Partial loss of ATP13A2 causes selective gliosis independent of robust lipofuscinosis.

Loss-of-function mutations in ATP13A2 are associated with three neurodegenerative diseases: a rare form of Parkinson's disease termed Kufor-Rakeb syndrome (KRS), a lysosomal storage disorder termed neuronal ceroid lipofuscinosis (NCL), and a form of hereditary spastic paraplegia (HSP). Furthermore, recent data suggests that heterozygous carriers of mutations in ATP13A2 may confer risk for the development of Parkinson's disease, similar to the association of mutations in glucocerebrosidase (GBA) with both Parkinson's disease and Gaucher's disease, a lysosomal storage disorder. Mutations in ATP13A2 are generally thought to be loss of function; however, the lack of human autopsy tissue has prevented the field from determining the pathological consequences of losing functional ATP13A2.

Health Status Disparities by Sex, Race/Ethnicity, and Socioeconomic Status in Outpatients With Heart Failure.

Objectives: This study sought to describe the health status of outpatients with heart failure and reduced ejection fraction (HFrEF) by sex, race/ethnicity, and socioeconomic status (SES).

Background: Although a primary goal in treating patients with HFrEF is to optimize health status, whether disparities by sex, race/ethnicity, and SES exist is unknown.

Methods: In the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, the associations among sex, race, and SES and health status, as measured by the Kansas City Cardiomyopathy Questionnaire-overall summary (KCCQ-os) score (range 0 to 100; higher scores indicate better health status) was compared among 3,494 patients from 140 U.

Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial.

Objective: The objective is to assess the safety, tolerability, and efficacy of sacubitril/valsartan compared with enalapril in patients with heart failure (HF) with a reduced ejection fraction (EF) stabilized during hospitalization for acute decompensated HF.

Background: Sacubitril/valsartan, a first-in-class angiotensin receptor-neprilysin inhibitor, improves survival among ambulatory HF patients with a reduced EF. However, there is very limited experience with the in-hospital initiation of sacubitril/valsartan in patients who have been stabilized following hospitalization for acute decompensated HF.

Health Status Variation Across Practices in Outpatients With Heart Failure: Insights From the CHAMP-HF (Change the Management of Patients With Heart Failure) Registry.

Background: Although a key treatment goal for patients with heart failure with reduced ejection fraction is to optimize their health status (their symptoms, function, and quality of life), the variability across outpatient practices in achieving this goal is unknown.

Methods And Results: In the CHAMP-HF (Change the Management of Patients With Heart Failure) registry, associations between baseline practice characteristics and Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary (OS) and Symptom Frequency (SF) scores were assessed in 3494 patients across 140 US practices using hierarchical regression after accounting for 23 patient and 11 treatment characteristics. We then calculated an adjusted median odds ratio to quantify the average difference in likelihood that a patient would have excellent (KCCQ-OS, ≥75) health status or minimal (monthly or fewer) symptoms (KCCQ-SF, ≥75) when treated at one practice versus another, at random.

A possible molecular basis for photoprotection in the minor antenna proteins of plants.

The bioenergetics of light-harvesting by photosynthetic antenna proteins in higher plants is well understood. However, investigation into the regulatory non-photochemical quenching (NPQ) mechanism, which dissipates excess energy in high light, has led to several conflicting models. It is generally accepted that the major photosystem II antenna protein, LHCII, is the site of NPQ, although the minor antenna complexes (CP24/26/29) are also proposed as alternative/additional NPQ sites.

Checks and balances? DNA replication and the cell cycle in Plasmodium.

It is over 100 years since the life-cycle of the malaria parasite Plasmodium was discovered, yet its intricacies remain incompletely understood - a knowledge gap that may prove crucial for our efforts to control the disease. Phenotypic screens have partially filled the void in the antimalarial drug market, but as compound libraries eventually become exhausted, new medicines will only come from directed drug development based on a better understanding of fundamental parasite biology. This review focusses on the unusual cell cycles of Plasmodium, which may present a rich source of novel drug targets as well as a topic of fundamental biological interest.

Microglial Immune Response to Low Concentrations of Combustion-Generated Nanoparticles: An In Vitro Model of Brain Health.

The brain is the central regulator for integration and control of responses to environmental cues. Previous studies suggest that air pollution may directly impact brain health by triggering the onset of chronic neuroinflammation. We hypothesize that nanoparticle components of combustion-generated air pollution may underlie these effects.

Surgical Anatomy of Vaginal Hysterectomy-Impact of a Resident-Constructed Simulation Model.

Objectives: Obstetrics and gynecology residents are less prepared to perform vaginal hysterectomy (VH), despite its advantages over other hysterectomy routes. The American Congress of Obstetricians and Gynecologists and Council on Resident Education in Obstetrics and Gynecology have prioritized simulation training in VH. Our objective was to improve residents' understanding of surgical anatomy of VH using a resident-constructed, low-cost, low-fidelity model.

Radical Polymerization of Alkyl 2-Cyanoacrylates.

Cyanoacrylates (CAs) are well-known fast-setting adhesives, which are sold as liquids in the presence of stabilizers. Rapid anionic polymerization on exposure to surface moisture is responsible for instant adhesion. The more difficult, but synthetically more useful radical polymerization is only possible under acidic conditions.

Genetic relatedness reveals total population size of white sharks in eastern Australia and New Zealand.

Conservation concerns exist for many sharks but robust estimates of abundance are often lacking. Improving population status is a performance measure for species under conservation or recovery plans, yet the lack of data permitting estimation of population size means the efficacy of management actions can be difficult to assess, and achieving the goal of removing species from conservation listing challenging. For potentially dangerous species, like the white shark, balancing conservation and public safety demands is politically and socially complex, often leading to vigorous debate about their population status.

Effect of suckler cow vaccination against glycoprotein E (gE)-negative bovine herpesvirus type 1 (BoHV-1) on passive immunity and physiological response to subsequent bovine respiratory disease vaccination of their progeny.

The study objectives were: 1) to characterise the development of immunocompetence in beef suckler calves from birth to three months of age, and 2) to trace glycoprotein E (gE)-negative bovine herpesvirus type 1 (BoHV-1) antibodies from dam to calf and subsequent vaccination against pneumonia. Thirty multiparous beef suckler, spring-calving cows, consisting of two genotypes were involved; Limousin×Friesian (LF) and Charolais×Limousin (CL). Cows were immunised against the inactivated antigen strain of BoHV-1 (gE- (IBR marker vaccine) at day -84 and received a booster at day -56 relative to the expected calving date (d 0).

In vitro evaluation of chitosan copper chelate gels as a multimicronutrient feed additive for cattle.

Background: Effective micronutrient supplementation strategies are critical to ensure optimal health and productivity in livestock. The objective of this study was to develop a copper and vitamin (multimicronutrient) delivery system based on chitosan gel beads, and test its suitability, in vitro, for use as a cattle feed additive.

Results: Chitosan was chelated with copper sulfate to produce millimetre-scale gel matrices (∼2 mm).

The prevalence of constant supportive observations in high, medium and low secure services.

Unlabelled: Aims and method We explored the prevalence and use of constant supportive observations (CSO) in high, medium and low secure in-patient services in a single National Health Service (NHS) mental health trust. From clinical records, we extracted data on the length of time of CSO, the reason for the initiation of CSO and associated adverse incidents for all individuals who were placed on CSO between July 2013 and June 2014.

Results: A small number of individuals accounted for a disproportionately large proportion of CSO hours in each setting.

Strong trans-Pacific break and local conservation units in the Galapagos shark (Carcharhinus galapagensis) revealed by genome-wide cytonuclear markers.

The application of genome-wide cytonuclear molecular data to identify management and adaptive units at various spatio-temporal levels is particularly important for overharvested large predatory organisms, often characterized by smaller, localized populations. Despite being "near threatened", current understanding of habitat use and population structure of Carcharhinus galapagensis is limited to specific areas within its distribution. We evaluated population structure and connectivity across the Pacific Ocean using genome-wide single-nucleotide polymorphisms (~7200 SNPs) and mitochondrial control region sequences (945 bp) for 229 individuals.

Genome-wide mosaicism in divergence between zoonotic malaria parasite subpopulations with separate sympatric transmission cycles.

Plasmodium knowlesi is a significant cause of human malaria transmitted as a zoonosis from macaque reservoir hosts in South-East Asia. Microsatellite genotyping has indicated that human infections in Malaysian Borneo are an admixture of two highly divergent sympatric parasite subpopulations that are, respectively, associated with long-tailed macaques (Cluster 1) and pig-tailed macaques (Cluster 2). Whole-genome sequences of clinical isolates subsequently confirmed the separate clusters, although fewer of the less common Cluster 2 type were sequenced.

The State of Physical Injury and Serious Physical Injury in New York Criminal Law.

The terms "physical injury" and "serious physical injury" are key elements of proof in assault cases in New York; the applicability of each element depends on the degree, or severity, of the crime. Jurisprudence in this area continues to evolve, as it is often very fact-specific, and the interpretation of what constitutes a physical injury or serious physical injury varies by the court considering individual cases. This article reviews recent New York cases in this area, and highlights, where applicable, the differences in outcome among the judicial departments in their treatment of physical injury and serious physical injury as elements of assault in New York criminal law.

Retraction Note: Transgenic mice overexpressing the ALS-linked protein Matrin 3 develop a profound muscle phenotype.

The authors are retracting this article. The article describes mice expressing wild-type human MATR3. However, since publication the authors have become aware that all of the lines of mice described express human MATR3 containing the F115C mutation.

On-the-Go Training: Downloadable Modules to Train Medical Students to Care for Adult Female Sexual Assault Survivors.

Introduction: Every medical provider encounters patients who have experienced sexual assault, and a patient's interaction with the medical system can impact long-term outcomes. Training to provide appropriate, compassionate care for this population is lacking in most medical school curricula. This educational resource contains three downloadable modules to train medical students in providing improved care for adult female survivors of sexual assault so students can feel more confident and empowered in caring for this population.

Strength in Numbers: an international consensus conference to develop a novel approach to care delivery for young adults with type 1 diabetes, the Study.

Plain English Summary: Many young adults with type 1 diabetes struggle with the day-to-day management of their condition. They often find it difficult to find the time to attend their clinic appointments and to meet with their diabetes healthcare team. Young adults living with type 1 diabetes are not routinely involved in research that may help improve health services other than being invited to take part in studies as research participants.

Orexin/hypocretin treatment restores hippocampal-dependent memory in orexin-deficient mice.

Orexin A is produced in neurons of the lateral, perifornical and dorsomedial regions of the lateral hypothalamic area, which then project widely throughout the central nervous system to regulate arousal state, sleep-wake architecture, energy homeostasis and cognitive processes. Disruption of orexin signaling leads to sleep disturbances and increased body mass index, but recent studies also indicate that orexin neuron activation improves learning and memory. We hypothesized that hippocampal orexin receptor activation improves memory.

Fine control of chlorophyll-carotenoid interactions defines the functionality of light-harvesting proteins in plants.

Photosynthetic antenna proteins can be thought of as "programmed solvents", which bind pigments at specific mutual orientations, thus tuning the overall energetic landscape and ensuring highly efficient light-harvesting. While positioning of chlorophyll cofactors is well understood and rationalized by the principle of an "energy funnel", the carotenoids still pose many open questions. Particularly, their short excited state lifetime (<25 ps) renders them potential energy sinks able to compete with the reaction centers and drastically undermine light-harvesting efficiency.

Path perturbation detection tasks reduce MSTd neuronal self-movement heading responses.

We presented optic flow and real movement heading stimuli while recording MSTd neuronal activity. Monkeys were alternately engaged in three tasks: visual detection of optic flow heading perturbations, vestibular detection of real movement heading perturbations, and auditory detection of brief tones. Push-button RTs were fastest for tones and slower for visual and vestibular heading perturbations, suggesting that the tone detection task was easier.

Trajectories of pain severity in juvenile idiopathic arthritis: results from the Research in Arthritis in Canadian Children Emphasizing Outcomes cohort.

We studied children enrolled within 90 days of juvenile idiopathic arthritis diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) prospective inception cohort to identify longitudinal trajectories of pain severity and features that may predict pain trajectory at diagnosis. A total of 1062 participants were followed a median of 24.3 months (interquartile range = 16.

Growth and weight gain in children with juvenile idiopathic arthritis: results from the ReACCh-Out cohort.

Background: With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort.

Methods: Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years.