Neuroinflammation is one of the hallmarks of Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to ...resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD - to modulate disease progression - still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.
The efficacy of standard rehabilitative therapy for improving upper limb functions after stroke is limited; thus, alternative strategies are needed. Vagus nerve stimulation (VNS) paired with ...rehabilitation is a promising approach, but the invasiveness of this technique limits its clinical application. Recently, a noninvasive method to stimulate vagus nerve has been developed. The aim of the present study was to explore whether noninvasive VNS combined with robotic rehabilitation can enhance upper limb functionality in chronic stroke. Safety and efficacy of this combination have been assessed within a proof-of-principle, double-blind, semirandomized, sham-controlled trial. Fourteen patients with either ischemic or haemorrhagic chronic stroke were randomized to robot-assisted therapy associated with real or sham VNS, delivered for 10 working days. Efficacy was evaluated by change in upper extremity Fugl–Meyer score. After intervention, there were no adverse events and Fugl–Meyer scores were significantly better in the real group compared to the sham group. Our pilot study confirms that VNS is feasible in stroke patients and can produce a slight clinical improvement in association to robotic rehabilitation. Compared to traditional stimulation, noninvasive VNS seems to be safer and more tolerable. Further studies are needed to confirm the efficacy of this innovative approach.
A 54-year-old man sought treatment at the ED for a productive cough with green phlegm of approximately 6 months’ duration that was accompanied by a 10-pound weight loss, night sweats, and occasional ...subjective fevers. He had made several prior visits to the ED for the cough and was hospitalized 4 months earlier for similar symptoms, at which time he underwent a bronchoscopy with BAL and was discharged with antibiotics for presumed pneumonia. He did not report any itching, rashes, sinus infections, joint swelling, joint pain, or GI symptoms. His long-term medications included omeprazole and amlodipine. The patient had a past medical history of grade III follicular lymphoma for which he completed six cycles of bendamustine 4 years before presentation and had been in remission since. He was a never smoker, had a recent travel history to the Dominican Republic 8 months before admission, and had no recent sick contacts.
The cellular response to DNA lesions entails the recruitment of several checkpoint and repair factors to damaged DNA, and chromatin modifications may play a role in this process. Here we show that in ...Saccharomyces cerevisiae epigenetic modification of histones is required for checkpoint activity in response to a variety of genotoxic stresses. We demonstrate that ubiquitination of histone H2B on lysine 123 by the Rad6-Bre1 complex, is necessary for activation of Rad53 kinase and cell cycle arrest. We found a similar requirement for Dot1-dependent methylation of histone H3. Loss of H3-Lys79 methylation does not affect Mec1 activation, whereas it renders cells checkpoint-defective by preventing phosphorylation of Rad9. Such results suggest that histone modifications may have a role in checkpoint function by modulating the interactions of Rad9 with chromatin and active Mec1 kinase.
the use of combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) for the functional evaluation of the cerebral cortex in health and disease is becoming increasingly ...common. However, there is still some ambiguity regarding the extent to which brain responses to auditory and somatosensory stimulation contribute to the TMS-evoked potential (TEP).
to measure separately the contribution of auditory and somatosensory stimulation caused by TMS, and to assess their contribution to the TEP waveform, when stimulating the motor cortex (M1).
19 healthy volunteers underwent 7 blocks of EEG recording. To assess the impact of auditory stimulation on the TEP waveform, we used a standard figure of eight coil, with or without masking with a continuous noise reproducing the specific time-varying frequencies of the TMS click, stimulating at 90% of resting motor threshold. To further characterise auditory responses due to the TMS click, we used either a standard or a sham figure of eight coil placed on a pasteboard cylinder that rested on the scalp, with or without masking. Lastly, we used electrical stimulation of the scalp to investigate the possible contribution of somatosensory activation.
auditory stimulation induced a known pattern of responses in electrodes located around the vertex, which could be suppressed by appropriate noise masking. Electrical stimulation of the scalp alone only induced similar, non-specific scalp responses in the in the central electrodes. TMS, coupled with appropriate masking of sensory input, resulted in specific, lateralized responses at the stimulation site, lasting around 300 ms.
if careful control of confounding sources is applied, TMS over M1 can generate genuine, lateralized EEG activity. By contrast, sensory evoked responses, if present, are represented by non-specific, late (100–200 ms) components, located at the vertex, possibly due to saliency of the stimuli. Notably, the latter can confound the TEP if masking procedures are not properly used.
•The use of combined TMS and EEG is becoming increasingly common.•The contribution of sensory stimulation to the TMS evoked potential is still controversial.•We found that auditory responses to TMS could be suppressed by noise masking.•Somatosensory stimulation of the scalp induced only non-specific responses.•It is possible to obtain EEG responses due to direct brain activation with TMS.
Many genes involved in Drosophila melanogaster innate immune processes have been identified, but whether naturally occurring polymorphism in these genes leads to variation in immune competence among ...wild flies has not been tested. We report here substantial variability among wild-derived D. melanogaster in the ability to suppress infection by a Gram-negative entomopathogen, Serratia marcescens. Variability in immune competence was significantly associated with nucleotide polymorphism in 16 innate immunity genes, corresponding primarily to pathogen recognition and intra-cellular signaling loci, and substantial epistasis was detected between intracellular signaling and antimicrobial peptide genes. Variation in these genes, therefore, seems to drive variability in immunocompetence among wild Drosophila.
Purpose
To assess quality of life (QoL) in adult people with epilepsy (PWE) and identify the main factors affecting it.
Methods
We enrolled consecutively 122 PWE. They were interviewed for a careful ...collection of demographic and clinical data. Patients completed dedicated questionnaires for the assessment of the quality of life (Quality of Life in Epilepsy Scale-31) (Q31) as well as psychosocial features: depressive symptoms (DS) (Beck Depression Inventory-II/BDI-II), difficulties of emotion regulation (Difficulties of Emotion Regulation Scale/DERS), and stigma related to epilepsy (Stigma Scale of Epilepsy/SSE and Jacoby’s Stigma Scale/JSS). The results of Q31 and their subscales were correlated with clinical details of PWE, as well as the other scores. A stepwise multiple regression analysis was applied to identify the main factors affecting QoL.
Results
Quality of life is inversely correlated mostly with psychosocial features, as DS, emotion dysregulation, and stigma perception, as well as with epilepsy-related factors, as the seizure frequency and number of antiseizure medications (ASMs). The combination of DS, perceived stigma, and number of ASMs best explained the QoL. Worse features of QoL were detected in females and in patients with age of epilepsy onset in adulthood.
Conclusion
Quality of life in adult PWE is predominantly affected by psychosocial factors more than epilepsy-related ones. These findings suggest that effective epilepsy management requires more than seizure control, and early detection of psychological dysfunction and tailored interventions to improve the QoL should be considered.
The house fly, Musca domestica, occupies an unusual diversity of potentially septic niches compared with other sequenced Dipteran insects and is a vector of numerous diseases of humans and livestock. ...In the present study, we apply whole-transcriptome sequencing to identify genes whose expression is regulated in adult flies upon bacterial infection. We then combine the transcriptomic data with analysis of rates of gene duplication and loss to provide insight into the evolutionary dynamics of immune-related genes. Genes up-regulated after bacterial infection are biased toward being evolutionarily recent innovations, suggesting the recruitment of novel immune components in the M. domestica or ancestral Dipteran lineages. In addition, using new models of gene family evolution, we show that several different classes of immune-related genes, particularly those involved in either pathogen recognition or pathogen killing, are duplicating at a significantly accelerated rate on the M. domestica lineage relative to other Dipterans. Taken together, these results suggest that the M. domestica immune response includes an elevated diversity of genes, perhaps as a consequence of its lifestyle in septic environments.
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