Reliability and Responsiveness of Clinical and Endoscopic Outcome Measures in Crohn's Disease.

Background: Regulatory guidance for Crohn's disease trials recommends coprimary efficacy end points that evaluate both symptoms and mucosal inflammation. We aimed to characterize the operating properties of commonly used disease activity assessments alone and in combination.

Methods: Endoscopic and clinical data were available for 129 participants from the Study of Biologic and Immunomodulator Naïve Patients in Crohn's Disease trial.

Standardizing Scoring Conventions for Crohn's Disease Endoscopy: An International RAND/UCLA Appropriateness Study.

Background And Aims: Endoscopic assessment of disease activity is integral for evaluating treatment response in patients with Crohn's disease (CD). We aimed to define appropriate items for evaluating endoscopic activity and conventions for consistent endoscopic scoring rules in CD.

Methods: A 2-round modified RAND/University of California at Los Angeles Appropriateness Method study was conducted.

Existing Bowel Preparation Quality Scales Are Reliable in the Setting of Centralized Endoscopy Reading.

Background: Development of bowel preparation products has been based upon colon cleansing rating by a local endoscopist. It is unclear how bowel preparation scales perform when centrally evaluated.

Aims: To evaluate the reliability of bowel preparation quality scales when assessed by central readers.

Effect of age on brain metabotropic glutamate receptor subtype 5 measured with [F]FPEB PET.

Objective: Metabotropic glutamate receptor subtype 5 (mGluR5) is integral to the brain glutamatergic system and cognitive function. This study investigated whether aging is associated with decreased brain mGluR5 availability.

Methods: Cognitively normal participants (n = 45), aged 18 to 84 years, underwent [F]FPEB positron emission tomography scans to quantify brain mGluR5.

Evaluating the optimum number of biopsies to assess histological inflammation in ulcerative colitis: a retrospective cohort study.

Background: The optimal ulcerative colitis biopsy protocol is unclear.

Aim: To evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitis METHODS: Biopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly.

PET imaging of mGluR5 in Alzheimer's disease.

Background: Metabotropic glutamate subtype 5 receptors (mGluR5) modulate synaptic transmission and may constitute an important therapeutic target in Alzheimer's disease (AD) by mediating the synaptotoxic action of amyloid-β oligomers. We utilized the positron emission tomography (PET) radioligand [F]FPEB to investigate mGluR5 binding in early AD.

Methods: Sixteen individuals with amnestic mild cognitive impairment (MCI) due to AD or mild AD dementia who were positive for brain amyloid were compared to 15 cognitively normal (CN) participants who were negative for brain amyloid.

Statin Use and Risk of Cognitive Decline in the ADNI Cohort.

Objective: To investigate associations between statin use and cognitive change, as well as diagnostic conversion, in individuals with cognitively normal (CN) status, mild cognitive impairment (MCI), and dementia due to Alzheimer disease (AD-dementia).

Methods: A multicenter cohort study with 1629 adults 48 to 91 years old with CN status, early MCI (EMCI), late MCI (LMCI), or AD-dementia at baseline followed prospectively for 24 months. Statin use was assessed at baseline, and cognition was measured over time with a composite memory score, a composite executive function score, and a global cognition score (Alzheimer's Disease Assessment Scale).

Spinal cord organogenesis model reveals role of Flk1 cells in self-organization of neural progenitor cells into complex spinal cord tissue.

A platform for studying spinal cord organogenesis in vivo where embryonic stem cell (ESC)-derived neural progenitor cells (NPC) self-organize into spinal cord-like tissue after transplantation in subarachnoid space of the spinal cord has been described. We advance the applicability of this platform by imaging in vivo the formed graft through T2w magnetic resonance imaging (MRI). Furthermore, we used diffusion tensor imaging (DTI) to verify the stereotypical organization of the graft showing that it mimics the host spinal cord.

Natalizumab for induction of remission in Crohn's disease.

Background: This systematic review update summarizes the current evidence on the use of natalizumab for induction of remission in Crohn's disease (CD).

Objectives: To determine the efficacy and safety of natalizumab for induction of remission in CD.

Search Methods: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD Group Specialized Trials Register, and clinicaltrials.

Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging.

Importance: Synaptic loss is well established as the major structural correlate of cognitive impairment in Alzheimer disease (AD). The ability to measure synaptic density in vivo could accelerate the development of disease-modifying treatments for AD. Synaptic vesicle glycoprotein 2A is an essential vesicle membrane protein expressed in virtually all synapses and could serve as a suitable target for synaptic density.

Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort.

Background: We investigated the relationship between sleep disturbance and cognitive decline or clinical conversion in individuals with normal cognition (CN), as well as those with mild cognitive impairment (MCI) and dementia due to Alzheimer disease (AD-dementia).

Methods: Secondary analysis of 1,629 adults between 48 and 91 years of age with up to 24 months of follow-up from the ADNI (Alzheimer's Disease Neuroimaging Initiative), a longitudinal cohort study.

Results: Sleep disturbance was not associated with decline in memory, executive function, or global cognition.

An Expedient Synthesis of Murrayaquinone A via a Novel Oxidative Free Radical Reaction.

Murrayaquinones A-D is a group of four bioactive carbazole-1,4-dione natural products isolated from the root bark of the plant hayata. Murrayaquinone is synthesized in five steps starting from the commercially available 2,4,5-trimethoxybenzaldehyde with an overall yield of 45%. The novelty of this murrayaquinone synthesis is in the use of a Mn(OAc) mediated oxidative radical reaction of a N-benzylaminoquinone derivative with 2-cyclohexen-1-one for the late-stage indole ring construction.

Interventions for treating collagenous colitis.

Background: Collagenous colitis is a cause of chronic diarrhea. This updated review was performed to identify therapies for collagenous colitis that have been assessed in randomized controlled trials (RCTs).

Objectives: The primary objective was to assess the benefits and harms of treatments for collagenous colitis.

Descriptive Epidemiology, Medical Evaluation, and Outcomes of Rock Climbing Injuries.

Objective: To gather epidemiologic data on injury type, treatment, and recovery from rock climbing injuries.

Methods: Design: retrospective cross-sectional study.

Setting: web-based survey.

Interventions for treating lymphocytic colitis.

Background: Lymphocytic colitis is a cause of chronic diarrhea. It is a subtype of microscopic colitis characterized by chronic, watery, non-bloody diarrhea and normal endoscopic and radiologic findings. The etiology of this disorder is unknown.

Responsiveness of Endoscopic Indices of Disease Activity for Crohn's Disease.

Objectives: The Crohn's Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however neither instrument is fully validated. We evaluated the responsiveness to change of the SES-CD and CDEIS using data from a trial of adalimumab, a drug therapy of known efficacy.

Methods: Paired video recordings (N=112) of colonoscopies (baseline and week 8-12) obtained from patients with CD who participated in a trial of adalimumab therapy were reviewed in random order, in duplicate, by four central readers (56 pairs of videos by 2 groups of readers).

Effect of Standardised Scoring Conventions on Inter-rater Reliability in the Endoscopic Evaluation of Crohn's Disease.

Background And Aims: The Crohn's Disease Endoscopic Index of Severity [CDEIS] and Simplified Endoscopic Score for Crohn's Disease [SES-CD] demonstrate consistent overall intra- and inter-rater reliability. However, the reliability of some index items is relatively poor. We evaluated scoring conventions to improve the reliability of these items.

Azathioprine and 6-mercaptopurine for maintenance of remission in ulcerative colitis.

Background: Maintenance of remission is a major issue in inflammatory bowel disease. In ulcerative colitis, the evidence for the effectiveness of azathioprine and 6-mercaptopurine for the maintenance of remission is still controversial.

Objectives: To assess the effectiveness and safety of azathioprine and 6-mercaptopurine for maintaining remission of ulcerative colitis.

Unfractionated or low-molecular weight heparin for induction of remission in ulcerative colitis.

Background: There are a limited number of treatment options for patients with ulcerative colitis (UC). An increased risk of thrombosis in UC coupled with an observation that UC patients being treated with anticoagulant therapy for thrombotic events had an improvement in their bowel symptoms led to trials examining the use of unfractionated heparin (UFH) and low molecular weight heparins (LMWH) in patients with active UC.

Objectives: To review randomized trials examining the efficacy of unfractionated heparin (UFH) or low molecular weight heparins (LMWH) for remission induction in patients with ulcerative colitis.

Activity-Based Restorative Therapies after Spinal Cord Injury: Inter-institutional conceptions and perceptions.

This manuscript is a review of the theoretical and clinical concepts provided during an inter-institutional training program on Activity-Based Restorative Therapies (ABRT) and the perceptions of those in attendance. ABRT is a relatively recent high volume and intensity approach toward the restoration of neurological deficits and decreasing the risk of secondary conditions associated with paralysis after spinal cord injury (SCI). ABRT is guided by the principle of neuroplasticity and the belief that even those with chronic SCI can benefit from repeated activation of the spinal cord pathways located both above and below the level of injury.

Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn's disease.

Objective: The Crohn's Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Score for Crohn's Disease (SES-CD) are commonly used to assess Crohn's disease (CD) activity; however, neither instrument has been fully validated. We assessed intra-rater and inter-rater reliability of these indices.

Design: Video recordings of colonoscopies obtained from 50 patients with CD who participated in an induction trial of a biological therapy were triplicated and reviewed in random order by four central readers.

NG2+ progenitors derived from embryonic stem cells penetrate glial scar and promote axonal outgrowth into white matter after spinal cord injury.

The glial scar resulting from spinal cord injury is rich in chondroitin sulfate proteoglycan (CSPG), a formidable barrier to axonal regeneration. We explored the possibility of breaching that barrier by first examining the scar in a functional in vitro model. We found that embryonic stem cell-derived neural lineage cells (ESNLCs) with prominent expression of nerve glial antigen 2 (NG2) survived, passed through an increasingly inhibitory gradient of CSPG, and expressed matrix metalloproteinase 9 (MMP-9) at the appropriate stage of their development.