Self-reports of sexual attraction change in a sample of male psychotherapy consumers in a private practice setting

The purpose of this study was to see if clients in a private practice therapy setting reported any changes in how they rated their sexual attraction, their stated goal. The therapy was conducted weekly, lasting at least one year. The sample was comprised of 30 men whose desired goal was toward a shift from same-sex attraction to opposite-sex attraction. A convenience sample from the author’s private practice, over a 5-year span, was used.  Clients were invited to complete surveys at intake, between 12-18 months into therapy, and one year afterwards. Following the format of the Klein Sexual Orientation Grid, clients were asked about sexual attraction on a measurable continuum.  A repeated-measures analysis of variance (ANOVA) was used to test the differences between the pre, mid, and post responses.  In this sample, at 1 year post-discharge, 10% reported their sexual attraction as “for the other sex somewhat” vs. 0 % at baseline; 17% reported their sexual attraction as “for the other sex mostly” vs. 0 % at baseline; and 23% reported their sexual attraction was “for the other sex only” vs. 0 % at baseline. These outcomes proved statistically significant changes from baseline compared to follow up.  Despite the study’s limitations, significant sexual attraction shifts from same-sex to opposite-sex were self-reported in a highly motivated clinical sample of men

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies

Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21% of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADs) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Solar Energy Guide

The goal of this project was to work with la Cámara de Industrias de Costa Rica (CICR) to address high industrial energy prices by promoting photovoltaic systems for self- generation. Through interviews with solar providers, electricity distributors, and companies who have photovoltaic systems, information was gathered on the installation process, system pricing, providers of technology, and success cases. This information was organized into a guide, tailored to Costa Rican industries, that brings the reader step- by-step through the necessary considerations for implementing a photovoltaic system

Effects of provider practice on functional independence in older adults.

ObjectivesTo examine provider determinants of new-onset disability in basic activities of daily living (ADLs) in community-dwelling elderly.DesignObservational study.SettingKing County, Washington.ParticipantsA random sample of 800 health maintenance organization (HMO) enrollees aged 65 and older participating in a prospective longitudinal cohort study of dementia and normal aging and their 56 primary care providers formed the study population.MeasurementsIncident ADL disability, defined as any new onset of difficulty performing any of the basic ADLs at follow-up assessments, was examined in relation to provider characteristics and practice style using logistic regression and adjusting for case-mix, patient and provider factors associated with ADL disability, and clustering by provider.ResultsNeither provider experience taking care of large numbers of elderly patients nor having a certificate of added qualifications in geriatrics was associated with patient ADL disability at 2 or 4 years of follow-up (adjusted odds ratio (AOR) for experience=1.29, 95% confidence interval (CI)=0.81-2.05; AOR for added qualifications=0.72, 95% CI=0.38-1.39; results at 4 years analogous). A practice style embodying traditional geriatric principles of care was not associated with a reduced likelihood of ADL disability over 4 years of follow-up (AOR for prescribing no high-risk medications=0.56, 95% CI=0.16-1.94; AOR for managing geriatric syndromes=0.94, 95% CI=0.40-2.19; AOR for a team care approach=1.35, 95% CI=0.66-2.75).ConclusionTaking care of a large number of elderly patients, obtaining a certificate of added qualifications in geriatrics, and practicing with a traditional geriatric orientation do not appear to influence the development of ADL disability in elder, community dwelling HMO enrollees

Evidence-Based Causal Chains for Linking Health, Development, and Conservation Actions

Sustainability challenges for nature and people are complex and interconnected, such that effective solutions require approaches and a common theory of change that bridge disparate disciplines and sectors. Causal chains offer promising approaches to achieving an integrated understanding of how actions affect ecosystems, the goods and services they provide, and ultimately, human well-being. Although causal chains and their variants are common tools across disciplines, their use remains highly inconsistent, limiting their ability to support and create a shared evidence base for joint actions. In this article, we present the foundational concepts and guidance of causal chains linking disciplines and sectors that do not often intersect to elucidate the effects of actions on ecosystems and society. We further discuss considerations for establishing and implementing causal chains, including nonlinearity, trade-offs and synergies, heterogeneity, scale, and confounding factors. Finally, we highlight the science, practice, and policy implications of causal chains to address real-world linked human-nature challenges

A CRISPR screen targeting PI3K effectors identifies RASA3 as a negative regulator of LFA-1–mediated adhesion in T cells

The integrin lymphocyte function–associated antigen 1 (LFA-1) helps to coordinate the migration, adhesion, and activation of T cells through interactions with intercellular adhesion molecule 1 (ICAM-1) and ICAM-2. LFA-1 is activated during the engagement of chemokine receptors and the T cell receptor (TCR) through inside-out signaling, a process that is partially mediated by phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol-3,4,5-trisphosphate (PIP(3)). To evaluate potential roles of PI3K in LFA-1 activation, we designed a library of CRISPR/single guide RNAs targeting known and potential PIP(3)-binding proteins and screened for effects on the ability of primary mouse T cells to bind to ICAM-1. We identified multiple proteins that regulated the binding of LFA-1 to ICAM-1, including the Rap1 and Ras GTPase-activating protein RASA3. We found that RASA3 suppressed LFA-1 activation in T cells, that its expression was rapidly reduced upon T cell activation, and that its activity was inhibited by PI3K. Loss of RASA3 in T cells led to increased Rap1 activation, defective lymph node entry and egress, and impaired responses to T-dependent immunization in mice. Our results reveal a critical role for RASA3 in T cell migration, homeostasis, and function