Neurophilic herpesvirus: a powerful tool for neuroscience research / 生物工程学报

Viruses are powerful tools for the study of modern neurosciences. Most of the research on the connection and function of neurons were done by using recombinant viruses, among which neurotropic herpesvirus is one of the most important tools. With the continuous development of genetic engineering and molecular biology techniques, several recombinant neurophilic herpesviruses have been engineered into different viral tools for neuroscience research. This review describes and discusses several common and widely used neurophilic herpesviruses as nerve conduction tracers, viral vectors for neurological diseases, and lytic viruses for neuro-oncology applications, which provides a reference for further exploring the function of neurophilic herpesviruses.

Encefalitis asociada a astrovirus bovino neurotrópico, ¿una enfermedad subdiagnosticada en Sudamérica? / Neurotropic bovine astrovirus-associated encephalitis: An underdiagnosed diseasein South America?

Resumen Describimos un caso de encefalitis asociada a infección por astrovirus bovino neu-rotrópico en una vaca lechera, raza Jersey, del departamento de San José, Uruguay. Esterepresenta el segundo caso reportado de esta condición en el hemisferio sur. La vaca, únicaafectada de un rodeo de 70 bovinos, manifestó signos clínicos neurológicos con curso de 2 días,luego de los que murió espontáneamente. El examen histopatológico reveló meningoencefalitislinfocítica, histiocítica y plasmacítica, con necrosis neuronal, sin cuerpos de inclusión. No sedetectaron en el cerebro otros agentes infecciosos, incluyendo el virus de la rabia (Lyssavirus),alfaherpesvirus bovino-1 y alfaherpesvirus bovino-5 (Varicellovirus), virus de la diarrea viralbovina (Pestivirus), virus del Nilo Occidental (Flavivirus), Listeria monocytogenes, Histophi-lus somni y otras bacterias. Dado que el descubrimiento de astrovirus neurotrópicos en variasespecies de mamíferos, incluidos humanos, es reciente, proponemos que los casos de encefalitis por astrovirus pudieron haber pasado inadvertidos en Sudamérica. Discutimos brevementeel diagnóstico patológico diferencial de encefalitis infecciosas en bovinos.

Abstract We describe a case of neurotropic bovine astrovirus-associated encephalitis in a Jer-sey dairy cow from the department of San José, Uruguay. This represents the second case of thiscondition reported in the Southern Hemisphere. The cow was the only one affected in a herd of70 cows, showing neurological signs with a 2-day clinical course, before dying spontaneously.Histopathological examination revealed lymphocytic, histiocytic, and plasmacytic meningoen-cephalitis with neuronal necrosis, without detectable inclusion bodies. Other infectious agents,including Rabies virus (Lyssavirus), Bovine alphaherpesvirus-1 and Bovine alphaherpesvirus-5(Varicellovirus), Bovine viral diarrhea virus (Pestivirus), West Nile virus (Flavivirus), Listeriamonocytogenes, Histophilus somni and other bacteria, were not detected in the brain. We pro-pose that given the recent discovery of neurotropic astroviruses in various mammalian species,including humans, cases of astrovirus encephalitis may have gone undetected in South America.We briefly discuss the differential pathologic diagnosis of infectious bovine encephalitis.

Application of exosomes in brain-targeted delivery / 药学学报

Brain-targeted delivery plays an important role in the diagnosis and treatment of neurological diseases, but the existence of blood brain barrier (BBB) limits the development of brain-targeted delivery. As cell-derived nanovesicles, exosomes can participate in the transportation of substances between cells to mediate the communication between cells to play a biological regulatory role in vivo. Due to the low immunogenicity, low toxicity, high engineering and natural crossing over BBB, exosomes play an important role in brain-targeted delivery. In this paper, the composition of exosomes, the mechanism of brain targeted delivery and its role in various brain diseases are systematically described.

Meningoencephalitis caused by Bovine alphaherpesvirus 5 in Pernambuco, Brazil / [Meningoencefalite causada pelo Bovine alphaherpesvirus 5 em Pernambuco, Brasil]

Objetivou-se descrever a ocorrência do Bovine alphaherpesvirus 5 (BoHV5) como causa de meningoencefalite não supurativa em bovinos do estado de Pernambuco, Brasil. Para tanto, 32 amostras de sistema nervoso embebidas em parafina foram obtidas de animais acometidos por doenças neurológicas atendidos na Clínica de Bovinos de Garanhuns da Universidade Federal Rural de Pernambuco (CBG-UFRPE), entre 2012 e 2016. As amostras foram analisadas quanto à presença do gene da glicoproteína C do BoHV5 por reação em cadeia da polimerase (PCR). Dois animais (6,25%) tiveram resultado positivo à PCR, e sua análise de sequenciamento indicou 100% de similaridade para o BoHV5. Os resultados histopatológicos desses dois animais revelaram lesões multifocais de meningoencefalite não supurativa associada à polioencefalomalácia, presença de corpúsculos de inclusão basofílicos, infiltração de células de Gitter e presença de manguitos perivasculares. A PCR se mostra uma importante ferramenta para diferenciação das infecções por BoHV5 de outras enfermidades neurológicas de bovinos, especialmente a raiva.(AU)

Neuroprotective Effects of Molecular Hydrogen: A Critical Review / 神经科学通报·英文版

Molecular hydrogen (H

The effects of implementation of neurological intensive care sub-specialized module on doctors satisfaction, nurses’ competency and patient’s outcome

@#Objective: This study aimed to evaluate the effects of implementation of a neurological sub-specialized nursing module in critically ill neurological patients. Methods: We selected 22 neurological nurses from our hospital in Nanchang, China as study subjects. The outcome of 100 neurological patients were documented and evaluated. The period from December 2017 to March 2018 was the preimplementation period, in which the conventional nursing was implemented in 50 patients. The time from April 2018 to July 2018 was the post-implementation period, in which the sub-specialized nursing module was implemented with another 50 patients. We conducted assessment and evaluation consisting of doctor satisfaction, nursing complications (aspiration, diarrhea, pressure sores, and ventilatorassociated pneumonia), and the comprehensive ability of nurses in the pre- and post-implementation periods. Results: The total comprehensive ability score of the nurses after implementing the nursing module was higher than that before the implementation (P < 0.05). The satisfaction rate of doctors after implementation (95.45%) was also higher (68.18%) (P < 0.05), and the incidences of nursing complications (aspiration, diarrhea, pressure sores, and ventilator-associated pneumonia) among patients were lower after implementing the nursing module (P < 0.05). Conclusion: The implementation of a sub-specialized nursing module in the care of patients with critically ill neurological diseases can improve the comprehensive ability of nurses and the satisfaction rate of doctors as well as reducing the incidence of nursing-related complications.

Congenital human cytomegalovirus infection and neurologic diseases in newborns / 中华医学杂志(英文版)

Objective@#This review aimed to summarize research progress regarding congenital cytomegalovirus (cCMV) infection-related nervous system diseases and their mechanisms.@*Data sources@#All literature quoted in this review was retrieved from PubMed and Web of Science using the keywords "Cytomegalovirus" and "Neurologic disease" in English. To identify more important information, we did not set time limits.@*Study selection@#Relevant articles were selected by carefully reading the titles and abstracts. Then, different diagnosis and clinical treatment methods for human CMV infection-related neurologic diseases were compared, and the main mechanism and pathogenesis of neurologic damage caused by CMV were summarized from the selected published articles.@*Results@#cCMV infection is a major cause of neonatal malformation. cCMV can infect the fetal encephalon during early gestation and compromise neurodevelopment, resulting in varying degrees of neurologic damage, mainly including hearing impairment, central nervous system (CNS) infection, neurodevelopmental disorders, ophthalmic complications, cerebral neoplasms, infantile autism, epilepsy, and other neurologic abnormalities.@*Conclusions@#cCMV infection-induced neurodevelopmental abnormalities, which were directly caused by fetal encephalon infection, thus inducing neuroimmune responses to damage nerve cells. Such abnormalities were also caused by suppression of the proliferation and differentiation of neural progenitor cells by CMV’s gene products. cCMV infection in the fetal encephalon can also inhibit neuronal migration and synapse formation and indirectly trigger placental inflammation and thus disrupt the oxygen supply to the fetus.

Study on risk factors of acute kidney injury in patients with critical neurological disease / 中国中西医结合急救杂志

Objective To investigate the risk factors of acute kidney injury (AKI) occurring in patients with critical neurological disease, and the related factors affecting their prognosis. Methods The clinical data of 207 patients with critical neurological disease admitted to the Department of Critical Care Medicine of Anhui Provincial Hospital Affiliated to Anhui Medical University (South District) from January 2016 to March 2017 were analyzed retrospectively, they were assigned into an AKI group (40 cases) and a non-AKI group (167 cases), and according to the prognosis, the patients with AKI were subdivided into a survival subgroup (14 cases) and a death subgroup (26 cases). Clinical data of Glasgow coma score (GCS), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), blood glucose, white blood cell count (WBC), central venous pressure (CVP), blood sodium, cystatin C, urea nitrogen (BUN) etc. index levels and the proportions of patients using glycerin fructose and furosemide before occurrence of AKI were collected. The indexes with statistical significant differences found in the univariate analysis were analyzed by multivariate logistic regression analysis to screen out the risk factors influencing the occurrence of AKI and the factors related to the prognosis of the AKI patients; the receiver operating characteristic curve (ROC) was drawn to assess the predictive value of risk factors in patients with severe neurological disease to develop AKI. Results The incidence of AKI was 19.3% (40/207) in the patients with critical neurological disease. The hospital mortality in AKI group was significantly higher than that in the non-AKI group [65.0% (26/40) vs. 22.2% (37/167), P < 0.01]. Compared with non-AKI group, GCS (4.44±1.65 vs. 5.39±1.62), CVP [cmH2O (1 cmH2O = 0.098 kPa): 7.69±2.66 vs. 8.98±2.56] were obviously lower in AKI group at admission, APACHEⅡ(24.50±3.67 vs. 20.05±4.42), blood glucose (mmol/L: 12.33±6.53 vs. 9.33±3.26), serum sodium (mmol/L: 144.75±10.85 vs. 140.58±5.23), WBC (×109/L: 16.15±6.25 vs. 12.79±4.22), Cystatin C (mg/L: 1.27±0.74 vs. 0.74±0.26) and BUN (mmol/L: 7.81±3.33 vs. 5.53±3.20) and proportion of male [77.5% (31/40) vs. 59.9% (100/167)], patients with the comorbidity of hypotension [37.5% (15/40) vs. 19.8% (33/167)], use of glycerin fructose [17.5% (17/40) vs. 3.6% (6/167)], or use of furosemide [70.0% (28/40) vs. 13.8%(6/167)] were significantly increased in AKI group, there was a statistically significant difference between the above two groups (all P < 0.05). Multivariate logistic regression analysis showed that the hyperglycemia [odds ratio (OR) = 1.201, 95% confidence interval (95%CI) = 1.01-1.42, P < 0.05] and use of furosemide for treatment (OR = 24.493, 95%CI =4.92-120.36, P < 0.01) were the independent risk factors for occurrence of AKI in critical neurological patients. ROC curve analysis showed that blood sugar had certain predictive value of developing AKI in patients with critical neurological disease, the area under the ROC curve (AUC) of blood glucose was 0.733, when the optimal cut-off value of blood glucose was 9.05 mmol/L, the sensitivity was 77.5% and the specificity was 62.6%. Compared with the survival subgroup in the patients with AKI, the GCS at admission in death subgroup was significantly lower (3.77±0.87 vs. 5.50±2.03), but their levels of blood glucose (mmol/L: 16.51±9.10 vs. 10.09±2.89) and BUN (mmol/L: 10.26±3.07 vs. 6.48±2.70) were obviously higher than those in the survival subgroup (all P < 0.05). Conclusion AKI is one of the common complications in patients with critical neurological disease, hyperglycemia and the use of furosemide are the independent risk factors of occurrence of AKI in such patients; the blood glucose has moderate predictive value; and lower GCS, higher glucose and BUN levels in AKI patients may enhance their risk of death.

Interference Effect of Prior Explicit Information on Motor Sequence Learning in Relapsing-Remitting Multiple Sclerosis Patients

Background: Multiple sclerosis (MS) is the most widespread disabling neurological condition in young adults around the world. The purpose of this study was to investigate the impact of explicit information (EI) on motor-sequence learning in MS patients. Methods: Thirty patients with relapsing-remitting MS (RRMS), age: 29.5 (SD = 5.6) years and 30 healthy gender-, age-, and education-matched control group participants, age: 28.8 (SD = 6.0) years, were recruited for this study. The participants in the healthy group were then randomly assigned into an EI (n = 15) group and a no-EI (n = 15) group. Similarly, the participants in the control group were then randomly assigned into EI (n = 15) and no-EI (n = 15) groups. The participants performed a serial reaction time (SRT) task and reaction times. A retention test was performed after 48 hours. Results: All participants reduced their reaction times across acquisition (MS group: 46.4 (SD = 3.3) minutes, P < 0.001, and healthy group: 39.4 (SD = 3.3) minutes, P < 0.001). The findings for the within-participants effect of repeated measures of time were significant (F(5.06, 283.7) = 71.33. P < 0.001). These results indicate that the interaction between group and time was significant (F(5.06, 283.7) = 6.44. P < 0.001), which indicated that the reaction time in both groups was significantly changed between the MS and healthy groups across times (B1 to B10). The main effect of the group (MS and healthy) (F(1, 56) = 22.78. P < 0.001) and also the main effect of no-EI vs EI (F(1, 56) = 4.71. P < 0.001) were significant.Conclusion: This study demonstrated that that RRMS patients are capable of learning new skills, but the provision of EI prior to physical practice is deleterious to implicit learning. It is sufficient to educate MS patients on the aim and general content of the training and only to provide feedback at the end of the rehabilitative session.

A survey of fall-related knowledge and behaviors and ways after injury by chief caregivers of inpatients with neurological disease / 现代临床护理

Objective To investigate the fall-related knowledge and behaviors and ways after injury by chief caregivers of inpatients with neurological disease.Method We designed a questionnaire of fall-related knowledge,behaviors and ways after injury and used it among 208 chief caregivers of inpatients with neurological disease.Results On fall-related knowledge,the three items with the lowest scores about fall-related knowledge included fall-related medicine,postural hypotension and abnormal excretion.Of fall-prevented behaviour score,the lowest 3 items were three steps for getting up,placing things correctly and using wheelchair protection derive.Of the inquiry and fall measures score,the lowest 3 item were helping the patient up,observation and prevention after fall.There were significant differences in the total scores on education,time for taking care of the patients,history of fall and health education on fall (P＜0.05).The scores of those with education of senior middle school,college or above were significantly higher than those with education of junior middle school or lower (P＜0.001).The following time for taking care of the patients were compared with statistics significant:＜1month and 3～6 month,＜1month and ＞6 months,1～3 months and 3～6 months (P＜0.001).Conclusion The caregivers of the patients with neurological disease are short of knowledge in fall-related knowledge,normal behaviors and should carry out individualized health education to them.

Endothelial Progenitor Cells' Classification and Application in Neurological Diseases

The therapeutic effects of endothelial progenitor cells (EPCs) on ischemic stroke have been extensively studied in recent years. However, the differences in early EPCs and endothelial outgrowth cells (EOCs) are still unclear. Clarifications of their respective properties and specific functioning characteristics contribute to better applications of EPCs in ischemic diseases. In this review, we discuss cellular origin, isolation, culture, surface markers of early EPCs and EOCs and relevant applications in neurological diseases. We conclude that EOCs possess all haracteristics of true endothelial progenitors and have potent advantages in EPC-based therapies for ischemic diseases. A number of preclinical and clinical applications of EPCs in neurological diseases are under study. More studies are needed to determine the specific characteristics of EPCs and the relevant mechanisms of EPCs for neurological diseases.

Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica

Centella asiatica, locally well known in Malaysia as pegaga, is a traditional herb that has been used widely in Ayurvedic medicine, traditional Chinese medicine, and in the traditional medicine of other Southeast Asian countries including Malaysia. Although consumption of the plant is indicated for various illnesses, its potential neuroprotective properties have been well studied and documented. In addition to past studies, recent studies also discovered and/or reconfirmed that C. asiatica acts as an antioxidant, reducing the effect of oxidative stress in vitro and in vivo. At the in vitro level, C. asiatica promotes dendrite arborisation and elongation, and also protects the neurons from apoptosis. In vivo studies have shown that the whole extract and also individual compounds of C. asiatica have a protective effect against various neurological diseases. Most of the in vivo studies on neuroprotective effects have focused on Alzheimer’s disease, Parkinson’s disease, learning and memory enhancement, neurotoxicity and other mental illnesses such as depression and anxiety, and epilepsy. Recent studies have embarked on finding the molecular mechanism of neuroprotection by C. asiatica extract. However, the capability of C. asiatica in enhancing neuroregeneration has not been studied much and is limited to the regeneration of crushed sciatic nerves and protection from neuronal injury in hypoxia conditions. More studies are still needed to identify the compounds and the mechanism of action of C. asiatica that are particularly involved in neuroprotection and neuroregeneration. Furthermore, the extraction method, biochemical profile and dosage information of the C. asiatica extract need to be standardised to enhance the economic value of this traditional herb and to accelerate the entry of C. asiatica extracts into modern medicine.

Advance in Relationship between NMDA Receptors and Neurological Disease (review) / 中国康复理论与实践

This article introduced the biological characteristics of N-methyl-D-aspartate (NMDA), and reviewed the relationship be-tween NMDA receptor and neurological disease, including cerebral trauma, cerebral ischemia, epilepsy, neuropathic pain, depression and Al-zheimer disease.

Prevalencia de síndromes neuropsicológicos del adulto en una unidad de neuropsicología en Medellín, Colombia / Prevalence of adult neuropsychological syndromes in a neuropsychology unit in Medellin, Colombia

Introducción: en la Unidad de Neuropsicología del Instituto Neurológico de Colombia (INDEC), la evaluación y rehabilitación neuropsicológica de adultos con daños cerebrales, enfermedades neurológicas y trastornos neurodegenerativos, constituyen consultas de alta demanda e importancia en la ciudad de Medellín. Objetivo. Caracterizar la población mayor de 18 años que consulta en la unidad de neuropsicología del INDEC. Materiales y métodos: se seleccionaron 4,084 pacientes mayores de 18 años que consultaron a la Unidad entre 2009 y 2012. En ellos se estudiaron las variables de edad, sexo y diagnóstico. Resultados: de los 4,084 pacientes el 56.9% fue mujeres, los principales diagnósticos de la muestra fueron trastorno cognoscitivo leve (31.4%), demencia no especificada (9.2%) y secuelas de traumatismo intracraneal (5.4%). La prevalencia en los cuatro años de pacientes con síndromes fue en promedio de 2.6 (rango 1.46-3.57) por cada 10.000 habitantes. Conclusiones: las enfermedades como el TEC y las demencias se relacionan con la discapacidad de origen neurológico. El objetivo de la neuropsicología es realizar diagnósticos diferenciales e intervenciones terapéuticas para esta población con discapacidad neurológica, con el fin de beneficiar la funcionalidad del paciente. Es necesario contar con un sistema de clasificación diagnóstica específico para los síndromes neuropsicológicos.

Introduction: In the Neuropsychology Unit of the Colombian Neurological Institute (INDEC), the neuropsychological evaluation and rehabilitation of adults (18≤ years old) with cerebral damage, neurological diseases and neurodegenerative pathologies, are highly demanded. Objective: To characterize the adult population that consults in the Institute (INDEC). Patients and methods: 4.084 patients who attended the unit between 2009 and 2012 were selected. Their age, gender and diagnostics were studied. Results: 56.9% of the selected sample was female, the more prevalent diagnostics were: Mild Cognitive Disorder (31.4%), Unspecified Dementia (9.2%) and Traumatic Brain Injury (TBI) (5.4%). The prevalence of life on 4 years of neuropsychological syndromes was in average 2.6 (range 1.46-3.57), per 10.000 individuals. Conclusions: Diseases such as TBI and dementia, are related to neurological impairment. The aim of Neuropsychological interventions is to make differential diagnostics and therapeutical interventions directed to a population with neurological impairment to forward the patients functionality. It is necessary to count with a specific classification system for Neuropsychological Syndromes.

Drug Permeation across the Blood-Brain Barrier: Applications of Nanotechnology.

The blood-brain barrier (BBB) is a neurobiological frontier that isolates brain tissues from the blood vascular system. Its main role is to protect the brain and the central nervous system from external fluctuations in hormones, nutrients and drugs, while allowing the passage of water and small lipophilic molecules. Diffusion across the BBB can occur through several biological mechanisms, but the most common one is simple diffusion, which mainly depends on the size, lipid solubility and concentration gradient of the molecule. Because of the highly dense network of capillary endothelium cells found in the BBB, most of the drugs are not able to cross this physiological barrier. Delivering therapeutic agents to the brain is thus a big challenge, which may prevent treatment of important neurological diseases. In order to overcome this difficulty, researchers have used nanotechnology to help the passage of drugs across the BBB. Nanotechnology has significantly contributed to the field of biotechnology by improving the strategies for drug delivery, and by providing novel carriers for safe and effective brain targeting. The aim of this review is to discuss in more details the anatomical structure and the functions of the BBB, as well as its significance in neurological diseases. A closer look will be given at the transport mechanisms across the BBB. This review finally explores the most recent advances in the field of nanotechnology for drug delivery in the brain, and gives meaningful examples of delivery systems developed including the micelles, liposomes, dendrimers, microcapsules and polymeric nanoparticles.

Lead poisoning in cattle and chickens in the state of Pará, Brazil / Intoxicação por chumbo em bovinos e galinhas no estado do Pará

The present study describes the occurrence of lead poisoning in cattle and chickens in Pará, Brazil. In a lot composed of 80 calves from a dairy herd, 10 animals became sick and nine died, but one animal recovered after being removed from the paddock. Upon inspection of this paddock, the presence of truck batteries used to store energy captured by solar panels was found. The clinical signs observed in calves included difficult breathing, nasal discharge, excessive salivation, corneal opacity, pushing of the head against objects and recumbency. The chickens had decreased oviposition and produced eggs with thin or malformed shells. The necropsy findings of the cattle, as well as the histopathological changes observed, were of little significance except for one animal that showed mild astrocytosis histopathology in the cerebral cortex. In one of the chickens, renal histopathology showed mild multifocal acute tubular necrosis. The mean lead concentrations in the livers and kidneys of the cattle were 93.91mg/kg and 209.76mg/kg, respectively, and the mean concentration detected in chicken livers was 105.02mg/kg. It was concluded that the source of lead poisoning in these calves and chickens were the truck battery plates, which were within reach of the animals.(AU)

O presente estudo descreve a ocorrência de intoxicação por chumbo em bovinos e galinhas no Pará, Brasil. Em um lote composto de 80 bezerros de um rebanho leiteiro, 10 animais ficaram doentes e nove morreram, e um animal se recuperou após ser removido do piquete. Após a inspeção deste piquete, foi observada a presença de baterias de caminhões usados para armazenar a energia captada por painéis solares. Os sinais clínicos observados nos bezerros incluíam dificuldade respiratória, corrimento nasal, salivação excessiva, opacidade da córnea, pressão da cabeça contra objetos e decúbito. As galinhas tinham diminuída oviposição e os ovos produzidos eram com cascas malformadas ou tinham a casca mais fina. Os achados de necropsia e as alterações histopatológicas observadas nos bovinos eram de pouco significado, com exceção de um animal que mostrou leve astrocitose no córtex cerebral. Em uma das galinhas, na histopatologia renal observou-se leve necrose tubular aguda multifocal. As concentrações de chumbo médios nos fígados e rins dos bovinos eram 93,91mg/kg e 209,76mg/kg, respectivamente, e a concentração média no fígado de galinhas foi 105,02mg/ kg. Concluiu-se que a fonte de contaminação por chumbo nesses bezerros e galinhas eram placas de bateria de caminhão, aos quais os animais tiveram acesso na pastagem.(AU)

Ventilación mecánica prolongada por enfermedad neurológica degenerativa / Long-lasting mechanical ventilation due to degenerative neurological disease

Paciente masculino, de tez blanca y 67 años de edad, con antecedentes de hipertensión arterial y gastritis crónica, que ingresa en la sala de Medicina del Hospital Militar Holguín en agosto del 2011 con el diagnóstico de una gastritis crónica agudizada. Pero previo al ingreso comienza con cuadro de debilidad distal del miembro inferior izquierdo y trastornos en la esfera afectiva. En sala hace cuadro de paro respiratorio y se traslada a la Unidad de Cuidados Intensivos, donde se mantiene bajo régimen de ventilación mecánica desde ese momento con imposibilidad para el destete. Ha presentado pocas infecciones respiratorias y la mayoría han evolucionado satisfactoriamente con antibiótico oral. Se le realizan estudios inmunológicos, imagenológicos y bioquímicos negativos, constatándose al examen físico del sistema neurológico hallazgos relacionados con una afección neuromuscular. Se realizó una revisión bibliográfica a la luz de los conocimientos actuales del tema, y se llegó a la conclusión que la ventilación prolongada en este paciente está en relación con una enfermedad neurológica degenerativa, en este caso una esclerosis lateral amiotrófica modificada.

A sixty-seven years old male Caucasian patient with a history of blood hypertension and chronic gastritis was admitted to the medicine ward of the military hospital in Holguin in August 2011. The diagnosis was acute chronic gastritis. Prior to hospitalization, he presented with distal weakness in the left lower limb and affecting disorders. He suffered respiratory arrest at the hospital ward and was then transferred to the intensive care unit where he was kept mechanically ventilated. Few respiratory infections attacked him, so the majority have evolved satisfactorily thanks to oral antibiotic treatment. The immunological, imaging and biochemical studies yielded negative results. The physical examination of the neurological condition showed symptoms related to a neuromuscular condition. A literature review about this topic was made in which it was determined that the long-lasting mechanical ventilation is related in this case to degenerative neurological disease, in this case modified amyotrophic lateral sclerosis.

Embedding the Future of Regenerative Medicine into the Open Epigenomic Landscape of Pluripotent Human Embryonic Stem Cells.

It has been recognized that pluripotent human embryonic stem cells (hESCs) must be transformed into fate-restricted derivatives before use for cell therapy. Realizing the therapeutic potential of pluripotent hESC derivatives demands a better understanding of how a pluripotent cell becomes progressively constrained in its fate options to the lineages of tissue or organ in need of repair. Discerning the intrinsic plasticity and regenerative potential of human stem cell populations reside in chromatin modifications that shape the respective epigenomes of their derivation routes. The broad potential of pluripotent hESCs is defined by an epigenome constituted of open conformation of chromatin mediated by a pattern of Oct-4 global distribution that corresponds genome-wide closely with those of active chromatin modifications. Dynamic alterations in chromatin states correlate with lossof- Oct4-associated hESC differentiation. The epigenomic transition from pluripotence to restriction in lineage choices is characterized by genome-wide increases in histone H3K9 methylation that mediates global chromatin-silencing and somatic identity. Human stem cell derivatives retain more open epigenomic landscape, therefore, more developmental potential for scale-up regeneration, when derived from the hESCs in vitro than from the CNS tissue in vivo. Recent technology breakthrough enables direct conversion of pluripotent hESCs by small molecule induction into a large supply of lineage-specific neuronal cells or heart muscle cells with adequate capacity to regenerate neurons and contractile heart muscles for developing safe and effective stem cell therapies. Nuclear translocation of NAD-dependent histone deacetylase SIRT1 and global chromatin silencing lead to hESC cardiac fate determination, while silencing of pluripotenceassociated hsa-miR-302 family and drastic up-regulation of neuroectodermal Hox miRNA hsa-miR-10 family lead to hESC neural fate determination. These recent studies place global chromatin dynamics as central to tracking the normal pluripotence and lineage progression of hESCs. Embedding lineage-specific genetic and epigenetic developmental programs into the open epigenomic landscape of pluripotent hESCs offers a new repository of human stem cell therapy derivatives for the future of regenerative medicine.

Constraining the Pluripotent Fate of Human Embryonic Stem Cells for Tissue Engineering and Cell Therapy – The Turning Point of Cell- Based Regenerative Medicine.

To date, the lack of a clinically-suitable source of engraftable human stem/progenitor cells with adequate neurogenic potential has been the major setback in developing safe and effective cell-based therapies for regenerating the damaged or lost CNS structure and circuitry in a wide range of neurological disorders. Similarly, the lack of a clinically-suitable human cardiomyocyte source with adequate myocardium regenerative potential has been the major setback in regenerating the damaged human heart. Given the limited capacity of the CNS and heart for self-repair, there is a large unmet healthcare need to develop stem cell therapies to provide optimal regeneration and reconstruction treatment options to restore normal tissues and function. Derivation of human embryonic stem cells (hESCs) provides a powerful in vitro model system to investigate molecular controls in human embryogenesis as well as an unlimited source to generate the diversity of human somatic cell types for regenerative medicine. However, realizing the developmental and therapeutic potential of hESC derivatives has been hindered by the inefficiency and instability of generating clinically-relevant functional cells from pluripotent cells through conventional uncontrollable and incomplete multi-lineage differentiation. Recent advances and breakthroughs in hESC research have overcome some major obstacles in bringing hESC therapy derivatives towards clinical applications, including establishing defined culture systems for de novo derivation and maintenance of clinical-grade pluripotent hESCs and lineage-specific differentiation of pluripotent hESCs by small molecule induction. Retinoic acid was identified as sufficient to induce the specification of neuroectoderm direct from the pluripotent state of hESCs and trigger a cascade of neuronal lineage-specific progression to human neuronal progenitors and neurons of the developing CNS in high efficiency, purity, and neuronal lineage specificity by promoting nuclear translocation of the neuronal specific transcription factor Nurr-1. Similarly, nicotinamide was rendered sufficient to induce the specification of cardiomesoderm direct from the pluripotent state of hESCs by promoting the expression of the earliest cardiacspecific transcription factor Csx/Nkx2.5 and triggering progression to cardiac precursors and beating cardiomyocytes with high efficiency. This technology breakthrough enables direct conversion of pluripotent hESCs into a large supply of high purity neuronal cells or heart muscle cells with adequate capacity to regenerate CNS neurons and contractile heart muscles for developing safe and effective stem cell therapies. Transforming pluripotent hESCs into fate-restricted therapy derivatives dramatically increases the clinical efficacy of graft-dependent repair and safety of hESC-derived cellular products. Such milestone advances and medical innovations in hESC research allow generation of a large supply of clinical-grade hESC therapy derivatives targeting for major health problems, bringing cell-based regenerative medicine to a turning point.

Guías clínicas para la alimentación en pacientes con trastorno de la deglución / Clinic guidelines for feeding in-patients with swallowing disorders

Feeding is crucial for children’s development at all ages. For that reason, it is necessary to implement timely and effective diagnosis and treatment for patients that present distress in this activity. Swallowing disorders are associated to multiple pathologies and they are accompanied by serious health conditions. This is the reason why the medical approach of each of these disorders is not considered. Due to this point, it is imperative to make sure an integral management where we should consider diagnosis and treatment for patients with swallowing disorders and general feeding problems. Clinical practice guidelines (gPC) are used as a tool to generate current existing evidence to help professionals and in-patients to solve specific health problems by helping solve diagnosis or therapeutic options for a specific condition. Since 2004, minsal has developed gPC associated to the different pathologies included in ges. Hospitals have worked in generating gPC and health care protocols in order to reduce variability and improve clinical practice.

La alimentación es crucial para el desarrollo de los niños en todas las edades, es por esto, que se hace necesario implementar el diagnóstico y tratamiento, oportuno y efectivo para los pacientes que presenten dificultades en esta actividad. Los trastornos de la deglución, se asocian a múltiples patologías y en general acompañan a graves condiciones de salud, es por esto que, en el abordaje particular de cada una de las enfermedades, en ocasiones no se considera. Dado lo anterior es que se hace imperativo realizar un manejo integral de estos pacientes en el que se debe considerar el diagnóstico y tratamiento de los trastornos de la deglución y de la alimentación en general. Como herramienta para generar y difundir las evidencias existentes en la actualidad sobre algunos temas se ha considerado la generación de guías de práctica clínica (gPC) las que constituyen un conjunto de recomendaciones desarrolladas de forma sistemática para ayudar a profesionales y pacientes en la toma de decisiones sobre problemas específicos de salud, ayudando a seleccionar las opciones diagnósticas o terapéuticas más adecuadas a una condición clínica específica. Desde el año 2004, el minsal ha desarrollado gPC asociadas a las patologías que se han incluido en el régimen de garantías explicitas en salud. Paralelamente en los distintos hospitales del país, públicos y privados se ha trabajado en la generación de gPC y protocolos de atención con el fin de reducir la variabilidad y mejorar la práctica clínica.