Clinical, epidemiological and therapeutic characterization of children with congenital heart disease

Introducción: la cardiología pediátrica ha evolucionado considerablemente en los últimos años sobre la base de nuevos conocimientos embriológicos, patológicos y fisiológicos. Este progreso no ha sido ajeno al desarrollo de nuevas tecnologías. Estimándose actualmente entre 650,000 y 1,300 000 adultos con malformaciones cardiacas. Objetivo: caracterizar de forma clínica, epidemiológica y terapéutica de los pacientes con cardiopatías congénitas ingresados en el Hospital Infantil Norte en el período comprendido de enero 2017 a diciembre del año 2019. Variables clínicas, epidemiológicas y terapéuticas.Métodos: se realizó un estudio descriptivo y transversal con el objetivo de caracterizar los pacientes ingresados en el Hospital Infantil Norte Docente “Juan de la Cruz Martínez Maceira” con el diagnóstico de Cardiopatías Congénitas.Resultados: se evidenció que el 71 % correspondió al sexo masculino, en pacientes de un año a cinco años fueron los de mayor número con (58 %) en este grupo predomino el sexo masculino con 39 %, el síntoma que tuvo mayor presencia fue el soplo cardiaco con 53 %, este a su vez en el sexo masculino con un 20 %. En lo referente al diagnóstico se observó dominio de los pacientes con comunicación interauricular, con un 37 % de estos un 20 % fueron del sexo masculino. Conclusiones: los pacientes con cardiopatías congénitas constituyen un grupo con especificidades tales como; la edad, el momento del diagnóstico y la terapéutica empleada, la cual los ubica como una entidad de observación relativamente frecuente en la población pediátrica.Introduction: pediatric cardiology has evolved considerably in recent years on the basis of new embryological, pathological and physiological knowledge. This progress has not been unrelated to the development of new technologies. It is currently estimated that between 650,000 and 1,300,000 adults have cardiac malformations. Objective: to characterize clinically, epidemiologically and therapeutically the patients with congenital heart disease admitted to the Hospital Infantil Norte from January 2017 to December 2019. Clinical, epidemiological and therapeutic variables.Methods: a descriptive and cross-sectional study was carried out with the aim of characterizing patients admitted to the Hospital Infantil Norte Docente "Juan de la Cruz Martínez Maceira" with the diagnosis of Congenital Heart Disease.ResResults: it was evidenced that 71 % corresponded to the male sex, in patients from one year to five years old were the ones with the highest number (58 %) in this group the male sex predominated with 39 %, the symptom that had the highest presence was the cardiac murmur with 53 %, this in turn in the male sex with 20 %. Regarding the diagnosis, 37% of the patients with atrial septal defect were male, 20 % of whom were male.Conclusions: patients with congenital heart disease constitute a group with specificities such as age, time of diagnosis and therapy used, which places them as an entity of relatively frequent observation in the pediatric population

ATXN3 controls DNA replication and transcription by regulating chromatin structure

The deubiquitinating enzyme Ataxin-3 (ATXN3) contains a polyglutamine (PolyQ) region, the expansion of which causes spinocerebellar ataxia type-3 (SCA3). ATXN3 has multiple functions, such as regulating transcription or controlling genomic stability after DNA damage. Here we report the role of ATXN3 in chromatin organization during unperturbed conditions, in a catalytic-independent manner. The lack of ATXN3 leads to abnormalities in nuclear and nucleolar morphology, alters DNA replication timing and increases transcription. Additionally, indicators of more open chromatin, such as increased mobility of histone H1, changes in epigenetic marks and higher sensitivity to micrococcal nuclease digestion were detected in the absence of ATXN3. Interestingly, the effects observed in cells lacking ATXN3 are epistatic to the inhibition or lack of the histone deacetylase 3 (HDAC3), an interaction partner of ATXN3. The absence of ATXN3 decreases the recruitment of endogenous HDAC3 to the chromatin, as well as the HDAC3 nuclear/cytoplasm ratio after HDAC3 overexpression, suggesting that ATXN3 controls the subcellular localization of HDAC3. Importantly, the overexpression of a PolyQ-expanded version of ATXN3 behaves as a null mutant, altering DNA replication parameters, epigenetic marks and the subcellular distribution of HDAC3, giving new insights into the molecular basis of the disease.Spanish Agencia Estatal de Investigacion´ [PID2019- 109222RB-I00/AEI/10.13039/501100011033]; European Union Regional Funds (FEDER) (to R.F., V.A.J.S.); Agencia Canaria de Investigacion, ´ Innovacion´ y Sociedad de la Informacion´ [ProID2020010109]; FEDER (to R.F.); Agencia Canaria de Investigacion, ´ Innovacion´ y European Social Fund integrated Operational programme of the Canary Islands Sociedad de la Informacion´ de la Consejer´ıa de Econom´ıa, Industria, Comercio y Conocimiento and the 2014–2020, Eje 3 Tema Prioritario 74 (85%) (to E.H.C.); Medical Research Council Programme [MR/X006409/1 to K.R.]; Breast Cancer Now [2019DecPR1406 to K.R.]. Funding for open access charge: Agencia Canaria de Investigacion, ´ Innovacion´ y Sociedad de la Informacion´ [ProID2020010109]; European Union Regional Funds (FEDER)

Transplantation of Predegenerated Peripheral Nerves after Complete Spinal Cord Transection in Rats: Effect of Neural Precursor Cells and Pharmacological Treatment with the Sulfoglycolipid Tol-51

Following spinal cord injury (SCI), the regenerative capacity of the central nervous system (CNS) is severely limited by the failure of axonal regeneration. The regeneration of CNS axons has been shown to occur by grafting predegenerated peripheral nerves (PPNs) and to be promoted by the transplantation of neural precursor cells (NPCs). The introduction of a combinatorial treatment of PPNs and NPCs after SCI has to address the additional problem of glial scar formation, which prevents regenerating axons from leaving the implant and making functional connections. Previously, we discovered that the synthetic sulfoglycolipid Tol-51 inhibits astrogliosis. The objective was to evaluate axonal regeneration and locomotor function improvement after SCI in rats treated with a combination of PPN, NPC, and Tol-51. One month after SCI, the scar tissue was removed and replaced with segments of PPN or PPN+Tol-51; PPN+NPC+Tol-51. The transplantation of a PPN segment favors regenerative axonal growth; in combination with Tol-51 and NPC, 30% of the labeled descending corticospinal axons were able to grow through the PPN and penetrate the caudal spinal cord. The animals treated with PPN showed significantly better motor function. Our data demonstrate that PPN implants plus NPC and Tol-51 allow successful axonal regeneration in the CNS.Grant PID2021-128446NB funded by MICIU/AE/10.13039/501100011033 and ERDF7EU to JM. VBA received a postdoctoral fellowship, CVU 33557, from the Consejo Nacional de Ciencia, Humanidades y Técnología CONACHYT México. AAC received a scholarschip “Yo Investigo” from the Consejería de Educación Castilla-La Mancha, Spain.Peer reviewe

El reencuentro con la naturaleza: voces femeninas en el tiempo

Este texto contribuye al análisis científico de diferentes áreas del conocimiento la filosofía social, la educación para el cuidado del medio ambiente mediante la sustentabilidad que incide en diversas unidades de aprendizaje en Educación para la Salud y de la Maestria en Sociología de la SaludEl relato de las voces femeninas que se escuchan en el tiempo, narran las luchas por defender un ideal, con frecuencia en la organización de las mujeres que pugnan por estabilizar el equilibrio de la naturaleza, por medio de tácticas educativas que van recorriendo el bachillerato, la normal y la universidad

Effectiveness and costs of phototest in dementia and cognitive impairment screening

<p>Abstract</p> <p>Background</p> <p>To assess and compare the effectiveness and costs of Phototest, Mini Mental State Examination (MMSE), and Memory Impairment Screen (MIS) to screen for dementia (DEM) and cognitive impairment (CI).</p> <p>Methods</p> <p>A phase III study was conducted over one year in consecutive patients with suspicion of CI or DEM at four Primary Care (PC) centers. After undergoing all screening tests at the PC center, participants were extensively evaluated by researchers blinded to screening test results in a Cognitive-Behavioral Neurology Unit (CBNU). The gold standard diagnosis was established by consensus of expert neurologists. Effectiveness was assessed by the proportion of correct diagnoses (diagnostic accuracy [DA]) and by the kappa index of concordance between test results and gold standard diagnoses. Costs were based on public prices and hospital accounts.</p> <p>Results</p> <p>The study included 140 subjects (48 with DEM, 37 with CI without DEM, and 55 without CI). The MIS could not be applied to 23 illiterate subjects (16.4%). For DEM, the maximum effectiveness of the MMSE was obtained with different cutoff points as a function of educational level [k = 0.31 (95% Confidence interval [95%CI], 0.19-0.43), DA = 0.60 (95%CI, 0.52-0.68)], and that of the MIS with a cutoff of 3/4 [k = 0.63 (95%CI, 0.48-0.78), DA = 0.83 (95%CI, 0.80-0.92)]. Effectiveness of the Phototest [k = 0.71 (95%CI, 0.59-0.83), DA = 0.87 (95%CI, 0.80-0.92)] was similar to that of the MIS and higher than that of the MMSE. Costs were higher with MMSE (275.9 ± 193.3€ [mean ± sd euros]) than with Phototest (208.2 ± 196.8€) or MIS (201.3 ± 193.4€), whose costs did not significantly differ. For CI, the effectiveness did not significantly differ between MIS [k = 0.59 (95%CI, 0.45-0.74), DA = 0.79 (95%CI, 0.64-0.97)] and Phototest [k = 0.58 (95%CI, 0.45-0.74), DA = 0.78 (95%CI, 0.64-0.95)] and was lowest for the MMSE [k = 0.27 (95%CI, 0.09-0.45), DA = 0.69 (95%CI, 0.56-0.84)]. Costs were higher for MMSE (393.4 ± 121.8€) than for Phototest (287.0 ± 197.4€) or MIS (300.1 ± 165.6€), whose costs did not significantly differ.</p> <p>Conclusion</p> <p>MMSE is not an effective instrument in our setting. For both DEM and CI, the Phototest and MIS are more effective and less costly, with no difference between them. However, MIS could not be applied to the appreciable percentage of our population who were illiterate.</p

Risk of suicide attempt repetition after an index attempt: A systematic review and meta-analysis

© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).[Objectives] To estimate the risk of suicide attempt repetition among individuals with an index attempt. It also aims to study the role of risk factors and prevention programme in repetition.[Methods] This systematic review and meta-analysis was conducted in keeping with the PRISMA 2020 guidelines. Studies on attempt repetition (both cohort studies and intervention studies) were searched from inception to 2022.[Results] A total of 110 studies comprising 248,829 attempters was reviewed. The overall repetition rate was 0.20 (0.17, 0.22). Repetition risk linearly increased over time. A higher risk of attempt repetition was associated with female sex and index attempts in which self-cutting methods were used. Moreover, a mental disorder diagnosis was associated with an increasing repetition risk (OR = 2.02, p < .01). The delivery of a preventive programme reduced the repetition risk, OR = 0.76, p < .05; however, this effect was significant for psychotherapy interventions, OR = 0.38, p < .01.[Conclusion] One in five suicide attempters will engage in a new suicide attempt. An elevated repetition risk is associated with being female, more severe index methods and psychiatric disorder diagnosis. Preventive programmes, particularly psychotherapy, may contribute to reducing repetition risk and eventually save lives.This study was supported by the Instituto de Salud Carlos III-FIS research grants (PI16/00187, PI19/00236, PI19/00569, PI19/00685, PI19/00941, PI19/00954, PI19/01027, PI19/01256, PI19/01484, PI20/00229), co-funded by the European Regional Development Fund (ERDF) “A Way to Build Europe”; the Government of the Principality of Asturias (grant ref.: PCTI-2018-2022 IDI/2018/235); Secretaria d'Universitats i Recerca from the Departament d'Economia i Coneixement (ref.: 2017SGR1365 and 2017SGR134), and Generalitat de Catalunya (Government of Catalonia), CERCA Programme.Peer reviewe

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6&nbsp;years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P &lt; 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100&nbsp;years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data