Collagen IV deficiency causes hypertrophic remodeling and endothelium-dependent hyperpolarization in small vessel disease with intracerebral hemorrhage.

Background: Genetic variants in COL4A1 and COL4A2 (encoding collagen IV alpha chain 1/2) occur in genetic and sporadic forms of cerebral small vessel disease (CSVD), a leading cause of stroke, dementia and intracerebral haemorrhage (ICH). However, the molecular mechanisms of CSVD with ICH and COL4A1/COL4A2 variants remain obscure.

Methods: Vascular function and molecular investigations in mice with a Col4a1 missense mutation and heterozygous Col4a2 knock-out mice were combined with analysis of human brain endothelial cells harboring COL4A1/COL4A2 mutations, and brain tissue of patients with sporadic CSVD with ICH.

An investigation of sleep problems, gastrointestinal symptoms, comorbid psychopathology and challenging behavior in children and adolescents with Down Syndrome.

Background: Down syndrome (DS) is one of the most common chromosomal abnormalities, and children with DS have increased risks of receiving diagnoses of specific comorbidities.

Aims: This study aimed to assess the frequencies and relationships between sleep problems, gastrointestinal (GI) symptoms, comorbid psychopathology, and challenging behavior.

Methods And Procedures: The Children's Sleep Habits Questionnaire, Gastrointestinal Symptom Inventory, Autism Spectrum Disorder-Comorbid for Children, and Behavior Problems Inventory-Short Form were completed by 123 parents of children and adolescents with DS.

A novel method for the percutaneous induction of myocardial infarction by occlusion of small coronary arteries in the rabbit.

Arrhythmic sudden cardiac death (SCD) is an important cause of mortality following myocardial infarction (MI). The rabbit has similar cardiac electrophysiology to humans and is therefore an important small animal model to study post-MI arrhythmias. The established approach of surgical coronary ligation results in thoracic adhesions that impede epicardial electrophysiological studies.

The high cost of care and limited evidence on cost-effective strategies for Lewy body dementia: systematic review of evidence.

Background: Lewy body dementia (LBD) is a prevalent yet frequently underdiagnosed form of dementia, accounting for up to 15% of all dementia cases.

Aims: This study aims to increase awareness and advocacy for LBD by gathering and critically assessing the economic evidence, including the cost of illness and cost-effectiveness of interventions for managing LBD.

Method: A systematic literature review was undertaken with EMBASE, Medline, CINAHL, PsycINFO, NHS Economic Evaluation Database and EconLit.

A novel binary pesticidal protein from Chryseobacterium arthrosphaerae controls western corn rootworm by a different mode of action to existing commercial pesticidal proteins.

The western corn rootworm (WCR) Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae) remains one of the economically most important pests of maize (Zea mays) due to its adaptive capabilities to pest management options. This includes the ability to develop resistance to some of the commercial pesticidal proteins originating from different strains of Bacillus thuringiensis. Although urgently needed, the discovery of new, environmentally safe agents with new modes of action is a challenge.

The role of basement membranes in cardiac biology and disease.

Basement membranes (BMs) are highly specialised extracellular matrix (ECM) structures that within the heart underlie endothelial cells (ECs) and surround cardiomyocytes and vascular smooth muscle cells. They generate a dynamic and structurally supportive environment throughout cardiac development and maturation by providing physical anchorage to the underlying interstitium, structural support to the tissue, and by influencing cell behaviour and signalling. While this provides a strong link between BM dysfunction and cardiac disease, the role of the BM in cardiac biology remains under-researched and our understanding regarding the mechanistic interplay between BM defects and their morphological and functional consequences remain important knowledge-gaps.

Defining treatment-resistant depression.

Background: Varying conceptualizations of treatment-resistant depression (TRD) have made translating research findings or systematic reviews into clinical practice guidelines challenging and inconsistent.

Methods: We conducted a review for the Centers for Medicare & Medicaid Services and the Agency for Healthcare Research and Quality to clarify how experts and investigators have defined TRD and to review systematically how well this definition comports with TRD definitions in clinical trials through July 5, 2019.

Results: We found that no consensus definition existed for TRD.

Mice Lacking Alternatively Activated (M2) Macrophages Show Impairments in Restorative Sleep after Sleep Loss and in Cold Environment.

The relationship between sleep, metabolism and immune functions has been described, but the cellular components of the interaction are incompletely identified. We previously reported that systemic macrophage depletion results in sleep impairment after sleep loss and in cold environment. These findings point to the role of macrophage-derived signals in maintaining normal sleep.

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Postmenopausal status coincides with increased risks for chronic conditions such as heart disease, osteoporosis, cognitive impairment, or some types of cancers. Previously, hormone therapy was used for the primary prevention of these chronic conditions.

Objective: To update evidence for the US Preventive Services Task Force on the benefits and harms of hormone therapy in reducing risks for chronic conditions.

Comparative Benefits and Harms of Complementary and Alternative Medicine Therapies for Initial Treatment of Major Depressive Disorder: Systematic Review and Meta-Analysis.

Objectives: To report the comparative benefits and harms of exercise and complementary and alternative medicine (CAM) treatments with second-generation antidepressants (SGA) for major depressive disorder (MDD).

Design: Systematic review and meta-analysis.

Settings: Outpatient clinics.

Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Five to ten percent of individuals with latent tuberculosis infection (LTBI) progress to active tuberculosis (TB) disease. Identifying and treating LTBI is a key component of the strategy for reducing the burden of TB disease.

Objective: To review the evidence about targeted screening and treatment for LTBI among adults in primary care settings to support the US Preventive Services Task Force in updating its 1996 recommendation.

Effects of Macrophage Depletion on Sleep in Mice.

The reciprocal interaction between the immune system and sleep regulation has been widely acknowledged but the cellular mechanisms that underpin this interaction are not completely understood. In the present study, we investigated the role of macrophages in sleep loss- and cold exposure-induced sleep and body temperature responses. Macrophage apoptosis was induced in mice by systemic injection of clodronate-containing liposomes (CCL).

Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians.

Background: Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear.

Purpose: To compare the benefits and harms of second-generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD.

Comparative benefits and harms of second generation antidepressants and cognitive behavioral therapies in initial treatment of major depressive disorder: systematic review and meta-analysis.

Study Question: What are the benefits and harms of second generation antidepressants and cognitive behavioral therapies (CBTs) in the initial treatment of a current episode of major depressive disorder in adults?

Methods: This was a systematic review including qualitative assessment and meta-analyses using random and fixed effects models. Medline, Embase, the Cochrane Library, the Allied and Complementary Medicine Database, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature were searched from January 1990 through January 2015. The 11 randomized controlled trials included compared a second generation antidepressant CBT.

Prodrug applications for targeted cancer therapy.

Prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. To date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. Macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug development for cancer therapy.

Structural complementation of the catalytic domain of pseudomonas exotoxin A.

The catalytic moiety of Pseudomonas exotoxin A (domain III or PE3) inhibits protein synthesis by ADP-ribosylation of eukaryotic elongation factor 2. PE3 is widely used as a cytocidal payload in receptor-targeted protein toxin conjugates. We have designed and characterized catalytically inactive fragments of PE3 that are capable of structural complementation.

A molecular picture of motion in polyolefins.

We examined three united atom models in light of their description of polyolefin dynamics and investigated the relative influence of various potentials on the resulting dynamics. Results were compared with a collection of experimental data on polyethylene, poly(ethylene-alt-propylene), polypropylene, and head-to-head polypropylene, including quasielastic neutron scattering measurements that we report for two of these materials. For materials with branching, differences between force fields are apparent at low temperature, with the NERD force field most accurate.