Schwann cell mitochondrial metabolism supports long-term axonal survival and peripheral nerve function

Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produced through the tissue-specific deletion of the mitochondrial transcription factor A gene (Tfam), which is essential for mitochondrial DNA (mtDNA) transcription and maintenance. Tfam-SCKOs were viable but, as they aged, they developed a progressive peripheral neuropathy characterized by nerve conduction abnormalities as well as extensive muscle denervation. Morphological examination of Tfam-SCKO nerves revealed early preferential loss of small unmyelinated fibers followed by prominent demyelination and degeneration of larger-caliber axons. Tfam-SCKOs displayed sensory and motor deficits consistent with this pathology. Remarkably, the severe mtDNA depletion and respiratory chain abnormalities in Tfam-SCKO mice did not affect SC proliferation or survival. Mitochondrial function in SCs is therefore essential for maintenance of axonal survival and normal peripheral nerve function, suggesting that SC mitochondrial dysfunction contributes to human peripheral neuropathies

El test de transformación de los linfocitos (TTL): Algunas aplicaciones del mismo en el laboratorio de análisis biológicos

Se estudió el test de transformación de linfocitos (TTL) analizándose algunos de los resultados obtenidos en sujetos no alérgicos y enfermos sensibilizados a diferentes sustancias: alergias alimenticias, alergias inhalantes, sustancias nitrogenadas específicas, sensibilizaciones medicamentosas y frente a células tumorales irradiadas empleando poblaciones linfoides autólogas. Se realizan finalmente unas consideraciones generales a las técnicas.The test transformation lymphocite (TTL) was studied, and the results obtained were analyzed in subjects with different substances (foods specific mitogens, inhalants alergens, drugs) and against irradiated tumor cells using autologous linfoide population. Finally general considerations to the technique were made

Silent cerebral infarct after cardiac catheterization as detected by diffusion weighted Magnetic Resonance Imaging: a randomized comparison of radial and femoral arterial approaches

Background and objective: Cerebral microembolism detected by transcranial Doppler (TCD) occurs systematically during cardiac catheterization, but its clinical relevance, remains unknown. Studies suggest that asymptomatic embolic cerebral infarction detectable by diffusion-weighted (DW) MRI might exist after percutaneous cardiac interventions with a frequency as high as 15 to 22% of cases. We have set up, for the first time, a prospective multicenter trial to assess the rate of silent cerebral infarction after cardiac catheterization and to compare the impact of the arterial access site, comparing radial and femoral access, on this phenomenon. Study design: This prospective study will be performed in patients with severe aortic valve stenosis. To assess the occurrence of cerebral infarction, all patients will undergo cerebral DW-MRI and neurological assessment within 24 hours before, and 48 hours after cardiac catheterization and retrograde catheterization of the aortic valve. Randomization for the access site will be performed before coronary angiography. A subgroup will be monitored by transcranial power M-mode Doppler during cardiac catheterization to observe cerebral blood flow and track emboli. Neuropsychological tests will also be recorded in a subgroup of patients before and after the interventional procedures to assess the impact of silent brain injury on potential cognitive decline. The primary end-point of the study is a direct comparison of ischemic cerebral lesions as detected by serial cerebral DW-MRI between patients explored by radial access and patients explored by femoral access. Secondary end-points include comparison of neuropsychological test performance and number of microembolism signals observed in the two groups. Implications: Using serial DW-MRI, silent cerebral infarction rate will be defined and the potential influence of vascular access site will be evaluated. Silent cerebral infarction might be a major concern during cardiac catheterization and its potential relationship to cognitive decline needs to be assessed. Study registration: The SCIPION study is registered through National Institutes of Health-sponsored clinical trials registry and has been assigned the Identifier: NCT 00329979

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions

Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair.

The brain is enriched in arachidonic acid (ARA) and docosahexaenoic acid (DHA), long-chain polyunsaturated fatty acids (LCPUFA) of the n-6 and n-3 series, respectively. Both are essential for optimal brain development and function. Dietary enrichment with DHA and other long-chain n-3 PUFA, such as eicosapentaenoic acid (EPA) have shown beneficial effects on learning and memory, neuroinflammatory processes and synaptic plasticity and neurogenesis. ARA, DHA and EPA are precursors to a diverse repertoire of bioactive lipid mediators, including endocannabinoids. The endocannabinoid system comprises cannabinoid receptors, their endogenous ligands, the endocannabinoids, and their biosynthetic and degradation enzymes. Anandamide (AEA) and 2-archidonoylglycerol (2-AG) are the most widely studied endocannabinoids, and are both derived from phospholipid-bound ARA. The endocannabinoid system also has well established roles in neuroinflammation, synaptic plasticity and neurogenesis, suggesting an overlap in the neuroprotective effects observed with these different classes of lipids. Indeed, growing evidence suggests a complex interplay between n-3 and n-6 LCPUFA and the endocannabinoid system. For example, long-term DHA and EPA supplementation reduces AEA and 2-AG levels, with reciprocal increases in levels of the analogous endocannabinoid-like DHA and EPA-derived molecules. This review summarises current evidence of this interplay and discusses the therapeutic potential for brain protection and repair

When Music and Long-Term Memory Interact: Effects of Musical Expertise on Functional and Structural Plasticity in the Hippocampus

The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus

Parental breeding age effects on descendants' longevity interact over 2 generations in matrilines and patrilines

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does and that breeding age effects can interact over 2 generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over 2 generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grand-parental ages at breeding on descendants' mortality rate and life span in both matrilines and patrilines. These breeding age effects were not modulated by grand-parental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intrapopulation variation in mortality and longevity

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

Ensayo a campo de la eficacia de acaricidas comerciales para el control de Varroa destructor (Acari: varroidae)

La varroosis, causada por Varroa destructor Anderson & Trueman, es una de las principales parasitosis de Apis mellifera L. El objetivo de este trabajo fue evaluar a campo la eficacia del control otoñal con acaricidas comerciales en el partido de Olavarría (Buenos Aires, Argentina). Se utilizó un diseño completamente aleatorizado con cuatro tratamientos y cinco repeticiones en un apiario en producción: 1- Cumavar®, 2- Amivar®, 3- Wang´s Manpu®, y 4- Testigo. Al final del tratamiento se realizó un tratamiento de "choque" con los dos principios activos diferentes al del tratamiento principal. Se monitoreó la infección de ácaros pre y postratamiento; semanalmente se contaron los ácaros caídos para calcular la eficacia de control porcentual (E) y ajustada (Ea) por la fórmula de Abbott. Los acaricidas evaluados resultaron igualmente eficaces en controlar el ácaro V. destructor cuando fueron comparados al tratamiento testigo. Cumavar® tuvo mayor E y Ea (99,5% y 98,9%, respectivamente), las cuales no difirieron (p<0,05) de las obtenidas con Amivar® (89,2% y 87%, respectivamente). Con Wang¿s Manpu® se obtuvo una E de 78% y no difirió estadísticamente (p<0,05) de la E de los otros acaricidas. Sin embargo, la Ea de Wang¿s Manpu® (74,7%) fue significativamente (p<0,05) diferente de la de Cumavar ®. El volteo con Cumavar® fue superior al 90% del total de ácaros a los 14 días de iniciado el ensayo. Con Amivar® y Wang¿s Manpu® el volteo fue de 70% al cabo del mismo período. Los resultados obtenidos ponen de manifiesto la importancia de evaluar regionalmente los diferentes acaricidas comerciales para considerar sus interacciones con el sitio y detectar posibles casos de ácaros resistentes