Explore the vast range of titles available.

The therapeutic strategies currently available for neurodegenerative diseases such as Parkinson's disease target only the symptoms of the disease. Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy can be summarized as synucleinopathies, as they are all characterized by the aggregation and accumulation of alpha-synuclein (α-syn) in the brain. Targeting α-syn by its formation and progression opens a new and promising disease-modifying therapeutic strategy. Thus, several distinct immunotherapeutic approaches are currently being evaluated in clinical trials. The objective of this article is to review, from a biological perspective, the most important properties of these passive and active immunotherapies to point out their relevance and suitability for the treatment of synucleinopathies.

In mammalians, toll-like receptors (TLR) signal-transduction pathways induce the expression of a variety of immune-response genes, including inflammatory cytokines. It is therefore plausible to assume that TLRs are mediators in glial cells triggering the release of cytokines that ultimately kill DA neurons in the substantia nigra in Parkinson disease (PD). Accordingly, recent data indicate that TLR4 is up-regulated by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment in a mouse model of PD. Here, we wished to evaluate the role of TLR4 in the acute mouse MPTP model of PD: TLR4-deficient mice and wild-type littermates control mice were used for the acute administration way of MPTP or a corresponding volume of saline. We demonstrate that TLR4-deficient mice are less vulnerable to MPTP intoxication than wild-type mice and display a decreased number of Iba1+ and MHC II+ activated microglial cells after MPTP application, suggesting that the TLR4 pathway is involved in experimental PD.

Demographic change is causing society to age. At the same time, technological progress is changing the way ageing individuals are cared for and medically treated. Several smart wearables and garments have recently been developed for this purpose. Based on previous research, we see a research gap in the use of smart clothing in the care and support of elderly people, especially with regard to concrete application potentials and example products. The aim of this study was to provide an overview of the latest studies and developments in smart clothing with a focus on usability and acceptance for an elderly individuals. A systematic literature search was performed in five databases using a predefined set of keyword. A total of 169 articles published between 1/2000 and 2/2023 were identified and assessed. The literature search followed a previously prepared research protocol according to the criteria of a systematic literature search. The research field of smart clothing is expanding with smart shirts being a major focus; however other products are also being investigated, each with specific capabilities. In particular, vital parameters are constantly optimized; representative products are described and assessed according to their potential applicability to elderly people. The future applications of smart clothing in health care are promising. Many studies on basic applications of smart textiles have been done, and some studies have already involved older people. Furthermore, newly developed suggestions for possible categorizations of smart wearables as well as smart clothing as a subtype are presented based on the researched literature. We found an overall positive impression of the development and application of smart clothing, especially in geriatric settings. However, aspects such as data collection, skin compatibility, wearing comfort, and integration of geriatric factors into known acceptance models need further investigation. Over the last two decades, there have been many developments in the field of smart clothing. For the care and support of elderly people, smart clothing is an important development with great potential. Continued advancement in these products is needed to adequately address the special needs of older people.

To investigate the outcomes of geriatric COVID-19 patients in a German academic setting during the pandemic. This study included 468 consecutive geriatric patients (≥ 70 years) who tested positive for SARS-CoV-2 and were treated at the University of Duisburg-Essen from 2/2020 to 3/2021. 74 patients were transferred to a geriatric hospital and a 12-month follow-up (prospective study) was performed in 51 patients. Clinical assessments evaluated depression (GDS), apathy (AES), cognitive status (MMST), mobility (TUG), health status (EQ-5D-5 L), and daily living activities (Barthel Index). Demographic and clinical data were also analyzed. Results showed that the mortality in this vulnerable group was 52% ( n  = 209). Long-term survival was higher in patients who received comprehensive geriatric treatment (74.3% vs. 51.8%). The duration of inpatient stay at the primary hospital was 13.3 ± 3.6 days, with 28.8% ( n  = 135) requiring intensive care. At the 12-month mark more patients with geriatric treatment lived in nursing homes. Barthel-Index/Timed-Up-and-Go-Test/MMST/AES/GDS, and EQ-5D-5 L indicated worse outcomes in the group who received geriatric treatment. Specialized geriatric care may improve survival in geriatric COVID-19 patients despite decreased long-term outcomes. Further research, including international studies like NAPKON, are encouraged to confirm these findings and explore potential interventions for improved outcomes in this vulnerable population.

Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1–11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09–3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02–4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials. Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund.

Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50–85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)1–40 between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ1–40 was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (–18·0 [range −1347·0 to 1068·5] for 0·2 g/kg, −364·3 [–5834·5 to 1953·5] for 0·5 g/kg, and −351·8 [–1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs −116·3 [–1379·0 to 5266·0] for placebo; and −13·8 [–1729·0 to 307·0] for 0·1 g/kg, and −32·5 [–1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ1–40 between the 0·4 g/kg every 2 weeks group (47·0 [range −341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease. Octapharma AG.

Background Alzheimer’s disease (AD) and Parkinson’s disease (PD) are leading neurodegenerative disorders marked by protein aggregation, with AD featuring amyloid-beta (Aβ) and tau proteins, and PD alpha-synuclein (αSyn). Dementia with Lewy bodies (DLB) often presents with a mix of these pathologies. This study explores naturally occurring autoantibodies (nAbs), including Immunoglobulin (Ig)G, IgM, and IgA, which target αSyn, Aβ and tau to maintain homeostasis and were previously found altered in AD and PD patients, among others. Main text We extended this investigation across AD, PD and DLB patients investigating both the affinities of IgGs and levels of IgGs, IgMs and IgAs towards αSyn, Aβ and tau utilizing chemiluminescence assays. We confirmed that AD and PD patients exhibited lower levels of high-affinity anti-Aβ and anti-αSyn IgGs, respectively, than healthy controls. AD patients also showed diminished levels of high-affinity anti-αSyn IgGs, while anti-tau IgG affinities did not differ significantly across groups. However, DLB patients exhibited increased anti-αSyn IgG but decreased anti-αSyn IgM levels compared to controls and PD patients, with AD patients showing a similar pattern. Interestingly, AD patients had higher anti-Aβ IgG but lower anti-Aβ IgA levels than DLB patients. DLB patients had reduced anti-Aβ IgM levels compared to controls, and anti-tau IgG levels were lower in AD than PD patients, who had reduced anti-tau IgM levels compared to controls. AD patients uniquely showed higher anti-tau IgA levels. Significant correlations were observed between clinical measures and nAbs, with negative correlations between anti-αSyn IgG affinity and levels in DLB patients and a positive correlation with anti-αSyn IgA levels in PD patients. Disease-specific changes in nAb levels and affinity correlations were identified, highlighting altered immune responses. Conclusion This study reveals distinctive nAb profiles in AD, DLB, and PD, pinpointing specific immune deficiencies against pathological proteins. These insights into the autoreactive immune system’s role in neurodegeneration suggest nAbs as potential markers for vulnerability to protein aggregation, offering new avenues for understanding and possibly diagnosing these conditions.

Background: Recent studies have described higher incidences of concussion, with more severe symptoms and worse outcomes in female athletes compared with male athletes. Purpose: To compile current knowledge about sex-specific differences in incidence, biomechanics, biomarkers, imaging, and outcomes of concussion in athletes participating in contact sports to better understand which fields should be explored in more detail. Study Design: Scoping review; Level of evidence, 3. Methods: The PubMed database was searched for articles published between January 2000 and November 2020 using the Medical Subject Headings terms “craniocerebral trauma” and “brain concussion” combined with the contact sports “football,”“soccer,”“hockey,” and “boxing.” Eligibility criteria were based on the recommendations of the Scottish Intercollegiate Guidelines Network. It focused on sex-specific differences within 5 major topics: (1) epidemiology, (2) biomechanics, (3) biomarkers, (4) imaging, and (5) specific concussion outcome variables, including neurocognitive performance, injury severity, and behavioral and psychological symptoms. Results: A total of 22 studies were included. Eight studies investigated the incidence of concussion, with 4 of the 8 finding a significantly higher incidence rate for female versus male athletes. Six studies that focused on biomechanics found that female athletes received fewer impacts with lower magnitudes. One study addressed biomarkers, showing that S100 calcium-binding protein B and neuron-specific enolase were increased after a game in female athletes, and the level of increase was similar to the changes found in male athletes. Based on the 3 imaging studies, affected brain tissue was greatest in areas associated with tau pathology in chronic traumatic encephalopathy. One study showed a lower hypointensity burden index after a season of ice hockey for female athletes, while another study showed more regions with white matter alterations. Seven studies examined concussion outcomes, with 4 studies showing more severe neuropsychological deficits; in addition, female athletes reported more and worse symptoms than male athletes. Conclusion: The results of this review indicated that female athletes had a higher risk of sustaining a concussion, although they received fewer impacts with lower magnitudes than male athletes. Biomarkers were able to be used equally for both sexes. Female athletes also had a higher neuropsychological deficit and increasingly worse symptoms after a concussion.