Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates.

Although neuromelanin is a dark pigment characteristic of dopaminergic neurons in the human substantia nigra pars compacta, its potential role in the pathogenesis of Parkinson's disease (PD) has often been neglected since most commonly used laboratory animals lack neuromelanin. Here we took advantage of adeno-associated viral vectors encoding the human tyrosinase gene for triggering a time-dependent neuromelanin accumulation within substantia nigra pars compacta dopaminergic neurons in macaques up to similar levels of pigmentation as observed in elderly humans. Furthermore, neuromelanin accumulation induced an endogenous synucleinopathy mimicking intracellular inclusions typically observed in PD together with a progressive degeneration of neuromelanin-expressing dopaminergic neurons. Moreover, Lewy body-like intracellular inclusions were observed in cortical areas of the frontal lobe receiving dopaminergic innervation, supporting a circuit-specific anterograde spread of endogenous synucleinopathy by permissive trans-synaptic templating. In summary, the conducted strategy resulted in the development and characterization of a new macaque model of PD matching the known neuropathology of this disorder with unprecedented accuracy. Most importantly, evidence is provided showing that intracellular aggregation of endogenous α-synuclein is triggered by neuromelanin accumulation, therefore any therapeutic approach intended to decrease neuromelanin levels may provide appealing choices for the successful implementation of novel PD therapeutics.

Glucocerebrosidase Gene Therapy Induces Alpha-Synuclein Clearance and Neuroprotection of Midbrain Dopaminergic Neurons in Mice and Macaques.

Mutations in the GBA1 gene coding for glucocerebrosidase (GCase) are the main genetic risk factor for Parkinson's disease (PD). Indeed, identifying reduced GCase activity as a common feature underlying the typical neuropathological signatures of PD-even when considering idiopathic forms of PD-has recently paved the way for designing novel strategies focused on enhancing GCase activity to reduce alpha-synuclein burden and preventing dopaminergic cell death. Here we have performed bilateral injections of a viral vector coding for the mutated form of alpha-synuclein (rAAV9-SynA53T) for disease modeling purposes, both in mice as well as in nonhuman primates (NHPs), further inducing a progressive neuronal death in the substantia nigra pars compacta (SNpc). Next, another vector coding for the GBA1 gene (rAAV9-GBA1) was unilaterally delivered in the SNpc of mice and NHPs one month after the initial insult, together with the contralateral delivery of an empty/null rAAV9 for control purposes. Obtained results showed that GCase enhancement reduced alpha-synuclein burden, leading to improved survival of dopaminergic neurons. Data reported here support using GCase gene therapy as a disease-modifying treatment for PD and related synucleinopathies, including idiopathic forms of these disorders.

Adeno-Associated Viral Vectors as Versatile Tools for Parkinson's Research, Both for Disease Modeling Purposes and for Therapeutic Uses.

It is without any doubt that precision medicine therapeutic strategies targeting neurodegenerative disorders are currently witnessing the spectacular rise of newly designed approaches based on the use of viral vectors as Trojan horses for the controlled release of a given genetic payload. Among the different types of viral vectors, adeno-associated viruses (AAVs) rank as the ones most commonly used for the purposes of either disease modeling or for therapeutic strategies. Here, we reviewed the current literature dealing with the use of AAVs within the field of Parkinson's disease with the aim to provide neuroscientists with the advice and background required when facing a choice on which AAV might be best suited for addressing a given experimental challenge. Accordingly, here we will be summarizing some insights on different AAV serotypes, and which would be the most appropriate AAV delivery route. Next, the use of AAVs for modeling synucleinopathies is highlighted, providing potential readers with a landscape view of ongoing pre-clinical and clinical initiatives pushing forward AAV-based therapeutic approaches for Parkinson's disease and related synucleinopathies.

Retroclival epidural haematoma: a diagnosis to suspect. Report of three cases and review of the literature.

Retroclival epidural haematoma (REDH) has been reported infrequently. It is a rare entity which is probably underdiagnosed. It is most commonly seen in the paediatric population and is generally associated with high-velocity injuries. We report three cases of paediatric patients diagnosed with REDHs: two of them secondary to high-energy trauma related to a motor-vehicle accident and the other a low-energy trauma after a slip while playing football. All three patients were managed conservatively by cervical immobilisation with favourable outcome. REDH is probably underdiagnosed by computed tomography scan. When the suspicion is high, sagittal reconstructions or magnetic resonance imaging should be considered to confirm the diagnosis. Usually, it is related to hyperflexion or hyperextension cervical injuries secondary to motor vehicle accident. However, it can also be observed in milder injuries.

[Giant cell tumor of the lumbar spine. Case report and review of the literature]. / Tumor de células gigantes de raquis lumbar. Caso clínico y revisión de la literatura.

We report the case of a 32-year-old patient complaining of chronic low back pain radiating to his left thigh. His MRI showed a lytic L1 vertebral body injury. A transpedicular biopsy confirmed the diagnosis of giant cell tumor. He underwent a L1 vertebrectomy and vertebral body replacement with a titanium cylinder using anterior approach, followed by the removal of the L1 posterior arch and the placement of pedicle screws through a posterior approach. The giant cell tumor is a rare benign primary bone tumor that can be locally aggressive and can potentially spread to other areas, usually to the lungs. Although it most frequently affects long bones, approximately 10% of tumors are located in the spine. To minimise the risk of recurrence, the elective management option is surgery.

Occurrence of free-living amoebae in streams of the Mexico Basin.

Free-living amoebae (FLA) are protozoa that are widely distributed in nature. They are important in the cycling of nutrients in aquatic food chains, but their distribution in natural aquatic environments is not well known. We conducted a survey to determine the presence and distribution of FLA and their relation to some physicochemical parameters in streams of the Mexico Basin in Central Mexico. Thirty-two sites from 18 streams were sampled. Samples were centrifuged and cultured onto NNA-media to isolate amoebae. Identifications were based on morphology. The pathogenicity of Acanthamoeba isolates was tested. Oxygen saturation, temperature, pH, specific conductance, water flow, dissolved reactive phosphorus, nitrites, nitrates, ammonia, dissolved inorganic nitrogen and coliforms were determined. One hundred-and-twenty FLA representing 18 genera were identified. The most frequent genera were Vannella, Rosculus and Acanthamoeba. The frequency of potentially pathogenic FLA was low and only 3 Acanthamoeba isolates were invasive in mice. The highest species richness of FLA was found in streams located into agriculture activity areas and those close to small villages that discharge wastewater into them. Water temperatures were always below 17°C. Oxygen saturation and pH were within the limits for the growth of most FLA. The presence of Acanthamoeba and Naegleria was low; nevertheless, they include potentially pathogenic species and can act as vectors and reservoirs for microbial pathogens and can produce human infections.

Effects of Submerged Macrophytes on Demography and Filtration Rates of Daphnia and Simocephalus (Crustacea: Cladocera).

Macrophytes and cladocerans represent the main antagonistic groups that regulate phytoplankton biomass; however, the mechanism behind this interaction is unclear. In laboratory conditions, we separately evaluated the effects of three submerged macrophytes (Ceratophyllum demersum, Myriophyllum aquaticum, and Stuckenia pectinata), as well as their exudates, and plant-associated microbiota (POM < 25 µm) + exudates on the population growth of Daphnia cf. pulex and Simocephalus cf. mixtus. Living Ceratophyllum, exudates, and POM < 25 µm + exudates exhibited the most robust positive effects on Simocephalus density and the rate of population increase (r). Subsequently, we examined the effects of Ceratophyllum on the filtration and feeding rates of Simocephalus and Daphnia, revealing significant (p < 0.001) promotion of filtration and feeding in Simocephalus but not in Daphnia. To elucidate the specific effects of this macrophyte on Simocephalus demography, we assessed selected life table variables across the same treatments. The treatments involving exudates and living Ceratophyllum resulted in approximately 40% longer survivorship and significantly (p < 0.01) enhanced fecundity. Our findings indicate that exudates from submerged macrophytes positively influence Simocephalus demography by increasing filtration rates, survivorship, and fecundity. This synergy suggests a substantial impact on phytoplankton abundance.

Automated Computer-Assisted Medical Decision-Making System Based on Morphological Shape and Skin Thickness Analysis for Asymmetry Detection in Mammographic Images.

Breast cancer is a significant health concern for women, emphasizing the need for early detection. This research focuses on developing a computer system for asymmetry detection in mammographic images, employing two critical approaches: Dynamic Time Warping (DTW) for shape analysis and the Growing Seed Region (GSR) method for breast skin segmentation. The methodology involves processing mammograms in DICOM format. In the morphological study, a centroid-based mask is computed using extracted images from DICOM files. Distances between the centroid and the breast perimeter are then calculated to assess similarity through Dynamic Time Warping analysis. For skin thickness asymmetry identification, a seed is initially set on skin pixels and expanded based on intensity and depth similarities. The DTW analysis achieves an accuracy of 83%, correctly identifying 23 possible asymmetry cases out of 20 ground truth cases. The GRS method is validated using Average Symmetric Surface Distance and Relative Volumetric metrics, yielding similarities of 90.47% and 66.66%, respectively, for asymmetry cases compared to 182 ground truth segmented images, successfully identifying 35 patients with potential skin asymmetry. Additionally, a Graphical User Interface is designed to facilitate the insertion of DICOM files and provide visual representations of asymmetrical findings for validation and accessibility by physicians.

Adeno-Associated Viral Vectors as Versatile Tools for Neurological Disorders: Focus on Delivery Routes and Therapeutic Perspectives.

It is without doubt that the gene therapy field is currently in the spotlight for the development of new therapeutics targeting unmet medical needs. Thus, considering the gene therapy scenario, neurological diseases in general and neurodegenerative disorders in particular are emerging as the most appealing choices for new therapeutic arrivals intended to slow down, stop, or even revert the natural progressive course that characterizes most of these devastating neurodegenerative processes. Since an extensive coverage of all available literature is not feasible in practical terms, here emphasis was made in providing some advice to beginners in the field with a narrow focus on elucidating the best delivery route available for fulfilling any given AAV-based therapeutic approach. Furthermore, it is worth nothing that the number of ongoing clinical trials is increasing at a breath-taking speed. Accordingly, a landscape view of preclinical and clinical initiatives is also provided here in an attempt to best illustrate what is ongoing in this quickly expanding field.

Trachelomonas (Euglenophyta) from a eutrophic reservoir in Central Mexico.

This study provides valuable information on the ultrastructure and environmental conditions of the Trachelomonas Ehr. (Euglenophyceae) genus in the Guadalupe Dam, a eutrophic reservoir located in the suburbs of Mexico City, which receives a considerable volume of wastewaters. Specimens were collected at surface level between November 2005 and May 2006. Using LM and SEM twelve taxa from phytoplankton were identified of which, 9 are new records for Mexico. The reservoir is warm monomictic, with basic pH values (7.4-10.1), a high concentration of chlorophyll a(18-101 microg l(-1), a permanent anoxic bottom, specific conductivity (K25) of 205 to 290 microS cm(-1), N-NO3, 0.19-1.2 mg l(-1) and P-PO4 0.22-1.6 mg l(-1). Water temperature was 15.6-23.0 degrees C. Most of the Trachelomonas species were found during the dry season, when concentrations of organic matter, nitrogen and phosphorus as well as the temperature were the highest. Higher species richness was also associated with the warmer months. This research contributes to increase our knowledge on Trachelomonas in Mexico and constitutes the first detailed description of lorica ultrastructure of 12 taxa that grow in a body of water with high concentration of nutrients and a moderate amount of mineral contents.

Planktonic ciliates in a hypertrophic pond: functional role and importance.

Taxonomical composition and abundance of the planktonic ciliate assemblage in a Lake Tezozomoc, a hypertrophic pond located into an urban park in Mexico City, was investigated along the rainy season (May to October). The aims of the study were to know the main trophic roles and ecological significance of ciliates in a highly productive environment. A low number of taxa (27) and a wide abundance fluctuation (104-387 cil ml(-1)) were found. The most abundant species (up to 162 cil ml(-1)) was Halteria grandinella, an oligotrich ciliate that graze on bacteria and picoplankton, but also several big body sized species that feed on pico and nanoplankton were abundant. Sudden temporal changes in species dominance occurred. Ciliate biomass was very high and fluctuated widely (1.6-88 10(6) microm(3) ml(-1)) being dominated by the >50 microm size fraction that mainly included the pico and nanoplankton feeders. Ciliates are a very important component in the plankton of hypertrophic lakes and their main control factor seems to be the grazing by big-body size Daphnia species.

Longitudinal atlantoaxial dislocation associated with type III odontoid fracture due to high-energy trauma. Case report and literature review.

INTRODUCTION: Traumatic upper cervical spine injuries are frequently associated with high-energy trauma. The potential injuries to vital organs associated to a possible neurological damage marks the severity of this pathology. The neurological structures can be affected by a primary injury, spinal cord, cranial nerves and spinal nerves; or secondary to a vascular compromise, mainly the vertebral arteries. The dislocation of the atlantoaxial joint causes an unstable cervical spine that could be often associated with fracture of the Atlas and Axis. Evidently, these have a high morbimortality rate. CASE PRESENTATION: A young woman who suffered a severe polytrauma secondary to a motor vehicle collision was diagnosed with a sagittal plane atlantoaxial joint dislocation associated with a type III odontoid fracture, despite an adequate initial polytrauma management, the neurological damage was too critical, ultimately the decease of the patient. DISCUSSION: The atlantoaxial joint dislocation is a rare condition of the upper cervical spine and is usually secondary to a high-energy traumatism. The disruption of the atlantoaxial ligaments originates the considered most unstable cervical spine lesion and with the highest mortality. Attributable to the kinetic the bone fracture of the Atlas and Axis are commonly related, specially the odontoid process. Early immobilization followed by surgical decompression and stabilization is primordial. Typically, these injuries have an ominous prognosis, that is aggravated if added a polytrauma affecting adjacent neurological structures and other vital organs.

Remarks on Mastigodiaptomus (Calanoida: Diaptomidae) from Mexico using integrative taxonomy, with a key of identification and three new species.

BACKGROUND: In Mexico, species of four families of free-living calanoid copepods have been recorded as inhabitants of several freshwater systems. These families are Centropagidae, Temoridae, Pseudodiaptomidae and Diaptomidae. The genera Leptodiaptomus and Mastigodiaptomus are the most speciose diaptomid genera in Mexico, and they inhabit natural and artificial lakes, ephemeral ponds, springs, and caverns. Leptodiaptomus is considered as an endemic Nearctic genus, whereas Mastigodiaptomus is a widely distributed Neotropical genus in the southern USA, Mexico, the Caribbean Islands and Central America. Based on new and recent evidence, Mastigodiaptomus diversity has been underestimated: six species of the genus were known before 2000. In this work three new Mastigodiaptomus species have been described from different regions of Mexico by using integrative taxonomy. We also gave amended diagnosis of M. nesus Bowman (1986) and M. patzcuarensis s. str. (Kiefer, 1938). METHODS: In this work, the taxonomic status of the species was clarified using modern, integrative method based on the COI gene as a DNA marker, plus micro-structural analysis (based on SEM and ligth microscopy). RESULTS: Three new species of Mastigodiaptomus were described based on genetic and morphological analyses: M. alexei sp. n., M. ha sp. n. and M. cihuatlan sp. n. Also amended description of M. nesus, morphological variation of M. patzcuarensis s. str., and a comparison of them with all known sequences within the genus are provided. These new findings show that in Mastigodiaptomus differences in several cuticular microstructures of several appendages (such as the antennules, the fifth legs, or the urosomites of these copepods) agree with the interspecific genetic divergence >3% observed in sequences of the COI gene, and the integration of this information is a powerful tool in species delineation.

Effect of Ursolic Acid on Insulin Resistance and Hyperinsulinemia in Rats with Diet-Induced Obesity: Role of Adipokines Expression.

Excess of visceral adipose tissue (VAT) characteristic of obesity leads to a proinflammatory state disrupting the insulin signaling pathway, triggering insulin resistance (IR) and inflammation, the main processes contributing to obesity comorbidities. Ursolic acid (UA), a pentacyclic triterpenoid occurring in a variety of plant foods, exhibits anti-inflammatory properties. The aim of this study was to evaluate UA effects on IR, hyperinsulinemia, and inflammation in experimental diet-induced obesity. Forty male Wistar rats were randomly assigned to eight groups (n = 5). One group was used for time 0. Three groups were labeled as OBE (control): receiving high-fat diet (HFD; fat content 45.24% of energy) during 3, 6, or 9 weeks; three groups UA-PREV: exposed to simultaneous HFD and UA during 3, 6, or 9 weeks to evaluate UA preventive effects; one group UA-REV: receiving HFD for 6 weeks, followed by simultaneous HFD and UA for three additional weeks to analyze UA reversal effects. Measurements were performed after 3, 6, or 9 weeks of treatment. Adiposity was calculated by weighing VAT after sacrifice. Serum markers were quantified through colorimetric and enzyme-linked immunosorbent assay methods. VAT adipokines RNAm expression was evaluated by quantitative reverse transcriptase-polymerase chain reaction. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests. UA significantly decreased adiposity, IR, hyperinsulinemia, triacylglycerides, and cholesterol levels, and also VAT mRNA expression of MCP-1 (monocyte chemoattractant protein-1), IL (interleukin)-1ß and IL-6, concomitantly increasing adiponectin levels. UA metabolic effects demonstrated in this study support its potential therapeutic utility to improve IR, hyperinsulinemia, and inflammation observed in obesity and diabetes.

Atención psiquiátrica en Galicia en el siglo XIX: crónica sobre la fundación del “Manicomio de Conxo” / Assistência psiquiátrica na Galiza no século XIX: uma história sobre a fundaçãodo “Manicomio de Conxo” / Psychiatric care in Galicia in the 19th century: a story about the foundation of the “Manicomio de Conxo”

Objective: the aim of this article is to reconstruct the history of the foundation of“Manicomio de Conxo”, an essential institution to understand the development of psychiatry inGalicia during the 19th century. Reconstruction was done by the analysis of the journals of thetime. Method: we searched in journals published between 1845 – 1890 in the digital archivesGaliciana and Biblioteca Nacional de España. Finally, a search of scientific articles was carriedout for the discussion of the results. Results: the findings indicate the project started in 1862, withthe propositions of the Condesa de Espoz y Mina and the governor of A Coruña. Finally, theSantiago sanatorium was inaugurated the 1st of July 1885, under the patronage of Arzobispo Payáy Rico.Conclusions: The non-existence of asylums and the expensive transfers justified thefoundation of a psychiatric institution in Galicia. During the second half of the 19th century, thepolitical and social instability influenced the paralysis and resumption of the project, and theHISTORIA53Cultura de los Cuidados. 1º Cuatrimestre 2022. Año XXVI. nº 62negotiations and discussions between different entities for a long time. The asylum was thereference for other institutions, despite its perpetual confinement and its private management.(AU)

Objetivo: reconstituir la historia de la fundación y apertura del Manicomio de Conxo,institución imprescindible para comprender el desarrollo de la psiquiatría gallega durante el sigloXIX, a través del análisis de la prensa profesional de la época. Método: búsqueda documentalpublicada entre 1845 y 1890 en las hemerotecas digitales Galiciana y Biblioteca Nacional deEspaña. Posteriormente, se realizó una pesquisa de artículos científicos para la discusión de losresultados. Resultados: Los hallazgos obtenidos fijan 1862 como fecha de partida del proyecto,con las propuestas de la Condesa de Espoz y Mina y el gobernador de A Coruña. Finalmente, el1 de julio de 1885 se inaugura el sanatorio santiagués, gracias al mecenazgo del Arzobispo Payáy Rico. Conclusiones: La ausencia de manicomios en el territorio gallego y los costosos trasladosjustificaban la fundación de una institución psiquiátrica en Galicia. La inestabilidad política ysocial durante la segunda mitad del siglo XIX, propició la paralización y reanudación delproyecto, negociaciones y discusiones entre diferentes entes y su prolongación en el tiempo. Elmanicomio fue centro de referencia para otras instituciones, a pesar de su carácter reclusorioperpetuo y su gestión privada.(AU)

Objetivo: reconstruir a história da fundação do “Manicomio de Conxo”, instituiçãoessencial para compreender o desenvolvimento da psiquiatria galega durante o século XIX,analisando os jornais da época. Método: pesquisa de artigos de jornais publicados entre 1845 e1890 nos arquivos do jornal digital Galiciana e na Biblioteca Nacional de España.Posteriormente, foi realizada uma pesquisa de artigos científicos para discussão dos resultados.Resultados: de acordo com os resultados, o projeto começou em 1862, com as propostas daCondessa de Espoz y Mina e do governador de A Coruña. Finalmente, em 1º de julho de 1885,foi inaugurado o sanatório Santiagués, graças ao patrocínio do Arcebispo Payá y Rico.Conclusões: a ausência de manicômios no território galego e as despesas de viagem justificarama fundação de uma instituição psiquiátrica na Galiza. A instabilidade política e social durante asegunda metade do século XIX levou à paralisação e retomada do projeto. As negociações ediscussões entre diferentes entidades foram estendidas ao longo do tempo. O manicômio era umcentro de referência para outras instituições, apesar de seu caráter perpétuo e de sua gestãoprivada.(AU)

IRS-1 pY612 and Akt-1/PKB pT308 Phosphorylation and Antiinflammatory Effect of Diindolylmethane in Adipocytes Cocultured with Macrophages.

BACKGROUND: 3,3'-Diindolylmethane (DIM) is a condensation product of indole-3-carbinol, a glucosinolate naturally occurring in Brassica genus vegetables. The antiinflammatory properties of DIM through the inhibition of NF-κB, as well as its ameliorating effects on glucose tolerance and hyperglicemic states, have been described. A subclinical proinflammatory profile resultant from the interaction of adipocytes and macrophages has been reported in obesity, affecting the insulin signaling pathway, contributing to insulin resistance. OBJECTIVE: The aim of this study was to evaluate the effect of DIM on proinflammatory cytokines and phosphorylation of IRS-1 pY612 and Akt-1/PKB pT308 in an obesity-induced inflammation model. METHODS: Differentiated 3T3-L1 adipocytes were co-cultured with RAW 264.7 macrophages and exposed to 20 µM, 40 µM and 60 µM DIM for 24 h followed by 100 nM insulin for 20 min. MCP-1, IL-6 and TNFα were quantified in the supernatant through individual ELISAs. Adipocyte lysates were used to determine the relative expression of the proinflammatory mediators by qPCR, and the phosphorylation of IRS-1 pY612 and Akt-1/PKB pT308 proteins by western blot analysis. RESULTS: DIM significantly (p<0.05) reduced the production and mRNA expression of MCP-1, IL-6, and TNFα in a DIM concentration dependent manner, concomitantly increasing the abundance of IRS-1 pY612 and Akt-1/PKB pT308. CONCLUSION: Our results suggest that DIM influences the insulin transduction pathway by exerting an antiinflammatory effect. The potential therapeutic benefits of DIM in the treatment of glucose metabolic disorders deserve further studies.

El enfermo mental en el Hospital de Nuestra Señora de Gracia en el siglo XV / Os doentes mentais no Hospital de Nuestra Señora de Gracia no século XV / The mentally ill in the Hospital de Nuestra Señora de Gracia in the fifteenth century

Objetivos: describir la fundación, organización y funcionamiento del Hospital de NuestraSeñora de Gracia de Zaragoza en el siglo XV, y su relevancia histórica en la atención del enfermomental desde un planteamiento interdisciplinar. Método: se buscaron artículos científicos y otrosdocumentos en varias bases de datos. Tras el análisis y filtrado de los resultados, se consultaronlas referencias bibliográficas de los documentos seleccionados.Resultados: el hospital se fundóen 1425 y la atención sanitaria era universal. Era asimétrico e irregular, debido a la adaptación delos edificios ya existentes, con numerosas estancias. Las Ordenaciones de 1496 describen el roldel “enfermero mayor” y la “mujer enfermera”. No hay registro de que se realizase terapiaocupacional en el siglo XV en la institución. Conclusiones: el edificio no sigue el diseñoarquitectónico predominante de aquella época, ni segrega al demente del resto de pacientes. Seconsideraba fundamental la atención alimentaria e higiene de todos los pacientes para surecuperación. A pesar de no haber registro de cuidados psiquiátricos específicos, es razonable pensar que los dementes realizaran labores de mantenimiento y agricultura en el hospital duranteel siglo XV, aunque con fines productivos más que terapéuticos.(AU)

Objectivos: descrever a fundação, organização e funcionamento do Hospital de NuestraSeñora de Gracia em Saragoça no século XV e a sua relevância histórica no cuidado dos doentesmentais a partir de uma abordagem interdisciplinar. Método: artigos e outros documentosrelacionados foram pesquisados em várias bases de dados. Após análise e filtragem, foramconsultadas as referências bibliográficas dos documentos selecionados. Resultados: o hospital foifundado em 1425 e os cuidados de saúde eram universais. Era assimétrico e irregular, devido àadaptação dos edifícios existentes, com inúmeras divisões. As Ordenações de 1496 descrevem opapel do “enfermero mayor” e da “mujer enfermera”. Não há registro de terapia ocupacionalrealizada no século 15 na instituição. Conclusões: o edifício não segue o projeto arquitetônicopredominante da época, nem separa os loucos do resto dos pacientes. Os cuidados alimentares ede higiene de todos os pacientes foram considerados essenciais para a sua recuperação. Apesar daausência de registro de atendimento psiquiátrico específico, é razoável pensar que os loucosrealizavam manutenção e agricultura no hospital durante o século XV, embora com finsprodutivos e não terapêuticos.(AU)

Objectives: to describe the foundation, organization and operation of the Hospital deNuestra Señora de Gracia in Zaragoza in the 15th century and its historical relevance in the careof the mentally ill from an interdisciplinary approach.Method: scientific articles and otherdocuments were searched in various databases. After analyzing and filtering the results, thebibliographic references of the selected documents were consulted.Results: the hospital it wasfounded in 1425 and all were treated healthily. It was asymmetrical and irregular, due to theadaptation of the existing buildings, with numerous rooms. The Ordinations of 1496 describe therole of the “enfermero mayor” and the “mujer enfermera”. There is no record of occupationaltherapy being performed in the 15th century at the institution.Conclusions: the building does notfollow the predominant architectural design of that time, nor does it segregate the mental patientsfrom the rest of the people. Feeding and hygiene care was considered essential for the recoveryof all patients. Despite the absence of a record of specific psychiatric care, it is reasonable to thinkthat the insane made different tasks in the hospital during the 15th century, although forproductive rather than therapeutic purposes.(AU)

Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in macaques: changes following experimental parkinsonism.

Although type 1 cannabinoid receptors (CB1Rs) are expressed abundantly throughout the brain, the presence of type 2 cannabinoid receptors (CB2Rs) in neurons is still somewhat controversial. Taking advantage of newly designed CB1R and CB2R mRNA riboprobes, we demonstrate by PCR and in situ hybridization that transcripts for both cannabinoid receptors are present within labeled pallidothalamic-projecting neurons of control and MPTP-treated macaques, whereas the expression is markedly reduced in dyskinetic animals. Moreover, an in situ proximity ligation assay was used to qualitatively assess the presence of CB1Rs and CB2Rs, as well as CB1R-CB2R heteromers within basal ganglia output neurons in all animal groups (control, parkinsonian and dyskinetic macaques). A marked reduction in the number of CB1Rs, CB2Rs and CB1R-CB2R heteromers was found in dyskinetic animals, mimicking the observed reduction in CB1R and CB2R mRNA expression levels. The fact that chronic levodopa treatment disrupted CB1R-CB2R heteromeric complexes should be taken into consideration when designing new drugs acting on cannabinoid receptor heteromers.

Inflammation and malnutrition as predictors of mortality in patients on hemodialysis.

BACKGROUND: Low albumin and high C-reactive protein (CRP) are significant predictors of mortality in hemodialysis (HD) patients. Although, classically, hypoalbuminemia has been attributed to malnutrition, inflammation can also predict the serum albumin concentration in dialysis patients. OBJECTIVE: To establish the influence of nutritional status and inflammation on mortality in HD patients. METHODS: A cross-sectional study was conducted in 64 patients (35 males; 9 diabetics; mean age 64 +/- 12 years), who had been on HD for 64 +/- 58 months. Nutritional status was assessed from estimated protein caloric intake, dietary recall, anthropometric and biochemical parameters, and serum levels of insulin-like growth factor-1 (IGF-1). CRP was used as a marker of inflammation. Comorbidity was measured using a modified M. Charlson index. The dialysis doses (Kt/V) and protein catabolic rate (PCR) were measured and standardized for actual and ideal body weight. The incidence and causes of death were recorded during the two-year follow-up. RESULTS: During the follow-up period, 18 patients died and 11 were withdrawn from the study after receiving a renal transplant. In multivariante analysis (Cox proportional hazards model), total comorbidity and the levels of CRP and hematocrit (increased) and IGF-1 (decreased) were independent predictors of mortality. CONCLUSIONS: Inflammation, as measured by CRP, and malnutrition, as measured by IGF-1 levels, are associated with mid-term mortality in HD patients. High hematocrit was an independent risk factor for mortality. Comorbidity, measured by disease and the degree of functional impairment, was a good predictor of mortality.