Search

50 Pág., In March 2022, following the annual International Committee on Taxonomy of Viruses (ICTV) ratifcation vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by two new families (bunyaviral Discoviridae and Tulasviridae), 41 new genera, and 98 new species. Three hundred forty-nine species were renamed and/or moved. The accidentally misspelled names of seven species were corrected. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV, This work was supported in part through Laulima Govern ment Solutions, LLC prime contract with the US National Institute of Allergy and Infectious Diseases (NIAID) under Contract No. HHSN272201800013C. J.H.K. performed this work as an employee of Tunnell Government Services (TGS), a subcontractor of Laulima Gov ernment Solutions, LLC under Contract No. HHSN272201800013C. This work was also funded in part by Contract No. HSHQDC 15-C-00064 awarded by DHS S&T for the management and operation of The National Biodefense Analysis and Countermeasures Center, a federally funded research and development center operated by the Battelle National Biodefense Institute (V.W.); and NIH contract HHSN272201000040I/HHSN27200004/D04 and grant R24AI120942 (N.V., R.B.T.). S.S. acknowledges support from the Mississippi Agri cultural and Forestry Experiment Station (MAFES), USDA-ARS pro ject 58-6066-9-033 and the National Institute of Food and Agriculture, US Department of Agriculture, Hatch Project, under Accession Num ber 1021494.

IntroductionGrowing data support the safe and efficacious use of ablative radiotherapy in the setting of liver metastases, with some studies suggesting that patients with metastatic breast cancer (MBCa) do better than patients with metastases from other cancers. This study aims to retrospectively review clinical outcomes of patients with MBCa following liver radiotherapy (RT).Materials and MethodsPatients with MBCa who received liver hypo fractionated ablative RT between 2004 – 2020 were classified according to metastatic classification and treatment intent (i.e., oligo-metastatic (OM) or oligo-progressive (OP)). Demographics, disease characteristics and treatment characteristics were collated. Primary outcome was local control (LC) of treated metastases. Secondary outcomes included overall survival (OS), progression-free survival (PFS), and time to next line systemic therapy (ST), analyzed by univariate (UVA) and multi-variable analysis (MVA).ResultsThirty MBCa patients with 50 liver metastases treated with 5 – 10 fraction ablative intent RT were identified for analysis. Median follow-up was 14.6 months (range 0.9 - 156.2 months). Mean age was 55.6 years (range 32.1 - 79.3 years); 53% were ER+/HER2-ve and 33% HER2+ve. Class of metastatic disease was described as – induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (3 patients, 10%) (1 synchronous, 2 metachronous). Indication of treatment was OP (73%) and OM (27%). Median size of treated liver metastases (LM) was 3.1 cm (range 1cm – 8.8 cm) and the median dose delivered was 40Gy (range 30Gy-60Gy). 1 and 3-year LC rates were 100%. Median OS was 57.7-months with size of treated liver metastases predictive of overall survival (HR 1.35, p=0.023) on UVA. Median time to progression post treatment was 4.8 months (0.8 – 114.7). Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p=0.01) on UVA compared to others, which trended to significance on MVA (HR 3.23, p=0.051).ConclusionHypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC. Further studies assessing the impact, ideal sequencing, and indications of RT in each metastatic class in MBCa are required.

Purpose The aim was to develop and update a guideline which would improve the quality of care offered to women with gestational and non-gestational trophoblastic disease, a group of diseases characterized by their rarity and biological heterogeneity. Methods In accordance with the method used to compile S2k-guidelines, the guideline authors carried out a search of the literature (MEDLINE) for the period 1/2020 to 12/2021 and evaluated the recent literature. No key questions were formulated. No structured literature search with methodical evaluation and assessment of the level of evidence was carried out. The text of the precursor version of the guideline from 2019 was updated based on the most recent literature, and new statements and recommendations were drafted. Recommendations The updated guideline contains recommendations for the diagnosis and therapy of women with hydatidiform mole (partial and complete moles), gestational trophoblastic neoplasia after pregnancy or without prior pregnancy, persistent trophoblastic disease after molar pregnancy, invasive moles, choriocarcinoma, placental site nodules, placental site trophoblastic tumor, hyperplasia at the implantation site und epithelioid trophoblastic tumor. Separate chapters cover the determination and assessment of human chorionic gonadotropin (hCG), histopathological evaluation of specimens, and the appropriate molecular pathological and immunohistochemical diagnostic procedures. Separate chapters on immunotherapy, surgical therapy, multiple pregnancies with simultaneous trophoblastic disease, and pregnancy after trophoblastic disease were formulated, and the corresponding recommendations agreed upon.

Repeated sampling of spatially distributed river chemistry can be used to assess the location, scale, and persistence of carbon and nutrient contributions to watershed exports. Here, we provide a comprehensive set of water chemistry measurements and ecohydrological metrics describing the biogeochemical conditions of permafrost-affected Arctic watersheds. These data were collected in watershed-wide synoptic campaigns in six stream networks across northern Alaska. Three watersheds are associated with the Arctic Long-Term Ecological Research site at Toolik Field Station (TFS), which were sampled seasonally each June and August from 2016 to 2018. Three watersheds were associated with the National Park Service (NPS) of Alaska and the U.S. Geological Survey (USGS) and were sampled annually from 2015 to 2019. Extensive water chemistry characterization included carbon species, dissolved nutrients, and major ions. The objective of the sampling designs and data acquisition was to characterize terrestrial–aquatic linkages and processing of material in stream networks. The data allow estimation of novel ecohydrological metrics that describe the dominant location, scale, and overall persistence of ecosystem processes in continuous permafrost. These metrics are (1) subcatchment leverage, (2) variance collapse, and (3) spatial persistence. Raw data are available at the National Park Service Integrated Resource Management Applications portal (O'Donnell et al., 2021, https://doi.org/10.5066/P9SBK2DZ) and within the Environmental Data Initiative (Abbott, 2021, https://doi.org/10.6073/pasta/258a44fb9055163dd4dd4371b9dce945).

Background: The purpose of this research is to estimate the rate of concordance, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of colposcopy for high-grade squamous lesions and carcinomas (HSIL+). Methods: We conducted a retrospective study of colposcopies performed in the certified Dysplasia Unit in Erlangen between January 2015 and May 2022 (7.5 years). The colposcopic findings were correlated with biopsies obtained during examinations or surgery. Cases without histology were excluded. The primary outcome was the rate of concordance between the colposcopic and histological findings in relation to the type of transformation zone (TZ), examiner’s level of experience and age of the patients. Results: A total of 4778 colposcopies in 4001 women were analyzed. The rates of concordance for CIN I/LSIL, CIN II/HSIL, CIN III/HSIL, and carcinoma were 43.4%, 59.5%, 78.5%, and 53.9%, respectively. The rate of concordance was lowest for TZ3 and highest for colposcopists with more than 10 years’ experience. Conclusions: Colposcopy is an important, feasible, and effective method. Careful work-up needs to be performed for women with TZ3 who are over 35 years old, as they are at the highest risk of being misdiagnosed. The highest concordance for detecting HSIL+ was seen for colposcopists with >10 years’ experience.

Background: A new nationwide screening strategy was implemented in Germany in January 2020. No data are available for women referred to certified dysplasia units for secondary clarification after primary diagnosis by a local physician. We therefore investigated combined testing with Papanicolaou smears and high-risk human papillomavirus (hrHPV) and compared the data with the final histological findings. Methods: Between January 2015 and October 2020, all referred women who underwent colposcopy of the uterine cervix in our certified dysplasia unit were included. Cytology findings were classified using the Munich III nomenclature. Results: A total of 3588 colposcopies were performed in 3118 women, along with Pap smear and hrHPV co-testing, followed by histology. Women with Pap II-p (ASC-US) and a positive hrHPV co-test had a 22.4% risk for cervical intraepithelial neoplasia (CIN) 3/high-grade squamous intraepithelial lesion (HSIL). The risk of CIN 3/HSIL was 83.8% in women with Pap IVa-p (HSIL) and a positive hrHPV co-test. A positive hrHPV co-test increased the risk for HSIL+ (OR 5.942; 95% CI, 4.617 to 7.649; p < 0.001) as compared to a negative hrHPV co-test. Conclusions: The accuracy of Pap smears is comparable with the screening results. A positive hrHPV test increases the risk for HSIL+ fivefold. Colposcopy is necessary to diagnose HSIL+ correctly.

Simple Summary In node-positive vulvar squamous cell cancer, questions of when and how to perform pelvic lymphadenectomy (LAE) as well as the optimal extent of pelvic treatment in general have been surrounded by considerable controversy. In Germany, systematic pelvic LAE is currently recommended as a staging procedure in patients at risk for pelvic nodal involvement in order to prevent morbidity caused by pelvic radiotherapy (RT) in patients without histologically-confirmed pelvic involvement. However, the population at risk for pelvic metastases remains insufficiently described, resulting in the potential overtreatment of a considerable proportion of patients with groin-positive disease. This applies to the indication to perform surgical staging but also to adjuvant RT of the pelvis without previous pelvic staging. Our study aims to describe the risk for pelvic lymph node metastasis with regard to positive groin nodes and to clarify the indication criteria for pelvic treatment in node-positive vulvar cancer. Abstract The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

Climate change has the potential to impact headwater streams in the Arctic by thawing permafrost and subsequently altering hydrologic regimes and vegetation distribution, physiognomy and productivity. Permafrost thaw and increased subsurface flow have been inferred from the chemistry of large rivers, but there is limited empirical evidence of the impacts to headwater streams. Here we demonstrate how changing vegetation cover and soil thaw may alter headwater catchment hydrology using water budgets, stream discharge trends, and chemistry across a gradient of ground temperature in northwestern Alaska. Colder, tundra-dominated catchments shed precipitation through stream discharge, whereas in warmer catchments with greater forest extent, evapotranspiration (ET) and infiltration are substantial fluxes. Forest soils thaw earlier, remain thawed longer, and display seasonal water content declines, consistent with greater ET and infiltration. Streambed infiltration and water chemistry indicate that even minor warming can lead to increased infiltration and subsurface flow. Additional warming, permafrost loss, and vegetation shifts in the Arctic will deliver water back to the atmosphere and to subsurface aquifers in many regions, with the potential to substantially reduce discharge in headwater streams, if not compensated by increasing precipitation. Decreasing discharge in headwater streams will have important implications for aquatic and riparian ecosystems.

To evaluate the safety and impact of biopsy tract plugging with gelatin sponge slurry in percutaneous liver biopsy. 300 consecutive patients (158 females, 142 males; median age, 63 years) who underwent computed tomography-guided core biopsy of the liver in coaxial technique (16/18 Gauge) with and without biopsy tract plugging were retrospectively reviewed (January 2013 to May 2018). Complications were rated according to the common criteria for adverse events (NCI-CTCAE). The study cohort was dichotomized into a plugged (71%; n = 214) and an unplugged (29%; n = 86) biopsy tract group. Biopsy tract plugging with gelatin sponge slurry was technically successful in all cases. Major bleeding events were only observed in the unplugged group (0.7%; n = 2), whereas minor bleedings (4.3%) were observed in both groups (plugged, 3.6%, n = 11; unplugged, 0.7%, n = 2). Analysis of biopsies and adverse events showed a significant association between number of needle-passes and overall (P = 0.038; odds ratio: 1.395) as well as minor bleeding events (P = 0.020; odds ratio: 1.501). No complications associated with gelatin sponge slurry were observed. Biopsy tract plugging with gelatin sponge slurry is a technically easy and safe procedure that can prevent major bleeding events following liver biopsy.

European perch (Perca fluviatilis) are increasingly farmed as a human food source. Viral infections of European perch remain largely unexplored, thereby putting farm populations at incalculable risk for devastating fish epizootics and presenting a potential hazard to consumers. To address these concerns, we applied metatranscriptomics to identify disease-associated viruses in European perch farmed in Switzerland. Unexpectedly, in clinically diseased fish we detected novel freshwater fish filoviruses, a novel freshwater fish hantavirus, and a previously unknown rhabdovirus. Hantavirus titers were high, and we demonstrated virus in macrophages and gill endothelial cells by using in situ hybridization. Rhabdovirus titers in organ samples were low, but virus could be isolated on cell culture. Our data add to the hypothesis that filoviruses, hantaviruses, and rhabdoviruses are globally distributed common fish commensals, pathogens, or both. Our findings shed new light on negative-sense RNA virus diversity and evolution. ispartof: EMERGING INFECTIOUS DISEASES vol:27 issue:12 pages:3082-3091 ispartof: location:United States status: published

Emerging single-cell technologies provide high-resolution measurements of distinct cellular modalities opening new avenues for generating detailed cellular atlases of many and diverse tissues. The high dimensionality, sparsity, and inaccuracy of single cell sequencing measurements, however, can obscure discriminatory information, mask cellular subtype variations and complicate downstream analyses which can limit our understanding of cell function and tissue heterogeneity. Here, we present a novel pre-processing method (scPSD) inspired bypower spectral densityanalysis that enhances the accuracy for cell subtype separation from large-scale single-cell omics data. We comprehensively benchmarked our method on a wide range of single-cell RNA-sequencing datasets and showed that scPSD pre-processing, while being fast and scalable, significantly reduces data complexity, enhances cell-type separation, and enables rare cell identification. Additionally, we applied scPSD to transcriptomics and chromatin accessibility cell atlases and demonstrated its capacity to discriminate over 100 cell types across the whole organism and across different modalities of single-cell omics data.

Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced to help establish a new measure: difference in distribution functions (DDF), which captures the difference of reshaping one's mean diffusivity (MD) distribution to a reference MD distribution. This new DWI measure was developed using a population-based cohort (n=19,369) from the UK Biobank. Validation was conducted using the data drawn from two independent cohorts: the Sydney Memory and Ageing Study, a community-dwelling sample (n=402), and the Renji Cerebral Small Vessel Disease Cohort Study (RCCS), which consisted of cerebral small vessel disease (CSVD) patients (n=171) and cognitively normal controls (NC) (n=43). DDF was associated with age across all three samples and better explained the variance of changes than other established DWI measures, such as fractional anisotropy, mean diffusivity and peak width of skeletonized mean diffusivity (PSMD). Significant correlations between DDF and cognition were found in the UK Biobank cohort and the MAS cohort. Binary logistic analysis and receiver operator characteristic curve analysis of RCCS demonstrated that DDF had higher sensitivity in distinguishing CSVD patients from NC than the other DWI measures. To demonstrate the flexibility of DDF, we calculated regional DDF which also showed significant correlation with age and cognition. DDF can be used as a marker for monitoring the white matter microstructural changes and ageing related cognitive decline in the elderly.

Background: Individuals on the autism spectrum are often described as having atypical social interactions. Ideally, interactional synchrony helps any interaction flow smoothly with each individual responding verbally, non-verbally, and/or emotionally within a short timeframe. Differences in interactional synchrony may impact how individuals on the autism spectrum experience social encounters.Method: This mixed methods pilot study examined interactional synchrony in five cases of adolescents and adults on the autism spectrum through secondary analysis of video of the participants in movement-based mirroring tasks during dance/movement therapy. Raters described the movement and interactions of the participants while they were leading and following mirroring and engaged in open-ended free dances with a partner. Videos were also scored on measures of affective engagement, flow of the interaction, and synchrony.Results: One of the most striking findings of this study was the difference between engagement in the instructions of the task and engagement with the partner: participants often followed the instructions for the mirroring tasks with little further social engagement with their partner. When participants did engage in moments of social initiation, attunement to the partner, and interactive behaviors, these did not develop into longer interactions. A paired t-test of the correlation coefficients for each participant showed that scores on synchrony and affective engagement were more strongly positively correlated in the less structured open-ended dance and in video clips of interactive behaviors, than in the videos of simply leading or following mirroring. Synchrony was also significantly more strongly positively correlated with the observed flow of the interaction than with observed affective engagement. With the small sample size, however, most of the correlation coefficients were not significant and should be tested on a larger sample.Discussion: Interpersonal synchrony may not be sufficient to effectively support social engagement when individuals on the autism spectrum simply follow instructions to synchronize their movements. Synchrony-based interventions may therefore need to include more complex open-ended social scenarios as interactional synchrony may then be more correlated with perceived interaction quality. Therapists may also need to partner with participants to model using non-verbal social behaviors to develop interactions within mirroring tasks.

Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases of the mouse spinal cord have been published in recent years but have not been integrated together. Here, we generate an atlas of spinal cell types based on single-cell transcriptomic data, unifying the available datasets into a common reference framework. We report a hierarchical structure of postnatal cell type relationships, with location providing the highest level of organization, then neurotransmitter status, family, and finally, dozens of refined populations. We validate a combinatorial marker code for each neuronal cell type and map their spatial distributions in the adult spinal cord. We also show complex lineage relationships among postnatal cell types. Additionally, we develop an open-source cell type classifier, SeqSeek, to facilitate the standardization of cell type identification. This work provides an integrated view of spinal cell types, their gene expression signatures, and their molecular organization., Single-cell profiling has led to the identification of diverse cell types. Here, the authors generate a harmonized cell atlas of the mouse post-natal spinal cord. They also provide spatial analysis of the distribution of the identified cell types and an open-source cell type classifier.

Empirical studies in the creative arts therapies (CATs; i.e., art therapy, dance/movement therapy, drama therapy, music therapy, psychodrama, and poetry/bibliotherapy) have grown rapidly in the last 10 years, documenting their positive impact on a wide range of psychological and physiological outcomes (e.g., stress, trauma, depression, anxiety, and pain). However, it remains unclearhowandwhythe CATs have positive effects, and which therapeutic factors account for these changes. Research that specifically focuses on the therapeutic factors and/or mechanisms of change in CATs is only beginning to emerge. To gain more insight into how and why the CATs influence outcomes, we conducted a scoping review (Nstudies= 67) to pinpoint therapeutic factors specific to each CATs discipline, joint factors of CATs, and more generic common factors across all psychotherapy approaches. This review therefore provides an overview of empirical CATs studies dealing with therapeutic factors and/or mechanisms of change, and a detailed analysis of these therapeutic factors which are grouped into domains. A framework of 19 domains of CATs therapeutic factors is proposed, of which the three domains are composed solely of factors unique to the CATs: “embodiment,” “concretization,” and “symbolism and metaphors.” The terminology used in change process research is clarified, and the implications for future research, clinical practice, and CATs education are discussed.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients’ functional status (rp = −0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs’ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs’ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required., publishedVersion

The rapid spread of the SARS-CoV-2 lineages B.1.1.7 (N501Y.V1) throughout the UK, B.1.351 (N501Y.V2) in South Africa, and P.1 (B.1.1.28.1; N501Y.V3) in Brazil has led to the definition of variants of concern (VoCs) and recommendations for lineage specific surveillance. In Switzerland, during the last weeks of December 2020, we established a nationwide screening protocol across multiple laboratories, focusing first on epidemiological and microbiological definitions. In January 2021, we validated and implemented an N501Y-specific PCR to rapidly screen for VoCs, which are then confirmed using amplicon sequencing or whole genome sequencing (WGS). A total of 13,387 VoCs have been identified since the detection of the first Swiss case in October 2020, with 4194 being B.1.1.7, 172 B.1.351, and 7 P.1. The remaining 9014 cases of VoCs have been described without further lineage specification. Overall, all diagnostic centers reported a rapid increase of the percentage of detected VOCs, with a range of 6 to 46% between 25 to 31 of January 2021 increasing towards 41 to 82% between 22 to 28 of February. A total of 739 N501Y positive genomes were analysed and show a broad range of introduction events to Switzerland. In this paper, we describe the nationwide coordination and implementation process across laboratories, public health institutions, and researchers, the first results of our N501Y-specific variant screening, and the phylogenetic analysis of all available WGS data in Switzerland, that together identified the early introduction events and subsequent community spreading of the VoCs., Microorganisms, 9 (4)

Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and EuroQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort. At inclusion, the mean ALSAQ-5 total score was 56.93 (max. 100, best = 0) with a better QoL associated with a less severe disease status (β = −1.96 per increase of one point in the ALSFRS-R score, p < 0.001). “Limb-onset” ALS (lALS) was associated with a better QoL than “bulbar-onset” ALS (bALS) (mean ALSAQ-5 total score 55.46 versus 60.99, p = 0.040). Moreover, with the ALSFRS-R as a covariate, using a mobility aid (β = −7.60, p = 0.001), being tracheostomized (β = −14.80, p = 0.004) and using non-invasive ventilation (β = −5.71, p = 0.030) were associated with an improved QoL, compared to those at the same disease stage who did not use these aids. In contrast, antidepressant intake (β = 5.95, p = 0.007), and increasing age (β = 0.18, p = 0.023) were predictors of worse QoL. Our results showed that the ALSAQ-5 was better-suited for ALS patients than the EQ-5D-5L. Further, the early and symptom-specific clinical management and supply of assistive devices can significantly improve the individual HRQoL of ALS patients. Appropriate QoL questionnaires are needed to monitor the impact of treatment to provide the best possible and individualized care., publishedVersion

A paradigm shift in the way of rearing heifer calves from restricted feeding and early weaning towards greater feed allowances and later weaning ages is ongoing. We aimed at characterizing the oxidative status in Holstein heifer calves fed with milk replacer (MR) at either a restrictive (RES) or a high (HIGH) level for 14 weeks. We compared two groups: HIGH (10 L MR/d, n = 18) and RES (5.7 L/d, n = 19) from day five until week 14 of life. In blood samples collected at birth, and then fortnightly from week 8–16, and in week 20, the antioxidative capacity measured as ferric reducing ability of plasma (FRAP), oxidative damage of lipids measured as thiobarbituric acid reactive substances (TBARS) and oxidative damage of proteins measured as advanced oxidation products of proteins (AOPP), free radicals measured as reactive oxidative metabolites (dROM), and the glutathione peroxidase (GSH-Px) activity, as well as leptin, adiponectin and haptoglobin were assessed. The time course of these variables during the first 20 weeks of life showed characteristic patterns, group differences were limited to adiponectin, AOPP, and FRAP. RES calves had lower growth rates, showed signs of hunger, but did not differ from HIGH in their intake of solid starter feed and in health status. This work characterizes the changes in oxidative status of dairy calves with increasing age and confirms the benefits of a high feeding plane with regard to welfare and development.

Hypomyelination is a rare consequence of in utero bovine viral diarrhoea virus (BVDV) infection. We describe a BVDV outbreak in a naïve Holstein dairy herd in northern Italy, with an unusually high prevalence of calves with neurological signs, generalised tremors and ataxia. Histological analysis showed that hypomyelination was the predominant lesion and that the most typical BVDV neuropathological findings (e.g. cerebellar hypoplasia) were absent. Virological and molecular analyses showed that non-cytopathic BVDV genotype 1b was associated with the calves’ neurological signs and excluded other viruses responsible for congenital infection or neurological disorders. Whole-genome sequencing of BVDVs from the brain of a calf with neurological signs and the whole blood of a persistently infected herd-mate with no such sign showed >99.7 % sequence identity. Analysis of the quasispecies distribution revealed the greatest variation rates in regions coding for the structural proteins E1 and E2. Variation was slightly greater in the brain- than in the blood-derived sequence and occurred at different sites, suggesting the occurrence of distinct evolutionary processes in the two persistently infected calves. Molecular characterisation of BVDV genomes from five other calves with neurological signs from the same farm confirmed that the E1 and E2 regions were the most variable. Several factors, including genetic variability and host factors, appear to have contributed to the observed unique BVDV disease phenotype, characterised by hypomyelination and neurological signs.

Pathologic alterations of Transactivation response DNA-binding protein 43 kilo Dalton (TDP-43) are a major hallmark of amyotrophic lateral sclerosis (ALS). In this pilot study, we analyzed the secondary structure distribution of TDP-43 in cerebrospinal fluid of ALS patients (n = 36) compared to Parkinson´s disease patients (PD; n = 30) and further controls (Ctrl; n = 24) using the immuno-infrared sensor technology. ALS patients could be discriminated from PD and Ctrl with a sensitivity/specificity of 89 %/77 % and 89 %/83 %, respectively. Our findings demonstrate that TDP-43 misfolding measured by the immuno-infrared sensor technology has the potential to serve as a biomarker candidate for ALS. CA extern

Purpose This is an official guideline, published and coordinated by the Gynecological Oncology Working Group (AGO) of the German Cancer Society (DKG) and the German Society for Gynecology and Obstetrics (DGGG). Vaginal cancers are rare tumors, which is why there is very little evidence on these tumors. Knowledge about the optimal clinical management is limited. This first German S2k guideline on vaginal cancer has aimed to compile the most current expert knowledge and offer new recommendations on the appropriate treatment as well as providing pointers about individually adapted therapies with lower morbidity rates than were previously generally available. The purpose of this guideline is also to set up a register to record data on treatment data and the course of disease as a means of obtaining evidence in future. Methods The present S2k guideline was developed by members of the Vulvar und Vaginal Tumors Commission of the AGO in an independently moderated, structured, formal consensus process and the contents were agreed with the mandate holders of the participating scientific societies and organizations. Recommendations To optimize the daily care of patients with vaginal cancer: 1. Monitor the spread pattern; 2. Follow the step-by-step diagnostic workup based on initial stage at detection; 3. As part of individualized clinical therapeutic management of vaginal cancer, follow the sentinel lymph node protocol described here, where possible; 4. Participate in the register study on vaginal cancer.

The Rho kinase (ROCK) inhibitor Fasudil is a promising drug for a disease-modifying therapy of amyotrophic lateral sclerosis (ALS). In preclinical models, Fasudil was shown to increase motor neuron survival, inhibit axonal degeneration, enhance axonal regeneration and modulate microglial function in vitro and in vivo. It prolonged survival and improved motor function of SOD1-G93A-mice. Recently, a phase IIa clinical trial has been commenced to investigate the safety, tolerability, and efficacy of Fasudil in ALS patients at an early stage of disease (ROCK-ALS trial, NCT03792490, Eudra-CT-Nr.: 2017-003676-31). Although Fasudil has been approved in Japan for many years for the treatment of vasospasms following subarachnoid hemorrhage and is known to have a favorable side effect profile in these patients, there is no data on its use in human patients with ALS or any other neurodegenerative conditions. Here, we report the first three cases of compassionate use of Fasudil in patients with ALS. Between May 2017 and February 2019, one male (66 years old) and two female (62 and 68 years old) subjects with probable or definite ALS according to the El Escorial criteria (one of the females having a pathogenic SOD1 mutation) were administered Fasudil 30 mg intravenously twice daily over 45 min on 20 consecutive working days. Blood pressure, heart rate and routine laboratory tests were constantly controlled. All three subjects tolerated the Fasudil infusions well without any obvious side effects. Interestingly, the slow vital capacity showed a significant increase in one of the patients. Taken together, we report here the first compassionate use of the ROCK inhibitor Fasudil in three ALS patients, which was well-tolerated.

Human prion diseases are associated with misfolded prion protein (Prion Protein Scrapie, PrPSc) causing rapidly and irreversibly progressive encephalopathic syndromes. PrPSc builds insoluble aggreg...

We present the result of an experiment to measure the electric dipole moment (EDM) of the neutron at the Paul Scherrer Institute using Ramsey’s method of separated oscillating magnetic fields with ultracold neutrons. Our measurement stands in the long history of EDM experiments probing physics violating time-reversal invariance. The salient features of this experiment were the use of a 199Hg comagnetometer and an array of optically pumped cesium vapor magnetometers to cancel and correct for magnetic-field changes. The statistical analysis was performed on blinded datasets by two separate groups, while the estimation of systematic effects profited from an unprecedented knowledge of the magnetic field. The measured value of the neutron EDM is dn=(0.0±1.1stat±0.2sys)×10−26 e.cm., Physical Review Letters, 124 (8), ISSN:0031-9007, ISSN:1079-7114

An array of 16 laser-pumped scalar Cs magnetometers was part of the neutron electric dipole moment (nEDM) experiment taking data at the Paul Scherrer Institute in 2015 and 2016. It was deployed to measure the gradients of the experiment's magnetic field and to monitor their temporal evolution. The originality of the array lies in its compact design, in which a single near-infrared diode laser drives all magnetometers that are located in a high-vacuum chamber, with a selection of the sensors mounted on a high-voltage electrode. We describe details of the Cs sensors' construction and modes of operation, emphasizing the accuracy and sensitivity of the magnetic-field readout. We present two applications of the magnetometer array directly beneficial to the nEDM experiment: (i) the implementation of a strategy to correct for the drift of the vertical magnetic-field gradient and (ii) a procedure to homogenize the magnetic field. The first reduces the uncertainty of the nEDM result. The second enables transverse neutron spin relaxation times exceeding 1500 s, improving the statistical sensitivity of the nEDM experiment by about 35% and effectively increasing the rate of nEDM data taking by a factor of 1.8. An array of sixteen laser-pumped scalar Cs magnetometers was part of the neutron electric dipole moment (nEDM) experiment taking data at the Paul Scherrer Institute in 2015 and 2016. It was deployed to measure the gradients of the experiment's magnetic field and to monitor their temporal evolution. The originality of the array lies in its compact design, in which a single near-infrared diode laser drives all magnetometers that are located in a high-vacuum chamber, with a selection of the sensors mounted on a high-voltage electrode. We describe details of the Cs sensors' construction and modes of operation, emphasizing the accuracy and sensitivity of the magnetic field readout. We present two applications of the magnetometer array directly beneficial to the nEDM experiment: (i) the implementation of a strategy to correct for the drift of the vertical magnetic field gradient and (ii) a procedure to homogenize the magnetic field. The first reduces the uncertainty of the new nEDM result. The second enables transverse neutron spin relaxation times exceeding 1500 s, improving the statistical sensitivity of the nEDM experiment by about 35% and effectively increasing the rate of nEDM data taking by a factor of 1.8.

Background Daysy is a fertility monitor that uses the fertility awareness method by tracking and analyzing the individual menstrual cycle. In addition, Daysy can be connected to the application DaysyView to transfer stored personal data from Daysy to a smartphone or tablet (IOS, Android). This combination is interesting because as it is shown in various studies, the use of apps is increasing patients´ focus on their disease or their health behavior. The aim of this study was to investigate if by the additional use of an App and thereby improved usability of the medical device, it is possible to enhance the typical-use related as well as the method-related pregnancy rates. Result In the resultant group of 125 women (2076 cycles in total), 2 women indicated that they had been unintentionally pregnant during the use of the device, giving a typical-use related Pearl-Index of 1.3. Counting only the pregnancies which occurred as a result of unprotected intercourse during the infertile (green) phase, we found 1 pregnancy, giving a method-related Pearl-Index of 0.6. Calculating the pregnancy rate resulting from continuous use and unprotected intercourse exclusively on green days, gives a perfect-use Pearl-Index of 0.8. Conclusion It seems that combining a specific biosensor-embedded device (Daysy), which gives the method a very high repeatable accuracy, and a mobile application (DaysyView) which leads to higher user engagement, results in higher overall usability of the method.

We report the identification of a neurotropic astrovirus associated with encephalitis in a sheep. This virus is genetically almost identical to an astrovirus recently described in neurologically diseased cattle. The similarity indicates that astroviruses of the same genotype may cause encephalitis in different species.