Recent evidence suggests that the vagus nerve and autonomic dysfunction play an important role in the pathogenesis of Parkinson’s disease. Using heart rate variability analysis, the autonomic modulation of cardiac activity can be investigated. This meta-analysis aims to assess if analysis of heart rate variability may indicate decreased parasympathetic tone in patients with Parkinson’s disease. The MEDLINE, EMBASE and Cochrane Central databases were searched on 31 December 2020. Studies were included if they: (1) were published in English, (2) analyzed idiopathic Parkinson’s disease and healthy adult controls, and (3) reported at least one frequency- or time-domain heart rate variability analysis parameter, which represents parasympathetic regulation. We included 47 studies with 2772 subjects. Random-effects meta-analyses revealed significantly decreased effect sizes in Parkinson patients for the high-frequency spectral component (HFms²) and the short-term measurement of the root mean square of successive normal-to-normal interval differences (RMSSD). However, heterogeneity was high, and there was evidence for publication bias regarding HFms². There is some evidence that a more advanced disease leads to an impaired parasympathetic regulation. In conclusion, short-term measurement of RMSSD is a reliable parameter to assess parasympathetically impaired cardiac modulation in Parkinson patients. The measurement should be performed with a predefined respiratory rate.

This prospective observational trial investigated effects and safety of periodic fasting in subjects with and without type 2 diabetes mellitus (T2DM). The primary end point was set as the change of fatty liver index (FLI) as a surrogate parameter of non-alcoholic fatty liver disease (NAFLD). Six-hundred and ninety-seven subjects (38 with T2DM) were enrolled. A baseline FLI ≥ 60 (the threshold for fatty liver) was found in 264 subjects (37.9%). The mean duration of fasting was 8.5 ± 4.0 days (range 6–38). FLI decreased significantly (−14.02 ± 11.67; p < 0.0001), with a larger effect in individuals with T2DM (−19.15 ± 11.0; p < 0.0001; p = 0.002 compared to non-diabetic subjects). Body mass index (BMI) decreased by −1.51 ± 0.82 kg/m², and 49.9% of the subjects lost ≥5% body weight. After fasting, nearly half of the 264 subjects with FLI ≥ 60 (highest risk category) shifted to a lower category. The improvement of FLI correlated with the number of fasting days (r = −0.20, p < 0.0001) and with the magnitude of BMI reduction (r = 0.14, p = 0.0001). Periodic fasting with concomitant weight reduction leads to significant rapid improvement of FLI in subjects with and without T2DM.

About half of all carious lesions in primary teeth of German 6- to 7-year-old children remain untreated, but no data regarding the clinical consequences of untreated dental caries are available. Therefore, this cross-sectional observational study aimed to assess the prevalence and experience of caries and odontogenic infections in the primary dentition of 5- and 8-year-old German children. Dental examinations were performed in 5-year-old pre-school children (n = 496) and in 8-year-old primary school children (n = 608) living in the Westphalian Ennepe-Ruhr district. Schools and preschools were selected by sociodemographic criteria including size, area, ownership, socio-economic status. Caries was recorded according to WHO criteria (1997). The Lorenz curves were used to display the polarisation of dental caries. Caries pattern in 5-year-olds was categorized by Wyne’s (1997) definition of early childhood caries (ECC). Odontogenic infections as clinical consequence of untreated dental caries were assessed by the pufa index. The ‘untreated caries-pufa ratio’ was calculated, and the Spearman’s rank correlation coefficient (ρ) was used for evaluating the correlation between dmft and pufa scores. Categorical data were compared between groups using the chi-square test and continuous data were analysed by t-test. Caries prevalence and experience in the primary dentition was 26.2 %/0.9 ± 2.0 dmft in 5-year-olds and 48.8 %/2.1 ± 2.8 dmft in 8-year-olds. ECC type I (22 %) was the prevalent caries pattern in 5-year-olds. About 30 % of the tooth decay was treated (5y: 29.7 %/8y: 39.3 %). The Lorenz curves showed a strong caries polarisation on 20 % of the children. Pufa prevalence and experience was 4.4 %/0.1 ± 0.5 pufa in 5-year-olds and 16.6 %/0.3 ± 0.9 pufa in 8-year-olds. In 5-year-olds 14.2 % and in 8-year-olds 34.2 % of the d-component had progressed mainly to the pulp. A significant correlation between dmft and pufa scores exists in both age groups (5y: ρ = 0.399; 8y: ρ = 0.499). First deciduous molars were most frequently affected by odontogenic infections, presenting virtually all pufa scores (>95 %). Prevalence and experience of odontogenic infections and the untreated caries-pufa ratio were increasing from the younger to the elder children. Dmft and pufa scores in primary teeth predict a higher caries risk in permanent teeth. The pufa index highlights relevant information for decision makers to develop effective oral health care programs for children at high risk for caries.

Background: Autoimmune encephalitis is a new spectrum of autoimmune disorders of the central nervous system (CNS), which are characterized by pathogenic autoantibodies against neuronal surface antigens. Clinical presentations range from acute to subacute encephalopathy with neurological and psychiatric symptoms, and life-threatening autonomic dysfunction in severe cases. There exist no approved therapies nor is data available from controlled clinical trials. Patients are usually treated with diverse combinations of immunotherapy. However, effect of immunotherapy on antibody-producing cells and thus on levels of pathogenic autoantibodies is insufficient. Therefore, therapeutic response is sometimes prolonged with necessity of long-time intensive care treatment and also irreversible deficits occur in severe cases. This trial will investigate the efficacy and safety of bortezomib, a proteasome inhibitor known to selectively deplete plasma cells, in patients with severe autoimmune encephalitis who have been treated with rituximab with insufficient response. Methods: Generate-Boost is an investigator-initiated, multicenter, double-blinded, randomized controlled phase II trial which will be conducted in specialized neurological hospitals within the GENERATE (GErman NEtwork for Research on AuToimmune Encephalitis) network in Germany. Adult patients with severe autoimmune encephalitis (modified Rankin scale, mRS ≥ 3), autoantibodies against neuronal surface antigens, and pretreatment with rituximab are eligible for study participation. Fifty patients will be randomized 1:1 and undergo up to 3 cycles (each 21 days with 4 s. c. applications) of bortezomib or placebo. All patients will receive concomitant medication with dexamethasone, acyclovir and co-trimoxazole. The primary efficacy endpoint is the mRS score 17 weeks after first treatment application. Secondary endpoints are neurocognitive function, antibody titers, markers of neuronal cell damage, length of ICU/hospital stay, and mRS and Glasgow coma scale scores throughout the trial up to week 17. General and bortezomib-specific adverse events are monitored continuously. Discussion: The expected outcome of the study is to obtain first reliable data on a hypothesis-driven therapeutic option in severe and difficult-to-treat autoimmune encephalitis. If treatment with bortezomib is beneficial in these cases, this will be the basis for implementation in the current guidelines. Trial registration: Clinicaltrials.gov, NCT03993262. Registered June 20, 2019; German Clinical Trials Register, DRKS00017497.

Angioplasty of femoropopliteal lesions with the paclitaxel-coated balloon proved to be superior to conventional balloon angioplasty with regard to restenosis and need for repeat revascularization t... Background Paclitaxel drug-coated balloon (DCB) catheter angioplasty is the preferred treatment for revascularization of femoropopliteal lesions in peripheral artery disease, but mortality is a saf...

Stroke increases neurogenesis in the adult dentate gyrus in the short term, however, long-term effects at the cellular and functional level are poorly understood. Here we evaluated the impact of an early stroke lesion on neurogenesis and cognitive function of the aging brain. We hypothesized that a stroke disturbs dentate neurogenesis during aging correlate with impaired flexible learning. To address this issue a stroke was induced in 3-month-old C57Bl/6 mice by a middle cerebral artery occlusion (MCAO). To verify long-term changes of adult neurogenesis the thymidine analogue BrdU (5-Bromo-2′-deoxyuridine) was administrated at different time points during aging. One and half months after BrdU injections learning and memory performance were assessed with a modified version of the Morris water maze (MWM) that includes the re-learning paradigm, as well as hippocampus-dependent and -independent search strategies. After MWM performance mice were transcardially perfused. To further evaluate in detail the stroke-mediated changes on stem- and progenitor cells as well as endogenous proliferation nestin-green-fluorescent protein (GFP) mice were used. Adult nestin-GFP mice received a retroviral vector injection in the hippocampus to evaluate changes in the neuronal morphology. At an age of 20 month the nestin-GFP mice were transcardially perfused after MWM performance and BrdU application 1.5 months later. The early stroke lesion significantly decreased neurogenesis in 7.5- and 9-month-old animals and also endogenous proliferation in the latter group. Furthermore, immature doublecortin (DCX)-positive neurons were reduced in 20-month-old nestin-GFP mice after lesion. All MCAO groups showed an impaired performance in the MWM and mostly relied on hippocampal-independent search strategies. These findings indicate that an early ischemic insult leads to a dramatical decline of neurogenesis during aging that correlates with a premature development of hippocampal-dependent deficits. Our study supports the notion that an early stroke might lead to long-term cognitive deficits as observed in human patients after lesion.