Timing of oral anticoagulation in atrial fibrillation patients after acute ischaemic stroke and outcome after 3 months: results of the multicentre Berlin Atrial Fibrillation Registry.

Background: Oral anticoagulation (OAC) is key in stroke prevention in patients with atrial fibrillation (AF) but there is uncertainty regarding the optimal timing of OAC (re)initiation after stroke, as recent large randomised controlled trials have methodological weaknesses and excluded stroke patients on therapeutic anticoagulation at stroke onset as well as patients started on a vitamin K antagonist after stroke. The '1-3-6-12 days rule', based on expert consensus and referring to stroke severity, was used in clinical practice to initiate OAC after acute ischaemic stroke or transient ischaemic attack (TIA) since publication in 2013.

Methods: We retrospectively assessed whether compliance to the '1-3-6-12 days rule' was associated with the composite endpoint (recurrent stroke, systemic embolism, myocardial infarction, major bleeding or all-cause death).

Structural basis for TBP displacement from TATA box DNA by the Swi2/Snf2 ATPase Mot1.

The Swi2/Snf2 family transcription regulator Modifier of Transcription 1 (Mot1) uses adenosine triphosphate (ATP) to dissociate and reallocate the TATA box-binding protein (TBP) from and between promoters. To reveal how Mot1 removes TBP from TATA box DNA, we determined cryogenic electron microscopy structures that capture different states of the remodeling reaction. The resulting molecular video reveals how Mot1 dissociates TBP in a process that, intriguingly, does not require DNA groove tracking.

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry.

Aims: We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke.

Methods: The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke.

Results: At stroke onset, an off-label daily dose was prescribed in 61 (25.

Weather conditions associated with subarachnoid hemorrhage: a multicenter case-crossover study.

Background: Most spontaneous subarachnoid hemorrhages (SAH) occur unexpectedly and independently of classical risk factors. In the light of increasing climate variability and change, we investigated weather and rapid weather changes as possible short-term risk factors for SAH.

Methods: Seven hundred ninety one patients admitted to three major hospitals in Germany for non-traumatic SAH with a determinable onset of SAH symptoms were included in this hospital-based, case-crossover study.

C-Terminal Motifs of the MTW1 Complex Cooperatively Stabilize Outer Kinetochore Assembly in Budding Yeast.

Kinetochores are macromolecular protein assemblies at centromeres that mediate accurate chromosome segregation during cell division. The outer kinetochore KNL1, MIS12, and NDC80 complexes assemble the KMN network, which harbors the sites of microtubule binding and spindle assembly checkpoint signaling. The buildup of the KMN network that transmits microtubule pulling forces to budding yeast point centromeres is poorly understood.

Auto-inhibition of Mif2/CENP-C ensures centromere-dependent kinetochore assembly in budding yeast.

Kinetochores are chromatin-bound multi-protein complexes that allow high-fidelity chromosome segregation during mitosis and meiosis. Kinetochore assembly is exclusively initiated at chromatin containing Cse4/CENP-A nucleosomes. The molecular mechanisms ensuring that subcomplexes assemble efficiently into kinetochores only at centromeres, but not anywhere else, are incompletely understood.

Association of Surgical Hematoma Evacuation vs Conservative Treatment With Functional Outcome in Patients With Cerebellar Intracerebral Hemorrhage.

Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established.

Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH.

Design, Setting, And Participants: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015).

Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.

Aims: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke.

Methods And Results: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient.

ABSENCE OF MACULAR DEGENERATION IN A PATIENT WITH ACERULOPLASMINEMIA.

Purpose: To describe the clinical, histological, electrophysiologic, and multimodal imaging findings in a 76-year-old patient with aceruloplasminemia with low genetic risk of age-related macular degeneration (AMD).

Methods: Clinical examination as well as multimodal imaging including fundus photography, optical coherence tomography, fluorescence lifetime imaging ophthalmoscopy imaging, and full-field and multifocal electroretinography were performed on one patient with aceruloplasminemia. The ceruloplasmin gene was sequenced to confirm a known mutation.

The COMA complex interacts with Cse4 and positions Sli15/Ipl1 at the budding yeast inner kinetochore.

Kinetochores are macromolecular protein complexes at centromeres that ensure accurate chromosome segregation by attaching chromosomes to spindle microtubules and integrating safeguard mechanisms. The inner kinetochore is assembled on CENP-A nucleosomes and has been implicated in establishing a kinetochore-associated pool of Aurora B kinase, a chromosomal passenger complex (CPC) subunit, which is essential for chromosome biorientation. By performing crosslink-guided in vitro reconstitution of budding yeast kinetochore complexes we showed that the Ame1/Okp1 heterodimer, which forms the COMA complex with Ctf19/Mcm21, selectively bound Cse4 nucleosomes through the Cse4 N-terminus.

Characteristics in Non-Vitamin K Antagonist Oral Anticoagulant-Related Intracerebral Hemorrhage.

Background and Purpose- Given inconclusive studies, it is debated whether clinical and imaging characteristics, as well as functional outcome, differ among patients with intracerebral hemorrhage (ICH) related to vitamin K antagonists (VKA) versus non-vitamin K antagonist (NOAC)-related ICH. Notably, clinical characteristics according to different NOAC agents and dosages are not established. Methods- Multicenter observational cohort study integrating individual patient data of 1328 patients with oral anticoagulation-associated ICH, including 190 NOAC-related ICH patients, recruited from 2011 to 2015 at 19 tertiary centers across Germany.

Heparin for prophylaxis of venous thromboembolism in intracerebral haemorrhage.

Objective: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH.

Methods: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC.

An Evaluation of Depth and Size Perception on a Spherical Fish Tank Virtual Reality Display.

Fish Tank Virtual Reality (FTVR) displays create a compelling 3D spatial effect by rendering to the perspective of the viewer with head-tracking. Combining FTVR with a spherical display enhances the 3D experience with unique properties of the spherical screen such as the enclosing shape, consistent curved surface, and borderless views from all angles around the display. The ability to generate a strong 3D effect on a spherical display with head-tracked rendering is promising for increasing user's performance in 3D tasks.

A conserved filamentous assembly underlies the structure of the meiotic chromosome axis.

The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that 'axis core proteins' from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify 'closure motifs' in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination.

Weather, Weather Changes and the Risk of Bell's Palsy: A Multicenter Case-Crossover Study.

Background: To evaluate if weather or changes in weather are risk factors for Bell's palsy (BP) as exposure to draught of cold air has been popularly associated with the occurrence of BP.

Methods: Using a multicenter hospital-based case-crossover study, we analyzed the association between ambient temperature, atmospheric pressure, relative air humidity or their 24 h changes and the risk for BP in 825 patients or subgroups.

Results: One day following a 24 h increase in atmospheric pressure of more than 6 hPa, the risk for BP increased by 35% (OR 1.

Management of therapeutic anticoagulation in patients with intracerebral haemorrhage and mechanical heart valves.

Aims: Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH.

Methods And Results: We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses.

Allergens of permanent hair dyes induces epidermal damage, skin barrier loss and IL-1 α increase in epidermal in vitro model.

Allergic and irritant skin reactions caused by topical exposure to permanent hair dyes are a common problem. For regulatory and ethnical purposes, it is required to perform chemical safety assessment following the replacement, reduction, and refinement of animal testing (3Rs). Permanent hair dyes are formed by a mixture of ingredients that vary from low to extreme skin sensitizing potency and that inter-react to form unknown by-products.

The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding.

Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed "closure motifs". The AAA+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain-closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31 We show that p31 binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 "pore loops", which then unfold MAD2 in the presence of ATP N-terminal truncation of MAD2 renders it refractory to TRIP13 action , and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function.

Changes of individual BrainAGE during the course of the menstrual cycle.

Brain morphology varies during the course of the menstrual cycle, with increases in individual gray matter volume at the time of ovulation. This study implemented our previously presented BrainAGE framework to analyze short-term neuroanatomical changes in healthy young women due to hormonal changes during the menstrual cycle. The BrainAGE approach determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain MRIs.

Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage.

Importance: Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH).

Objective: To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption.

Design, Setting, And Participants: Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption.

Isolated reversible splenial lesion in tick-borne encephalitis: a case report and literature review.

Here, we demonstrate a first case of tick-borne encephalitis (TBE) associated with an isolated reversible splenial corpus callosum lesion (IRSL) and highlight the wide range of different clinical entities in which such alterations have been observed. A 42-year-old man showed fever, cephalgia and mild disturbance of coordination and gait. Diagnosis was ascertained by slight CSF-pleiocytosis and positive TBE-IgG as well as by positive intrathekal specific antibody index on follow-up.