 healthcare professionals from 31 PC centers. Interventions: In both experimental and control groups, a workshop on managing patients with risky alcohol consumption and the resolution of two videotaped clinical cases with standardized patients were conducted. The experimental group attended a workshop on motivational interviewing. Main measurements: Knowledge about managing risky alcohol use, clinical performance in patients with this health problem, and assessment of the motivational interview. Results: Mean age was 39.50±13.06 – SD – (95% CI: 36.59–42.41); 71.3% (95% CI: 61.1–80.9%) were women. The average score of both groups in the knowledge questionnaire before the training program was 15.10±4.66, becoming 21.99±3.93 points after the training (95% CI: 5.70–7.92; p<0.001). The experimental group showed an average score of 18.53±13.23 before the intervention with the motivational interview and 28.33±11.86 after this intervention (p=0.002). In contrast, no significant variation was found in the score of the control group. Conclusions: A training program aimed at PC professionals designed to increase knowledge on how to manage risky alcohol use and acquire communication skills in motivational interviewing is effective.(AU)

Objetivo: Evaluar la efectividad de un programa de formación para profesionales de Atención Primaria (AP) para incrementar conocimientos, actitudes y habilidades en el manejo de pacientes con consumo de riesgo de alcohol y en la entrevista motivacional. Diseño: Ensayo clínico controlado, abierto, aleatorizado, multicéntrico, paralelo de dos brazos. Emplazamiento: Centros de AP del Servicio Andaluz de Salud. Participantes: Fue completado por 80 profesionales sanitarios de 31 centros. Intervenciones: En el grupo experimental y en el control se realizó un taller de manejo de pacientes con consumo de riesgo de alcohol y la resolución de dos casos clínicos videograbados con pacientes estandarizados. El grupo experimental asistió a un taller sobre entrevista motivacional. Mediciones principales: Conocimiento sobre el manejo del consumo de riesgo de alcohol, desempeño clínico en pacientes con este problema de salud y valoración de la entrevista motivacional. Resultados: La edad media fue 39.50±13,06 -DE- (IC 95%: 36,59-42,41); El 71,3% (IC 95%: 61,1%-80,9%) eran mujeres. La puntuación media en el cuestionario de conocimientos antes del programa de formación fue de 15,10±4,66, siendo 21,99±3,93 puntos después del entrenamiento (IC 95%:5,70-7,92; p<0,001). La puntuación promedio del grupo experimental antes de la intervención con la entrevista motivacional era de 18,53±13,23 y después de 28,33±11,86 (p=0,002). No se encontró variación significativa en la puntuación del grupo control. Conclusiones: Un programa de formación para profesionales de AP, para incrementar el conocimiento sobre cómo gestionar el consumo de riesgo de alcohol y adquirir habilidades comunicativas en la entrevista motivacional es efectivo.(AU)

Use of Muscle Ultrasonography in Morphofunctional Assessment of Amyotrophic Lateral Sclerosis (ALS).

Amyotrophic lateral sclerosis (ALS) is a progressive disease with a high prevalence of malnutrition that can influence prognosis. The main objective of this study is to compare the validity of muscle ultrasonography in the diagnosis of malnutrition and the prognosis of patients with ALS. METHODS: This is a prospective observational study that analyzes the nutritional status of patients at the beginning of nutritional monitoring. The morphofunctional assessment included the examination of anthropometric variables such as weight, height, body mass index (BMI), arm circumference, and calf circumference. Additionally, electrical bioimpedanciometry (BIA) was used to measure electrical parameters and estimate other relevant metrics. Muscle ultrasonography® (quadriceps rectus femoris (QRF)) assessed muscle mass parameters, including muscle area index (MARAI), anteroposterior diameter of the QRF (Y-axis) (cm), transverse diameter of the QRF (X-axis) (cm), and the sum of the quadriceps thickness (RF+VI) (cm), as well as muscle quality parameters such as echogenicity and the Y-X index. RESULTS: A total of 37 patients diagnosed with amyotrophic lateral sclerosis (ALS) were included in this study. Of these patients, 51.4% were men. The mean age was 64.27 (12.59) years. A total of 54.1% of the patients had a bulbar onset of amyotrophic lateral sclerosis, and 45.9% had spinal onset. The percentage of subjects with malnutrition diagnosed by the Global Leadership Initiative on Malnutrition (GLIM) criteria was 45.9% of patients. There was a direct correlation between muscle mass parameters assessed by muscle ultrasonography (RF+VI) and active mass markers measured by bioimpedanciometry (body cellular mass index (BCMI) (r = 0.62; p < 0.01), fat-free mass index (FFMI) (r = 0.75; p < 0.01), and appendicular skeletal mass index (ASMI) (r = 0.69; p < 0.01)). There was a direct correlation between echogenicity and resistance (r = 0.44; p = 0.02), as well as between the fat-free mass index and the Y-X index (r = 0.36; p = 0.14). Additionally, there was a negative correlation between echogenicity and BCMI (r = -0.46; p < 0.01) and ASMI (r = 0.34; p = 0.06). Patients with low quadriceps thickness (male < 2.49 cm; female < 1.84 cm) showed an increased risk of hospital admission adjusted by age, sex, and presence of dysphagia (OR: 7.84 (CI 95%: 1.09-56.07); p-value = 0.04), and patients with low-quality mass (Y-X index < 0.35) had a higher risk of hospital admission adjusted by age, sex, and presence of dysphagia (OR: 19.83 (CI 95%: 1.77-222.46); p-value = 0.02). CONCLUSIONS: In patients with ALS, ultrasonography echogenicity was inversely related to BCMI, FFMI, and ASMI, and the Y-X index was directly related to FFMI. The lowest quartiles of quadriceps thickness and Y-X index are risk factors for hospital admission.

Comparison of the Effect of Two Different Handling Conditions at Slaughter in Saliva Analytes in Pigs.

In this report, different handling conditions at slaughterhouse were studied to assess changes in salivary biomarkers. For this purpose, finishing pigs were divided into two groups, one in which handling was improved to minimize stress (Group A, n = 24, transported and stabled at the slaughterhouse at low density without mixing with unfamiliar animals throughout the whole process) and another one in which animals had a more stressful handling process (Group B, n = 24, transported and stabled at high density with unfamiliar animals). Saliva samples were taken the day before transport to the slaughterhouse at 8:00 a.m. (B0) and 12:00 a.m. (B4), and the day of slaughter just after unloading animals at the slaughterhouse at approximately 8:00 a.m. (S0) and after 4 h of lairage at approximately 12:00 a.m. (S4). Group B showed significantly higher cortisol, total esterase activity, oxytocin, adenosine deaminase and haptoglobin levels than the Group A at both S0 and S4 sampling times, and higher levels of calprotectin and creatine kinase at S4 sampling time. This report indicates that differences in the way in which the pigs are handled at the slaughterhouse can lead to changes in salivary biomarkers and opens the possibility of the use of biomarker at slaughter to monitor handling conditions.

DCLK1-Mediated Regulation of Invadopodia Dynamics and Matrix Metalloproteinase Trafficking Drives Invasive Progression in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a major health concern due to its high mortality from poor treatment responses and locoregional tumor invasion into life sustaining structures in the head and neck. A deeper comprehension of HNSCC invasion mechanisms holds the potential to inform targeted therapies that may enhance patient survival. We previously reported that doublecortin like kinase 1 (DCLK1) regulates invasion of HNSCC cells. Here, we tested the hypothesis that DCLK1 regulates proteins within invadopodia to facilitate HNSCC invasion. Invadopodia are specialized subcellular protrusions secreting matrix metalloproteinases that degrade the extracellular matrix (ECM). Through a comprehensive proteome analysis comparing DCLK1 control and shDCLK1 conditions, our findings reveal that DCLK1 plays a pivotal role in regulating proteins that orchestrate cytoskeletal and ECM remodeling, contributing to cell invasion. Further, we demonstrate in TCGA datasets that DCLK1 levels correlate with increasing histological grade and lymph node metastasis. We identified higher expression of DCLK1 in the leading edge of HNSCC tissue. Knockdown of DCLK1 in HNSCC reduced the number of invadopodia, cell adhesion and colony formation. Using super resolution microscopy, we demonstrate localization of DCLK1 in invadopodia and colocalization with mature invadopodia markers TKS4, TKS5, cortactin and MT1-MMP. We carried out phosphoproteomics and validated using immunofluorescence and proximity ligation assays, the interaction between DCLK1 and motor protein KIF16B. Pharmacological inhibition or knockdown of DCLK1 reduced interaction with KIF16B, secretion of MMPs, and cell invasion. This research unveils a novel function of DCLK1 within invadopodia to regulate the trafficking of matrix degrading cargo. The work highlights the impact of targeting DCLK1 to inhibit locoregional invasion, a life-threatening attribute of HNSCC.

Role of rs2282679 in 25-hydroxyvitamin D levels and insulin resistance after a sleeve gastrectomy.

BACKGROUND & AIMS: Some studies have reported links between 25-hydroxyvitamin D levels and the presence of obesity and some genetic variants. The aim of our design was to evaluate the effects of rs2282679 genetic variant of CG gene on 25-hydroxyvitamin D levels, weight loss and metabolic parameters after a robotic sleeve gastrectomy in premenopausal females with obesity. METHODS: 76 participants were enrolled. 25-hydroxyvitamin D levels, biochemical evaluation and anthropometric parameters were registered before surgery and after 3, 6 and 12 months follow up. Genotype of rs2282679 CG gene was evaluated. RESULTS: The improvements in anthropometric parameters, blood pressure and lipid profile were similar in both genotypes (TT vs TG + GG). Basal insulin levels and HOMA-IR were greater in G allele carriers than non-carriers (Delta: 6.7 ± 1.2 mUI/L; p = 0.01) and (Delta: 1.3 ± 0.1 units; p = 0.02). 25-hydroxyvitamin D levels were lower in G allele carriers than non-carriers (Delta: 8.1 ± 1.1 ng/dl; p = 0.03). The levels of insulin and HOMA-IR remained greater in G allele carriers than non-carriers throughout all the visits. The levels of 25-hydroxyvitamin D remained lower in G allele carriers than non-G allele. The average level of 25-hydroxyvitamin D at 12 months in non-G allele carriers were above 30 ng/dl (36.0 ± 3.1 ng/dl) and the level in G allele carriers were below (24.9 ± 4.9 ng/dl). CONCLUSIONS: rs 2282679 (GC) was related with low 25 hydroxyvitamin D levels and insulin resistance. In addition, the presence of G allele produced a decrease in the improvement of 25-hydroxyvitamin D levels and insulin resistance after weight loss during 12 months.

[Molecular mimicry between human thyroid peroxidase, thyroglobulin, cosinophil peroxidase, IL-24 and microorganisms antigens]. / Mimetismo molecular entre peroxidasa tiroidea humana, tiroglobulina, peroxidasa de eosinófilos, IL-24 y antígenos de microorganismos.

OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.

OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.

We know that we don't know: Children's understanding of common ignorance in a coordination game.

Common ground is the knowledge, beliefs, and suppositions shared between partners in an interaction. Previous research has focused extensively on what partners know they know together, that is, "common knowledge." However, another important aspect of common ground is what partners know they do not know together, that is, "common ignorance." A new coordination game was designed to investigate children's use of common ignorance. Without communicating or seeing each other's decisions, 4- to 8-year-olds needed to make the same decision as their partner about whether to try to retrieve a reward. To retrieve it, at least one of them needed to know a secret code. The knowledge/ignorance of both partners was ostensively manipulated by showing one partner, both partners, or neither partner the secret code in four conditions: common knowledge (both knew the code), common ignorance (neither partner knew the code), common privileged self knowledge (only children knew the code), and common privileged other knowledge (only their partner knew the code). Children's decisions, latency, and uncertainty were coded. Results showed that the common ignorance states were generally more difficult than the common knowledge states. Unexpectedly, children at all ages had difficulty with coordinating when their partner knew the code but they themselves did not (common privileged other knowledge). This study shows that, along with common knowledge, common ignorance and common privileged self knowledge and other knowledge also play important roles in coordinating with others but may develop differently.

Programa de vacunación en prisiones: impacto del virus SARS-CoV-2 y retos de futuro / Prison vaccination programmes: the impact of the SARS-CoV-2 virus and future challenges

La vacunación ha sido tradicionalmente una de las actividades de prevención primaria a la que mayor esfuerzo se ha dedicado en las instituciones penitenciarias españolas. Una vez más, la pandemia de coronavirus de tipo 2 causante del síndrome respiratorio agudo severo (SARS-CoV-2) ha puesto de manifiesto la importancia de la vacunación en el control de las enfermedades inmunoprevenibles. Tras superar la emergencia sanitaria provocada por la enfermedad del coronavirus de 2019 (COVID-19), tenemos por delante el reto de recuperar las coberturas vacunales que teníamos antes de la pandemia, además de aumentar las de otras vacunas con menor implantación en nuestro medio. Entre las estrategias de mejora que se deben implementar, estaría la optimización de la transmisión de la información sanitaria entre centros penitenciarios dependientes de diferentes administraciones. También sería deseable poder acceder a los sistemas de información sobre vacunas de las diferentes comunidades autónomas, tanto para conocer el estado vacunal de los pacientes como para notificar las dosis administradas durante el periodo de internamiento, así como mejorar las estadísticas vacunales disponibles en prisión.(AU)

Vaccination has traditionally been one of the primary prevention activities to which most effort has been devoted in Spanish penitentiary institutions. Once again, the type 2 coronavirus pandemic causing severe acute respiratory syndrome (SARS-CoV-2) pandemic has highlighted the importance of vaccination in the control of immunopreventable diseases.After overcoming the health emergency caused by the coronavirus disease 2019 (COVID-19), we face the challenge of recovering the vaccination coverage we had before the pandemic, in addition to increasing the coverage of other vaccines with lesser implantation in our environment. Among the improvement strategies to be implemented would be the optimization of the transmission of health information between penitentiary centers dependent on different administrations. It would also be desirable to be able to access the vaccine information systems of the different autonomous communities, both to know the vaccination status of patients and to report the doses administered during the period of internment, as well as to improve the vaccine statistics available in prison.(AU)

Epidemiological characteristics of mortality from infectious intestinal diseases (diarrhea) Paraguay (2015-2019)

Introduction: Infectious intestinal diseases (diarrhea) are a major cause of morbidity and mortality worldwide. In 2015, it constituted the ninth leading cause of death for all ages. Objective: To describe the epidemiological characteristics of mortality due to infectious intestinal diseases (diarrhea) in Paraguay from 2015 to 2019. Methods: Descriptive, ecological, cross-sectional, retrospective, and non-probabilistic sampling of consecutive cases was performed. ICD-10 deaths included cholera (A01), typhoid and paratyphoid fever (A01), shigellosis (A03), other bacterial intestinal infections (A04), other bacterial food poisoning (A05), amebiasis (A06), other intestinal diseases due to protozoa (A07), intestinal infections due to viruses (A08), and diarrhea and gastroenteritis of presumed infectious origin (A09). Open access data were obtained from the WEB page of the General Directorate of Strategic Information in Health of the MSP and BS of all the Departments of the country. Crude and adjusted rates (per 100,000 inhabitants) were calculated. Excel and EPI INFO 7.0 were used. Results: 495 deaths were registered; the highest prevalence was in 2019 (adjusted rate of 1.83) and the lowest in 2017 (1.36). The months with the highest mortality rates were January and July (9.9%). 51.72% were women (256), 30.91% were over 80 years old and 28.28% (140) were under 5 years old, average age 50.8, single 56.77% (281) and without any type of education 41.82% (207). A total of 80.61% (399) of the respondents resided in urban areas. The highest rates were registered in Boquerón (33.3) and Amambay (15.2). Diarrhea and gastroenteritis of infectious origin accounted for 95.56% of the cases (473). Discussion: There was a high percentage of mortality from infectious diarrhea. Extremes of life were the most vulnerable populations.

Introducción: Las enfermedades infecciosas intestinales (diarrea) son una causa importante de morbilidad y mortalidad a nivel mundial. En 2015, constituyeron la novena causa principal de muerte para todas las edades. Objetivo: describir las características epidemiológicas de la mortalidad por enfermedades infecciosas intestinales (diarreas) en Paraguay durante los años 2015 al 2019. Metodología: Estudio descriptivo, ecológico, transversal, retrospectivo, muestreo no probabilístico de casos consecutivos. Se consideraron los óbitos del CIE - 10, que incluyen al cólera (A01), fiebres tifoidea y paratifoidea (A01), shigelosis (A03), otras infecciones intestinales bacterianas (A04), otras intoxicaciones alimentarias bacterianas (A05), amebiasis (A06), otras enfermedades intestinales debidas a protozoarios (A07), infecciones intestinales debidas a virus (A08) y diarrea y gastroenteritis de presunto origen infeccioso (A09). Se utilizaron datos de acceso abierto de la página WEB de la Dirección General de Información Estratégica en Salud del MSP y BS de todos los Departamentos del país. Se calcularon tasas crudas y ajustadas (por 100.000 habitantes). Se utilizaron Excel y EPI INFO 7.0. Resultados: Se registraron 495 muertes, la mayor prevalencia fue en 2019 (tasa ajustada de 1,83) y menor en 2017 (1,36). Los meses con mayor mortalidad fueron enero y julio (9,9%). El 51,72% fueron mujeres (256), 30,91% mayores de 80 años y 28,28% (140) menores de 5 años, edad promedio 50,8, solteros 56,77% (281) y sin ningún tipo de educación 41,82% (207). El 80,61% (399) residía en área urbana. Las mayores tasas se registraron en Boquerón (33,3) y Amambay (15,2). El 95,56% (473) fueron diarreas y gastroenteritis de origen infeccioso. Discusión: Se registra alto porcentaje de mortalidad de diarreas de origen infeccioso. Los extremos de la vida constituyen la población más vulnerable.

Tattoos: risks and complications, clinical and histopathological approach.

BACKGROUND: Skin modification through tattoos is as old as humanity itself. However, this trend is on the rise, and with the use of different types of pigments and application practices, both cutaneous and systemic complications can arise. Adverse reactions can be grouped into five classes: inflammatory, infectious, neoplastic, aesthetic, and miscellaneous. On histopathology, inflammatory reactions can exhibit a lichenoid pattern or present as spongiotic dermatitis, granulomatous reactions, pseudolymphoma, pseudoepitheliomatous hyperplasia, or scleroderma/morphea-like changes. This article reviews tattoo complications, including their clinical and histopathological characteristics. METHODS: An open search was conducted on PubMed using the terms "tattoo", "complications", and "skin". No limits were set for period, language, or publication type of the articles. RESULTS: Reactions to tattoos are reported in up to 67% of people who get tattooed, with papulonodular and granulomatous reactions being the most common. Some neoplastic complications have been described, but their causality is still debated. Any pigment can cause adverse reactions, although red ink is more frequently associated with them. Patients with pre-existing dermatoses may experience exacerbation or complications of their diseases when getting tattoos; therefore, this procedure is not recommended for this patient group. CONCLUSIONS: Dermatological consultation is recommended before getting a tattoo, as well as a histopathological examination in case of complications. In patients who develop cutaneous inflammatory reactions following tattooing, additional studies are recommended to investigate systemic diseases such as sarcoidosis, pyoderma gangrenosum, atopic dermatitis, and neoplasms. It is important for physicians to be trained in providing appropriate care in case of complications.

A Technical Note on Alternating Laminectomies Plus Folding Cystectomy: A Novel Technique for Spinal Arachnoid Cyst.

We report the case of a 33-year-old male patient with no past medical history presenting to our tertiary referral center with progressive (two years) deficit of lower limb motor impairment (2/5 Medical Research Council [MRC] scale) and sensory impairment. T2- and T1-weighted MRI images clarified the nature of the cyst from T3 to T8. In our case, surgical management was warranted to relieve tension over the spinal cord, thus improving symptoms. Two multilevel laminectomies were performed, one centered on the proximal pole and the other on the distal pole; subsequently, the epidural cyst was gradually folded until it was totally extracted without complications. In the present study, we discuss a technique of extended spinal compressive arachnoid cyst. To the best of our knowledge, this technique has not been previously described in the existing body of literature. Here, we present a case of a successful procedure that seems both efficient and safe. Further study will be required to confirm its safety and efficacy.

A predator-prey fractional model with disease in the prey species.

In this paper, we study a generalized eco-epidemiological model of fractional order for the predator-prey type in the presence of an infectious disease in the prey. The proposed model considers that the disease infects the prey, causing them to be divided into two classes, susceptible prey and infected prey, with different density-dependent predation rates between the two classes. We propose logistic growth in both the prey and predator populations, and we also propose that the predators have alternative food sources (i.e., they do not feed exclusively on these prey). The model is evaluated from the perspective of the global and local generalized derivatives by using the generalized Caputo derivative and the generalized conformable derivative. The existence, uniqueness, non-negativity, and boundedness of the solutions of fractional order systems are demonstrated for the classical Caputo derivative. In addition, we study the stability of the equilibrium points of the model and the asymptotic behavior of its solution by using the Routh-Hurwitz stability criteria and the Matignon condition. Numerical simulations of the system are presented for both approaches (the classical Caputo derivative and the conformable Khalil derivative), and the results are compared with those obtained from the model with integro-differential equations. Finally, it is shown numerically that the introduction of a predator population in a susceptible-infectious system can help to control the spread of an infectious disease in the susceptible and infected prey population.