A Multidisciplinary Approach Improves Sexual Health Care for Youth with Duchenne Muscular Dystrophy.

We sought to determine the prevalence of sexual health counseling in patients with Duchenne muscular dystrophy in a single-institution setting. Keywords related to sexual health and development concerns were documented at least once for 75% of patients across the duration of their care. Integration of sexual health discussions was facilitated by comprehensive multidisciplinary support, particularly with the inclusion of specialists in endocrinology and adolescent medicine.

The APP intracellular domain promotes expression to enable feed-forward neurodegenerative mechanisms in Parkinson's disease.

Gain-of-function mutations in the leucine-rich repeat kinase 2 () gene are common in familial forms of Parkinson's disease (PD), which is characterized by progressive neurodegeneration that impairs motor and cognitive function. We previously demonstrated that LRRK2-mediated phosphorylation of β-amyloid precursor protein (APP) triggers the production and nuclear translocation of the APP intracellular domain (AICD). Here, we connected LRRK2 to AICD in a feed-forward cycle that enhanced LRRK2-mediated neurotoxicity.

Need for Increased Awareness of International Male Circumcision Variations and Associated Complications: A Contemporary Review.

Male circumcision is a prevalent, straightforward procedure. Cultural, religious, and/or social factors are the main determinants in the decision to undergo circumcision. The method of circumcision and age of the patient at the time of circumcision varies, dependent on the deciding determinant: cultural or religious tradition, personal hygiene, preventive health, or medical need.

Multiplex proteomics identifies novel CSF and plasma biomarkers of early Alzheimer's disease.

To date, the development of disease-modifying therapies for Alzheimer's disease (AD) has largely focused on the removal of amyloid beta Aβ fragments from the CNS. Proteomic profiling of patient fluids may help identify novel therapeutic targets and biomarkers associated with AD pathology. Here, we applied the Olink™ ProSeek immunoassay to measure 270 CSF and plasma proteins across 415 Aβ- negative cognitively normal individuals (Aβ- CN), 142 Aβ-positive CN (Aβ+ CN), 50 Aβ- mild cognitive impairment (MCI) patients, 75 Aβ+ MCI patients, and 161 Aβ+ AD patients from the Swedish BioFINDER study.

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of PF-06751979, a Potent and Selective Oral BACE1 Inhibitor: Results from Phase I Studies in Healthy Adults and Healthy Older Subjects.

PF-06751979 is a selective inhibitor of the beta-site amyloid precursor protein cleaving enzyme-1, which is a key aspartyl protease in the generation of amyloid-β (Aβ) peptides, thought to be critical for the cerebral degeneration observed in Alzheimer's disease. Two Phase I studies (NCT02509117, NCT02793232) investigated the safety/tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-06751979. Single-ascending doses up to 540 mg and multiple-ascending doses up to 275 mg once daily (QD) in healthy adults, and multiple doses of 50 mg or 125 mg QD in healthy older subjects were assessed.

The National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease: Perspectives from the Research Roundtable.

The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the "A, T, N System" (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development.

Pulsed focused ultrasound changes nerve conduction of earthworm giant axonal fibers.

This study examined the effects of pulsed focused ultrasound (FUS) in disrupting nerve conduction. FUS operating at a 210 kHz fundamental frequency was administered to the medial and lateral giant axonal nerve fibers of earthworms in a burst of pulses (1 ms tone burst duration, 20 Hz pulse repetition frequency). The magnitude and latencies of the nerve potentials induced by electrical stimulation were measured under three experimental conditions - (I) no sonication, (II) sonication at 600 mW/cm spatial-peak temporal-average intensity (Ispta), and (III) sonication at 200 mW/cm Ispta.

A Phase II, Randomized, Double-Blind, Placebo-Controlled Study of Safety, Pharmacokinetics, and Biomarker Results of Subcutaneous Bapineuzumab in Patients with mild to moderate Alzheimer's disease.

Background: Bapineuzumab, a humanized monoclonal antibody, targets amyloid-β (Aβ1-40/1 -42) that is believed to play a key role in the pathogenesis of Alzheimer disease (AD).

Objectives: To assess the effects of monthly subcutaneous (SC) bapineuzumab versus placebo on cerebral amyloid signal in amyloid-positive patients with mild to moderate AD. The incidence of amyloid-related imaging abnormalities-edema/effusion (ARIA-E), pharmacokinetics, pharmacodynamics, immunogenicity, and other safety aspects of bapineuzumab were also evaluated.

The roles of inflammation and immune mechanisms in Alzheimer's disease.

The Alzheimer's Association's Research roundtable met in April 2015 to explore the role of neuroinflammatory mechanisms in the progression of Alzheimer's disease (AD). The ability of innate immune cells, particularly microglia and astrocytes, to mediate neuroinflammation in AD has been implicated as a significant contributor to disease pathogenesis. Adaptive immunity, which plays an important role in responding to injury and some diseases of the central nervous system, may contribute to neuroinflammation in AD as well.

An integrated multi-study analysis of intra-subject variability in cerebrospinal fluid amyloid-β concentrations collected by lumbar puncture and indwelling lumbar catheter.

Introduction: Amyloid-β (Aβ) has been investigated as a diagnostic biomarker and therapeutic drug target. Recent studies found that cerebrospinal fluid (CSF) Aβ fluctuates over time, including as a diurnal pattern, and increases in absolute concentration with serial collection. It is currently unknown what effect differences in CSF collection methodology have on Aβ variability.

Amyloid-β 11C-PiB-PET imaging results from 2 randomized bapineuzumab phase 3 AD trials.

Objective: To evaluate the effects of bapineuzumab on brain β-amyloid (Aβ) burden using (11)C-Pittsburgh compound B ((11)C-PiB)-PET.

Methods: Two phase 3 clinical trials, 1 each in apolipoprotein APOE ε4 carriers and noncarriers, were conducted in patients with mild to moderate Alzheimer disease dementia. Bapineuzumab, an anti-Aβ monoclonal antibody, or placebo, was administered by IV infusion every 13 weeks for 78 weeks.

The influence of biological and technical factors on quantitative analysis of amyloid PET: Points to consider and recommendations for controlling variability in longitudinal data.

In vivo imaging of amyloid burden with positron emission tomography (PET) provides a means for studying the pathophysiology of Alzheimer's and related diseases. Measurement of subtle changes in amyloid burden requires quantitative analysis of image data. Reliable quantitative analysis of amyloid PET scans acquired at multiple sites and over time requires rigorous standardization of acquisition protocols, subject management, tracer administration, image quality control, and image processing and analysis methods.

Amyloid PET imaging in Alzheimer's disease: a comparison of three radiotracers.

Purpose: The increasing use of amyloid PET in Alzheimer's disease research and clinical trials has motivated efforts to standardize methodology. We compared retention of the (11)C radiotracer Pittsburgh Compound B (PiB) and that of two (18)F amyloid radiotracers (florbetapir and flutemetamol) using two study populations. We also examined the feasibility of converting between tracer-specific measures, using PiB as the common link between the two (18)F tracers.

Depression in older patients with neurologic illness: causes, recognition, management.

Depression is common in the elderly, particularly in older persons with neurologic illness. Its etiology in this population is incompletely understood and likely to be multifactorial. Identifying depression in elderly patients with neurologic illness can be a challenge, as many of its features resemble symptoms of the underlying neurologic disease or of the aging process itself.

Idebenone treatment fails to slow cognitive decline in Alzheimer's disease.

Objective: To determine the effect of idebenone on the rate of decline in Alzheimer's disease (AD).

Methods: A 1-year, multicenter, double-blind, placebo-controlled, randomized trial was conducted. Subjects were over age 50 with a diagnosis of probable AD and had Mini-Mental State Examination (MMSE) scores between 12 and 25.

Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS).

Context: Goal-directed delivery of sedative and analgesic medications is recommended as standard care in intensive care units (ICUs) because of the impact these medications have on ventilator weaning and ICU length of stay, but few of the available sedation scales have been appropriately tested for reliability and validity.

Objective: To test the reliability and validity of the Richmond Agitation-Sedation Scale (RASS).

Design: Prospective cohort study.

The impact of delirium in the intensive care unit on hospital length of stay.

Study Objective: To determine the relationship between delirium in the intensive care unit (ICU) and outcomes including length of stay in the hospital.

Design: A prospective cohort study.

Setting: The adult medical ICU of a tertiary care, university-based medical center.

Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU).

Context: Delirium is a common problem in the intensive care unit (ICU). Accurate diagnosis is limited by the difficulty of communicating with mechanically ventilated patients and by lack of a validated delirium instrument for use in the ICU.

Objectives: To validate a delirium assessment instrument that uses standardized nonverbal assessments for mechanically ventilated patients and to determine the occurrence rate of delirium in such patients.

Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).

Objective: To develop and validate an instrument for use in the intensive care unit to accurately diagnose delirium in critically ill patients who are often nonverbal because of mechanical ventilation.

Design: Prospective cohort study.

Setting: The adult medical and coronary intensive care units of a tertiary care, university-based medical center.

Increased CSF F2-isoprostane concentration in probable AD.

Objective: To quantify F2-isoprostane levels in CSF obtained from the lumbar cistern of patients with AD, ALS, and controls.

Background: Studies of human postmortem tissue and experimental models have suggested a role for oxidative damage in the pathogenesis of several neurodegenerative diseases, especially AD and ALS. F2-isoprostanes are exclusive products of free-radical-mediated peroxidation of arachidonic acid that have been widely used as quantitative biomarkers of lipid peroxidation in vivo in humans.

Effect of geometrical distortion correction in MR on image registration accuracy.

In this article we investigate the effect of geometrical distortion correction in MR images on the accuracy of the registration of X-ray CT and MR head images for both a fiducial marker (extrinsic point) method and a surface-matching technique. We use CT and T2-weighted MR image volumes acquired from seven patients who underwent craniotomies in a stereotactic neurosurgical clinical trial. Each patient had four external markers attached to transcutaneous posts screwed into the outer table of the skull.

Severe global amnesia presenting as Wernicke-Korsakoff syndrome but resulting from atypical lesions.

A female alcoholic presented with Wernicke's encephalopathy subsequent to administration of diazepam and glucose (without thiamine) for treatment of withdrawal seizures. Nystagmus and cerebellar ataxia quickly resolved when administered thiamine, although severe global amnesia consistent with Korsakoff's syndrome persisted. Magnetic resonance imaging (MRI) revealed infarction of the right temporal lobe with hippocampal atrophy, but no lesions of thalamus or atrophy of mammillary bodies.