Glial activation precedes alpha-synuclein pathology in a mouse model of Parkinson's disease

Neuroinflammation is increasingly recognized as an important feature in the pathogenesis of Parkinson's disease (PD). However, it remains unclear whether neuroinflammation contributes to nigral degeneration in PD or is merely a secondary marker of neurodegeneration. We aimed to investigate the temporal relationship between synucleopathy, neuroinflammation and nigrostriatal degeneration in a mouse model of PD. Mice received unilateral intrastriatal injection of alpha-synuclein pre-formed fibrils, alpha-synuclein monomer or vehicle and were sacrificed at 15, 30 and 90 days post-injection. Intrastriatal inoculation of alpha-synuclein fibrils led to significant alpha-synuclein aggregation in the substantia nigra peaking at 30 days after injection while the significant increase in Iba-1 cells, GFAP cells and IL-1β expression peaked earlier at 15 days. At 90 days, the striatal dopaminergic denervation was associated with astroglial activation. Alpha-synuclein monomer did not result in long-term glia activation or increase in inflammatory markers. The spread of alpha-synuclein aggregates into the cortex was not associated with any changes to neuroinflammatory markers. Our results demonstrate that in the substantia nigra glial activation is an early event that precedes alpha-synuclein inclusion formation, suggesting neuroinflammation could play an important early role in the pathogenesis of PD

Lipomatosis epidural lumbosacra idiopática: revisión de la bibliografía y caso clínico

La lipomatosis epidural es una afección que aparece generalmente en relación con hipercortisolismos endógenos o exógenos, siendo más raras las formas idiopáticas, de las que se han descrito únicamente 17 casos. Se presenta un nuevo caso con sintomatología compatible con estenosis de canal, y que tras estudios de imagen se demostró que correspondía con una lipomatosis epidural lumbosacra. Se le encomendó al paciente una reducción de peso, con lo que se alivió parcialmente la sintomatología, permaneciendo estable en la actualidad. Se revisa la bibliografía de este raro proceso, exponiendo los distintos hallazgos encontrados. Algunos autores proponen una reducción de peso, lo cual puede aliviar la sintomatología. Para casos rebeldes está indicada la laminectomía asociada al despegamiento de la grasa sin realizar exploración intradural.Epidural lipomatosis is an affection that is usually related to endogenic or exogenous hipercortisolism. Less frequently, it can be idiopathic. To date only 17 cases have been documented. A new case is presented in a patient suffering from symptoms resembling lumbar spinal stenosis. The radiological studies revealed a compression of the dural sac at lumbosacral levéis, caused by tissue similar in density to fat. Weight reduction, was recommended to the patients and a partial relief of symptoms was achieved. The authors reviewed the pathogeny of epidural lipomatosis and its various different treatments. In the idiopathic form, weight reduction is recomended first, reserving surgery for those cases that do not respond to this initial treatment. Surgical treatment should consist of laminectomy and fat debulking, and should not include intradural exploration

A classe Cytisetea scopario-striati em Portugal continental

Giestais são a designação vulgar em português para as comunidades silicícolas que se inserem na classe Cytisetea scopario-striati e são dominadas por espécies de leguminosas dos géneros Cytisus, Genista, Adenocarpus e Retama. Esta classe tem o seu óptimo na Península Ibérica e representa normalmente as orlas ou etapas de regressão de bosques climácicos da Quercetalia roboris e da Quercion broteroi. No presente trabalho apresentam-se as diversas comunidades da classe Cytisetea scopario-striati que ocorrem em Portugal continental. Propõem-se os seguintes novos sintáxones: Ulici latebracteati-Cytisetum striati cytisetosum grandiflori, Cytiso multiflori-Retametum sphaerocarpae cytisetosum scoparii, Cytiso multiflori-Retametum sphaerocarpae cytisetosum eriocarpi, Cytisetum cabezudo

Autosuficiencia energética en la vivienda

Resumen Los edificios, junto al transporte suponen más de la mitad del consumo energético actual de combustible y de la contaminación a este asociada, de difícil solución por la dispersión de los procesos de combustión en poblaciones o carreteras. Esta distribución en la edificación de la demanda favorece el uso de energía solar, el recurso renovable más abundante y de fácil acceso sobre la superficie terrestre, especialmente adecuado en nuestro clima. El uso de tecnología solar requiere procesos de acumulación que garanticen la disponibilidad del calor excesivo del verano durante las frías noches de invierno así como la iluminación o las comunicaciones durante la noche en base a la radiación recibida en las horas de radiación solar. El trabajo describe la posibilidad de captura térmica en la cubierta con almacenamiento selectivo en el subsuelo capaz de satisfacer la demanda de energía para climatización de la vivienda a lo largo del año a un coste ,muy bajo. La energía eléctrica de "alta calidad" se genera y acumulé1localmente en forma de hidrógeno para alimentar según demanda mediante una pila de combustible. Con la tecnología actual, aún en pleno desarrollo, el balance es claramente positivo lo que significa la posibilidad de autosuficiencia energética para una parte considerable de las viviendas.El MEC ha financiado el desarrollo de nuevos dispositivos de hidrógeno en el proyecto "Diseño y realización de una nueva Pila de Combustible polimérica de bajo coste y alta eficacia" MCYT- ENE2005-09124-C04-02/ALT. y el CSIC ha financiado la generación de hidrógeno a partir de residuos orgánicos. El P.S.E. INVISO para industrialización de la vivienda sostenible financia el desarrollo integral de estos sistemas.Peer reviewe

Utility of the MoCA for cognitive impairment screening in long-term psychosis patients

Cognitive impairment is a key feature in patients with psychotic disorders. The Montreal Cognitive Assessment (MoCA) is a brief tool that has been shown to be effective in identifying mild cognitive impairment and early dementia. This study explores the usefulness of this instrument to detect cognitive impairment in long-term psychotic disorders. One hundred-forty stabilized patients were re-evaluated more than 15 years after a First Episode of Psychosis (FEP). Patients were psychopathologically assessed, and the MoCA test and MATRICS Consensus Cognitive Battery (MCCB) were administered. Two cut-off scores for cognitive impairment using the MCCB were applied (T score <40 and < 30). Concurrent validation was found between the total scores of the MoCA and MCCB. We also found significant associations between 5 out of 7 MoCA subtests (visuospatial-executive, attention, language, abstraction and delayed recall) and MCCB subtests but not for the naming and orientation MoCA subtests. Receiver operating characteristic (ROC) analysis suggested a <25 cut-off for cognitive impairment instead of the original <26. Our results suggest that the MoCA test is a useful screening instrument for assessing cognitive impairment in psychotic patients and has some advantages over other available instruments, such as its ease-of-use and short administration time

Characterization and assessment of new fibrillar collagen inks and bioinks for 3D printing and bioprinting

Collagen is a cornerstone protein for tissue engineering and 3D bioprinting due to its outstanding biocompatibility, low immunogenicity, and natural abundance in human tissues. Nonetheless, it still poses some important challenges, such as complicated and limited extraction processes, usually accompanied by batchto-batch reproducibility and influence of factors, such as temperature, pH, and ionic strength. In this work, we evaluated the suitability and performance of new, fibrillar type I collagen as standardized and reproducible collagen source for 3D printing and bioprinting. The acidic, native fibrous collagen formulation (5% w/w) performed remarkably during 3D printing, which was possible to print constructs of up to 27 layers without collapsing. On the other hand, the fibrous collagen mass has been modified to provide a fast, reliable, and easily neutralizable process. The neutralization with TRIS-HCl enabled the inclusion of cells without hindering printability. The cell-laden constructs were printed under mild conditions (50–80 kPa, pneumatic 3D printing), providing remarkable cellular viability (>90%) as well as a stable platform for cell growth and proliferation in vitro. Therefore, the native, type I collagen masses characterized in this work offer a reproducible and reliable source of collagen for 3D printing and bioprinting purposes.This research was funded by Viscofan (S.A.) Centro para el Desarrollo Tecnológico Industrial (CDTI) IDI-20210050 and the Basque Country Government/Eusko Jaurlaritza (Department of Education, University and Research, Consolidated Groups IT907-16). Author Sandra Ruiz-Alonso thanks the Basque Country Government for the granted fellowship PRE_2021_2_0153. José M. Rey thanks the funding from the European’s Union Horizon 2020 research and Innovation framework program (Triankle Project; Grant Agreement #952981). BioRender.com has been used as support for some figures assembly

Systemic Exosomal Delivery of shRNA Minicircles Prevents Parkinsonian Pathology

The development of new therapies to slow down or halt the progression of Parkinson's disease is a health care priority. A key pathological feature is the presence of alpha-synuclein aggregates, and there is increasing evidence that alpha-synuclein propagation plays a central role in disease progression. Consequently, the downregulation of alpha-synuclein is a potential therapeutic target. As a chronic disease, the ideal treatment will be minimally invasive and effective in the long-term. Knockdown of gene expression has clear potential, and siRNAs specific to alpha-synuclein have been designed; however, the efficacy of siRNA treatment is limited by its short-term efficacy. To combat this, we designed shRNA minicircles (shRNA-MCs), with the potential for prolonged effectiveness, and used RVG-exosomes as the vehicle for specific delivery into the brain. We optimized this system using transgenic mice expressing GFP and demonstrated its ability to downregulate GFP protein expression in the brain for up to 6 weeks. RVG-exosomes were used to deliver anti-alpha-synuclein shRNA-MC therapy to the alpha-synuclein preformed-fibril-induced model of parkinsonism. This therapy decreased alpha-synuclein aggregation, reduced the loss of dopaminergic neurons, and improved the clinical symptoms. Our results confirm the therapeutic potential of shRNA-MCs delivered by RVG-exosomes for long-term treatment of neurodegenerative diseases

Improved detection and management of advanced HIV disease through a community adult TB‐contact tracing intervention with same‐day provision of the WHO‐recommended package of care including ART initiation in a rural district of Mozambique

Introduction: AIDS-mortality remains unacceptably high in sub-Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact-tracing intervention (Xpatial-TB). The aim was to assess the burden of AHD among high-risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO-recommended package of care to this population. Methods: All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial-TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4 < 200 cells/μL or WHO stage 3 or 4) were offered a package of interventions in a single visit, including testing for cryptococcal antigen (CrAg) and TB-lipoarabinomannan (TB-LAM), prophylaxis and treatment for opportunistic infections, adherence support or accelerated ART initiation. We collected information on follow-up visits carried out under routine programmatic conditions for six months. Results: A total of 2881 adults were identified in the Xpatial TB-contact intervention. Overall, 23% (673/2881) were HIV positive, including 351 TB index (64.2%) and 322 TB contacts (13.8%). Overall, 159/673 PLHIV (24%) were ART naïve or had suboptimal ART adherence, of whom 155 (97%, 124 TB index and 31 TB-contacts) consented to the study and were screened for AHD. Seventy percent of TB index-patients (87/124) and 16% of TB contacts (5/31) had CD4 < 200 cells/µL. Four (13%) of the TB contacts had TB, giving an overall AHD prevalence among TB contacts of 29% (9/31). Serum-CrAg was positive in 4.6% (4/87) of TB-index patients and in zero TB contacts. All ART naïve TB contacts without TB initiated ART within 48 hours of HIV diagnosis. Among TB cases, ART timing was tailored to the presence of TB and cryptococcosis. Six-month mortality was 21% among TB-index cases and zero in TB contacts. Conclusions: A TB contact-tracing outreach intervention identified undiagnosed HIV and AHD in TB patients and their contacts, undiagnosed cryptococcosis among TB patients, and resulted in an adequate provision of the WHO-recommended package of care in this rural Mozambican population. Same-day and accelerated ART initiation was feasible and safe in this population including among those with AHD

Relationship between cognition and age at onset of first-episode psychosis: comparative study between adolescents, young adults, and adults

Psychotic disorders typically manifest from late adolescence to early adulthood, and an earlier onset might be associated with greater symptom severity and a worse long-term prognosis. This study aimed to compare the cognitive characteristics of patients with first-episode psychosis (FEP) by their age at onset. We included 298 patients diagnosed with FEP and classified them as having an early onset (EOS), youth onset (YOS), or adult onset (AOS) based on age limits of = 25 years (N = 116), respectively. Socio-demographic and clinical variables included age at baseline, gender, socio-economic status, antipsychotic medication, DSM-IV diagnoses assessed by clinical semi-structured interview, psychotic symptom severity, and age at onset. Neuropsychological assessment included six cognitive domains: premorbid intelligence, working memory, processing speed, verbal memory, sustained attention, and executive functioning. The EOS group had lower scores than the YOS or AOS groups in global cognition, executive functioning, and sustained attention. Although the scores in the YOS group were intermediate to those in the EOS and AOS groups for most cognitive factors, no statistically significant differences were detected between the YOS and AOS groups. Age at onset results in specific patterns of cognitive interference. Of note, impairment appears to be greater with EOS samples than with either YOS or AOS samples. A longitudinal study with a larger sample size is needed to confirm our findings

Relapse, cognitive reserve, and their relationship with cognition in first episode schizophrenia: a 3-year follow-up study

Schizophrenia is frequently characterized by the presence of multiple relapses. Cognitive impairments are core features of schizophrenia. Cognitive reserve (CR) is the ability of the brain to compensate for damage caused by pathologies such as psychotic illness. As cognition is related to CR, the study of the relationship between relapse, cognition and CR may broaden our understanding of the course of the disease. We aimed to determine whether relapse was associated with cognitive impairment, controlling for the effects of CR. Ninety-nine patients with a remitted first episode of schizophrenia or schizophreniform disorder were administered a set of neuropsychological tests to assess premorbid IQ, attention, processing speed, working memory, verbal and visual memory, executive functions and social cognition. They were followed up for 3 years (n=53) or until they relapsed (n=46). Personal and familial CR was estimated from a principal component analysis of the premorbid information gathered. Linear mixed-effects models were applied to analyse the effect of time and relapse on cognitive function, with CR as covariate. Patients who relapsed and had higher personal CR showed less deterioration in attention, whereas those with higher CR (personal and familial CR) who did not relapse showed better performance in processing speed and visual memory. Taken together, CR seems to ameliorate the negative effects of relapse on attention performance and shows a positive effect on processing speed and visual memory in those patients who did not relapse. Our results add evidence for the protective effect of CR over the course of the illness