Genetic predictors of survival in behavioral variant frontotemporal degeneration.

Objective: To determine autosomal dominant genetic predictors of survival in individuals with behavioral variant frontotemporal degeneration (bvFTD).

Methods: A retrospective chart review of 174 cases with a clinical phenotype of bvFTD but no associated elementary neurologic features was performed, with diagnosis either autopsy-confirmed (n = 57) or supported by CSF evidence of non-Alzheimer pathology (n = 117). Genetic analysis of the 3 most common genes with pathogenic autosomal dominant mutations associated with frontotemporal degeneration was performed in all patients, which identified cases with expansion (n = 28), progranulin () mutation (n = 12), and microtubule-associated protein tau mutation (n = 10).

Chronic Pancreatitis Leading to Pancreatogenic Diabetes Presenting in Diabetic Ketoacidosis: A Rare Entity.

Diabetes mellitus type 3c (DM3c) is an uncommon cause of diabetes due to pancreatic pathology. Its prevalence reaches about 5-10% among all diabetics in the Western world, largely due to chronic pancreatitis. DM3c occurs due to the destruction of the endocrine islet cells.

Cognitive and Neuroanatomic Accounts of Referential Communication in Focal Dementia.

The primary function of language is to communicate-that is, to make individuals reach a state of mutual understanding about a particular thought or idea. Accordingly, daily communication is truly a task of social coordination. Indeed, successful interactions require individuals to (1) track and adopt a partner's perspective and (2) continuously shift between the numerous elements relevant to the exchange.

Epidermotropic CXCR3 positive marginal zone lymphoma: a distinctive clinical histopathological entity potentially originating in the skin; it does not always indicate splenic marginal zone lymphoma.

Epidermotropic B cell lymphoma represents a rare form of marginal zone lymphoma presenting as a disseminated skin rash resembling pityriasis rosea. To date there are 8 reported cases. In addition to the widespread nature of the skin rash, there is a proclivity for spleen and bone marrow involvement raising consideration regarding its categorization as a systemic lymphoma.

Reducing Unplanned Extubations Across a Children's Hospital Using Quality Improvement Methods.

Introduction: Children who require an endotracheal (ET) tube for care during critical illness are at risk of unplanned extubations (UE), or the unintended dislodgement or removal of an ET tube that can lead to significant patient harm. A proposed national benchmark is 1 UE per 100 ventilator days. We aimed to reduce the rate of UEs in our intensive care units (ICUs) from 1.

Empiric Methods to Account for Pre-analytical Variability in Digital Histopathology in Frontotemporal Lobar Degeneration.

Digital pathology is increasingly prominent in neurodegenerative disease research, but variability in immunohistochemical staining intensity between staining batches prevents large-scale comparative studies. Here we provide a statistically rigorous method to account for staining batch effects in a large sample of brain tissue with frontotemporal lobar degeneration with tau inclusions (FTLD-Tau, = 39) or TDP-43 inclusions (FTLD-TDP, = 53). We analyzed the relationship between duplicate measurements of digital pathology, i.

Postpartum Nurses' Experience Caring for Infants With Neonatal Abstinence Syndrome.

Objectives: In previous years, otherwise healthy infants with neonatal abstinence syndrome (NAS) in our hospital were transferred to the NICU and frequently treated with medication. Currently, infants with NAS room-in with their mothers and rarely require medication. We sought to understand the lived experience of nurses on maternity and well-newborn units caring for infants with NAS.

Suboptimal stimulation by weak agonist epitope variants does not drive dysfunction of HIV-1-specific cytotoxic T lymphocyte clones.

Objective: To assess whether weakly recognized epitope variants induce anergy in HIV-1-specific CD8 T lymphocyte (CTL) clones as a mechanism of dysfunction.

Design: HIV-1-specific CTL clones were exposed to suboptimally recognized epitope variants, and screened for anergy and other T-cell dysfunction markers, and subsequent capability to kill target cells bearing index epitope.

Methods: In addition to the optimally recognized index epitope, two suboptimally recognized epitope variants were selected based on titration curves for killing of peptide-labeled target cells by three HIV-1-specific CTL clones targeting the epitopes SLYNTVATL (Gag 77-85, A02-restricted), RPAEPVPLQL (Rev 66-75, B07-restricted), and KRWIIMGLNK (Gag 263-272, B27-restricted).

Thermal biology of mosquito-borne disease.

Mosquito-borne diseases cause a major burden of disease worldwide. The vital rates of these ectothermic vectors and parasites respond strongly and nonlinearly to temperature and therefore to climate change. Here, we review how trait-based approaches can synthesise and mechanistically predict the temperature dependence of transmission across vectors, pathogens, and environments.

Reduction in Length of Stay and Morphine Use for NAS With the "Eat, Sleep, Console" Method.

Objectives: To reduce average length of stay (ALOS) in infants with neonatal abstinence syndrome (NAS) transferred to the inpatient floor from the mother-infant unit. Secondarily, we aimed to reduce morphine exposure in these infants.

Methods: Using quality improvement methodology, we redesigned our approach to NAS on the inpatient floor.

Individualized atrophy scores predict dementia onset in familial frontotemporal lobar degeneration.

Introduction: Some models of therapy for neurodegenerative diseases envision starting treatment before symptoms develop. Demonstrating that such treatments are effective requires accurate knowledge of when symptoms would have started without treatment. Familial frontotemporal lobar degeneration offers a unique opportunity to develop predictors of symptom onset.

Upper Gastrointestinal Crohn's Disease: Literature Review and Case Presentation.

Upper gastrointestinal tract predominant Crohn's Disease (CD) remains an elusive clinical entity, manifesting limited or vague symptomatology, eluding clinical suspicion, and delaying subsequent diagnostic evaluation. As a result, it has not been widely described and there is a lack of clear recommendations for diagnosis or management. Standard IBD evaluation including serologic testing, imaging, and endoscopy may initially not be fruitful.

Longitudinal progression of grey matter atrophy in non-amnestic Alzheimer's disease.

Recent models of Alzheimer's disease progression propose that disease may be transmitted between brain areas either via local diffusion or long-distance transport via white matter fibre pathways. However, it is unclear whether such models are applicable in non-amnestic Alzheimer's disease, which is associated with domain-specific cognitive deficits and relatively spared episodic memory. To date, the anatomical progression of disease in non-amnestic patients remains understudied.

Clinical Correlates of Alzheimer's Disease Cerebrospinal Fluid Analytes in Primary Progressive Aphasia.

While primary progressive aphasia (PPA) is associated with frontotemporal lobar degeneration (FTLD) pathology due to tau or TDP, clinical-pathological studies also demonstrate many cases have Alzheimer's disease (AD) pathology. The logopenic variant of PPA (lvPPA) is most often associated with AD pathology, but this has proven to be the least reliable PPA to diagnose using published clinical criteria. In this study, we used cerebrospinal fluid (CSF) analytes to identify patients with likely AD pathology, and relate phenotypic features of lvPPA to CSF.

Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia.

Background: Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD.

Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial.

Background: Progressive supranuclear palsy is a rare neurodegenerative disease associated with dysfunctional tau protein. BIIB092 is a humanised monoclonal antibody that binds to N-terminal tau and is thus being assessed as a potential novel treatment for progressive supranuclear palsy. We aimed to investigate the safety and tolerability of BIIB092 in individuals with progressive supranuclear palsy.

Is placebo analgesia for heat pain a sensory effect? An exploratory study on minimizing the influence of response bias.

We explored the ongoing question of whether placebo analgesia alters afferent nociceptive processing in a novel paradigm designed to minimize the role of response bias in placebo measurement. First, healthy adult participants received a standard heat placebo induction and conditioning procedure using a topical "analgesic" cream applied to one arm. During a subsequent placebo testing procedure, participants rated stimuli on the placebo-treated arm and untreated arm, using a task that minimized subjects' ability to guess the expected response, thus reducing experimenter demand.

A longitudinal study of speech production in primary progressive aphasia and behavioral variant frontotemporal dementia.

We examined longitudinal change in language expression during a semi-structured speech sample in 48 patients with primary progressive aphasia (PPA) or behavioral variant frontotemporal dementia (bvFTD) and related this to longitudinal neuroimaging of cortical thickness available in 25 of these patients. All patient groups declined significantly on measures of both speech fluency and grammar, although patients with nonfluent/agrammatic PPA (naPPA) declined to a greater extent than patients with the semantic variant, the logopenic variant, and bvFTD. These patient groups also declined on several neuropsychological measures, but there was no correlation between decline in speech expression and decline in neuropsychological performance.

Pancreatic Solid Pseudopapillary Tumor Associated with Elevated DHEA and Testosterone.

Solid pseudopapillary neoplasms (SPN) of the pancreas are extremely rare epithelial tumors with low malignant potential. They account for only 1-2% of pancreatic lesions. These masses often go unnoticed and when they become symptomatic it is often due to mass effect on neighboring structures.

Novel CSF biomarkers in genetic frontotemporal dementia identified by proteomics.

Objective: To identify novel CSF biomarkers in -associated frontotemporal dementia (FTD) by proteomics using mass spectrometry (MS).

Methods: Unbiased MS was applied to CSF samples from 19 presymptomatic and 9 symptomatic mutation carriers and 24 noncarriers. Protein abundances were compared between these groups.

Persistent and Progressive Outer Retina Thinning in Frontotemporal Degeneration.

Objective: While Alzheimer's disease is associated with inner retina thinning measured by spectral-domain optical coherence tomography (SD-OCT), our previous cross-sectional study suggested outer retina thinning in frontotemporal degeneration (FTD) patients compared to controls without neurodegenerative disease; we sought to evaluate longitudinal changes of this potential biomarker.

Methods: SD-OCT retinal layer thicknesses were measured at baseline and after 1-2 years. Clinical criteria, genetic analysis, and a cerebrospinal fluid biomarker (total tau: β-amyloid) to exclude likely underlying Alzheimer's disease pathology were used to define a subgroup of predicted molecular pathology (i.