Malformations of the sacculus and the semicircular canals in spider morph pythons

Spider morph ball pythons are a frequently-bred designer morph with striking alterations of the skin color pattern. We created high-resolution μCT-image series through the otic region of the skulls, used 3D-reconstruction software for rendering anatomical models, and compared the anatomy of the semicircular ducts, sacculus and ampullae of wildtype Python regius (ball python) with spider morph snakes. All spider morph snakes showed the wobble condition (i.e., twisting movements of the head, impaired locomotion, difficulty striking or constricting prey items). We describe the inner ear structures in wildtype and spider morph snakes and report a deviant morphology of semicircular canals, ampullae and sacculus in the latter. We also report about associated differences in the desmal skull bones of spider morph snakes, which were characterized by wider semicircular canals, ampullae widened and difficult to discern in μCT, a deformed crus communis, and a small sacculus with a highly deviant X-ray morphology as compared to wildtype individuals. We observed considerable intra- and interindividual variability of these features. This deviant morphology in spider morph snakes could easily be associated with an impairment of sense of equilibrium and the observed neurological wobble condition. Limitations in sample size prevent statistical analyses, but the anatomical evidence is strong enough to support an association between the wobble condition and a malformation of the inner ear structures. A link between artificially selected alterations in pattern and specific color design with neural-crest associated developmental malformations of the statoacoustic organ as known from other vertebrates is discussed

Impact of an online guided physical activity training on cognition and gut-brain axis interactions in older adults: protocol of a randomized controlled trial

IntroductionBy 2050, the worldwide percentage of people 65 years and older is assumed to have doubled compared to current numbers. Therefore, finding ways of promoting healthy (cognitive) aging is crucial. Physical activity is considered an effective approach to counteract not only physical but also cognitive decline. However, the underlying mechanisms that drive the benefits of regular physical activity on cognitive function are not fully understood. This randomized controlled trial aims to analyze the effect of an eight-week standardized physical activity training program in older humans on cognitive, brain, and gut-barrier function as well as the relationship between the resulting changes.Methods and analysisOne-hundred healthy participants aged 60 to 75 years will be recruited. First, participants will undergo an extensive baseline assessment consisting of neurocognitive tests, functional and structural brain imaging, physical fitness tests, and gut-microbiome profiling. Next, participants will be randomized into either a multi-component physical activity group (experimental condition) or a relaxation group (active control condition), with each training lasting 8 weeks and including an equal number and duration of exercises. The whole intervention will be online-based, i.e., participants will find their intervention schedule and all materials needed on the study website. After the intervention phase, participants will have their post-intervention assessment, which consists of the same measures and tests as the baseline assessment. The primary outcome of this study is the change in the cognitive parameter of visual processing speed from baseline to post-measurement, which will on average take place 10 weeks after the randomization. Secondary outcomes related to cognitive, brain, and microbiome data will be analyzed exploratory.Clinical trial registration:https://drks.de/search/de/trial/DRKS0002802

Retrospective, multicenter analysis comparing conventional with oncoplastic breast conserving surgery: oncological and surgical outcomes in women with high-risk breast cancer from the OPBC-01/iTOP2 study

Introduction: Recent data suggest that margins ≥2 mm after breast-conserving surgery may improve local control in invasive breast cancer (BC). By allowing large resection volumes, oncoplastic breast-conserving surgery (OBCII; Clough level II/Tübingen 5-6) may achieve better local control than conventional breast conserving surgery (BCS; Tübingen 1-2) or oncoplastic breast conservation with low resection volumes (OBCI; Clough level I/Tübingen 3-4). Methods: Data from consecutive high-risk BC patients treated in 15 centers from the Oncoplastic Breast Consortium (OPBC) network, between January 2010 and December 2013, were retrospectively reviewed. Results: A total of 3,177 women were included, 30% of whom were treated with OBC (OBCI n = 663; OBCII n = 297). The BCS/OBCI group had significantly smaller tumors and smaller resection margins compared with OBCII (pT1: 50% vs. 37%, p = 0.002; proportion with margin <1 mm: 17% vs. 6%, p < 0.001). There were significantly more re-excisions due to R1 (“ink on tumor”) in the BCS/OBCI compared with the OBCII group (11% vs. 7%, p = 0.049). Univariate and multivariable regression analysis adjusted for tumor biology, tumor size, radiotherapy, and systemic treatment demonstrated no differences in local, regional, or distant recurrence-free or overall survival between the two groups. Conclusions: Large resection volumes in oncoplastic surgery increases the distance from cancer cells to the margin of the specimen and reduces reexcision rates significantly. With OBCII larger tumors are resected with similar local, regional and distant recurrence-free as well as overall survival rates as BCS/OBCI

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

The T1 phenotype of follicular helper T cells indicates an IFN-γ-associated immune dysregulation in patients with CD21low common variable immunodeficiency.

BACKGROUND A subgroup of patients with common variable immunodeficiency (CVID) experience immune dysregulation manifesting as autoimmunity, lymphoproliferation, and organ inflammation and thereby increasing morbidity and mortality. Therefore treatment of these complications demands a deeper comprehension of their cause and pathophysiology. OBJECTIVES On the basis of the identification of an interferon signature in patients with CVID with secondary complications and a skewed follicular helper T-cell differentiation in defined monogenic immunodeficiencies, we sought to determine the profile of CD4 memory T cells in blood and secondary lymphatic tissues of these patients. METHODS We quantified T1/T2/T17 CD4 memory T cells in blood and lymph nodes of patients with CVID using flow cytometry, analyzed their function, and correlated all findings to the burden of immune dysregulation. RESULTS Patients with CVID with immune dysregulation had a skewed memory CD4 T-cell differentiation toward a CXCR3CCR6 T1 phenotype both in blood and lymph nodes. Consistent with our phenotypic findings, we observed a higher IFN-γ production in peripheral CD4 memory T cells and lymph node-derived follicular helper T cells of patients with CVID compared with those of healthy control subjects. Increased IFN-γ production was accompanied by a poor germinal center output, an accumulation of T-box transcription factor (T-bet) B cells in lymph nodes, and an accumulation of T-betCD21 B cells in peripheral blood of affected patients. CONCLUSION Identification of excessive IFN-γ production by blood and lymph node-derived T cells of patients with CVID with immune dysregulation will offer new therapeutic avenues for this subgroup. CD21 B cells might serve as a marker of this IFN-γ-associated dysregulation