The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study.

Parkinson's disease (PD) is diagnosed when striatal dopamine (DA) loss exceeds a certain threshold and the cardinal motor features become apparent. The presymptomatic compensatory mechanisms underlying the lack of motor manifestations despite progressive striatal depletion are not well understood. Most animal models of PD involve the induction of a severe dopaminergic deficit in an acute manner, which departs from the typical, chronic evolution of PD in humans. We have used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administered to monkeys via a slow intoxication protocol to produce a more gradual development of nigral lesion. Twelve control and 38 MPTP-intoxicated monkeys were divided into four groups. The latter included monkeys who were always asymptomatic, monkeys who recovered after showing mild parkinsonian signs, and monkeys with stable, moderate and severe parkinsonism. We found a close correlation between cell loss in the substantia nigra pars compacta (SNc) and striatal dopaminergic depletion and the four motor states. There was an overall negative correlation between the degree of parkinsonism (Kurlan scale) and in vivo PET ((18)F-DOPA K(i) and (11)C-DTBZ binding potential), as well as with TH-immunoreactive cell counts in SNc, striatal dopaminergic markers (TH, DAT and VMAT2) and striatal DA concentration. This intoxication protocol permits to establish a critical threshold of SNc cell loss and dopaminergic innervation distinguishing between the asymptomatic and symptomatic parkinsonian stages. Compensatory changes in nigrostriatal dopaminergic activity occurred in the recovered and parkinsonian monkeys when DA depletion was at least 88% of control, and accordingly may be considered too late to explain compensatory mechanisms in the early asymptomatic period. Our findings suggest the need for further exploration of the role of non-striatal mechanisms in PD prior to the development of motor features.

Diverging metabolic effects of 2 energy-restricted diets differing in nutrient quality: a 12-week randomized controlled trial in subjects with abdominal obesity.

BACKGROUND: Despite the established relation between energy restriction (ER) and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still a subject of debate. OBJECTIVES: The aim of the study was to examine the additional effects of nutrient quality on top of ER. METHODS: A parallel-designed, 12-week 25% ER dietary intervention study was conducted (clinicaltrials.gov: NCT02194504). Participants aged 40-70 years with abdominal obesity were randomized over 3 groups: a 25% ER high-nutrient-quality diet (n = 40); a 25% ER low-nutrient-quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, and the high-nutrient-quality ER diet was enriched in MUFAs, n-3 PUFAs, fiber, and plant protein and reduced in fructose. Before and after the intervention, intrahepatic lipids, body fat distribution, fasting and postprandial responses to a mixed-meal shake challenge test of cardiometabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. RESULTS: The high-nutrient-quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low-nutrient-quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an antiatherogenic lipoprotein profile, and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low-quality ER diet. Explorative analyses showed that the difference in weight loss between the two ER diets was specifically present in insulin-sensitive subjects (HOMA-IR ≤ 2.5), in whom the high-nutrient-quality diet induced 3.9 kg more weight loss than the low-nutrient-quality diet. CONCLUSIONS: A high-nutrient-quality 25% ER diet is more beneficial for cardiometabolic health than a low-nutrient-quality 25% ER diet. Overweight, insulin-sensitive subjects may benefit more from a high- than a low-nutrient-quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue.

New MRI, 18F-DOPA and 11C-(+)-alpha-dihydrotetrabenazine templates for Macaca fascicularis neuroimaging: advantages to improve PET quantification.

Normalization of neuroimaging studies to a stereotaxic space allows the utilization of standard volumes of interest (VOIs) and voxel-based analysis (SPM). Such spatial normalization of PET and MRI studies requires a high quality template image. The aim of this study was to create new MRI and PET templates of (18)F-DOPA and (11)C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) of the Macaca fascicularis brain, an important animal model of Parkinson's disease. MRI template was constructed as a smoothed average of the scans of 15 healthy animals, previously transformed into the space of one representative MRI. In order to create the PET templates, (18)F-DOPA and (11)C-DTBZ PET of the same subjects were acquired in a dedicated small animal PET scanner and transformed to the created MRI template space. To validate these templates for PET quantification, parametric values obtained with a standard VOI-map applied after spatial normalization to each template were statistically compared to results computed using individual VOIs drawn for each animal. The high correlation between both procedures validated the utilization of all the templates, improving the reproducibility of PET analysis. To prove the utility of the templates for voxel-based quantification, dopamine striatal depletion in a representative monkey treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was assessed by SPM analysis of (11)C-DTBZ PET. A symmetric reduction in striatal (11)C-DTBZ uptake was detected in accordance with the induced lesion. In conclusion, templates of M. fascicularis brain have been constructed and validated for reproducible and automated PET quantification. All templates are electronically available via the internet.

Integrated Analys of High-Fat Challenge-Induced Changes in Blood Cell Whole-Genome Gene Expression.

SCOPE: Several studies have examined the whole-genome gene expression response in blood cells to high-fat challenges with differing results. The study aims to identify consistently up- or downregulated genes and pathways in response to a high-fat challenge using several integration methods. METHODS AND RESULTS: Three studies measuring the gene expression response to a high-fat challenge in white blood cells are evaluated for common trends using several integration methods. Overlap in differentially expressed genes between separate studies is examined, p-values of each separate study are combined, and data are analyzed as one merged dataset. Differentially expressed genes and pathways are compared between these methods. Selecting genes differentially expressed in the three separate studies result in 67 differentially expressed genes, primarily involved in circadian pathways. Using the Fishers p-value method and a merged dataset analysis, changes in 1097 and 1182 genes, respectively, are observed. The upregulated genes upon a high-fat challenge are related to inflammation, whereas downregulated genes are related to unfolded protein response, protein processing, cholesterol biosynthesis, and translation. CONCLUSION: A general gene expression response to a high-fat challenge is identified. Compared to separate analyses, integrated analysis provides added value for the discovery of a consistent gene expression response.

Pure flavonoid epicatechin and whole genome gene expression profiles in circulating immune cells in adults with elevated blood pressure: A randomised double-blind, placebo-controlled, crossover trial.

Cocoa consumption has beneficial cardiometabolic effects, but underlying mechanisms remain unclear. Epicatechin, the cocoa major monomeric flavan-3-ol, is considered to contribute to these cardio-protective effects. We investigated effects of pure epicatechin supplementation on gene expression profiles of immune cells in humans. In a double blind, placebo-controlled cross-over trial, 32 (pre)hypertensive subjects aged 30 to 80, received two 4-week interventions, i.e. epicatechin (100mg/day) or placebo with a 4-week wash-out between interventions. Gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Epicatechin regulated 1180 genes, of which 234 differed from placebo. Epicatechin upregulated gene sets involved in transcription and tubulin folding and downregulated gene sets involved in inflammation, PPAR signalling and adipogenesis. Several negatively enriched genes within these gene sets were involved in insulin signalling. Most inhibited upstream regulators within the epicatechin intervention were cytokines or involved in inflammation. No upstream regulators were identified compared to placebo. Epicatechin, a cocoa flavan-3-ol, reduces gene expression involved in inflammation, PPAR-signalling and adipogenesis in immune cells. Effects were mild but our findings increase our understanding and provide new leads on how epicatechin rich products like cocoa may affect immune cells and exert cardiometabolic protective effects.

Rehabilitación neuromotora en unidades de tratamiento del ataque cerebrovascular / Neuromotor rehabilitation in stroke treatment units

RESUMEN: Introducción: El Ataque Cerebro Vascular (ACV) es la segunda causa de muerte a nivel mundial y primera causa de discapacidad en el adulto. Su complejidad requiere de una atención integral a través de un equipo multiprofesional, implementado en las denominadas Unidades de Tratamiento del Ataque Cerebrovascular (UTAC). Considerando su relevancia e impacto en el pronóstico, es fundamental conocer las acciones desarrolladas en el ámbito de la rehabilitación neuromotora en estas unidades, información que actualmente es limitada. Método: Estudio descriptivo de corte transversal, la muestra fue por conveniencia, participaron 5 kinesiólogos de establecimientos públicos de salud. La recolección de información se realizó con una encuesta en línea enfocada a las acciones que se realiza en la UTAC. El análisis de datos se realizó con STATA 15 y ATLAS TI 8.0. Resultados: El inicio y frecuencia de la rehabilitación neuromotora es variable, ocurre entre las 24 y 48 horas posterior al diagnóstico. Diariamente se realizan entre una a tres sesiones por usuario, su duración varía desde 25 a 90 minutos. Las acciones neuromotoras son de carácter integral y multiprofesional, el abordaje incluye el componente neuromotor, respiratorio y estado cognitivo. Las acciones neuromotoras incorporan técnicas de facilitación de la postura más alta lograda por el usuario y estimulación sensorial, entre otras. Conclusiones: La rehabilitación neuromotora en las UTAC de Chile muestra realidades diferentes en cuanto a la identificación, funcionamiento y la intervención neuromotora.

ABSTRACT Background: Stroke is the second leading cause of death in the world and the first cause of disability in adults. Its complexity requires comprehensive care provided by a multiprofessional team, implemented in the so-called Stroke Treatment Units (STUs). In view of their relevance and impact on the prognosis, identifying activities developed in the framework of neuromotor rehabilitation is of fundamental importance, information which, at present, is not readily available. Methods: Cross-sectional descriptive study, convenience sampling with the participation of 5 kinesiologists from public health centers in Chile. Information was collected by means of an online survey focused on the work being carried out in the STUs. Data analysis was performed using STATA 15 and ATLAS TI 8.0 software. Results: Initiation and frequency of neuromotor rehabilitation is variable and occurs between 24 and 48 hours after diagnosis. Between one and three daily sessions per user are performed and their duration varies from 25 to 90 minutes. Neuromotor activities are integral and multiprofessional; the approach includes neuromotor, respiratory and cognitive components. Neuromotor activities incorporate facilitation techniques for the most advanced user posture achieved and sensory stimulation, among others. Conclusions: Neuromotor rehabilitation in Chile´s STUs shows different realities in terms of identification, functioning and neurokinetic intervention.

[Value of radioguided surgery with dobutamine 99mTc-MIBI in persistent secondary hyperparathyroidism]. / Valor de la cirugía radioguiada con 99mTc-MIBI sensibilizada con dobutamina en el hiperparatiroidismo secundario persistente.

99mTc-MIBI is a radiopharmaceutical that has been successfully used for the detection of hyperfunctioning parathyroid glands and for radioguided surgery techniques. We report on the case of a 55 year old woman in hemodialysis, with secondary persistent hyperparathyroidism after total parathyroidectomy. The conventional double-phase 99mTc-MIBI parathyroid scintigraphy was negative. The study was repeated after sensibilization with intravenous low-dose dobutamine showing an area of increased focal uptake in the lower cervical region. With this finding, radioguided 99mTc-MIBI surgery was performed after dobutamine administration, using a hand held gamma probe. The technique was considered successful with the resection of parathyroid cervical tissue which was further confirmed as nodular hyperplasia. We conclude that this methodology has the potential of being a an useful tool for the intraoperative localization of remanent tissue in patients with secondary persistent/recurrent hyperparathyroidism.

Recomendaciones higiénicas para servicios alimenticios en entornos hospitalarios durante el confinamiento por COVID-19: Revisión Panorámica / Hygienic Recommendations for Food Service in Hospital Environments During COVID-19 Confinement: Scoping Review

Objetivo: Explorar las principales medidas de higiene alimentaria para servicios alimentarios en contextos hospitalarios durante el período de pandemia por COVID-19.Métodos: Se desarrolló una revisión panorámica de artículos publicados entre el 1 de diciembre 2019 al 30 de octubre del año 2020, en las bases de datos de EMBASE y PubMed respectivamente. Como criterios de elegibilidad se incluyeron estudios que informaran medidas de resultado, como lavado de manos, distanciamiento social, contaminación de alimentos y desinfección de superficies. Resultados: Se identificaron 151 artículos, de los cuales10 fueron analizados. Los resultados sugieren que las medidas higiénicas recomendadas como el lavado de manos, distanciamiento social, supervisión en la manipulación de alimentos son fundamentales para la prevención de la contaminación por el SARS-CoV-2, en servicios alimentarios en contextos hospitalarios. Conclusiones: La literatura analizada da cuenta de la necesidad de contar con mayor evidencia científica para respaldar los efectos de las recomendaciones higiénicas indicadas a los servicios alimentarios en contextos hospitalarios. Este estudio sienta las bases para futuras revisiones sistemáticas y metaanálisis para las principales medidas de prevención establecidas por los organismos sanitarios. (AU)

Objective: Explore the main hygienic measures for food services in hospital contexts during the period of the COVID-19 pandemic. Methods: A panoramic review of articles published between December 1, 2019, and October 30, 2020, was developed in the EMBASE and Pubmed/MEDLINE databases respectively. Studies reporting outcome measures such as hand washing, social distancing, food contamination, and surface disinfection were included as eligibility criteria. Results: Based on the search strategy, 150 articles were identified, of which 10 research papers were incorporated into the analysis. The results show that the recommended hygienic measures such as hand washing, social distancing, and supervision in the handling of food are essential for the prevention of the spread of COVID-19, in-hospital food services. Conclusions: The data analyzed shows the need for more scientific evidence to support the effects of the hygienic recommendations indicated to food services in hospital contexts. This study lays the foundations for future systematic reviews and meta-analysis for the main prevention measures established for health agencies. (AU)

Apolipoprotein E genotype status affects habitual human blood mononuclear cell gene expression and its response to fish oil intervention.

SCOPE: People who carry the apolipoprotein E4 (APOE4) single nucleotide polymorphism have an increased risk of cardiovascular disease (CVD). Fish-oil supplementation may help in the prevention of CVD, though interindividual differences in the response to n-3 PUFAs have been observed. We aimed to assess the impact of APOE genotype on peripheral blood mononuclear cell whole genome gene expression at baseline and following a fish-oil intervention. METHODS AND RESULTS: Participants received 6 months of fish-oil supplementation containing 1800 mg of eicosapentaenoic acid and docosahexaenoic acid per day. APOE genotype and peripheral blood mononuclear cell whole genome gene expression before and after supplementation were measured. We characterized the differences in gene expression profiles in carriers of APOE4 (N = 8) compared to noncarriers (N = 15). At baseline, 1320 genes were differentially expressed and the fish-oil supplementation differentially regulated 866 genes between APOE4 carriers and noncarriers. Gene set enrichment analysis showed that carriers had a higher gene expression of cholesterol biosynthesis and IFN signaling pathways. Fish-oil supplementation reduced expression of IFN-related genes in carriers only. CONCLUSION: The increased expression of IFN signaling and cholesterol biosynthesis pathways might explain part of the association between APOE4 and CVD. Fish-oil supplementation may particularly benefit APOE4 carriers by decreasing expression of IFN-related genes.

Arm dermolipectomy with a quadrangular flap and "T" closure.

We present a technique for the correction of obesity and/or ptosis of the arms. It consists of raising a lower quadrangular advancement flap, sliding the upper wound margin downward, cutting the excess off the quadrangular flap, and a T-shaped closure. A compressive elastic bandage is worn continuously for 3 months to help keep the closure scar flat and prevent its hypertrophy.

Ear cartilage grafts to the nose.

We present our experience in the treatment of secondary nasal deformities caused by excessive resection of the nasal dorsum. We have used ear cartilage autografts, with good results and (on the whole) little or no resorption (some have been followed for 10 years). We consider it essential to correctly shape the transplant and to hold it firmly in the proper position for a period of not less than one week.

Use of rotation scalp flaps for treatment of occipital baldness.

We have used 25 rotation scalp flaps to treat occipital baldness associated with fronto-parietal baldness (the third flap), and 35 such flaps for the correction of isolated occipital baldness. We have not had any flap necrosis, and our patients have been well satisfied with the results of this surgery.

Neighboring flaps and cartilage grafts for correction of serious secondary nasal deformities.

When the secondary nasal deformity is so serious that it presents loss of the soft structures, often its correction requires a neighboring flap besides the cartilage auto-grafts. In such serious cases, which are fortunately infrequent, the surgeon must resort to reconstructive techniques that typically provide very good results. Such is the case with the midforehead Indian flap, which rotated 180 degrees, allows reconstruction of the columella in the same surgical stage. In the same manner, Denonvilliers' flap may be employed to restore contour of the nasal ala, since its scar sequel is very acceptable, and Dieffenbach's flap may be used to reconstruct the columella. The flap of labial mucosa (which other authors have employed to correct septal perforations) is rotated 90 degrees to appose with another similar contralateral flap and is used to correct the seriously retracted columella. In this paper we present some cases that demanded the application of these techniques.

Ear replantation.

The authors' tactical and technical contribution to this type of microsurgical replantation can be summarized in three main points: (1) direct sutures to the superficial temporal vessels, when these are undamaged, which simplifies the operation and makes it safer; (2) use of Kunlin's technique to make up for the great difference in diameter between the arterial vessels; and (3) deepithelialization of the posterior auricular skin to allow for creation of venous drainage channels during the first postoperative days and the enlargement of the area of contact with the recipient bed, which also helps to better immobilize the amputated part.

Correction of the secondary nasal tip and of alar and/or columellar collapse.

The authors present their surgical technique for the correction of the secondary nasal tip with alar and/or columellar collapse. They employ a cartilage autograft in the form of an anchor or half an anchor which is taken from the auricular concha and is designed according to the requirements of the pathology to be corrected. In their experience, they have observed neither complications with the use of these grafts nor unacceptable scars in the columellar incision.

¿Tiene la acupuntura un rol en el tratamiento de la enfermedad de Parkinson? / Is acupuncture an alternative for the treatment of Parkinson's Disease?

INTRODUCCIÓN: Se postula que la acupuntura podría tener diversos beneficios para pacientes con enfermedad de Parkinson. No obstante, su real efectividad clínica aún es discutida. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos nueve revisiones sistemáticas que en conjunto incluyen 53 estudios primarios, de los cuales 45 corresponden a ensayos aleatorizados. Concluimos que la acupuntura podría tener un efecto mínimo en mejorar los síntomas motores y la discapacidad en la enfermedad de Parkinson, pero la certeza de la evidencia es baja.

INTRODUCTION: It has been proposed that acupuncture has several benefits for patients with Parkinson's disease. However, its real clinical effect is still under discussion. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified nine systematic reviews including 53 studies overall, of which 45 were randomized trials. We concluded acupuncture might have a small effect in improving motor symptoms and disability in Parkinson's disease, but the certainty of the evidence is low.

¿Es efectivo el tratamiento con células madre en la enfermedad de Parkinson? / Is treatment with stem cells effective in Parkinson's disease?

Resumen INTRODUCCIÓN: Muchos pacientes con enfermedad de Parkinson tienen una respuesta limitada con el tratamiento farmacológico convencional. Se ha postulado el uso de células madre como una alternativa, aunque su efectividad sigue siendo un tema de controversia. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos dos revisiones sistemáticas que en conjunto incluyeron 21 estudios primarios, de los cuales tres corresponden a ensayos aleatorizados. Concluimos que no está claro si las células madre podrían tener algún efecto sobre la sintomatología de la enfermedad de Parkinson porque la certeza de la evidencia disponible es muy baja.

Abstract INTRODUCTION: There are many patients with Parkinson's disease who have a limited response to conventional pharmacological treatment. The use of stem cells has been postulated as an alternative, although its effectiveness remains a matter of controversy. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified two systematic reviews including 21 studies overall, of which three were randomized trials. We concluded it is not clear whether stem cells have any effect on the symptoms of Parkinson's disease because the certainty of the available evidence is very low.