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Misfolded alpha-synuclein (αSyn) aggregates are a hallmark event in Parkinson’s disease (PD) and other synucleinopathies. Recently, αSyn seed amplification assays (αSyn-SAAs) have shown promise as a test for biochemical diagnosis of synucleinopathies. αSyn-SAAs use the intrinsic self-replicative nature of misfolded αSyn aggregates (seeds) to multiply them in vitro. In these assays, αSyn seeds circulating in biological fluids are amplified by a cyclical process that includes aggregate fragmentation into smaller self-propagating seeds, followed by elongation at the expense of recombinant αSyn (rec-αSyn). Amplification of the seeds allows detection by fluorescent dyes specific for amyloids, such as thioflavin T. Several αSyn-SAA reports have been published in the past under the names ‘protein misfolding cyclic amplification’ (αSyn-PMCA) and ‘real-time quaking-induced conversion’. Here, we describe a protocol for αSyn-SAA, originally reported as αSyn-PMCA, which allows detection of αSyn aggregates in cerebrospinal fluid samples from patients affected by PD, dementia with Lewy bodies or multiple-system atrophy (MSA). Moreover, this αSyn-SAA can differentiate αSyn aggregates from patients with PD versus those from patients with MSA, even in retrospective samples from patients with pure autonomic failure who later developed PD or MSA. We also describe modifications to the original protocol introduced to develop an optimized version of the assay. The optimized version shortens the assay length, decreases the amount of rec-αSyn required and reduces the number of inconclusive results. The protocol has a hands-on time of ~2 h per 96-well plate and can be performed by personnel trained to perform basic experiments with specimens of human origin. The amplification of misfolded alpha-synuclein aggregates in vitro can be used for the detection, via fluorescent dyes, of pathologic amyloids in cerebrospinal fluid samples from patients affected by Parkinson’s disease, dementia with Lewy bodies or multiple-system atrophy.

Covid-19 has caused significant distress around the globe. Apart from the evident physical symptoms in infected cases, it has caused serious damage to public mental health. India, like other countries, implemented a nationwide lockdown to contain and curb the transmission of the virus. The current research is an attempt to explore psychological distress among people residing in India during the lockdown. Four hundred and three participants were asked to complete a questionnaire with questions around symptoms of depression, anxiety, stress, and family affluence. The results indicated that people who do not have enough supplies to sustain the lockdown were most affected, and family affluence was found to be negatively correlated with stress, anxiety, and depression. Among different professions, students and healthcare professionals were found to experience stress, anxiety, and depression more than others. Despite the current situation, stress, anxiety, and depression were found to be in normal ranges for mental health professionals highlighting their capabilities to remain normal in times of distress. Policymakers and other authorities may take the assistance of mental health professionals to help overcome psychological issues related to Covid-19.

The purpose of the present study was to expand the knowledge on trauma and posttraumatic growth (PTG) by exploring this relationship in parents who lost their children in Kashmir (India). The main aim of the present study was to examine whether spirituality and self-compassion mediate the relationship between trauma and PTG. Data were collected from 80 parents in the age range of 35-80 years (Mean Age = 52.09). Traumatic Grief scale Prigerson et al. (in Am J Psychiatry 154:616-623, 1997), Daily Spirituality Scale (Underwood and Teresi, Ann Behav Med 24(1):22-33, 2002), Self-Compassion Scale (Raes et al., Clin Psychol Psychoth 18:250-255, 2011), and PTG Inventory (Tedeschi and Calhoun, J Trauma Stress 9(3):455-471, 1996) scales were used to measure trauma, spirituality, selfcompassion, and PTG, respectively. Results of the study indicated the presence of average amount of spirituality and high amount of trauma among the participants. High level of self-compassion and post-traumatic growth was also found among the participants. The results showed that there is no significant direct relationship between trauma and PTG; however, both the indirect paths (trauma, spirituality, and PTG as well as trauma, self-compassion, and PTG) were found to be significant. The results of the present study supported serial mediation model of Trauma and PTG through spirituality and self-compassion. It implies that trauma would lead to spirituality which in turn would lead to self-compassion and which would finally result in PTG. The result provided another lens to see the relationship between trauma and PTG.

The role of individual variables (COVID-19 anxiety, perceived susceptibility, perceived severity, optimistic bias and personal identity) as predictors of quality of life (QoL) during the novel coronavirus or COVID-19 pandemic is explored. Impact of group related variables (identification to family, religious group and nation) on QoL is also examined. Sample comprised 305 male and female Indian respondents, aged 18 to 78 years. Standardized measures have been utilised to assess the constructs. Results revealed that QoL was significantly influenced by individual variables (COVID-19 anxiety and personal identity) and group variables (identification with family and nation). The effect of COVID-19 anxiety and personal identity as individual variables is over and above that of demographic variables on QoL. Group variables (family and national identification) significantly impacted QoL over and above the individual variables. Findings would indeed, aid in the rehabilitation and assistance of people to live in COVID-19 crisis, and thereafter.

Pathology consisting of intracellular aggregates of alpha-Synuclein (α-Syn) spread through the nervous system in a variety of neurodegenerative disorders including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. The discovery of structurally distinct α-Syn polymorphs, so-called strains, supports a hypothesis where strain-specific structures are templated into aggregates formed by native α-Syn. These distinct strains are hypothesised to dictate the spreading of pathology in the tissue and the cellular impact of the aggregates, thereby contributing to the variety of clinical phenotypes. Here, we present evidence of a novel α-Syn strain induced by the multiple system atrophy-associated oligodendroglial protein p25α. Using an array of biophysical, biochemical, cellular, and in vivo analyses, we demonstrate that compared to α-Syn alone, a substoichiometric concentration of p25α redirects α-Syn aggregation into a unique α-Syn/p25α strain with a different structure and enhanced in vivo prodegenerative properties. The α-Syn/p25α strain induced larger inclusions in human dopaminergic neurons. In vivo, intramuscular injection of preformed fibrils (PFF) of the α-Syn/p25α strain compared to α-Syn PFF resulted in a shortened life span and a distinct anatomical distribution of inclusion pathology in the brain of a human A53T transgenic (line M83) mouse. Investigation of α-Syn aggregates in brain stem extracts of end-stage mice demonstrated that the more aggressive phenotype of the α-Syn/p25α strain was associated with an increased load of α-Syn aggregates based on a Förster resonance energy transfer immunoassay and a reduced α-Syn aggregate seeding activity based on a protein misfolding cyclic amplification assay. When injected unilaterally into the striata of wild-type mice, the α-Syn/p25α strain resulted in a more-pronounced motoric phenotype than α-Syn PFF and exhibited a “tropism” for nigro-striatal neurons compared to α-Syn PFF. Overall, our data support a hypothesis whereby oligodendroglial p25α is responsible for generating a highly prodegenerative α-Syn strain in multiple system atrophy.

Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients’ brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and MSA patients’ brains, as well as SAA-amplified α-Syn aggregates from LBD and MSA patients’ CSF samples, were used to treat synuclein biosensor cells, and induced intracellular α-Syn inclusions were analyzed by confocal microscopy. Our data indicate that induced α-Syn aggregates from LBD and MSA patients’ brains have similar seeding properties and morphological characteristics in the α-Syn biosensor cells as those amplified from LBD and MSA patients’ brains, as well as those amplified from LBD and MSA patients’ CSF samples. In this study, we demonstrated that, regardless of the source of aggregates, the seeds from LBD and MSA produce cellular accumulation of α-Syn with distinct morphologies, confirming the presence of different conformational strains of α-Syn in LBD and MSA and allowing us to differentiate synucleinopathies based on the morphology of aggregates and seeding properties.

This study presents a thorough technique for creating and assessing intelligent medical robotic systems, based on the integration of artificial intelligence (AI), sophisticated sensor networks, and autonomous control frameworks. The proposed approach is multi-phase optimization from preoperative planning to intraoperative assistance and postoperative monitoring. Data acquisition from various biomedical sensors, with AIdriven diagnostic inference, is key, but adaptive learning via federated and explainable AI (XAI) models is the key module. Furthermore, the methodology brings into play recent imaging, haptics and integrates with the Internet of Medical Things (IoMT) to promote surgical precision and reduce human error. The performance benchmarking under clinical constraints is proposed to be executed via simulation-based testing and real-time validation. We also discuss applications in case-driven evaluations of robotics applications in robotic-assisted orthopaedic and microsurgical procedures to demonstrate usefulness. The intention of this study is to bridge the technological gap between the current robotic systems to future autonomous healthcare products. This methodology can be used as a blueprint for the researchers and developers working at the robotics and AI healthcare intersection to provide for the innovation, safety, and operational efficiency in surgical environments.

Parkinson’s disease (PD), Dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are characterized by the misfolding and aggregation of alpha-synuclein (αSyn). Compelling evidence showed that αSyn aggregates exist as distinct conformational strains in different synucleinopathies. Recently, we reported that the αSyn Seed Amplification Assay (αSyn-SAA) can amplify and distinguish αSyn strains from PD and MSA. In this study, we investigate whether MSA-seeded, SAA-amplified αSyn fibrils retain the biological and structural properties of the αSyn seeds present in MSA brains. We study the biological activities of both brain-derived and SAA-amplified αSyn aggregates using an αSyn “biosensor” cell model and a synucleinopathy transmission mouse model. Our in vitro and in vivo findings reveal that the SAA-amplified αSyn fibrils preserve the biological properties of the brain-derived MSA strain. Detailed analyses of the in vivo studies demonstrate that both brain-derived and SAA-generated αSyn aggregates induce a similar disease, with comparable incubation periods, neuropathological damages and clinical manifestations. High-resolution cryo-EM analysis of SAA-amplified αSyn fibrils demonstrates that their conformation at the protofilament level closely resembles one of the αSyn filaments previously identified in MSA patient brains. Our findings suggest that SAA can amplify disease-specific misfolded αSyn conformation while preserving its main biological properties. Alpha-synuclein (αSyn) aggregates implicated in synucleinopathies can be amplified by a seed amplification assay (SAA). Here, the authors show that SAA amplified αSyn aggregates from the CSF of a multiple system atrophy patient retain the biological and structural properties of the aggregates deposited in the brain

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. The disease is characterized by progressive memory loss, cerebral atrophy, extensive neuronal loss, synaptic alterations, brain inflammation, extracellular accumulation of amyloid-β (Aβ) plaques, and intracellular accumulation of hyper-phosphorylated tau (p-tau) protein. Many recent clinical trials have failed to show therapeutic benefit, likely because at the time in which patients exhibit clinical symptoms the brain is irreversibly damaged. In recent years, induced pluripotent stem cells (iPSCs) have been suggested as a promising cell therapy to recover brain functionality in neurodegenerative diseases such as AD. To evaluate the potential benefits of iPSCs on AD progression, we stereotaxically injected mouse iPSC-derived neural precursors (iPSC-NPCs) into the hippocampus of aged triple transgenic (3xTg-AD) mice harboring extensive pathological abnormalities typical of AD. Interestingly, iPSC-NPCs transplanted mice showed improved memory, synaptic plasticity, and reduced AD brain pathology, including a reduction of amyloid and tangles deposits. Our findings suggest that iPSC-NPCs might be a useful therapy that could produce benefit at the advanced clinical and pathological stages of AD.

MicroRNA-7-5p (miR-7-5p) may play a neuroprotective role in people with Parkinson's disease (PwP), as it has been found to regulate -synuclein (α-syn) and the NLRP3 inflammasome in animal models of Parkinson's disease (PD). The study aimed to investigate the use of miR-7-5p as a potential biomarker for disease progression in PwP by correlating it with time, clinical measures, and neurofilament light chain (NfL). We performed a longitudinal retrospective analysis of blood miR-7-5p levels in 303 PwP and 159 healthy controls (HCs) from the Parkinson's Progression Markers Initiative (PPMI) cohort. In PwP, a linear mixed-effects model was used to examine the association between miR-7-5p levels and time in the study. In addition, linear mixed-effects models were used to examine the associations between longitudinal changes in miR-7-5p and scores on the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), both for motor and total scores, as well as serum NfL levels. These models were also used to compare the associations between changes in miR-7-5p, time in the study, and NfL levels in both PwP and HCs. miR-7-5p levels decreased more rapidly in PwP compared to HCs (  = 0.02). In PwP, miR-7-5p levels correlated with time in the study (  < 0.001) and with changes in the MDS-UPDRS motor (  = 0.007) and total scores (  = 0.01). However, when time in study was taken into account, the correlations were no longer significant. Additionally, miR-7-5p levels decreased longitudinally as NfL levels increased in PwP (  = 0.03), but this did not remain significant when time in the study was considered. This pattern suggests that miR-7-5p may reflect both upstream pathogenic mechanisms and downstream neuroaxonal damage. However, the loss of significance when time in the study was included in the model indicates that the changes may reflect parallel degenerative processes involving NfL and miR-7-5p. This study is novel in that it demonstrates a correlation between miR-7-5p levels, clinical severity, and NfL levels.