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.