Efficient Multiplexed Integration of Synergistic Alleles and Metabolic Pathways in Yeasts via CRISPR-Cas.

CRISPR-Cas genome engineering in yeast has relied on preparation of complex expression plasmids for multiplexed gene knockouts and point mutations. Here we show that co-transformation of a single linearized plasmid with multiple PCR-generated guide RNA (gRNA) and donor DNA cassettes facilitates high-efficiency multiplexed integration of point mutations and large constructs. This technique allowed recovery of marker-less triple-engineering events with 64% efficiency without selection for expression of all gRNAs.

Probing Implicit Learning in Obsessive-Compulsive Disorder: Moderating Role of Medication on the Weather Prediction Task.

Deficits in implicit learning, a process by which knowledge is acquired accretively through practice independent of conscious awareness, have been implicated in Obsessive-Compulsive Disorder (OCD). The weather-prediction task (WPT) was used to assess implicit learning in 26 unmedicated patients with OCD and 23 healthy controls. An additional analysis compared these two groups with 25 medicated patients with OCD.

How to do (or not to do)… gender analysis in health systems research.

Gender-the socially constructed roles, behaviours, activities and attributes that a given society considers appropriate for males, females and other genders-affects how people live, work and relate to each other at all levels, including in relation to the health system. Health systems research (HSR) aims to inform more strategic, effective and equitable health systems interventions, programs and policies; and the inclusion of gender analysis into HSR is a core part of that endeavour. We outline what gender analysis is and how gender analysis can be incorporated into HSR content, process and outcomes Starting with HSR content, i.

The molecular neurobiology of the sleep-deprived, fuzzy brain.

Sleep deprivation is well established to cause diminution of cognitive function, including disruption of both minute-to-minute working memory and decrements in the stabilization of long-term memories. Moreover, "replay" during sleep of episodes and sequences of events that were experienced during wakefulness has been implicated in consolidation of long-term memories. However, the molecular mechanisms underlying the role of sleep in memory function are just starting to be defined.

Sagittal plane lumbar loading when navigating an obstacle and carrying a load.

The current study quantified lumbar loading while carrying an anterior load mass and navigating an obstacle. Eight healthy male participants walked down a walkway and crossed an obstacle under three randomised LOAD conditions; empty-box (2 KG), five kilogram (5 KG) and ten kilogram (10 KG). Each walk was assessed at two events: left foot mid-stance (LMS) and right toe-crossing (TC) to characterise any changes from approach to crossing.

The impact of resilience among older adults.

The purpose of this literature review was to provide an overview of resilience for the purpose of informing potential intervention designs that may benefit older adults. While numerous reviews have focused on various specific aspects of resilience, none have provided the necessary information required to design an effective resilience intervention. Research examining resilience suggests that older adults are capable of high resilience despite socioeconomic backgrounds, personal experiences, and declining health.

Adropin reduces paracellular permeability of rat brain endothelial cells exposed to ischemia-like conditions.

Adropin is a peptide encoded by the energy homeostasis associated gene (Enho) and plays a critical role in the regulation of lipid metabolism, insulin sensitivity, and endothelial function. Little is known of the effects of adropin in the brain and whether this peptide modulates ischemia-induced blood-brain barrier (BBB) injury. Here, we used an in vitro BBB model of rat brain microvascular endothelial cells (RBE4) and hypothesized that adropin would reduce endothelial permeability during ischemic conditions.

Access to chlamydia testing in remote and rural Scotland.

Introduction: The aim of this study was to assess access to sexual health care in remote and rural settings using testing as a focus by measuring the extent of Chlamydia testing and positivity across the Scottish Highlands in relation to the Scottish Index of Multiple Deprivation Quintile (SIMD) and Urban Rural 8-fold index (UR8).

Methods: Tests processed through Raigmore Hospital in Inverness, the main testing laboratory for microbiology tests in North and West and South and Mid Highlands, were studied. Where people are tested in relation to where they live was assessed, as well as the type of test they opt for.

Epigenetic suppression of neprilysin regulates breast cancer invasion.

In women, invasive breast cancer is the second most common cancer and the second cause of cancer-related death. Therefore, identifying novel regulators of breast cancer invasion could lead to additional biomarkers and therapeutic targets. Neprilysin, a cell-surface enzyme that cleaves and inactivates a number of substrates including endothelin-1 (ET1), has been implicated in breast cancer, but whether neprilysin promotes or inhibits breast cancer cell progression and metastasis is unclear.

Utility of pretransplant psychological measures to predict posttransplant outcomes in liver transplant patients: a systematic review.

Objective: Evaluation of liver transplant (LT) candidacy involves psychosocial evaluation to ensure appropriate organ allocation. However, the utility of pre-LT psychiatric and neuropsychological factors in predicting posttransplant outcomes remains uncertain. We reviewed current evidence on the prognostic value of pre-LT psychological factors for outcomes after LT.

NRF2 Orchestrates the Metabolic Shift during Induced Pluripotent Stem Cell Reprogramming.

The potential of induced pluripotent stem cells (iPSCs) in disease modeling and regenerative medicine is vast, but current methodologies remain inefficient. Understanding the cellular mechanisms underlying iPSC reprogramming, such as the metabolic shift from oxidative to glycolytic energy production, is key to improving its efficiency. We have developed a lentiviral reporter system to assay longitudinal changes in cell signaling and transcription factor activity in living cells throughout iPSC reprogramming of human dermal fibroblasts.

The Impact of Personalized Preventive Care on Health Care Quality, Utilization, and Expenditures.

The objective of this study was to evaluate the impact on health care utilization and expenditure trends over time of a personalized preventive medicine program delivering individualized care focused on lifestyle behavior modification, disease prevention, and compliance with quality-related metrics. MD-Value in Prevention (MDVIP) is a network of affiliated primary care physicians who utilize a model of health care delivery based on an augmented physician-patient relationship and focused on personalized preventive health care. Multivariate modeling was used to control for demographics, socioeconomics, supply of health care services, and health status among 10,186 MDVIP members and randomly selected, matched nonmembers.

A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease.

The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12-15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins.

Detrimental role of the EP1 prostanoid receptor in blood-brain barrier damage following experimental ischemic stroke.

Cyclooxygenase-2 (COX-2) is activated in response to ischemia and significantly contributes to the neuroinflammatory process. Accumulation of COX-2-derived prostaglandin E2 (PGE2) parallels the substantial increase in stroke-mediated blood-brain barrier (BBB) breakdown. Disruption of the BBB is a serious consequence of ischemic stroke, and is mainly mediated by matrix metalloproteinases (MMPs).

Feasibility and Smokers' Evaluation of Self-Generated Text Messages to Promote Quitting.

Introduction: Cigarette smoking is a leading cause of preventable mortality. Mobile technologies, including text messaging, provide opportunities to promote quitting. Many text messaging-based cessation interventions contain content created by experts.

Preliminary outcomes of implementing cognitive processing therapy for posttraumatic stress disorder across a national veterans' treatment service.

Background: Posttraumatic stress disorder (PTSD) is a significant problem for military veterans. There is an international imperative to improve access to effective treatments, but more research is needed to ascertain the extent to which treatments found to be efficacious in research settings translate to successful national implementation efforts.

Method: This study reports the clinical outcomes for the first 100 clients treated following the implementation of cognitive processing therapy (CPT) across a national community-based veterans' mental health service that commenced in May 2012.

Bedside Ultrasound Reduces Diagnostic Uncertainty and Guides Resuscitation in Patients With Undifferentiated Hypotension.

Objectives: Utilization of ultrasound in the evaluation of patients with undifferentiated hypotension has been proposed in several protocols. We sought to assess the impact of an ultrasound hypotension protocol on physicians' diagnostic certainty, diagnostic ability, and treatment and resource utilization.

Design: Prospective observational study.

A Meta-Analysis of Typhoid Diagnostic Accuracy Studies: A Recommendation to Adopt a Standardized Composite Reference.

Novel typhoid diagnostics currently under development have the potential to improve clinical care, surveillance, and the disease burden estimates that support vaccine introduction. Blood culture is most often used as the reference method to evaluate the accuracy of new typhoid tests; however, it is recognized to be an imperfect gold standard. If no single gold standard test exists, use of a composite reference standard (CRS) can improve estimation of diagnostic accuracy.

Representation of Latinos and Blacks in screening for and enrollment into preventive HIV vaccine trials in New York City.

Introduction: In the United States, Latinos and Blacks are disproportionately affected by HIV/AIDS, but have been underrepresented in HIV vaccine trials. We assessed screening and enrollment of Blacks and Latinos for preventive HIV vaccine trials conducted in New York City, 2009-2012.

Methods: A retrospective analysis was conducted among 18-50 year old men and transgender women screening for four preventive phase 1 and 2 HIV vaccine trials.

The Effects of Temperature on Clot Microstructure and Strength in Healthy Volunteers.

Background: Anesthesia, critical illness, and trauma are known to alter thermoregulation, which can potentially affect coagulation and clinical outcome. This in vitro preclinical study explores the relationship between temperature change and hemostasis using a recently validated viscoelastic technique. We hypothesize that temperature change will cause significant alterations in the microstructural properties of clot.

Cognitive and functional status predictors of delirium and delirium severity after coronary artery bypass graft surgery: an interim analysis of the Neuropsychiatric Outcomes After Heart Surgery study.

Background: Cognitive and functional impairment increase risk for post-coronary artery bypass graft (CABG) surgery delirium (PCD), but how much impairment is necessary to increase PCD risk remains unclear.

Methods: The Neuropsychiatric Outcomes After Heart Surgery (NOAHS) study is a prospective, observational cohort study of participants undergoing elective CABG surgery. Pre-operative cognitive and functional status based on Clinical Dementia Rating (CDR) scale and neuropsychological battery are assessed.

Semantic Assessment of the Barkin Index of Maternal Functioning in a Medically Underserved Obstetric Population.

Purpose: This study aims to evaluate the fitness of the Barkin Index of Maternal Functioning (BIMF) for postpartum functional assessment in a low-income obstetric population in medically underserved, Central Georgia (USA).

Design And Methods: Cognitive interviewing, a best practices approach to instrument development and validation, was performed on 24 new mothers.

Findings: The BIMF was comprehensible to this population of disadvantaged women.

Psychosocial adjustment and quality of life in children undergoing screening in a specialist paediatric hypertrophic cardiomyopathy clinic.

Objective: This study aimed to assess the psychological well-being and quality of life in children with hypertrophic cardiomyopathy and the potential psychosocial impact of screening.

Methods: A total of 152 children (aged 3-18 years) attending a specialist paediatric hypertrophic cardiomyopathy clinic, and their parents completed the Generic Core Scales and Cardiac Module of the Paediatric Quality of Life Inventory (PedsQL) questionnaire as well as the Strengths and Difficulties Questionnaire; 21 patients (14%) had hypertrophic cardiomyopathy (group A); 23 children (15%) harboured hypertrophic cardiomyopathy-causing sarcomeric mutations with normal echocardiograms (group G); and 108 children (71%) had a family history of hypertrophic cardiomyopathy with normal investigations and attended for clinical cardiological screening (group S).

Results: In group A, mean PedsQLTM total scores reported by children and parents were lower than those reported by unaffected children (p<0.

Snap shots from a photo competition: what does it reveal about close-to-community providers, gender and power in health systems?

In this commentary, we discuss a photography competition, launched during the summer of 2014, to explore the everyday stories of how gender plays out within health systems around the world. While no submission fees were charged nor financial awards involved, the winning entries were exhibited at the Global Symposium on Health Systems Research in Cape Town, South Africa, in October 2014, with credits to the photographers involved. Anyone who had an experience of, or interest in, gender and health systems was invited to participate.