A new era of stem cell and developmental biology: from blastoids to synthetic embryos and beyond.

Recent discoveries in stem cell and developmental biology have introduced a new era marked by the generation of in vitro models that recapitulate early mammalian development, providing unprecedented opportunities for extensive research in embryogenesis. Here, we present an overview of current techniques that model early mammalian embryogenesis, specifically noting models created from stem cells derived from two significant species: Homo sapiens, for its high relevance, and Mus musculus, a historically common and technically advanced model organism. We aim to provide a holistic understanding of these in vitro models by tracing the historical background of the progress made in stem cell biology and discussing the fundamental underlying principles. At each developmental stage, we present corresponding in vitro models that recapitulate the in vivo embryo and further discuss how these models may be used to model diseases. Through a discussion of these models as well as their potential applications and future challenges, we hope to demonstrate how these innovative advances in stem cell research may be further developed to actualize a model to be used in clinical practice.

Discovery of (E)-3-(3-((2-Cyano-4'-dimethylaminobiphenyl-4-ylmethyl)cyclohexanecarbonylamino)-5-fluorophenyl)acrylic Acid Methyl Ester, an Intestine-Specific, FXR Partial Agonist for the Treatment of Nonalcoholic Steatohepatitis.

A series of fexaramine analogs were synthesized and evaluated to develop an intestine-selective/specific FXR partial agonist. Introduction of both a CN substituent at the C-2 in the biphenyl ring and a fluorine at the C-5 in the aniline ring in fexaramine markedly increased FXR agonistic activity. 27c showed 53 ± 3% maximum efficacy relative to GW4064 in an FXR agonist assay. A substantial amount of 27c was absorbed in the intestine after oral administration in rats, and then it was rapidly metabolized to inactive carboxylic acid 44 by serum esterases. In CDAHFD-fed mice, oral administration of 27c strongly induced multiple intestinal FXR target genes, FGF15, SHP, IBABP, and OST-α, but failed to activate SHP in the liver. 27c significantly reduced the liver fibrogenesis area, hepatic fibrosis markers, and serum level of AST. Rational optimization of fexaramine has led to the identification of an intestine-specific FXR partial agonist 27c.

Carbon-encapsulated multi-phase nanocomposite of W2C@WC1-x as a highly active and stable electrocatalyst for hydrogen generation.

The major challenges related to the activity, stability, and cost of electrocatalysts are being increasingly raised to achieve highly efficient and cost-effective hydrogen generation. Herein, multiphase nanocomposites of W2C@WC1-x encapsulated within graphitic carbon layers were prepared via a facile and effective process of electrical explosion of wires and subsequent heat treatment to serve as a highly active and stable electrocatalyst without any noble metal for hydrogen generation. The single-phase comprising less than 15 nm WC1-x nanoparticles embedded in a lump of amorphous carbon were successfully synthesized via the EEW process in oleic acid used as a carbon source at room temperature. Subsequent heat treatment facilitates the desired phase transition of WC1-x to W2C without the formation of any secondary phases, maintaining the initial particle size and simultaneously eliminating excess amorphous carbon adhered to the nanoparticles. The few graphitic carbon layer-encapsulated nanoparticles with the main W2C phase prepared by this simple method exhibit high efficiency for hydrogen generation with a low overpotential of 240 mV at a current density of 10 mA cm-2 and a low Tafel slope of 86 mV dec-1. Moreover, the overpotential is well maintained at a constantly injected current density of 10 mA cm-2 for 100 h with a low η100/ηi value of 1.03 (ηi: initial overpotential, η100: overpotential after 100 h), demonstrating superior catalytic stability in acidic media. This work proposes and evaluates a facile strategy for the synthesis of highly efficient electrocatalysts based on metal carbides without noble metals.

Unusual Case of Cerebral Venous Thrombosis in Patient with Crohn's Disease.

The development of cerebral venous thrombosis (CVT) as a secondary complication of Crohn's disease (CD) seems to be rare, but it is generally accepted that the disease activity of CD contributes to the establishment of a hypercoagulable state. Here, we describe a case of CVT that developed outside the active phase of CD. A 17-year-old male visited the emergency room because of a sudden onset of right-sided weakness and right-sided hypesthesia. He had been diagnosed with CD 1 year before and was on a maintenance regimen of mesalazine and azathioprine. He did not exhibit any symptoms indicating a CD flare-up (bloody stools, abdominal pain, complications, or weight loss). A brain MRI scan revealed an acute infarction of the left frontal cortex and a cortical subarachnoid hemorrhage. Additionally, a magnetic resonance venography revealed a segmental filling defect in the superior sagittal sinus and also the non-visualizability of some bilateral cortical veins. The characteristics of the present case suggest that the risk of CVT is most likely related to CD per se rather than disease activity associated with CD.

Predictive value of the Essen Stroke Risk Score and Ankle Brachial Index in acute ischaemic stroke patients from 85 German stroke units.

BACKGROUND: Risk stratification can contribute to individualised optimal secondary prevention in patients with cerebrovascular disease. OBJECTIVE: To prospectively investigate the prediction of the Essen Stroke Risk Score (ESRS) and a pathological Ankle Brachial Index (ABI) in consecutive patients hospitalised with acute ischaemic stroke or transient ischaemic attack (TIA) in 85 neurological stroke units throughout Germany. METHODS: 852 patients were prospectively documented on standardised case report forms, including assessment of ESRS and ABI. After 17.5 months, recurrent cerebrovascular events, functional outcome or death could be assessed in 729 patients predominantly via central telephone interview. RESULTS: After discharge from the documenting hospital, recurrent stroke occurred in 41 patients (5.6%) and recurrent TIA in 15 patients (2.1%). 52 patients (7.1%) had died, 33 (4.5%) from cardiovascular causes. Patients with an ESRS > or = 3 (vs <3) had a significantly higher risk of recurrent stroke or cardiovascular death (9.7% vs 5.1%; odds ratio (OR) 2.00, 95% confidence interval (CI) 1.08 to 3.70) and a higher recurrent stroke risk (6.9% vs 3.7%; OR 1.93, 95% CI 0.95 to 3.94). Patients with an ABI < or = 0.9 (vs > 0.9) had a significantly higher risk of recurrent stroke or cardiovascular death (10.4% vs 5.5%; OR 2.00, 95% CI 1.12 to 3.56) and a higher recurrent stroke risk (6.6% vs 4.6%; OR 1.47, 95% CI 0.76 to 2.83). CONCLUSION: Our prospective follow-up study shows a significantly higher rate of recurrent stroke or cardiovascular death and a clear trend for a higher rate of recurrent stroke in patients with acute cerebrovascular events classified as high risk by an ESRS > or = 3 or a pathological ABI.

Systemic risk score evaluation in ischemic stroke patients (SCALA): a prospective cross sectional study in 85 German stroke units.

BACKGROUND AND PURPOSE: Stratification of patients with transient ischemic attack (TIA) or ischemic stroke (IS) by risk of recurrent stroke can contribute to optimized secondary prevention. We therefore aimed to assess cardiovascular risk factor profiles of consecutive patients hospitalized with TIA/IS to stratify the risk of recurrent stroke according to the Essen Stroke Risk Score (ESRS) and of future cardiovascular events according to the ankle brachial index (ABI) as a marker of generalized atherosclerosis METHODS: In this cross-sectional observational study, 85 neurological stroke units throughout Germany documented cardiovascular risk factor profiles of 10 consecutive TIA/IS patients on standardized questionnaires. Screening for PAD was done with Doppler ultrasonography to calculate the ABI. RESULTS: A total of 852 patients (57% men) with a mean age of 67+/-12.4 years were included of whom 82.9 % had IS. The median National Institutes of Health stroke sum score was 4 (TIA: 1). Arterial hypertension was reported in 71%, diabetes mellitus in 26%, clinical PAD in 10%, and an ABI < or = 0.9 in 51%. An ESRS > or = 3 was observed in 58%, which in two previous retrospective analyses corresponded to a recurrent stroke risk of > or = 4%/year. The correlation between the ESRS and the ABI was low (r = 0.21). CONCLUSION: A high proportion of patients had asymptomatic atherosclerotic disease and a considerable risk of recurrent stroke according to the ABI and ESRS category. The prognostic accuracy as well as the potential benefit of various risk stratification scores in secondary stroke prevention require validation in a larger prospective study.

Reliability and validity of arm function assessment with standardized guidelines for the Fugl-Meyer Test, Action Research Arm Test and Box and Block Test: a multicentre study.

OBJECTIVES: To establish: (1) inter-rater and test-retest reliability of standardized guidelines for the Fugl-Meyer upper limb section, Action Research Arm Test and Box and Block Test in patients with paresis secondary to stroke, multiple sclerosis or traumatic brain injury and (2) correlation between these arm motor scales and more general measures of impairment and activity limitation. DESIGN: Multicentre cohort study. SETTING: Three European referral centres for neurorehabilitation. SUBJECTS: Thirty-seven stroke, 14 multiple sclerosis and five traumatic brain injury patients. MAIN MEASURES: Scores of the Fugl-Meyer Test (arm section), Action Research Arm Test, and Box and Block Test derived from video information. RESULTS: All three motor tests showed very high inter-rater and test-retest reliability (ICC and rho for main variables > 0.95). Correlation between the motor scales was very high (rho > 0.92). Motor scales correlated moderately highly with the Hemispheric Stroke Scale, a measure of impairment (rho = 0.660-0.689), but not with the Modified Barthel Index, a measure of the ability to cope with basic activities of daily living (rho = 0.044-0.086). CONCLUSIONS: The standardized guidelines assured comparability of test administration and scoring across clinical facilities. The arm motor scales provided information that was not identical to information from the Hemispheric Stroke Scale or the Modified Barthel Index.