CONCLUSIONS The use of Delphi in reporting guidelines is insufficient. Users and reviewers should carefully appraise the consensus building in the guidelines. PROTOCOL AND REGISTRATION We applied a pre-specified protocol to conduct this study (Banno M, Tsujimoto Y, Kataoka Y. Reporting quality of the Delphi technique in reporting guidelines a protocol for a systematic analysis of the EQUATOR Network Library. BMJ Open. 2019;9e024942). The study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) (Trial registration number UMIN000032685, URL https//upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037271). Parkinson’s disease (PD), a debilitating progressive degenerative movement disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra (SN), afflicts approximately one million people in the U.S., including a significant number of Veterans. Disease characteristics include tremor, rigidity, postural instability, bradykinesia, and at a cellular level, glial cell activation and Lewy body inclusions in DA neurons. The most potent medical/surgical treatments do not ultimately prevent disease progression. Therefore, new therapies must be developed to halt progression of the disease. While the mechanisms of the degenerative process in PD remain elusive, chronic inflammation, a common factor in many neurodegenerative diseases, has been implicated with associated accumulation of toxic aggregated α-synuclein in neurons. Calpain, a calcium-activated cysteine neutral protease, plays a pivotal role in SN and spinal cord degeneration in PD via its role in α-synuclein aggregation, activation/migration of microglia and T cells, and upregulation of inflammatory processes. Here we report an increased expression of a subset of CD4+ T cells in rodent models of PD, including MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mice and DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride]/6-hydroxydopamine rats, which produced higher levels of perforin and granzyme B – typically found in cytotoxic T cells. Importantly, the CD4+ cytotoxic subtype was attenuated following calpain inhibition in MPTP mice, suggesting that calpain and this distinct CD4+ T cell subset may have critical roles in the inflammatory process, disease progression, and neurodegeneration in PD. Published by Elsevier Inc.Despite internationally established diagnostic criteria, multiple system atrophy (MSA) is frequently misdiagnosed, particularly at disease onset. While neuropathological changes such as demyelination and iron deposition are typically detected in MSA, these structural hallmarks were so far only demonstrated post-mortem. Here, we examine whether myelin deficit observed in a transgenic murine model of MSA can be visualized and quantified in vivo using specific magnetic resonance imaging (MRI) approaches. Reduced myelin content was measured histologically in prototypical white matter as well as mixed grey-white matter regions i.e. corpus callosum, anterior commissure, and striatum of transgenic mice overexpressing human α-synuclein under the control of the myelin basic protein promotor (MBP29-hα-syn mice). Correspondingly, in vivo quantitative susceptibility mapping (QSM) showed a strongly reduced susceptibility contrast in white matter regions and T2-weighted MR imaging revealed a significantly reduced grey-white matter contrast in MBP29-hα-syn mice. In addition, morphological analysis suggested a pronounced, white matter-specific deposition of iron in MBP29-hα-syn mice. Importantly, in vivo MRI results were matched by comprehensive structural characterization of myelin, iron, and axonal directionality. Taken together, our results provide strong evidence that QSM is a very sensitive tool measuring changes in myelin density in conjunction with iron deposition in MBP29-hα-syn mice. This multimodal neuroimaging approach may pave the way towards a novel non-invasive technique to detect crucial neuropathological changes specifically associated with MSA. Several research lines are currently ongoing to address the multitude of facets of the pandemic COVID-19. In line with the One-Health concept, extending the target of the studies to the animals which humans are continuously interacting with may favor a better understanding of the SARS-CoV-2 biology and pathogenetic mechanisms; thus, helping to adopt the most suitable containment measures. YO-01027 in vivo The last two decades have already faced severe manifestations of the coronavirus infection in both humans and animals, thus, circulating epitopes from previous outbreaks might confer partial protection from SARS-CoV-2 infections. In the present study, we provide an in-silico survey of the major nucleocapsid protein epitopes and compare them with the homologues of taxonomically-related coronaviruses with tropism for animal species that are closely inter-related with the human beings population all over the world. Protein sequence alignment provides evidence of high sequence homology for some of the investigated proteins. Moreover, structural epitope mapping by homology modelling revealed a potential immunogenic value also for specific sequences scoring a lower identity with SARS-CoV-2 nucleocapsid proteins. These evidence provide a molecular structural rationale for a potential role in conferring protection from SARS-CoV-2 infection and identifying potential candidates for the development of diagnostic tools and prophylactic-oriented strategies. Altered gene expression related to Parkinson’s Disease (PD) has not been described in the living brain, yet this information may support novel discovery pertinent to disease pathophysiology and treatment. This study compared the transcriptome in brain biopsies obtained from living PD and Control patients. To evaluate the novelty of this data, a comprehensive literature review also compared differentially expressed gene (DEGs) identified in the current study with those reported in PD cadaveric brain and peripheral tissues. link2 RNA was extracted from rapidly cryopreserved frontal lobe specimens collected from PD and Control patients undergoing neurosurgical procedures. RNA sequencing (RNA-Seq) was performed and validated using quantitative polymerase chain reaction. DEG data was assessed using bioinformatics and subsequently included within a comparative analysis of PD RNA-Seq studies. 370 DEGs identified in living brain specimens reflected diverse gene groups and included key members of trophic signaling, apoptosis, inflammation and cell metabolism pathways. The comprehensive literature review yielded 7 RNA-Seq datasets generated from blood, skin and cadaveric brain but none from a living brain source. From the current dataset, 123 DEGs were identified only within the living brain and 267 DEGs were either newly found or had distinct directional change in living brain relative to other tissues. link3 This is the first known study to analyze the transcriptome in brain tissue from living PD and Control patients. The data produced using these methods offer a unique, unexplored resource with potential to advance insight into the genetic associations of PD. Advances in genomic science are informing an expansion of genetic testing for neurodegenerative diseases, which can be used for diagnostic and predictive purposes and performed in both medical and consumer genomics settings. Such testing-which is often for severe and incurable conditions like Huntington’s, Alzheimer’s, and Parkinson’s diseases-raises important ethical and health communication challenges. This review addresses such challenges in the contexts of clinical, research, and direct-to-consumer genetic testing; these include informed consent, risk estimation and communication, potential benefits and psychosocial harms of genetic information (e.g., genetic discrimination), access to services, education and workforce needs, and health policies. The review also highlights future areas of likely growth in the field, including polygenic risk scores, use of genetic testing in clinical trials, and return of individual research results. OBJECTIVES To evaluate patterns of use and perceived benefits and barriers to health/wellness applications (apps) and smart devices among people living with HIV (PLHIV) and their physicians. METHODS Online multicenter observational survey (October 15-19, 2018). RESULTS Study participation was accepted by 229 physicians and 838/1377 PLHIV followed in 46 centers, of which 325 (39%) responded online. Overall, 83/288 (29%) PLHIV had already downloaded at least one app these 'downloaders’ were younger (OR0.96±0.01, P=0.004), educated to at least university entry level (OR2.27±0.86, P=0.03), and more frequently used geolocation-based dating websites (OR3.00±1.09, P=0.002). However, 227/314 (72%) PLHIV claimed they were ready to use an app recommended by a physician. For the 60/83 PLHIV who answered, the ideal app would be a vaccination tracker (76%) to better communicate with their physician (68%). However, 96/277 (42%) physicians were unable to answer this question and for 94/227 (41%) of them, the ideal patient app would be for schedule management. Although PLHIV used smart devices, 231/306 (75%) would want to report the data to their physicians and 137/225 (61%) of physicians would welcome this exchange. The main physician-side barrier to this exchange was concerns over data security. CONCLUSION mHealth apps and smart devices have failed to garner adoption by PLHIV. There is a case for good-quality health data sharing and exchange if PLHIV are provided with appropriately secure tools and physicians are backed up by adapted legislation. The bacterial twin-arginine (Tat) pathway serves in the exclusive secretion of folded proteins with bound cofactors. While Tat pathways in Gram-negative bacteria and chloroplast thylakoids consist of conserved TatA, TatB and TatC subunits, the Tat pathways of Bacillus species and many other Gram-positive bacteria stand out for their minimalist nature with the core translocase being composed of essential TatA and TatC subunits only. Here we addressed the question whether the minimal TatAyCy translocase of Bacillus subtilis recruits additional cellular components that modulate its activity. To this end, TatAyCy was purified by affinity- and size exclusion chromatography, and interacting co-purified proteins were identified by mass spectrometry. This uncovered the cell envelope stress responsive LiaH protein as an accessory subunit of the TatAyCy complex. Importantly, our functional studies show that Tat expression is tightly trailed by LiaH induction, and that LiaH itself determines the capacity and quality of TatAyCy-dependent protein translocation. In contrast, LiaH has no role in high-level protein secretion via the general secretion (Sec) pathway. Altogether, our observations show that protein translocation by the minimal Tat translocase TatAyCy is tightly intertwined with an adequate bacterial response to cell envelope stress. This is consistent with a critical need to maintain cellular homeostasis, especially when the membrane is widely opened to permit passage of large fully-folded proteins via Tat. Both IFN-γ or high glucose have been linked to systemic inflammatory imbalance with serious repercussions not only for endothelial function but also for the formation of the atherosclerotic plaque. Although the uncontrolled opening of connexin hemichannels underpins the progression of various diseases, whether they are implicated in endothelial cell dysfunction and damage evoked by IFN-γ plus high glucose remains to be fully elucidated. In this study, by using live cell imaging and biochemical approaches, we demonstrate that IFN-γ plus high glucose augment endothelial connexin43 hemichannel activity, resulting in the increase of ATP release, ATP-mediated Ca2+ dynamics and production of nitric oxide and superoxide anion, as well as impaired insulin-mediated uptake and intercellular diffusion of glucose and cell survival. Based on our results, we propose that connexin 43 hemichannel inhibition could serve as a new approach for tackling the activation of detrimental signaling resulting in endothelial cell dysfunction and death caused by inflammatory mediators during atherosclerosis secondary to diabetes mellitus.