Asociación de funcionalidad y salud familiar con COVID-19 en familias de la ciudad de Veracruz, México

RESUMEN Introducción. La salud familiar involucra al individuo, la familia y la sociedad en interacción reciproca por lo que la pandemia de COVID-19 puede constituir un factor que altere su integración y cumplimiento de funciones. Objetivo. Determinar la asociación de COVID-19 con alteraciones de la salud y funcionalidad familiar. Metodología. Encuesta transversal analítica en derechohabientes del Hospital Naval de Especialidades de Veracruz. Se aplicó cuestionario de factores sociodemográficos y clínicos, instrumento de autopercepción de salud familiar y APGAR familiar. Se efectuó inferencia estadística y se calcularon razón de momios e intervalos de confianza de 95%. Resultados. Se incluyeron 382 individuos; 5 (1.3%) eran familias extensas, 35 (9.2%) monoparentales, 297 (77.7%) nucleares, 18 (4.7%) nucleares ampliadas y 27 (7.1%) reconstituidas. Enfermaron de COVID-19 280 (73.3%) pacientes de los cuáles en 13 (4.6%) se estableció mala salud familiar y 82 (29.3%) disfunción leve o severa comparado con 6 (5.9%) y 26 (25.5%) de las familias sin COVID-19, (p > 0.05). Conclusiones. Tres cuartas partes de las familias encuestadas presentaron casos de COVID-19; sin embargo, la frecuencia de alteraciones de la salud y funcionalidad familiar fue baja durante pandemia de COVID-19. Familias con la enfermedad presentaron mayor alteración de clima, integración, funcionalidad y afrontamiento

Knigth's Move in the Periodic Table, From Copper to Platinum, Novel Antitumor Mixed Chelate Copper Compounds, Casiopeinas, Evaluated by an in Vitro Human and Murine Cancer Cell Line Panel

We synthesized a novel anticancer agents based on mixed chelate copper (II) complexes, named Casiopeínas® has of general formula [Cu(N-N)(N-O)H2O]NO3 (where, N-N = diimines as 1,10- phenanthroline, 2,2-bipyridine, or substituted and N-O=aminoeidate or [Cu(N-N)(O-O)H2O]NO3 (where NN= diimines as 10-phenanthroline, 2,2-bipyridine or substituted Casiopeínas I, II, IV, V, VI, VII VIII and O-O=acetylacetonate, salicylaldehidate Casiopínas III). We evaluated the in vitro antitumor activity using a human cancer cell panel and some nurine cancer cells. Eleven Casiopeinas are evaluated in order to acquire some structure-activity correlations and some monodentated Casiopeinäs analogues; cisplatinum was used as control drug. The 50% growth inhibition observed is, in all cases reach with concentrations of Casiopeina's 10 or 100 times lower than cisplatinum. In a previous work we reported the induction of apoptosis by Casiopeina II. The results indicate that Casiopeinass are a promising new anticancer drug candidates to be developed further toward clinical trials

The Impact Of Rituximab Infusion Protocol On The Long-term Outcome In Anti-musk Myasthenia Gravis

Objective: To evaluate whether the clinical benefit and relapse rates in anti-muscle-specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed. Methods: This retrospective multicentre study in patients with MuSK MG compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan-Meier methods and survival analyses were undertaken using Cox proportional-hazards models. Results: Twenty-five patients were included: 11 treated with protocol 4 + 2 (375 mg/m(2)/4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m(2)/4 weeks). Mean follow-up was 5.0 years (SD 3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 (SD 1.5), 1.1 (SD 0.4), and 2.5 (SD 1.4) years, respectively. Based on Kaplan-Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log-rank test P = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 (HR 112.8, 95% CI, 5.7-2250.4, P = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 (HR 9.2, 95% CI 0.9-91.8, P = 0.059). InterpretationThis study provides class IV evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with MuSK MG

Distribution and genotype-phenotype correlation of GDAP1 mutations in Spain

Mutations in the GDAP1 gene can cause Charcot-Marie-Tooth disease. These mutations are quite rare in most Western countries but not so in certain regions of Spain or other Mediterranean countries. This cross-sectional retrospective multicenter study analyzed the clinical and genetic characteristics of patients with GDAP1 mutations across Spain. 99 patients were identified, which were distributed across most of Spain, but especially in the Northwest and Mediterranean regions. The most common genotypes were p.R120W (in 81% of patients with autosomal dominant inheritance) and p.Q163X (in 73% of autosomal recessive patients). Patients with recessively inherited mutations had a more severe phenotype, and certain clinical features, like dysphonia or respiratory dysfunction, were exclusively detected in this group. Dominantly inherited mutations had prominent clinical variability regarding severity, including 29% of patients who were asymptomatic. There were minor clinical differences between patients harboring specific mutations but not when grouped according to localization or type of mutation. This is the largest clinical series to date of patients with GDAP1 mutations, and it contributes to define the genetic distribution and genotype-phenotype correlation in this rare form of CMT

Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia

<p>Abstract</p> <p>Background</p> <p>Hereditary Spastic Paraplegias (HSP) are characterized by progressive spasticity and weakness of the lower limbs. At least 45 loci have been identified in families with autosomal dominant (AD), autosomal recessive (AR), or X-linked hereditary patterns. Mutations in the <it>SPAST </it>(<it>SPG4</it>) and <it>ATL1 </it>(<it>SPG3A</it>) genes would account for about 50% of the ADHSP cases.</p> <p>Methods</p> <p>We defined the <it>SPAST </it>and <it>ATL1 </it>mutational spectrum in a total of 370 unrelated HSP index cases from Spain (83% with a pure phenotype).</p> <p>Results</p> <p>We found 50 <it>SPAST </it>mutations (including two large deletions) in 54 patients and 7 <it>ATL1 </it>mutations in 11 patients. A total of 33 of the <it>SPAST </it>and 3 of the <it>ATL1 </it>were new mutations. A total of 141 (31%) were familial cases, and we found a higher frequency of mutation carriers among these compared to apparently sporadic cases (38% vs. 5%). Five of the <it>SPAST </it>mutations were predicted to affect the pre-mRNA splicing, and in 4 of them we demonstrated this effect at the cDNA level. In addition to large deletions, splicing, frameshifting, and missense mutations, we also found a nucleotide change in the stop codon that would result in a larger ORF.</p> <p>Conclusions</p> <p>In a large cohort of Spanish patients with spastic paraplegia, <it>SPAST </it>and <it>ATL1 </it>mutations were found in 15% of the cases. These mutations were more frequent in familial cases (compared to sporadic), and were associated with heterogeneous clinical manifestations.</p

A POGLUT1 mutation causes a muscular dystrophy with reduced Notch signaling and satellite cell loss

Skeletal muscle regeneration by muscle satellite cells is a physiological mechanism activated upon muscle damage and regulated by Notch signaling. In a family with autosomal recessive limb-girdle muscular dystrophy, we identified a missense mutation in 1 (protein O -glucosyltransferase 1), an enzyme involved in Notch posttranslational modification and function. In vitro and in vivo experiments demonstrated that the mutation reduces O -glucosyltransferase activity on Notch and impairs muscle development. Muscles from patients revealed decreased Notch signaling, dramatic reduction in satellite cell pool and a muscle-specific α-dystroglycan hypoglycosylation not present in patients' fibroblasts. Primary myoblasts from patients showed slow proliferation, facilitated differentiation, and a decreased pool of quiescent 7 + cells. A robust rescue of the myogenesis was demonstrated by increasing Notch signaling. None of these alterations were found in muscles from secondary dystroglycanopathy patients. These data suggest that a key pathomechanism for this novel form of muscular dystrophy is Notch-dependent loss of satellite cells

Efficacy of a church-based lifestyle intervention programme to control high normal blood pressure and/or high normal blood glucose in church members: a randomized controlled trial in Pretoria, South Africa

BACKGROUND: In persons 15 years and above in South Africa the prevalence of pre-diabetes and diabetes has been estimated at 9.1% and 9.6%, respectively, and the prevalence of systolic prehypertension and hypertension, 38.2% and 24.6%, respectively. Elevated blood glucose and elevated blood pressure are prototype of preventable chronic cardiovascular disease risk factors. Lifestyle interventions have been shown to control high normal blood pressure and/or high normal blood glucose. METHODS/DESIGN: This study proposes to evaluate the efficacy of a community (church)-based lifestyle intervention programme to control high normal blood pressure and/or high normal blood glucose in church members in a randomized controlled trial in Gauteng, South Africa. The objectives are to: (1) measure non-communicable diseases profile, including hypertension and diabetes, health behaviours, weight management and psychological distress of church members; (2) measure the reduction of blood glucose and blood pressure levels after the intervention; (3) prevent the development of impaired glucose tolerance; (4) compare health behaviours, weight management and psychological distress, blood glucose and blood pressure levels between intervention and control groups, and within group during 6, 12, 24 and 36 months during and post intervention. The study will use a group-randomized design, recruiting 300 church members from 12 churches. Churches will be randomly assigned to experimental and control conditions. DISCUSSION: Lifestyle interventions may prevent from the development of high blood pressure and/or diabetes. The findings will impact public health and will enable the health ministry to formulate policy related to lifestyle interventions to control blood pressure and glucose. TRIAL REGISTRATION NUMBER: PACTR20110500029715

Estudio prospectivo del síndrome de debilidad muscular aguda en la enfermedad crítica

FUNDAMENTO: Durante la enfermedad crítica puede aparecer un síndrome de debilidad muscular causado por una degeneración axonal de los nervios periféricos, un bloqueo neuromuscular farmacológico o una miopatía. OBJETIVOS. 1)Determinar la incidencia de debilidad muscular en los enfermos críticos. 2) Detectar que factores están relacionados con el desarrollo de la misma. 3)Estudiar la influencia del estado de gravedad en la función neuromuscular.4)Delimitar el síndrome de debilidad muscular en sus características clínicas, neurofisiológicas e histopatologías. PACIENTES Y MÉTODO: Estudio prospectivo y consecutivo de una serie de pacientes con puntuación en la escala APACHE II de 10 o más el día del ingreso en la UCI y 6 días después. Se estudiaron la exploración neurológica, examen neurofisiológico de nervio y músculo y determinaciones analíticas en 3 momentos del ingreso, y estudio histopatológico de nervio y músculo. RESULTADOS: De los 67 enfermos estudiados 33(49,25%) presentaron debilidad muscular. La incidencia aumentó al 66,6% en los enfermos con fracaso en la función de 3 o más órganos o sistemas. En 15 enfermos (22,4%) se detectó una mononeuropatía peroneal. En el 91% de los enfermos las alteraciones aparecieron antes del décimo día de ingreso. Los enfermos con debilidad muscular tuvieron una puntuación mayor en la escala APACHE II, mayor proporción de fallo multiorgánico, de dependencia de la ventilación mecánica y de fracaso en el destete y mayor mortalidad. Dos biopsias de nervio mostraron degeneración axonal y 4 fueron normales. En las biopsias musculares encontramos atrofia neurógena en 3 pacientes y signos de miopatía en 8, en 2 pacientes coincidieron ambos patrones. Los enfermos con miopatía y los enfermos con neuropatía no se diferenciaron en sus características clínicas ni neurofisiológicas. CONCLUSIONES: la debilidad muscular en la enfermedad crítica aparece de forma precoz, afecta a la mi

Junctophilin-1 is a modifier gene of GDAP1-related Charcot–Marie–Tooth disease

[EN] Mutations in the GDAP1 gene cause different forms of Charcot-Marie-Tooth (CMT) disease, and the primary clinical expression of this disease is markedly variable in the dominant inheritance form (CMT type 2K; CMT2K), in which carriers of the GDAP1 p.R120W mutation can display a wide range of clinical severity. We investigated the JPH1 gene as a genetic modifier of clinical expression variability because junctophilin-1 (JPH1) is a good positional and functional candidate. We demonstrated that the JPH1-GDAP1 cluster forms a paralogon and is conserved in vertebrates. Moreover, both proteins play a role in Ca(2+) homeostasis, and we demonstrated that JPH1 is able to restore the store-operated Ca(2+) entry (SOCE) activity in GDAP1-silenced cells. After the mutational screening of JPH1 in a series of 24 CMT2K subjects who harbour the GDAP1 p.R120W mutation, we characterized the JPH1 p.R213P mutation in one patient with a more severe clinical picture. JPH1(p.R213P) cannot rescue the SOCE response in GDAP1-silenced cells. We observed that JPH1 colocalizes with STIM1, which is the activator of SOCE, in endoplasmic reticulum-plasma membrane puncta structures during Ca(2+) release in a GDAP1-dependent manner. However, when GDAP1(p.R120W) is expressed, JPH1 seems to be retained in mitochondria. We also established that the combination of GDAP1(p.R120W) and JPH1(p.R213P) dramatically reduces SOCE activity, mimicking the effect observed in GDAP1 knock-down cells. In summary, we conclude that JPH1 and GDAP1 share a common pathway and depend on each other; therefore, JPH1 can contribute to the phenotypical consequences of GDAP1 mutations.This work was supported by the IRDiRC and funded by the Instituto de Salud Carlos III (ISCIII)-Subdireccion General de Evaluacion y Fomento de la Investigacion within the framework of the National R+D+I Plan (Grants no. IR11/TREAT-CMT and PI12/00453), cofunded with FEDER funds, and Ministry of Economy and Competitiveness (Grant no. SAF2012-32425). C.E. has a 'Miguel Servet' contract funded by the ISCIII and Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER) (Grant no. CP08/00053). E.C. has a FPU grant funded by the Ministerio de Educacion (Grant no. AP2009-0642). The CIBERER is an initiative from the ISCIII.Pla-Martín, D.; Calpena-Corpas, E.; Lupo, V.; Márquez, C.; Rivas, E.; Sivera, R.; Sevilla, T.... (2015). Junctophilin-1 is a modifier gene of GDAP1-related Charcot-Marie-Tooth disease. Human Molecular Genetics. 24(1):213-229. https://doi.org/10.1093/hmg/ddu44021322924