From single to combinatorial therapies in spinal cord injuries for structural and functional restoration.

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities; the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Traumatic Human Spinal Cord Injury: Are Single Treatments Enough to Solve the Problem?

Traumatic spinal cord injury (SCI) results in partial or complete motor deficits, such as paraplegia, tetraplegia, and sphincter control, as well as sensory disturbances and autonomic dysregulation such as arterial hypotension, lack of sweating, and alterations in skin lability. All this has a strong psychological impact on the affected person and his/her family, as well as costs to healthcare institutions with an economic burden in the short, medium, and long terms. Despite at least forty years of experimental animal studies and several clinical trials with different therapeutic strategies, effective therapy is not universally accepted. Most of the published works on acute and chronic injury use a single treatment, such as medication, trophic factor, transplant of a cell type, and so on, to block some secondary injury mechanisms or promote some mechanisms of structural/functional restoration. However, despite significant results in experimental models, the outcome is a moderate improvement in muscle strength, sensation, or eventually in sphincter control, which has been considered non-significant in human clinical trials. Here we present a brief compilation of successful individual treatments that have been applied to secondary mechanisms of action. These studies show limited neuroprotective or neurorestorative approaches in animal models and clinical trials. Thus, the few benefits achieved so far represent a rationale to further explore other strategies that seek better structural and functional restoration of the injured spinal cord.

Study of genetic variants and their clinical significance in Mexican pediatric patients with epilepsy.

BACKGROUND: The use of novel and accurate techniques to identify genetic variants (with or without a record in the National Center for Biotechnology Information (NCBI) database) improves diagnosis, prognosis, and therapeutics for patients with epilepsy, especially in populations for whom such techniques exist. The aim of this study was to find a genetic profile in Mexican pediatric epilepsy patients by focusing on ten genes associated with drug-resistant epilepsy (DRE). METHODS: This was a prospective, analytical, cross-sectional study of pediatric patients with epilepsy. Informed consent was granted by the patients' guardians or parents. Genomic DNA from the patients was sequenced using next-generation sequencing (NGS). For statistical analysis, Fisher's exact, Chi-square or Mann-Whitney U, and OR (95% CI) tests were performed, with significance values of p < 0.05. RESULTS: Fifty-five patients met the inclusion criteria (female 58.2%, ages 1-16 years); 32 patients had controlled epilepsy (CTR), and 23 had DRE. Four hundred twenty-two genetic variants were identified (71.3% with a known SNP registered in the NCBI database). A dominant genetic profile consisting of four haplotypes of the SCN1A, CYP2C9, and CYP2C19 genes was identified in most of the patients studied. When comparing the results between patients with DRE and CTR, the prevalence of polymorphisms in the SCN1A (rs10497275, rs10198801, and rs67636132), CYP2D6 (rs1065852), and CYP3A4 (rs2242480) genes showed statistical significance (p = 0.021). Finally, the number of missense genetic variants in patients in the nonstructural subgroup was significantly higher in DRE than in CTR (1 [0-2] vs. 3 [2-4]; p = 0.014). CONCLUSIONS: The Mexican pediatric epilepsy patients included in this cohort presented a characteristic genetic profile infrequent in the Mexican population. SNP rs1065852 (CYP2D6*10) is associated with DRE, especially with nonstructural damage. The presence of three genetic alterations affecting the CYP2B6, CYP2C9, and CYP2D6 cytochrome genes is associated with nonstructural DRE.

Predict the incidence of Guillain Barré Syndrome and arbovirus infection in Mexico, 2014-2019.

The Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) virus infections have been linked to Guillain-Barré syndrome (GBS). GBS has an estimated lethality of 4% to 8%, even with effective treatment. Mexico is considered a hyperendemic country for DENV due to the circulation of four serotypes, and the ZIKV and CHIKV viruses have also been circulating in the country. The objective of this study was to predict the number of GBS cases in relation to the cumulative incidence of ZIKV / DENV / CHIKV in Mexico from 2014 to 2019. A six-year time series ecological study was carried out from GBS cases registered in the Acute Flaccid Paralysis (AFP) Epidemiological Surveillance System (ESS), and DENV, ZIKV and CHIKV estimated cases from cases registered in the epidemiological vector-borne diseases surveillance system. The results shows that the incidence of GBS in Mexico is positively correlated with DENV and ZIKV. For every 1,000 estimated DENV cases, 1.45 GBS cases occurred on average, and for every 1,000 estimated ZIKV cases, 1.93 GBS cases occurred on average. A negative correlation between GBS and CHIKV estimated cases was found. The increase in the incidence of GBS cases in Mexico can be predicted by observing DENV and ZIKV cases through the epidemiological surveillance systems. These results can be useful in public health by providing the opportunity to improve capacities for the prevention of arbovirus diseases and for the timely procurement of supplies for the treatment of GBS.

[Fingerprints: origin, uses and challenges in the face of its verification failure]. / Huellas dactilares: origen, usos y desafíos que genera la incapacidad para su registro.

Considering that fingerprints are impressions of the epidermal ridges of the fingers with a unique, unrepeatable, and permanent pattern, they are the basis of the biometric identification method most used today. Among its various uses stand out identification for multiple activities such as authentication to access work and cell phones, operation of bank accounts, criminal investigations, etc. The absence or deterioration of the epidermal ridges, called adermatoglyphia, prevents identification by finger biometrics. Adermatoglyphia originates from multiple causes, including several skin diseases, traumatic injuries of the fingers, denervation, aging, chemotherapy, among others. The origin, uses, and systems for fingerprints verification are briefly addressed here. The main objective is to emphasize the existence of people with fingerprint verification failure, a relevant condition due to the potential risk of discrimination, especially when fingerprint verification is mandatory.

Considerando que las huellas dactilares son impresiones de las crestas epidérmicas de los dedos con un patrón único, irrepetible y permanente, estas son la base del método biométrico más empleado en la actualidad. Entre sus diversos usos destaca la identificación para múltiples actividades como acceder al trabajo o a teléfonos celulares, la operación de cuentas bancarias, las investigaciones criminales, etcétera. La ausencia o deterioro de las crestas epidérmicas, denominada adermatoglifia, impide la identificación por biometría dactilar. La adermatoglifia se origina por múltiples causas, incluyendo las enfermedades dermatológicas, lesiones traumáticas de los dedos, denervación, envejecimiento, quimioterapia, entre otras. Abordamos brevemente el origen, usos y sistemas para el registro de las huellas dactilares. El objetivo principal es enfatizar la existencia de personas con incapacidad para registrar sus huellas, una condición relevante por el riesgo potencial de discriminación, especialmente cuando el registro de las huellas es obligatorio.

Huellas dactilares: origen, usos y desafíos que genera la incapacidad para su registro / Fingerprints: origin, uses and challenges in the face of its verification failure

Considerando que las huellas dactilares son impresiones de las crestas epidérmicas de los dedos con un patrón único, irrepetible y permanente, estas son la base del método biométrico más empleado en la actualidad. Entre sus diversos usos destaca la identificación para múltiples actividades como acceder al trabajo o a teléfonos celulares, la operación de cuentas bancarias, las investigaciones criminales, etcétera. La ausencia o deterioro de las crestas epidérmicas, denominada adermatoglifia, impide la identificación por biometría dactilar. La adermatoglifia se origina por múltiples causas, incluyendo las enfermedades dermatológicas, lesiones traumáticas de los dedos, denervación, envejecimiento, quimioterapia, entre otras. Abordamos brevemente el origen, usos y sistemas para el registro de las huellas dactilares. El objetivo principal es enfatizar la existencia de personas con incapacidad para registrar sus huellas, una condición relevante por el riesgo potencial de discriminación, especialmente cuando el registro de las huellas es obligatorio.

Considering that fingerprints are impressions of the epidermal ridges of the fingers with a unique, unrepeatable, and permanent pattern, they are the basis of the biometric identification method most used today. Among its various uses stand out identification for multiple activities such as authentication to access work and cell phones, operation of bank accounts, criminal investigations, etc. The absence or deterioration of the epidermal ridges, called adermatoglyphia, prevents identification by finger biometrics. Adermatoglyphia originates from multiple causes, including several skin diseases, traumatic injuries of the fingers, denervation, aging, chemotherapy, among others. The origin, uses, and systems for fingerprints verification are briefly addressed here. The main objective is to emphasize the existence of people with fingerprint verification failure, a relevant condition due to the potential risk of discrimination, especially when fingerprint verification is mandatory.

Double-task exercise programmes to strengthen cognitive and vascular health in older adults at risk of cognitive decline: protocol for a randomised clinical trial.

INTRODUCTION: Cognitive and physical declines are frequent causes of disability among older adults (OAs) in Mexico that imposes significant burden on the health system and OAs' families. Programmes to prevent or delay OAs' cognitive and physical decline are scarce. METHODS AND ANALYSIS: A double-blind randomised clinical trial will be conducted. The study will aim to evaluate two 24-week double-task (aerobic and cognitive) square-stepping exercise programmes for OAs at risk of cognitive decline-one programme with and another without caregiver participation-and to compare these with an aerobic-balance-stretching exercise programme (control group). 300 OAs (100 per group) affiliated with the Mexican Institute of Social Security (IMSS) between 60 and 65 years of age with self-reported cognitive concerns will participate. They will be stratified by education level and randomly allocated to the groups. The intervention will last 24 weeks, and the effect of each programme will be evaluated 12, 24 and 52 weeks after the intervention. Participants' demographic and clinical characteristics will be collected at baseline. The outcomes will include: (1) general cognitive function; (2) specific cognitive functions; (3) dual-task gait; (4) blood pressure; (5) carotid intima-media thickness; (6) OAs' health-related quality of life; and (7) caregiver burden. The effects of the interventions on each outcome variable will be examined using a repeated-measures analysis of variance (ANOVA), with study groups as the between-subjects variable and time as the within-subject variable. ETHICS AND DISSEMINATION: The study was approved by the IMSS Ethics and Research Committees (registration number: 2018-785-095). All participants will sign a consent form prior to their participation. The study results will be disseminated to the IMSS authorities, healthcare providers and the research community. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04068376).

Role of SARS-CoV-2 neurotropism and neuroinvasion in COVID-19 patients disease severity.

The disease caused by the new SARS-CoV-2 coronavirus (COVID-19) spread rapidly from China to the entire world. Approximately one third of SARS-CoV-2-infected patients have neurological disorders, especially those classified as severe cases and that require mechanical ventilation. On the other hand, almost nine out of 10 patients admitted to an Intensive Care Unit could not breathe spontaneously, thus requiring invasive and non-invasive ventilatory support. So far, whether early neurological disorders such as hyposmia or anosmia, dysgeusia or ageusia, headache and vertigo are significant in the progression to the severe form of the disease or whether they are related to entry to the central nervous system via peripheral nerves has not been determined. Considering the great similarity between SARS-CoV and SARS-CoV-2, and that the severity of the condition that leads to death cannot be explained solely by lung involvement, it is important to determine whether SARS-CoV-2 potential invasion to the central nervous system is partially responsible for the severe respiratory component observed in patients with COVID-19.

La enfermedad (COVID-19) producida por el nuevo coronavirus SARS-CoV-2 se extendió rápidamente desde China a todo el mundo. Aproximadamente una tercera parte de los pacientes infectados de SARS-CoV-2 presenta alteraciones neurológicas, con mayor frecuencia los clasificados como graves que requirieron ventilación mecánica. Por otro lado, casi nueve de cada 10 pacientes admitidos en una unidad de cuidados intensivos no podían respirar espontáneamente, por lo que ameritaron apoyo ventilatorio invasivo y no invasivo. Hasta el momento no se ha determinado si las alteraciones neurológicas tempranas como la hiposmia o anosmia, disgeusia o ageusia, cefalea y vértigo son significativas en la progresión a la forma grave de la enfermedad y se relacionan con la entrada al sistema nervioso central a través de los nervios periféricos. Considerando la gran similitud entre SARS-CoV y SARS-CoV-2 y que la severidad del cuadro que conduce a la muerte no puede ser explicado únicamente por la afección pulmonar, es importante determinar si la invasión potencial del SARS-CoV-2 al sistema nervioso central es parcialmente responsable del componente respiratorio severo que presentan los pacientes con COVID-19.

Role of SARS-CoV-2 neurotropism and neuroinvasion in COVID-19 patients disease severity / Papel del neurotropismo y neuroinvasión de SARS-CoV-2 en la gravedad de los pacientes con COVID-19

Abstract The disease caused by the new SARS-CoV-2 coronavirus (COVID-19) spread rapidly from China to the entire world. Approximately one third of SARS-CoV-2-infected patients have neurological disorders, especially those classified as severe cases and that require mechanical ventilation. On the other hand, almost nine out of 10 patients admitted to an Intensive Care Unit could not breathe spontaneously, thus requiring invasive and non-invasive ventilatory support. So far, whether early neurological disorders such as hyposmia or anosmia, dysgeusia or ageusia, headache and vertigo are significant in the progression to the severe form of the disease or whether they are related to entry to the central nervous system via peripheral nerves has not been determined. Considering the great similarity between SARS-CoV and SARS-CoV-2, and that the severity of the condition that leads to death cannot be explained solely by lung involvement, it is important to determine whether SARS-CoV-2 potential invasion to the central nervous system is partially responsible for the severe respiratory component observed in patients with COVID-19.

Resumen La enfermedad (COVID-19) producida por el nuevo coronavirus SARS-CoV-2 se extendió rápidamente desde China a todo el mundo. Aproximadamente una tercera parte de los pacientes infectados de SARS-CoV-2 presenta alteraciones neurológicas, con mayor frecuencia los clasificados como graves que requirieron ventilación mecánica. Por otro lado, casi nueve de cada 10 pacientes admitidos en una unidad de cuidados intensivos no podían respirar espontáneamente, por lo que ameritaron apoyo ventilatorio invasivo y no invasivo. Hasta el momento no se ha determinado si las alteraciones neurológicas tempranas como la hiposmia o anosmia, disgeusia o ageusia, cefalea y vértigo son significativas en la progresión a la forma grave de la enfermedad y se relacionan con la entrada al sistema nervioso central a través de los nervios periféricos. Considerando la gran similitud entre SARS-CoV y SARS-CoV-2 y que la severidad del cuadro que conduce a la muerte no puede ser explicado únicamente por la afección pulmonar, es importante determinar si la invasión potencial del SARS-CoV-2 al sistema nervioso central es parcialmente responsable del componente respiratorio severo que presentan los pacientes con COVID-19.

Soluble Intercellular Adhesion Molecule-1 (sICAM-1) as a Biomarker of Vascular Cognitive Impairment in Older Adults.

BACKGROUND: Endothelial dysfunction and subsequent inflammation contribute to the development of vascular cognitive impairment (VCI). Soluble intercellular adhesion molecule-1 (sICAM-1) is upregulated in endothelial dysfunction and promotes an inflammatory response; however, the relationship between sICAM-1 and VCI remains equivocal. OBJECTIVE: To determine whether sICAM-1 contributes to the prediction of VCI. METHODS: Community-dwelling older adults (n = 172) from the "Cohort of Obesity, Sarcopenia and Frailty of Older Mexican Adults" (COSFOMA) study were identified as VCI or controls using standard neuropsychological evaluations and neuroimaging. sICAM-1 was quantified using ELISA, and multivariate logistic regression determined the association between sICAM-1 and VCI. RESULTS: A total of 31 VCI cases were identified. sICAM-1 was higher in VCI (VCI: 450.7 [241.6] ng/mL vs. controls: 296.9 [140.9] ng/mL). sICAM-1 concentrations above the 90th percentile (464.1 ng/mL) were associated with VCI group membership in all models (OR: 6.9, 95% CI: 1.1-42.2). The final saturated model explained 64% of the variance in VCI group membership. CONCLUSION: High concentrations of sICAM-1 are independently associated with VCI group membership. Efforts to further characterize the relationship between indices of endothelial dysfunction and pathological changes to the aging brain should be further pursued.

Perfil tromboelastométrico y coagulopatía aguda del paciente politraumatizado: implicaciones clínicas y pronósticas / Thromboelastometric Profile and Acute Coagulopathy of the Polytraumatized Patient: Clinical and Prognostic Implications

Introducción: El 25-35% de los pacientes politraumatizados presentan profundas alteraciones de la coagulación a su llegada al hospital (coagulopatía aguda traumática [CAT]). Los test viscoelásticos (ROTEM®) valoran rápidamente la capacidad hemostática y detectan precozmente la CAT. Los objetivos de este estudio son describir el tromboelastograma inicial de estos enfermos y determinar la prevalencia de CAT según unos perfiles tromboelastográficos predefinidos. Métodos: Estudio unicéntrico, observacional y prospectivo en pacientes politraumatizados. Se realizó analítica, prueba tromboelastográfica (ROTEM®) y se registraron datos prehospitalarios y hospitalarios, transfusiones, intervenciones quirúrgicas/arteriografía iniciales, paradas cardiorrespiratorias y fallecimientos. Los pacientes fueron clasificados en grupos según su ROTEM® inicial: «normal», «hipercoagulabilidad», «hipocoagulabilidad», «hipocoagulabilidad + hiperfibrinólisis» e «hiperfibrinólisis aislada». Resultados: Se analizaron 123 pacientes. En 32 casos (26%) se objetivó CAT: 15 pacientes presentaron hipocoagulabilidad, 9 hiperfibrinólisis aislada y 8 hipocoagulabilidad +hiperfibrinólisis. El grupo con CAT, respecto al grupo «normal», presentó mayor ISS (23 vs. 16; p < 0,01), mayor transfusión de hemoderivados (2,5 vs. 0; p = 0,001), más episodios de PCR (19 vs. 1%, p < 0,01) y mayor mortalidad (34 vs. 5%, p < 0,01). El subgrupo con hipocoagulabilidad +hiperfibrinólisis, respecto a los grupos con hipocoagulabilidad o hiperfibrinólisis aislada, presentó mayor ISS (41 vs. 25 vs. 15, p < 0,01), mayor necesidad de arteriografía (62% vs. 13% vs. 0%, p < 0,01) y mortalidad superior (75% vs. 33% vs. 0%, p = 0,05). Conclusiones: El 26% de los enfermos politraumatizados presenta coagulopatía precoz evaluada mediante tromboelastografía, asociada a mayor consumo de hemoderivados y menor supervivencia. El perfil combinado de «hipocoagulabilidad +hiperfibrinólisis» se asocia a mayor gravedad y necesidades superiores de hemoderivados y arteriografía (AU)

Introduction: About 25-35% of polytraumatized patients have a profound alteration of hemostasis on arrival at the hospital (acute traumatic coagulopathy [CAT]). Viscoelastic tests (ROTEM®) measure the hemostatic capacity and provide an early detection of CAT. The objectives of this study are to describe the initial thromboelastogram of these patients and to determine the prevalence of CAT according to predefined thromboelastographic profiles. Methods: Single-center, observational, prospective study in polytraumatic patients. Initial blood nd thromboelastographic test (ROTEM®) were made, and pre-hospital, hospital, transfusion, initial surgical/angiographic interventions, cardiac arrest and mortality data were collected. ROTEM®-based, patients were classified as: normal, hypercoagulable, hypocoagulable, hipocoagulable + hyperfibrinolytic and isolated hyperfibrinolysis. Results: One hundred and twenty-three patients were analyzed. 32 cases (26%) with CAT: 15 patients with hypocoagulability, 9 with hyperfibrinolysis alone and 8 with hypocoagulability + hyperfibrinolysis. The CAT group, related to the normal group, presented higher ISS (23 vs. 16, P < .01), higher blood products transfusion (2.5 vs. 0; P = .001), more cardiac arrest (19 vs. 1%, P < .01), and higher mortality (34 vs. 5%, P < .01). The subgroup with hypocoagulability/hyperfibrinolysis, related to the groups with hypocoagulability or hyperfibrinolysis alone, presented a higher ISS (41 vs. 25 vs. 15, P < .01), higher angiographic procedures (62% vs. 13% vs. 0%, P < .01) and higher mortality (75% vs. 33% vs. 0%, P=.05). Conclusions: Twenty-six percent of the polytrauma patients presented early coagulopathy assessed by thromboelastography. It is associated with higher consumption of blood products and lower survival. The presence of hypocoagulability + hyperfibrinolysis is associated with greater severity and a higher requirement of blood products (AU)

Thromboelastometric Profile and Acute Coagulopathy of the Polytraumatized Patient: Clinical and Prognostic Implications. / Perfil tromboelastométrico y coagulopatía aguda del paciente politraumatizado: implicaciones clínicas y pronósticas.

INTRODUCTION: About 25-35% of polytraumatized patients have a profound alteration of hemostasis on arrival at the hospital (acute traumatic coagulopathy [CAT]). Viscoelastic tests (ROTEM®) measure the hemostatic capacity and provide an early detection of CAT. The objectives of this study are to describe the initial thromboelastogram of these patients and to determine the prevalence of CAT according to predefined thromboelastographic profiles. METHODS: Single-center, observational, prospective study in polytraumatic patients. Initial blood and thromboelastographic test (ROTEM®) were made, and pre-hospital, hospital, transfusion, initial surgical/angiographic interventions, cardiac arrest and mortality data were collected. ROTEM®-based, patients were classified as: normal, hypercoagulable, hypocoagulable, hipocoagulable +hyperfibrinolytic and isolated hyperfibrinolysis. RESULTS: One hundred and twenty-three patients were analyzed. 32 cases (26%) with CAT: 15 patients with hypocoagulability, 9 with hyperfibrinolysis alone and 8 with hypocoagulability +hyperfibrinolysis. The CAT group, related to the normal group, presented higher ISS (23 vs. 16, P<.01), higher blood products transfusion (2.5 vs. 0; P=.001), more cardiac arrest (19 vs. 1%, P<.01), and higher mortality (34 vs. 5%, P<.01). The subgroup with hypocoagulability/hyperfibrinolysis, related to the groups with hypocoagulability or hyperfibrinolysis alone, presented a higher ISS (41 vs. 25 vs. 15, P<.01), higher angiographic procedures (62% vs. 13% vs. 0%, P<.01) and higher mortality (75% vs. 33% vs. 0%, P=.05). CONCLUSIONS: Twenty-six percent of the polytrauma patients presented early coagulopathy assessed by thromboelastography. It is associated with higher consumption of blood products and lower survival. The presence of hypocoagulability +hyperfibrinolysis is associated with greater severity and a higher requirement of blood products.

[Basic guidelines of the Instituto Mexicano del Seguro Social scientific research networks]. / Redes de investigación científica del Instituto Mexicano del Seguro Social. Lineamientos básicos.

Scientific Research Networks of the Instituto Mexicano del Seguro Social were proposed as a strategy to promote collaboration between health personnel, following basic guidelines to include the priority health problems of the Institute, the multidisciplinary, interdisciplinary and multicentric cooperation between researchers and health care personnel leaders in each field and discipline of knowledge, as well as the generation of confidence among the group of participants through the signing of confidentiality agreements, and avoiding the predominance of leadership. To achieve this, the Coordination of Health Research accompanies the personnel in the conduction of logistic and administrative aspects.

En el Instituto Mexicano del Seguro Social, las Redes de Investigación Científica se propusieron como una estrategia para favorecer la colaboración entre el personal de salud, siguiendo directrices básicas al incluir los problemas prioritarios de salud del Instituto, la cooperación multidisciplinaria, interdisciplinaria y multicéntrica entre investigadores y personal de salud líderes en cada campo y disciplina del conocimiento, evitando el predominio de liderazgos, y generando confianza entre los integrantes del grupo mediante la firma de documentos de confidencialidad, contando con el acompañamiento en la conducción y en los aspectos administrativos del personal de la Coordinación de Investigación en Salud.

MDR-1 and MRP2 Gene Polymorphisms in Mexican Epileptic Pediatric Patients with Complex Partial Seizures.

Although the Pgp efflux transport protein is overexpressed in resected tissue of patients with epilepsy, the presence of polymorphisms in MDR1/ABCB1 and MRP2/ABCC2 in patients with antiepileptic-drugs resistant epilepsy (ADR) is controversial. The aim of this study was to perform an exploratory study to identify nucleotide changes and search new and reported mutations in patients with ADR and patients with good response (CTR) to antiepileptic drugs (AEDs) in a rigorously selected population. We analyzed 22 samples In Material and Methods, from drug-resistant patients with epilepsy and 7 samples from patients with good response to AEDs. Genomic DNA was obtained from leukocytes. Eleven exons in both genes were genotyped. The concentration of drugs in saliva and plasma was determined. The concentration of valproic acid in saliva was lower in ADR than in CRT. In ABCB1, five reported SNPs and five unreported nucleotide changes were identified; rs2229109 (GA) and rs2032582 (AT and AG) were found only in the ADR. Of six SNPs associated with the ABCC2 that were found in the study population, rs3740066 (TT) and 66744T > A (TG) were found only in the ADR. The strongest risk factor in the ABCB1 gene was identified as the TA genotype of rs2032582, whereas for the ABCC2 gene the strongest risk factor was the T allele of rs3740066. The screening of SNPs in ACBC1 and ABCC2 indicates that the Mexican patients with epilepsy in this study display frequently reported ABCC1 polymorphisms; however, in the study subjects with a higher risk factor for drug resistance, new nucleotide changes were found in the ABCC2 gene. Thus, the population of Mexican patients with AED-resistant epilepsy (ADR) used in this study exhibits genetic variability with respect to those reported in other study populations; however, it is necessary to explore this polymorphism in a larger population of patients with ADR.

Quantifying the mortality caused by the H1N1 influenza virus during the 2009 pandemic in Mexico.

INTRODUCTION: The frequency and mortality of the pandemic caused by influenza A(H1N1)pdm09 might have been underestimated, especially in developing countries. This study was designed to quantify the possible underestimation of pandemic influenza mortality and evaluate the concordance between the data reported for A(H1N1)pdm09 mortality and the causes of death reported during the pandemic period of April 2009 to February 2010. METHODOLOGY: The death certificates of 754 confirmed cases of A(H1N1)pdm09 infection were included in the study. Data was analyzed using the United States Centers for Disease Control and Prevention's statistical model accounts for the variability in the proportion at each step using the Monte Carlo probabilistic model sampled from a uniform probability distribution. RESULTS: A total of 1,969 deaths were estimated, with an estimated lethality of 5.53 per 100,000 (range, 3.5-8.76 per 100,000) in contrast with the 754 deaths and a lethality of 1.98 per 100,000 infected patients officially reported. In 631 of 754 (83.7%) death certificates from A(H1N1)pdm09 influenza-positive patients, influenza was not mentioned as a cause of death. CONCLUSIONS: It is possible that the mortality of the pandemic was three times higher than officially reported in Mexico. One source of error that could explain this underestimation is in the completion of death certificates, because in > 80% of confirmed cases of infection with influenza virus, it was not reported as the cause of death.

Do the severity and the body region of injury correlate with long-term outcome in the severe traumatic patient?

BACKGROUND AND OBJECTIVES: To investigate if the Injury Severity Score (ISS) and the Abbreviated Injury Score (AIS) are correlated with the long-term quality of life in severe trauma patients. METHODS: Patients injured from 2005 to 2007 with an ISS≥15 were surveyed 16-24 months after injury. The Health Assessment Questionnaire (HAQ-DI) was used for measuring the functional status and the Short Form-12 (SF-12) was used for measuring the health status divided into its two components, the PCS (Physical Component Summary) and the MCS (Mental Component Summary). The results of the questionnaires were compared with the ISS and AIS components. Results of the SF-12 were compared with the values expected from the general population. RESULTS: Seventy-four patients filled the questionnaires (response rate 28%). The mean scores were: PCS 42.6±13.3; MCS 49.4±1.4; HAQ-DI 0.5±0.7. Correlation was observed with the HAQ-DI and the PCS (Spearman's Rho: -0.83; p<0.05) and no correlation between the HAQ-DI and the MCS neither between the MCS and PCS (Spearman's Rho=-0.21; and 0.01 respectively). The cutaneous-external and extremities-pelvic AIS punctuation were correlated with The PCS (Spearman's Rho: -0.39 and -0.34, p<0.05) and with the HAQ-DI (Spearman's Rho: 0.31 and 0.23; p<0.05). The physical condition compared with the regular population was worse except for the groups aged between 65-74 and 55-64. CONCLUSIONS: Patients with extremities and pelvic fractures are more likely to suffer long-term disability. The severity of the external injuries influenced the long-term disability.

A gravidade e a região da lesão corporal correlacionam com resultados a longo prazo em paciente com traumatismo grave? / Do the severity and the body region of injury correlate with long-term outcome in the severe traumatic patient? / ¿La gravedad y la región de la lesión corporal se correlacionan conlos resultados a largo plazo en un paciente con traumatismo grave?

Justificativa e objetivos: investigar se o índice de gravidade da lesão (ISS) e a escala abreviada de lesões (AIS) estão correlacionados com a qualidade de vida em longo prazo em pacientes com traumatismo grave. Métodos: pacientes que sofreram lesões de 2005 a 2007, com IGL≥15, foram pesquisados 16-24 meses após as lesões. O questionário de avaliação da saúde (HAQ-DI) foi usado para medir o estado funcional e o modelo abreviado do questionário com 12 itens (Short Form-12 [SF-12]) foi usado para medir o estado de saúde dividido em seus dois componentes: o resumo do componente saúde física (PCS) e o resumo do componente saúde mental (MCS). Os resultados dos questionários foram comparados com os componentes do ISS e da AIS. Os resultados do SF-12 foram comparados com os valores esperados da população geral. Resultados: preencheram os questionários 74 pacientes (taxa de resposta de 28%). A média dos escores foi: PCS 42,6 ± 13,3; MCS 49,4 ± 1,4; HAQ-DI 0,5 ±0,7. Houve correlação com HAQ-DI e PCS (Rho de Spearman: -0,83; p < 0,05) e nenhuma correlação entre HAQ-DI e MCS ou entre MCS e PCS (Rho de Spearman = -0,21 e 0,01, respectivamente). Os escores cutâneo-externo e extremidades-pélvico da AIS correlacionaram com o PCS (Rho de Spearman: -0,39 e -0,34, p < 0,05) e com o HAQ-DI (Rho de Spearman: 0,31 e 0,23; p < 0,05). A condição física em comparação com a população normal foi pior, exceto para os grupos com idades entre 65-74 e 55-64 anos. Conclusões: os pacientes com fraturas pélvicas e de extremidades são mais propensos a apresentar incapacidade em longo prazo. A gravidade das lesões externas influenciou a deficiência em longo prazo. .

Background and objectives: To investigate if the Injury Severity Score (ISS) and the Abbreviated Injury Score (AIS) are correlated with the long-term quality of life in severe trauma patients. Methods: Patients injured from 2005 to 2007 with an ISS ≥ 15 were surveyed 16-24 months after injury. The Health Assessment Questionnaire (HAQ-DI) was used for measuring the functional status and the Short Form-12 (SF-12) was used for measuring the health status divided into its two components, the PCS (Physical Component Summary) and the MCS (Mental Component Summary). The results of the questionnaires were compared with the ISS and AIS components. Results of the SF-12 were compared with the values expected from the general population. Results: Seventy-four patients filled the questionnaires (response rate 28%). The mean scores were: PCS 42.6 ± 13.3; MCS 49.4 ± 1.4; HAQ-DI 0.5 ± 0.7. Correlation was observed with the HAQ-DI and the PCS (Spearman's Rho: -0.83; p < 0.05) and no correlation between the HAQ-DI and the MCS neither between the MCS and PCS (Spearman's Rho = -0.21; and 0.01 respectively). The cutaneous-external and extremities-pelvic AIS punctuation were correlated with The PCS (Spearman's Rho: -0.39 and -0.34, p < 0.05) and with the HAQ-DI (Spearman's Rho: 0.31 and 0.23; p < 0.05). The physical condition compared with the regular population was worse except for the groups aged between 65 -74 and 55 -64. Conclusions: Patients with extremities and pelvic fractures are more likely to suffer long-term disability. The severity of the external injuries influenced the long-term disability. .

Justificación y objetivos: investigar si el Índice de Gravedad de la Lesión (Injury Severity Score [ISS]) y la Escala Abreviada de Lesiones (Abbreviated Injury Score [AIS]) están correlacionados con la calidad de vida a largo plazo en pacientes con traumatismo grave. Métodos: pacientes que sufrieron lesiones entre 2005 y 2007, con un ISS ≥ 15, fueron encuestados 16-24 meses después de las lesiones. Se usó el Cuestionario de Evaluación de la Salud-Índice de Incapacidad (Health Assessment Questionnaire-Disability Index [HAQ-DI]) para medir el estado funcional, y el modelo abreviado del cuestionario con 12 ítems (Short Form-12 [SF-12]) para medir el estado de salud dividido en 2 componentes: el índice de salud física (Physical Component Summary [PCS]) y el índice de salud mental (Mental Component Summary [MCS]). Los resultados de los cuestionarios fueron comparados con los componentes del ISS y del AIS. Los resultados del SF-12 fueron comparados con los valores esperados en la población general. Resultados: setenta y cuatro pacientes rellenaron los cuestionarios (tasa de respuesta de un 28%). Las puntuaciones medias fueron: PCS 42,6 ± 13,3; MCS 49,4 ± 1,4; HAQ-DI 0,5 ± 0,7. Se registró una correlación con HAQ-DI y PCS (rho de Spearman: −0,83; p < 0,05) y ninguna correla-ción entre HAQ-DI y MCS o entre MCS y PCS (rho de Spearman = −0,21; y 0,01, respectivamente). Las puntuaciones cutáneo-externas y extremidades-pélvicas de la AIS se correlacionaron con el PCS (rho de Spearman: −0,39 y −0,34; p < 0,05) y con el HAQ-DI (rho de Spearman: 0,31 y 0,23; p < 0,05). La condición física en comparación con la población normal fue peor, excepto para los grupos con edades entre 65-74 y 55-64 años. Conclusiones: los pacientes con fracturas pélvicas y de extremidades ...

Mecanismos de neurodegeneración en la epilepsia del lóbulo temporal / Mechanisms of neurodegeneration in temporal lobe epilepsy

Epilepsy affects 1 and 2 percent of the worldwide population, while temporal lobe epilepsy (TLE) covers 40 percent of all epilepsy cases. Controversy in defining epilepsy as a neurodegenerative disease exists because, no there is enough evidence to show seizures and status epilepticus (SE) as cause for irreversible neuronal damage. Epileptogenic insult at the beginning of the disease produces an acute and delayed neuronal death, resulting in gliosis, but also triggers compensatory processes such as angiogenesis, cell proliferation and reorganization of extracellular matrix as receptors, channels and drug transporter proteins. In neurogenesis and axonal regrowth, the age of onset is crucial for the formation of abnormal neurons and aberrant circuits as a result of seizures; approximately 30 percent begin in the temporal lobe. These disturbances continue in parallel or sequentially during the course of epilepsy, which implies a great challenge in the search of new treatments...

La epilepsia es una enfermedad que afecta entre el 1 al 2 por ciento de la población mundial, siendo la epilepsia del lóbulo temporal (ELT) la que abarca el 40 por ciento de todos los casos de epilepsia. La controversia en definir a la epilepsia como una enfermedad neurodegenerativa, se debe a que no hay pruebas suficientes que demuestren como las convulsiones y el estado de mal epiléptico (SE) provocan un daño neuronal irreversible. El insulto epileptógenico presente al inicio de la enfermedad genera la muerte neuronal aguda y tardía, para dar lugar a la gliosis; pero también se desencadenan procesos compensatorios como la angiogénesis, la proliferación celular y una reorganización tanto de la matriz extracelular como de los receptores, canales y proteínas transportadoras de fármacos. En el caso de la neurogénesis y recrecimiento axonal, la edad de inicio es determinante para la formación de neuronas anormales y circuitos aberrantes como consecuencia de las convulsiones, dónde aproximadamente un 30 por ciento comienzan en el lóbulo temporal. Estas alteraciones se continúan en paralelo o de forma secuencia! durante la evolución de la epilepsia, lo que implica un gran desafío en la búsqueda de nuevos tratamientos...

[Guideline for the assessment of clinical research proposals. Comisión Nacional de Investigación Científica del Instituto Mexicano del Seguro Social]. / Guía para evaluar protocolos de investigación clínica.

BACKGROUND: Medical research is a fundamental tool to achieve the advancement of science, through the improvement of strategies aimed to protect, promote and restore an individual's and society's health. Three characteristics are required to obtain approval of the research proposal: scientific relevance, technical quality and the accomplishment of ethical issues. OBJECTIVES: The present review aimed at the determination of the specific criteria to perform a critical review of research proposals. METHODS: A research was carried out in the PubMed, Medline, Ovid and Google Scholar databases, using the terms: peer review, research proposals, review and protocols, and reviewers. A total of 3546 related articles were reviewed, without finding a guide to critically assess research proposals. The guides to assess research articles consider that the quality criteria of the study should have been present since the study's conception; many of the issues described to review articles are incorporated in the review of the research proposals. RESULTS: The specific criteria were integrated to allow the reviewer to critically assess research proposals of different areas with scientific basis. CONCLUSIONS: The reviewer of research proposals should be considered as a professional that contributes to the promotion of knowledge advancement through his/her comments, which allow researchers to improve the quality of research proposals.

Antecedentes: la investigación médica es una herramienta fundamental para lograr el avance de la ciencia al mejorar las acciones encaminadas a proteger, promover y restaurar la salud del individuo y de la sociedad en general. Las tres características imprescindibles para que un protocolo de investigación sea autorizado son: relevancia científica, calidad técnica y el cumplimiento de los aspectos éticos. Material y métodos: estudio retrospectivo efectuado con base en la búsqueda específica en Pubmed, Medline, Ovid y Google Scholar con los términos: peer review, research proposals, review and protocols and reviewers. Debido a que no se identificó ningún artículo que refiriera específicamente los criterios para evaluar protocolos de investigación clínica, se hizo un consenso entre los vocales de la Comisión Nacional de Investigación Científica del Instituto Mexicano del Seguro Social, que está integrada por investigadores titulares de la institución, todos pertenecientes al Sistema Nacional de Investigadores. Se discutieron los criterios que debieran componer una revisión adecuada y cuáles debieran ser los rubros que deben incluirse en el análisis. Resultados: se integraron los criterios específicos que le permitirán al revisor de un protocolo de investigación realizar una crítica con bases metodológicas aceptadas por un consenso de investigadores. Conclusiones: un revisor debe ser considerado como un promotor del avance del conocimiento científico que, mediante sus comentarios y su dictamen, permite que los investigadores incrementen la calidad de sus protocolos de investigación.