Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency.

Background: G6PC3 deficiency is a rare genetic disorder that causes syndromic congenital neutropenia. It is driven by the intracellular accumulation of a metabolite named 1,5-anhydroglucitol-6-phosphate (1,5-AG6P) that inhibits glycolysis. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Objective: The G6PC3 c.210delC variant has been identified in patients of Mexican origin. We set out to study the origin and functional consequence of this mutation. Furthermore, we sought to characterize the clinical phenotypes caused by it. Methods: Using whole-genome sequencing data, we conducted haplotype analysis to estimate the age of this allele and traced its ancestral origin. We examined how this mutation affected G6PC3 protein expression and performed extracellular flux assays on patient-derived cells to characterize how this mutation impacts glycolysis. Finally, we compared the clinical presentations of patients with the c.210delC mutation relative to other G6PC3 deficient patients published to date. Results: Based on the length of haplotypes shared amongst ten carriers of the G6PC3 c.210delC mutation, we estimated that this variant originated in a common ancestor of indigenous American origin. The mutation causes a frameshift that introduces a premature stop codon, leading to a complete loss of G6PC3 protein expression. When treated with 1,5-anhydroglucitol (1,5-AG), the precursor to 1,5-AG6P, patient-derived cells exhibited markedly reduced engagement of glycolysis. Clinically, c.210delC carriers display all the clinical features of syndromic severe congenital neutropenia type 4 observed in prior reports of G6PC3 deficiency. Conclusion: The G6PC3 c.210delC is a loss-of-function mutation that arose from a founder effect in the indigenous Mexican population. These findings may facilitate the diagnosis of additional patients in this geographical area. Moreover, the in vitro 1,5-AG-dependent functional assay used in our study could be employed to assess the pathogenicity of additional G6PC3 variants.

Neuroprotective Effects of the Nutraceutical Dehydrozingerone and Its C2-Symmetric Dimer in a Drosophila Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons responsible for unintended or uncontrollable movements. Mutations in the leucine-rich repeat kinase 2 locus contribute to genetic forms of PD. The fruit fly Drosophila melanogaster carrying this mutation (LRRK2-Dm) is an in vivo model of PD that develops motor impairment and stands for an eligible non-mammalian paradigm to test novel therapeutic approaches. Dehydrozingerone (DHZ) is a natural phenolic compound isolated from ginger and presents anti-inflammatory, antioxidant and neuroprotective properties, making it a potential therapeutic target for PD. We administered DHZ and its C2-symmetric dimer (DHZ-DIM) at 0.5 and 1 mM for 14 and 21 days in the LRRK2-Dm, with the aim of assessing changes in rescuing motor behavior, brain dopaminergic neurons, mitochondria and synapses (T-bars). The shorter treatment with both molecules revealed efficacy at the higher dose, improving climbing behavior with a prevention of dopaminergic neuronal demise. After 21 days, a recovery of the motor disability, dopaminergic neuron loss, mitochondrial damage and T-bars failure was observed with the DHZ-DIM. Our data indicate that the DHZ-DIM exerts a more potent neuroprotective effect with respect to the monomer in LRRK2-Dm, prompting further investigation of these compounds in rodent models of PD.

Incidence of Respiratory Syncytial Virus-Associated Lower Respiratory Tract Illness in Infants in Low- and Middle-Income Regions During the Coronavirus Disease 2019 Pandemic.

Background: Incidence data of respiratory syncytial virus-associated lower respiratory tract illness (RSV-LRTI) are sparse in low- and middle-income countries (LMICs). We estimated RSV-LRTI incidence rates (IRs) in infants in LMICs using World Health Organization case definitions. Methods: This prospective cohort study, conducted in 10 LMICs from May 2019 to October 2021 (largely overlapping with the coronavirus disease 2019 [COVID-19] pandemic), followed infants born to women with low-risk pregnancies for 1 year from birth using active and passive surveillance to detect potential LRTIs, and quantitative reverse-transcription polymerase chain reaction on nasal swabs to detect RSV. Results: Among 2094 infants, 32 (1.5%) experienced an RSV-LRTI (8 during their first 6 months of life, 24 thereafter). Seventeen (0.8%) infants had severe RSV-LRTI and 168 (8.0%) had all-cause LRTI. IRs (95% confidence intervals [CIs]) of first RSV-LRTI episode were 1.0 (.3-2.3), 0.8 (.3-1.5), and 1.6 (1.1-2.2) per 100 person-years for infants aged 0-2, 0-5, and 0-11 months, respectively. IRs (95% CIs) of the first all-cause LRTI episode were 10.7 (8.1-14.0), 11.7 (9.6-14.0), and 8.7 (7.5-10.2) per 100 person-years, respectively. IRs varied by country (RSV-LRTI: 0.0-8.3, all-cause LRTI: 0.0-49.6 per 100 person-years for 0- to 11-month-olds). Conclusions: RSV-LRTI IRs in infants in this study were relatively low, likely due to reduced viral circulation caused by COVID-19-related nonpharmaceutical interventions. Clinical Trials Registration: NCT03614676.

[Autoimmunity and Freiburg classification in common variable immunodeficiency]. / Autoinmunidad y clasificación de Freiburg en pacientes con inmunodeficiencia común variable.

Introduction: Up to 25% of patients with common variable immunodeficiency (CVID) debut with autoimmunity, which is related to the Freiburg classification, which is based on flow cytometry. Objective: to determine the frequency and type of autoimmune diseases and their association with the Freiburg classification in adults with CVID. Methods: A cross-sectional, analytical and observational study was carried out with 33 patients belonging to the Primary Immunodeficiency Clinic of a third level hospital, with a diagnosis of CVID. They were divided into 3 phenotypes according to the Freiburg classification. Results: Of the 33 patients studied, 66.6% presented autoimmune diseases, 19 of them (86.3%) had cytopenia; 42.1% belonged to Freiburg group Ia, 36.8% to Ib and 21% to phenotype II. In 36.6% of the patients, autoimmune cytopenia were the first manifestation of CVID; and up to 70% of them belong to the Freiburg phenotype Ia (p = 0.086). Patients with autoimmune cytopenia had a lower percentage of isotype-switched memory B cells (p = 0.018), no higher percentage of CD21low B cells (p = 0.226). Conclusions: Classification by CVID phenotypes allows the identification of the patient's profile according to the percentage of memory B cells with isotype change, which is useful to intentionally search for non-infectious complications of the disease.

Introducción: hasta el 25% de los pacientes con inmunodeficiencia común variable (IDCV) debutan con autoinmunidad, la cual guarda relación con la clasificación de Freiburg, que se basa en la citometría de flujo. Objetivo: determinar la frecuencia y tipo de enfermedades autoinmunes y su asociación con la clasificación de Freiburg en adultos con IDCV. Métodos: se realizó un estudio transversal, analítico y observacional con 33 pacientes pertenecientes a la Clínica de Inmunodeficiencias Primarias de un hospital de tercer nivel con diagnóstico de IDCV. Se dividieron en tres fenotipos según la clasificación de Freiburg. Resultados: de los 33 pacientes estudiados, el 66.6% presentó enfermedades autoinmunes, de ellos 19 (86.3%) tuvieron citopenias. El 42.1% se clasificó en el grupo Ia de Freiburg, el 36.8% en el grupo Ib y el 21% en el fenotipo II. En el 36.6% de los pacientes las citopenias autoinmunes fueron la primera manifestación de IDCV, y hasta el 70% de ellos pertenecen al fenotipo Ia de Freiburg (p = 0.086). Los pacientes con citopenias autoinmunes tuvieron un menor porcentaje de células B de memoria con cambio de isotipo (p = 0.018), sin mayor porcentaje de células B CD21low (p = 0.226). Conclusiones: la clasificación por fenotipos en IDCV permite identificar el perfil del paciente y el tipo de manifestaciones asociadas, lo que es útil para buscar de manera intencionada complicaciones no infecciosas propias de la enfermedad.

Effects of memantine on mania-like phenotypes exhibited by Drosophila Shaker mutants.

INTRODUCTION: Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor antagonist memantine (Mem), such as antidepressant-like and mood-stabilizer drugs in clinical studies, its specific mechanisms of action are still uncertain. The present study aims to better characterize the Drosophila melanogaster fly Shaker mutants (SH), as a translational model of manic episodes within bipolar disorder in humans, and to investigate the potential anti-manic properties of Mem. METHODS AND RESULTS: Our findings showed typical behavioral abnormalities in SH, which mirrored with the overexpression of NMDAR-NR1 protein subunit, matched well to glutamate up-regulation. Such molecular features were associated to a significant reduction of SH brain volume in comparison to Wild Type strain flies (WT). Here we report on the ability of Mem treatment to ameliorate behavioral aberrations of SH (similar to that of Lithium), and its ability to reduce NMDAR-NR1 over-expression. CONCLUSIONS: Our results show the involvement of the glutamatergic system in the SH, given the interaction between the Shaker channel and the NMDA receptor, suggesting this model as a promising tool for studying the neurobiology of bipolar disorders. Moreover, our results show Mem as a potential disease-modifying therapy, providing insight on new mechanisms of action.

Synergic Action of Insulin-like Growth Factor-2 and miRNA-483 in Pterygium Pathogenesis.

Pterygium is a multifactorial disease in which UV-B is speculated to play a key role by inducing oxidative stress and phototoxic DNA damage. In search for candidate molecules that are useful for justifying the intense epithelial proliferation observed in pterygium, our attention has been focused on Insulin-like Growth Factor 2 (IGF-2), mainly detected in embryonic and fetal somatic tissues, which regulate metabolic and mitogenic functions. The binding between IGF-2 and its receptor Insulin-like Growth Factor 1 Receptor (IGF-1R) activates the PI3K-AKT pathway, which leads to the regulation of cell growth, differentiation, and the expression of specific genes. Since IGF2 is regulated by parental imprinting, in different human tumors, the IGF2 Loss of Imprinting (LOI) results in IGF-2- and IGF2-derived intronic miR-483 overexpression. Based on these activities, the purpose of this study was to investigate the overexpression of IGF-2, IGF-1R, and miR-483. Using an immunohistochemical approach, we demonstrated an intense colocalized epithelial overexpression of IGF-2 and IGF-1R in most pterygium samples (Fisher's exact test, p = 0.021). RT-qPCR gene expression analysis confirmed IGF2 upregulation and demonstrated miR-483 expression in pterygium compared to normal conjunctiva (253.2-fold and 12.47-fold, respectively). Therefore, IGF-2/IGF-1R co-expression could suggest their interplay through the two different paracrine/autocrine IGF-2 routes for signaling transfer, which would activate the PI3K/AKT signaling pathway. In this scenario, miR-483 gene family transcription might synergically reinforce IGF-2 oncogenic function through its boosting pro-proliferative and antiapoptotic activity.

Perfusión 2D por angiografía en oclusión arterial periférica. Método de evaluación inmediato posproceder / 2D perfusion by angiography in peripheral arterial occlusion. Post-procedural immediate evaluation method

La enfermedad arterial periférica se considera la mayor causa de hospitalización, con riesgo de amputación de la extremidad afectada y muerte debido a la enfermedad per se o sus complicaciones. Se reporta la experiencia del tratamiento a un paciente con macroangiopatía diabética, estenosis del 64 por ciento de la arteria ilíaca izquierda y afectación de los segmentos fémoro-poplíteos bilaterales, al cual, a través de un acceso percutáneo vía arteria braquial izquierda, se le realizó revascularización mediante la implantación de stent de cromo-cobalto liberado por balón catéter. El objetivo de este estudio fue describir la utilidad del 2D-ASD y su valor como herramienta para determinar el transproceder y la repercusión en el flujo sanguíneo de la revascularización realizada, y establecer un pronóstico funcional para el paciente. Se utilizó la angiografía por perfusión bidimensional como herramienta para evaluar el éxito técnico del proceder y la repercusión inmediata en la perfusión distal de la extremidad afecta, y describir la utilidad de la escala paramétrica de colores y las curvas de densidad en función del tiempo obtenidos en el estudio(AU)

Peripheral artery disease is considered the leading cause of hospitalization, with risk of amputation of the affected limb and death due to the disease per se or its complications. It is reported the experience of treatment in a patient with diabetic macroangiopathy, stenosis of 64 percent of the left iliac artery and involvement of the bilateral femoro-popliteal segments, to which, through a percutaneous access via the left brachial artery, revascularization was performed through the implantation of cobalt-chromium stent released by balloon catheter. The objective of this study was to describe the usefulness of 2D-ASD and its value as a tool to determine the trans-procedure and the impact on blood flow of the revascularization performed, and to establish a functional prognosis for the patient. Two-dimensional perfusion angiography was used as a tool to evaluate the technical success of the procedure and the immediate impact on distal perfusion of the affected limb, and to describe the usefulness of the parametric color scale and density curves as a function of the time obtained in the study(AU)

Perfusión 2D por angiografía en oclusión arterial periférica. Método de evaluación inmediato posproceder / 2D perfusion by angiography in peripheral arterial occlusion. Post-procedural immediate evaluation method

La enfermedad arterial periférica se considera la mayor causa de hospitalización, con riesgo de amputación de la extremidad afectada y muerte debido a la enfermedad per se o sus complicaciones. Se reporta la experiencia del tratamiento a un paciente con macroangiopatía diabética, estenosis del 64 por ciento de la arteria ilíaca izquierda y afectación de los segmentos fémoro-poplíteos bilaterales, al cual, a través de un acceso percutáneo vía arteria braquial izquierda, se le realizó revascularización mediante la implantación de stent de cromo-cobalto liberado por balón catéter. El objetivo de este estudio fue describir la utilidad del 2D-ASD y su valor como herramienta para determinar el transproceder y la repercusión en el flujo sanguíneo de la revascularización realizada, y establecer un pronóstico funcional para el paciente. Se utilizó la angiografía por perfusión bidimensional como herramienta para evaluar el éxito técnico del proceder y la repercusión inmediata en la perfusión distal de la extremidad afecta, y describir la utilidad de la escala paramétrica de colores y las curvas de densidad en función del tiempo obtenidos en el estudio(AU)

Peripheral artery disease is considered the leading cause of hospitalization, with risk of amputation of the affected limb and death due to the disease per se or its complications. It is reported the experience of treatment in a patient with diabetic macroangiopathy, stenosis of 64 precent of the left iliac artery and involvement of the bilateral femoro-popliteal segments, to which, through a percutaneous access via the left brachial artery, revascularization was performed through the implantation of cobalt-chromium stent released by balloon catheter. The objective of this study was to describe the usefulness of 2D-ASD and its value as a tool to determine the trans-procedure and the impact on blood flow of the revascularization performed, and to establish a functional prognosis for the patient. Two-dimensional perfusion angiography was used as a tool to evaluate the technical success of the procedure and the immediate impact on distal perfusion of the affected limb, and to describe the usefulness of the parametric color scale and density curves as a function of the time obtained in the study(AU)

Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer's Disease Progression.

Alzheimer's disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets.

Effects of Global Warming on Patients with Dementia, Motor Neuron or Parkinson's Diseases: A Comparison among Cortical and Subcortical Disorders.

Exposure to global warming can be dangerous for health and can lead to an increase in the prevalence of neurological diseases worldwide. Such an effect is more evident in populations that are less prepared to cope with enhanced environmental temperatures. In this work, we extend our previous research on the link between climate change and Parkinson's disease (PD) to also include Alzheimer's Disease and other Dementias (AD/D) and Amyotrophic Lateral Sclerosis/Motor Neuron Diseases (ALS/MND). One hundred and eighty-four world countries were clustered into four groups according to their climate indices (warming and annual average temperature). Variations between 1990 and 2016 in the diseases' indices (prevalence, deaths, and disability-adjusted life years) and climate indices for the four clusters were analyzed. Unlike our previous work on PD, we did not find any significant correlation between warming and epidemiological indices for AD/D and ALS/MND patients. A significantly lower increment in prevalence in countries with higher temperatures was found for ALS/MND patients. It can be argued that the discordant findings between AD/D or ALS/MND and PD might be related to the different features of the neuronal types involved and the pathophysiology of thermoregulation. The neurons of AD/D and ALS/MND patients are less vulnerable to heat-related degeneration effects than PD patients. PD patients' substantia nigra pars compacta (SNpc), which are constitutively frailer due to their morphology and function, fall down under an overwhelming oxidative stress caused by climate warming.

[Pollen-food syndrom. A rewiev with a twist]. / Síndrome polen-alimento. Revisión con un toque.

Pollen-food syndrome (PFS) is characterized by allergic sensitization to proteins of pollens of grasses, weeds, and trees, which produce a type I hypersensitivity reaction that is associated with the intake of plant-derived foods that are usually in raw form. The most frequently-associated protein families are: profilins, PR-10, and ns LTP; however, others such as thaumatins, isoflavones, reductases, and B1,2 glucanases have been documented. The prototype syndrome is birch-fruit-vegetables, and of these, the most common is birch-apple due to the fact that more than 70 % of patients who are sensitized to birch present symptoms associated with the intake of plant-derived foods. The symptoms are restricted to the oral cavity; however, some patients may present systemic symptoms, including anaphylaxis, so it is important to identify the type of protein that is involved since the type of reaction that the patient may present depends on that. In spite of everything, it is considered an entity that may be under diagnosed due to its complex diagnosis and treatment, since the procedure, in most cases, is an elimination diet, because treatment with immunotherapy is not yet available. The purpose of this review is to describe the pathophysiology, as well as the most common pollen-food syndromes.

El síndrome polen-alimento (SPA) se caracteriza por la sensibilización alérgica a proteínas de pólenes de pastos, malezas y árboles, que producen una reacción de hipersensibilidad de tipo I, asociada a la ingesta de alimentos derivados de plantas, usualmente en forma cruda. Las familias de proteínas que más frecuentemente están asociadas son las profilinas, las PR-10 y las ns LTP; sin embargo, se ha documentado otras, como las taumatinas, isoflavonas reductasas y las B1,2 gluconasas. El síndrome prototipo es el abedul-frutas-vegetales, y de ellos el más común es el abedul-manzana, debido a que más de 70 % de los pacientes sensibilizados al abedul presentan síntomas asociados a la ingesta de alimentos derivados de plantas. Los síntomas están restringidos a la cavidad oral; sin embargo, algunos pacientes pueden presentar síntomas sistémicos, incluso anafilaxia, por lo que es importante identificar el tipo de proteína implicada, ya que de eso depende el tipo de reacción que puede presentar el paciente. Pese a todo, se considera una entidad que puede estar subdiagnosticada debido a su valoración y tratamiento complejos, debido a que el procedimiento en la mayor parte de los casos es dieta de eliminación, ya que aún no está disponible el tratamiento con inmunoterapia. El objetivo de esta revisión es describir la fisiopatología, así como los síndromes polen-alimento más comunes.

Heavy Metals and Essential Metals Are Associated with Cerebrospinal Fluid Biomarkers of Alzheimer's Disease.

Various metals have been associated with the pathogenesis of Alzheimer's disease (AD), principally heavy metals that are environmental pollutants (such as As, Cd, Hg, and Pb) and essential metals whose homeostasis is disturbed in AD (such as Cu, Fe, and Zn). Although there is evidence of the involvement of these metals in AD, further research is needed on their mechanisms of toxicity. To further assess the involvement of heavy and essential metals in AD pathogenesis, we compared cerebrospinal fluid (CSF) AD biomarkers to macro- and microelements measured in CSF and plasma. We tested if macro- and microelements' concentrations (heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Na, Mg, K, Ca, Fe, Co, Mn, Cu, Zn, and Mo), essential non-metals (B, P, S, and Se), and other non-essential metals (Al, Ba, Li, and Sr)) are associated with CSF AD biomarkers that reflect pathological changes in the AD brain (amyloid ß1-42, total tau, phosphorylated tau isoforms, NFL, S100B, VILIP-1, YKL-40, PAPP-A, and albumin). We used inductively coupled plasma mass spectroscopy (ICP-MS) to determine macro- and microelements in CSF and plasma, and enzyme-linked immunosorbent assays (ELISA) to determine protein biomarkers of AD in CSF. This study included 193 participants (124 with AD, 50 with mild cognitive impairment, and 19 healthy controls). Simple correlation, as well as machine learning algorithms (redescription mining and principal component analysis (PCA)), demonstrated that levels of heavy metals (As, Cd, Hg, Ni, Pb, and Tl), essential metals (Ca, Co, Cu, Fe, Mg, Mn, Mo, Na, K, and Zn), and essential non-metals (P, S, and Se) are positively associated with CSF phosphorylated tau isoforms, VILIP-1, S100B, NFL, and YKL-40 in AD.

[Neurological manifestations in patients with severe COVID-19 in a tertiary care center]. / Manifestaciones neurológicas en pacientes con COVID-19 severo en un centro de tercer nivel de atención.

Background: The SARS-CoV-2 disease, called COVID-19, emerged in China has acquired pandemic dimensions. According to the WHO situational report of March 15, 2021, the global fatality rate is 2.2%; in Mexico, around 194 944 deaths have been confirmed by COVID-19. Studies in China identified that patients with severe COVID-19, when compared with those who had non-severe COVID-19, presented more severe neurological manifestations. Objective: To determine the frequency of neurological symptoms and manifestations in patients with severe COVID-19 in a tertiary care center. Material and methods: A cross-sectional, observational and analytical study was carried out at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, in patients hospitalized with severe COVID-19. Results: 183 cases were analyzed, of which 130 were men (71%). The median age was 55 years (IQR: 44-65). The neurological symptoms were: headache, anosmia and dysgeusia. Neurological manifestations occurred in 27 patients (16%), the most frequent was ischemic-type cerebrovascular disease (CVD) in 12 (44%), in patients older than 76.5 years vs. 54 years (p = 0.000), with history of cardiovascular disease. Conclusions: The most frequent neurological symptoms were headache, anosmia and dysgeusia. The most frequent neurological manifestation was ischemic CVD that appeared in older patients with severe COVID-19 with a history of cardiovascular disease.

Introducción: la enfermedad por SARS-CoV-2 denominada COVID-19 originada en China adquirió dimensiones pandémicas. De acuerdo con el reporte situacional de la OMS al 15 de marzo de 2021, la tasa de letalidad global es del 2.2%; en México se han confirmado alrededor de 194 944 defunciones por COVID-19. Estudios en China identificaron que los pacientes con COVID-19 severo, al compararlos con aquellos que cursaron con COVID-19 no severo, presentaron manifestaciones neurológicas más graves. Objetivo: determinar la frecuencia de síntomas y manifestaciones neurológicas en pacientes con COVID-19 severo en un centro de tercer nivel de atención. Material y métodos: estudio transversal, observacional y analítico, llevado a cabo en el Hospital de Especialidades del Centro Médico Nacional Siglo XXI, en pacientes hospitalizados con COVID-19 severo. Resultados: se analizaron 183 casos, de los cuales 130 eran hombres (71%). La mediana de edad fue de 55 años (RIC: 44-65). Los síntomas neurológicos fueron: cefalea, anosmia y disgeusia. Las manifestaciones neurológicas se presentaron en 27 pacientes, la más frecuente fue la enfermedad vascular cerebral tipo isquémica (EVC) en 12 pacientes (44%) en pacientes con mayor edad, 76.5 frente a 54 años (p = 0.000), y con antecedente de enfermedad cardiovascular. Conclusiones: los síntomas neurológicos más frecuentes fueron cefalea, anosmia y disgeusia. La manifestación neurológica más frecuente fue la EVC isquémica que se presentó en pacientes con COVID-19 severo de mayor edad y con antecedente de enfermedad cardiovascular.

Manifestaciones neurológicas en pacientes con COVID-19 severo en un centro de tercer nivel de atención / Neurological manifestations in patients with severe COVID-19 in a tertiary care center

Introducción: la enfermedad por SARS-CoV-2 denominada COVID-19 originada en China adquirió dimensiones pandémicas. De acuerdo con el reporte situacional de la OMS al 15 de marzo de 2021, la tasa de letalidad global es del 2.2%; en México se han confirmado alrededor de 194 944 defunciones por COVID-19. Estudios en China identificaron que los pacientes con COVID-19 severo, al compararlos con aquellos que cursaron con COVID-19 no severo, presentaron manifestaciones neurológicas más graves. Objetivo: determinar la frecuencia de síntomas y manifestaciones neurológicas en pacientes con COVID-19 severo en un centro de tercer nivel de atención. Material y métodos: estudio transversal, observacional y analítico, llevado a cabo en el Hospital de Especialidades del Centro Médico Nacional Siglo XXI, en pacientes hospitalizados con COVID-19 severo. Resultados: se analizaron 183 casos, de los cuales 130 eran hombres (71%). La mediana de edad fue de 55 años (RIC: 44-65). Los síntomas neurológicos fueron: cefalea, anosmia y disgeusia. Las manifestaciones neurológicas se presentaron en 27 pacientes, la más frecuente fue la enfermedad vascular cerebral tipo isquémica (EVC) en 12 pacientes (44%) en pacientes con mayor edad, 76.5 frente a 54 años (p = 0.000), y con antecedente de enfermedad cardiovascular. Conclusiones: los síntomas neurológicos más frecuentes fueron cefalea, anosmia y disgeusia. La manifestación neurológica más frecuente fue la EVC isquémica que se presentó en pacientes con COVID-19 severo de mayor edad y con antecedente de enfermedad cardiovascular.

Background: The SARS-CoV-2 disease, called COVID-19, emerged in China has acquired pandemic dimensions. According to the WHO situational report of March 15, 2021, the global fatality rate is 2.2%; in Mexico, around 194 944 deaths have been confirmed by COVID-19. Studies in China identified that patients with severe COVID-19, when compared with those who had non-severe COVID-19, presented more severe neurological manifestations. Objective: To determine the frequency of neurological symptoms and manifestations in patients with severe COVID-19 in a tertiary care center. Material and methods: A cross-sectional, observational and analytical study was carried out at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI, in patients hospitalized with severe COVID-19. Results: 183 cases were analyzed, of which 130 were men (71%). The median age was 55 years (IQR: 44-65). The neurological symptoms were: headache, anosmia and dysgeusia. Neurological manifestations occurred in 27 patients (16%), the most frequent was ischemic-type cerebrovascular disease (CVD) in 12 (44%), in patients older than 76.5 years vs. 54 years (p = 0.000), with history of cardiovascular disease. Conclusions: The most frequent neurological symptoms were headache, anosmia and dysgeusia. The most frequent neurological manifestation was ischemic CVD that appeared in older patients with severe COVID-19 with a history of cardiovascular disease.

Climate change and neurodegenerative diseases.

The climate change induced global warming, and in particular the increased frequency and intensity of heat waves, have been linked to health problems. Among them, scientific works have been reporting an increased incidence of neurological diseases, encompassing also neurodegenerative ones, such as Dementia of Alzheimer's type, Parkinson's Disease, and Motor Neuron Diseases. Although the increase in prevalence of neurodegenerative diseases is well documented by literature reports, the link between global warming and the enhanced prevalence of such diseases remains elusive. This is the main theme of our work, which aims to examine the connection between high temperature exposure and neurodegenerative diseases. Firstly, we evaluate the influence of high temperatures exposure on the pathophysiology of these disorders. Secondly, we discuss its effects on the thermoregulation, already compromised in affected patients, and its interference with processes of excitotoxicity, oxidative stress and neuroinflammation, all of them related with neurodegeneration. Finally, we investigate chronic versus acute stressors on body warming, and put forward a possible interpretation of the beneficial or detrimental effects on the brain, which is responsible for the incidence or progression of neurological disorders.

SmartFlareTM is a reliable method for assessing mRNA expression in single neural stem cells.

BACKGROUND: One of the most challenging tasks of modern biology concerns the real-time tracking and quantification of mRNA expression in living cells. On this matter, a novel platform called SmartFlareTM has taken advantage of fluorophore-linked nanoconstructs for targeting RNA transcripts. Although fluorescence emission does not account for the spatial mRNA distribution, NanoFlare technology has grown a range of theranostic applications starting from detecting biomarkers related to diseases, such as cancer, neurodegenerative pathologies or embryonic developmental disorders. AIM: To investigate the potential of SmartFlareTM in determining time-dependent mRNA expression of prominin 1 (CD133) and octamer-binding transcription factor 4 (OCT4) in single living cells through differentiation. METHODS: Brain fragments from the striatum of aborted human fetuses aged 8 wk postconception were processed to obtain neurospheres. For the in vitro differentiation, neurospheres were gently dissociated with Accutase solution. Single cells were resuspended in a basic medium enriched with fetal bovine serum, plated on poly-L-lysine-coated glass coverslips, and grown in a lapse of time from 1 to 4 wk. Live cell mRNA detection was performed using SmartFlareTM probes (CD133, Oct4, Actin, and Scramble). All the samples were incubated at 37 °C for 24 h. For nuclear staining, Hoechst 33342 was added. SmartFlareTM CD133- and OCT4-specific fluorescence signal was assessed using a semiquantitative visual approach, taking into account the fluorescence intensity and the number of labeled cells. RESULTS: In agreement with previous PCR experiments, a unique expression trend was observed for CD133 and OCT4 genes until 7 d in vitro (DIV). Fluorescence resulted in a mixture of diffuse cytoplasmic and spotted-like pattern, also detectable in the contacting neural branches. From 15 to 30 DIV, only few cells showed a scattered fluorescent pattern, in line with the differentiation progression and coherent with mRNA downregulation of these stemness-related genes. CONCLUSION: SmartFlareTM appears to be a reliable, easy-to-handle tool for investigating CD133 and OCT4 expression in a neural stem cell model, preserving cell biological properties in anticipation of downstream experiments.

MicroRNAs at the Crossroad of the Dichotomic Pathway Cell Death vs. Stemness in Neural Somatic and Cancer Stem Cells: Implications and Therapeutic Strategies.

Stemness and apoptosis may highlight the dichotomy between regeneration and demise in the complex pathway proceeding from ontogenesis to the end of life. In the last few years, the concept has emerged that the same microRNAs (miRNAs) can be concurrently implicated in both apoptosis-related mechanisms and cell differentiation. Whether the differentiation process gives rise to the architecture of brain areas, any long-lasting perturbation of miRNA expression can be related to the occurrence of neurodevelopmental/neuropathological conditions. Moreover, as a consequence of neural stem cell (NSC) transformation to cancer stem cells (CSCs), the fine modulation of distinct miRNAs becomes necessary. This event implies controlling the expression of pro/anti-apoptotic target genes, which is crucial for the management of neural/neural crest-derived CSCs in brain tumors, neuroblastoma, and melanoma. From a translational point of view, the current progress on the emerging miRNA-based neuropathology therapeutic applications and antitumor strategies will be disclosed and their advantages and shortcomings discussed.

Alanine tRNAs Translate Environment Into Behavior in Caenorhabditis elegans.

Caenorhabditis elegans nematodes produce and maintain imprints of attractive chemosensory cues to which they are exposed early in life. Early odor-exposure increases adult chemo-attraction to the same cues. Imprinting is transiently or stably inherited, depending on the number of exposed generations. We show here that the Alanine tRNA (UGC) plays a central role in regulating C. elegans chemo-attraction. Naive worms fed on tRNAAla (UGC) purified from odor-experienced worms, acquire odor-specific imprints. Chemo-attractive responses require the tRNA-modifying Elongator complex sub-units 1 (elpc-1) and 3 (elpc-3) genes. elpc-3 deletions impair chemo-attraction, which is fully restored by wild-type tRNAAla (UGC) feeding. A stably inherited decrease of odor-specific responses ensues from early odor-exposition of elpc-1 deletion mutants. tRNAAla (UGC) may adopt various chemical forms to mediate the cross-talk between innately-programmed and environment-directed chemo-attractive behavior.

[Activity of chronic spontaneous urticaria in euthyroid vs hypothyroid patients]. / Actividad de la urticaria crónica espontánea en pacientes eutiroideos versus hipotiroideos.

BACKGROUND: Chronic urticaria (CU) affects 5 % of the general population and it is associated with thyroid disease in up to 54 % of patients. There is scarce information on the activity of urticaria in patients with and without alterations in the thyroid function. OBJECTIVE: To compare the activity rate of urticaria using the UAS7 (Urticaria Activity Score 7) in patients with and without hypothyroidism. METHODS: A descriptive, cross-sectional, and comparative study of patients with CSU (chronic spontaneous urticaria) who were older than 18 years of age, who were classified into two groups based on their thyroid function: hypothyroid and euthyroid patients. UAS7 was applied to all of them. RESULTS: We analyzed 60 patients with CSU; 30 of them were euthyroid and 30 were hypothyroid. The female sex was predominant (76 %) and the average age was 49.1 years old. The activity in 40 % was moderate, in 25 % was severe, and it was mild in 23 %; only 12 % of them were controlled. In the group with hypothyroidism, the median TSH (Thyroid Stimulating Hormone) was of 6.8 µUI/mL. No statistically significant differences were found in matters of age, body mass index, comorbidities, or in the UAS7. CONCLUSIONS: We did not find a statistically significant difference in the Urticaria Activity Index between both groups. Identifying the influencing factors shall improve the quality of life of patients.

Antecedentes: La urticaria crónica afecta a 5 % de la población general y se asocia a enfermedad tiroidea hasta en 54 % de los pacientes. Existe escasa información de la actividad de la urticaria en los pacientes con y sin alteraciones de la función tiroidea. Objetivo: Comparar el índice de actividad de la urticaria con el UAS7 (Urticaria Activity Score 7) en pacientes con y sin hipotiroidismo. Métodos: Estudio descriptivo, transversal y comparativo de pacientes con urticaria crónica espontánea > 18 años, clasificados en dos grupos según su función tiroidea: con hipotiroidismo y eutiroideos. A todos se les aplicó el UAS7. Resultados: Se analizaron 60 pacientes con urticaria crónica espontánea, 30 eutiroideos y 30 hipotiroideos. Predominó el sexo femenino (76 %), la edad promedio fue de 49.1 años; 40 % tenía actividad moderada, 25 % grave, 23 % leve y 12 % estaba controlado. En el grupo con hipotiroidismo, la mediana de hormona estimulante de la tiroides fue de 6.8 µUI/mL. Entre los grupos no se encontraron diferencias estadísticamente significativas para la edad, índice de masa corporal y comorbilidades (hipertensión, diabetes o enfermedad alérgica) ni UAS7. Conclusiones: No encontramos diferencia estadísticamente significativa en el índice de actividad de la urticaria entre ambos grupos. Identificar qué factores permitirían mejorar la calidad de vida de los pacientes.