The Role of Vibrators in Women's Pelvic Health: An Alluring Tool to Improve Physical, Sexual, and Mental Health.

INTRODUCTION AND HYPOTHESIS: In limited studies vibrators have been shown to improve sexual function and pelvic floor health; however, there are even fewer studies on the effect of vibrator use on overall genitourinary and mental health. To investigate the effect of regular vibrator use on sexual, genitourinary, and mental health in addition to quality of life. METHODS: We performed a prospective pilot study of women aged 18 to 80 years recruited from a urogynecology clinic. Study participants were instructed to use a vibrator according to the protocol. Sexual function, pelvic floor function, mental health, and pelvic examination were assessed at the initial visit and at 3 months' follow-up using validated questionnaires. RESULTS: Of the 79 participants enrolled in the study, 53 women (66%) completed the study. The mean age of the participants was 54.7 years (range 19-80 years), and the majority of participants were white (n = 59, 74.7%), post-menopausal (n = 48, 60.8%), and not receiving systemic (n = 63, 79.7%) or local (n = 63, 79.7%) hormone therapy. Sexual function significantly improved over time (p = 0.002), whereas the rate of bothersome pelvic organ prolapse symptoms and pain scores significantly decreased (p = 0.034 and 0.0008 respectively). Rates of urge urinary incontinence decreased although this was not statistically significant (p = 0.059). There was a significant improvement in the gross appearance of lichen sclerosus lesions (p = 0.025) and in the severity of vaginal atrophy (p = 0.018). Rates of depression were significantly decreased (p = 0.011). CONCLUSIONS: Vibrator use was associated with improved sexual, genitourinary, and mental health.

H.O.P.E. grows: An academic-public health partnership to reimagine public health services and increase mental health access among socially vulnerable populations.

OBJECTIVE: To illustrate the process of developing and sustaining an academic-public health partnership for behavioral health integration through an expansion of the Aligning Systems for Health (ASfH) framework. STUDY SETTING: Practice-informed primary data (2017-2023) from the Holistic Opportunity Program for Everyone (HOPE) Initiative based in Charlotte, NC. STUDY DESIGN: The unit of analysis in this descriptive case study is inter-organizational, specifically focusing on an academic-public health relationship. We illustrate the partnership process across the ASfH four core areas, including key challenges and insights. DATA COLLECTION: Utilized a Critical Moments Reflection methodology and review of HOPE program data. PRINCIPAL FINDINGS: (1) Formal partnership structures and processes are essential to monitoring the four ASfH core components for on-going system alignment. (2) Aligning systems for health principally involves two ecologies: (i) the health program and (ii) the partnership. The vitality and sustainability of both ecologies require continuous attention and resource investment. (3) Relationships rest at the heart of aligning systems. (4) With comparative advantages in research methods, the academic sector is especially poised to collaborate with healthcare systems and human service organizations to study, develop, implement, and scale evidence-based health interventions. CONCLUSIONS: The academic sector shares overlapping purposes with the public health, healthcare, and social services sectors while providing complementary value. It is a critical sectoral partner in advancing population health and health equity.

Single cell optogenetics reveals attenuation-by-suppression in visual cortical neurons.

The relationship between neurons' input and spiking output is central to brain computation. Studies in vitro and in anesthetized animals suggest nonlinearities emerge in cells' input-output (activation) functions as network activity increases, yet how neurons transform inputs in vivo has been unclear. Here, we characterize cortical principal neurons' activation functions in awake mice using two-photon optogenetics and imaging. We find responses to fixed optogenetic input are nearly unchanged as neurons are excited, reflecting a linear response regime above neurons' resting point. In contrast, responses are dramatically attenuated by suppression. This attenuation is a powerful means to filter inputs arriving to suppressed cells, privileging other inputs arriving to excited neurons. These data have two major implications: first, neural activation functions in vivo accord with the activation functions used in recent machine learning systems, and second, neurons' IO functions can enhance sensory processing by attenuating some inputs while leaving others unchanged.

Training programme for community service providers who support adults with intellectual disabilities: A systematic quantitative literature review of single-case research.

BACKGROUND: Research on training direct support professionals to address challenging behaviour exhibited by adults with intellectual disabilities is essential in generating effective training approaches for this sector. This systematic review's objective was to evaluate the effects of training types and whether specific training delivery components influenced outcomes. METHODS: Following PRISMA (2020) guidelines, 16 single-case design studies were included that directly evaluated behaviour change of service providers training for adults with intellectual disabilities in community settings. Study quality was assessed using Horner et al. (Exceptional Children, 2005, 71(2), 165-180) criteria. The database searched included Academic Search Complete, CINAHL, Embase, ERIC, Psych Info, and Web of Science. RESULTS: Descriptive analysis of effect size outcomes suggested that all training types were associated with improved outcomes. Further, in situ training was associated with improved service provider performance. Interestingly, feedback was associated with poorer service provider performance. CONCLUSIONS: We provide possible explanations for this surprising outcome and propose future research.

The Moderating Effect of Vaccine Hesitancy on the Relationship between the COVID-19 Vaccine Coverage Index and Vaccine Coverage.

To examine COVID-19 vaccination barriers in the US, this study drew on publicly available county-level data (n = 3130) to investigate the impact of vaccine hesitancy on the relationship between county-level social/structural barriers and vaccine coverage. A hierarchical regression was performed to establish the relationship between the COVID-19 Vaccine Coverage Index (CVAC) and vaccine coverage, assess the moderating effect of vaccine hesitancy on this relationship, and explore the influence of ethno-racial composition on vaccine coverage. A significant, negative relationship (r2 = 0.11, f2 = 0.12) between CVAC and vaccine coverage by county was established (step 1). When vaccine hesitancy was introduced as a moderator (step 2), the model significantly explained additional variance in vaccine coverage (r2 = 0.21, f2 = 0.27). Simple slopes analysis indicated a significant interaction effect, whereby the CVAC-vaccine coverage relationship was stronger in low hesitancy counties as compared with high hesitancy counties. Counties with low social/structural barriers (CVAC) but high hesitancy were projected to have 14% lower vaccine coverage. When county-level ethno-racial composition was introduced (step 3), higher proportions of white residents in a county predicted decreased vaccination rates (p < 0.05). Findings indicate that CVAC should be paired with vaccine hesitancy measures to better predict vaccine uptake. Moreover, counties with higher proportions of white residents led to decreases in vaccine uptake, suggesting that future intervention strategies should also target whites to reach herd immunity. We conclude that public health leaders and practitioners should address both social/structural and psychological barriers to vaccination to maximize vaccine coverage, with a particular focus on vaccine hesitancy in communities with minimal social/structural barriers.

Importance of PLD2 in an IL-23 driven psoriasiform dermatitis model and potential link to human psoriasis.

Phospholipase D2 (PLD2), a major isoform of the PLD family, has been reported to regulate inflammatory responses. Thus far, the relevance of PLD2 in psoriasis, an inflammatory skin disease, has not been explored. In the current study, we examined PLD2 expression in the skin of psoriasis patients and the role of PLD2 in an interleukin (IL)-23-induced mouse model of psoriasiform dermatitis. Both in situ hybridization and bulk RNA sequencing showed PLD2 gene expression is significantly higher in lesional relative to non-lesional skin of psoriasis patients or the skin of healthy subjects. PLD2 expression is also enriched in residual lesions from patients on biologic therapies. Murine in vivo studies showed that PLD2 deficiency significantly reduced psoriasiform inflammation in IL-23-injected ears, as reflected by decreases in ear thickness, expression of defensin beta 4A and the S100 calcium binding protein A7A, macrophage infiltrate, and expression of CXCL10 and IL-6. However, the expression of type 17 cytokines, IL-17A and IL-17F, were not reduced. Dual knockout of PLD1 and PLD2 offered little additional protection compared to PLD2 knockout alone in the IL-23 model. In addition, pharmacological inhibition with a pan-PLD1/PLD2 inhibitor also suppressed IL-23-induced psoriasiform dermatitis. Bone-marrow-derived macrophages from wild type (WT) and PLD2 knockout (KO) mice exhibited little difference in viability and sensitivity to lipopolysaccharide and/or interferon gamma, or resiquimod (R848). PLD2 deficiency did not alter the differentiation and function of Th17 cells in an ex vivo study with splenocytes isolated from WT and PLD2 KO mice. Overall, these data suggest that PLD2 may play a role in the pathophysiology of psoriasis. Reducing macrophage infiltrate and cytokine/chemokine production might contribute to an anti-inflammatory effect observed in PLD2 knockout mice. Further studies are required to better understand the mechanisms by which PLD2 contributes to skin lesions in psoriasis patients and psoriasiform dermatitis models.

Female sexual health digital resources: women and health care providers need more options.

INTRODUCTION: Female sexual health and female sexual dysfunction (FSD) are usually poorly diagnosed and treated because of the numerous barriers providers and patients face. Internet platforms, such as mobile applications (apps) are potential tools that help overcome these barriers and improve patient access to education and management options for FSD. OBJECTIVES: The aim of this review was to identify existing applications on female sexual health and evaluate their educational content and services. METHODS: We searched the internet and Apple App Store using multiple keywords. A panel of physicians specialized in the treatment of FSD reviewed the apps for content quality, the scientific basis of provided information, interactivity, usability, and whether they would recommend it as a reference tool for patients. RESULTS: Of the 204 apps identified, 17 met the inclusion criteria and were reviewed further. The selected apps were organized into groups based on common themes such as educational (n = 6), emotions and communication (n = 2), relaxation and meditation (n = 4), general sexual health (n = 2), and social and fun (n = 3). All apps from the educational category provided scientific information in collaboration with health experts. When assessed for usability, 1 app received good and 5 received excellent scores based on the System Usability Scale. Most apps (n = 5) provided information on pathology and treatments of orgasmic dysfunction, but only 1 app, created by a physician, provided comprehensive information on all the types of FSD. CONCLUSION: Digital technology could be an effective way to overcome barriers to accessing information and ultimately care for female sexual health. Our review demonstrated that there is still a need for more accessible educational resources addressing female sexual health and FSD for patients and providers.

Intraoperative MRI use in transsphenoidal surgery for pituitary tumors: Trends and healthcare utilization.

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) use in transsphenoidal approach (TSA) for pituitary tumors (PTs) has been reported to improve the extent of resection (EOR). The aim of this study is to report the trends and the impact of iMRI on healthcare utilization in patients who underwent TSA for PTs. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT-4, from 2004 to 2020. We included patients ≥ 18 years of age PTs with > 1 year follow-up. Outcomes were length of stay (LOS), discharge disposition, hospital/emergency room (ER) re-admissions, outpatient services, medication refills and corresponding payments. RESULTS: A cohort of 10,192 patients were identified from the database, of these 141 patients (1.4%) had iMRI used during the procedure. Use of iMRI for PTs remained stable (2004-2007: 0.85%; 2008-2011: 1.6%; 2012-2015:1.4% and 2016-2019: 1.46%). No differences in LOS (median 3 days each), discharge to home (93% vs. 94%), complication rates (7% vs. 13%) and payments ($34604 vs. $33050) at index hospitalization were noted. Post-discharge payments were not significantly different without and with iMRI use at 6-months ($8315 vs. $ 7577, p = 0.7) and 1-year ($13,654 vs. $ 14,054, p = 0.70), following the index procedure. CONCLUSION: iMRI use during TSA for PTs remained stable with no impact on LOS, complications, discharge disposition and index payments. Also, there was no difference in combined index payments at 6-months, and 1-year after the index procedure in patients with and without iMRI use for PTs.

Feasibility of Transcranial Motor Evoked Potentials and Electromyography during MRI-Guided Laser Interstitial Thermal Therapy for Glioblastoma.

BACKGROUND: Intraoperative neuromonitoring (IONM) is routinely used during neurosurgical procedures. Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (LITT) is increasingly being used in patients with various brain lesions. Use of IONM (transcranial motor evoked potential [TcMEP] and electromyography [EMG]) during LITT of a brain lesion has not been described previously. METHODS: In this report, we describe a 70-year-old man who presented with motor weakness in whom imaging revealed a left thalamic lesion. Due to the difficulty in accessing the lesion and proximity to the motor tracts, patient was offered MRI-guided LITT using TcMEP and EMG. RESULTS: The patient underwent satisfactory ablation of the lesion with successful recording of the TcMEP and EMG. Technical nuances related to the set-up and procedure is discussed in this report. No procedure-related complications were encountered. CONCLUSIONS: We describe the first report of safety and feasibility of TcMEP and EMG during MRI-guided LITT for left thalamic glioblasatoma. This report paves the way for further prospective investigations regarding the utility of this technique for eloquent brain tumors.

A Proactive, Systematic Approach to Building the Capacity of Technical Assistance Providers.

Technical assistance (TA) is a major capacity building strategy used by the government sector to promote health outcomes in the United States. However, there is minimal literature about how to develop TA provider capacities. This article describes a systematic and proactive approach for developing TA provider capacity, referred to as Technical Assistance for Technical Assistance Providers (TAFTAP), which draws on three implementation science frameworks (Interactive Systems Framework for Dissemination and Implementation, Getting To Outcomes, and R = MC2). We present an application of TAFTAP within a federal agency providing a readiness-informed TA approach to health departments of states, territories, and tribal areas implementing comprehensive tobacco prevention control programs. Pilot data suggest that TAFTAP is a promising approach for improving the quality of TA delivery. At the end of the 2-year project period, TAFTAP recipients provided generally positive qualitative feedback about the support they received. They chose to sustain the readiness-informed TA by incorporating it into a future funding announcement. Downstream state-level TA grantee recipients reported positive outcomes (e.g., accelerated progress, enjoying more one-on-one time with TA providers) from receiving the TA innovation from TAFTAP recipients. We suggest that funding agencies and training and TA centers consider this approach to bolster the capacity and motivation of TA providers for downstream benefit to health and human services staff and their clients. Practical steps for employing TAFTAP to advance health outcomes are included in this article.

A model for fostering community capacity to support adults with intellectual disabilities who engage in challenging behaviour: A scoping review.

Developmental support agencies support many adults with intellectual disabilities in the community. Unfortunately, these adults often exhibit high rates of challenging behaviour, which present significant pressures on these service providers. Agencies need to develop effective means of increasing their capacity to provide quality support. Previous systematic reviews found that training staff in positive behaviour supports can improve outcomes; however, the factors facilitating training's effects, long-term effectiveness, and outcomes for service users have yet to be determined. We conducted a scoping review of 98 journal articles and book chapters to develop a model for fostering capacity development drawing from Organizational Behaviour Management and Knowledge Translation theories. Some relevant factors include features of the inner and outer organizational contexts, training approaches (e.g., behavioural skills training & in-situ coaching), ongoing support and feedback. This model may lead to more effective and enduring treatment programs and improved support for adults with intellectual disabilities.

Trends and Outcomes in Patients with Dementia Undergoing Spine Fusions: A Matched Nationwide Inpatient Sample Analysis.

BACKGROUND: The aim of our study was to define the trends and outcomes in patients with a preexisting diagnosis of dementia who underwent spine fusions using a large national database. METHODS: The Nationwide Inpatient Sample database was queried using the International Classification of Diseases, Ninth Revision and Tenth Revision, from 1998 to 2018. We included patients who underwent spine fusions with or without the diagnosis of dementia. Outcomes were trends, complications, length of stay (LOS), discharge disposition, and mortality. RESULTS: A cohort of 4495 patients (N = 1,390,657; 0.32%) with dementia who underwent spine fusions was identified. There was an increasing trend of spine fusions in patients with the diagnosis of dementia. Most patients with dementia were white (77% vs. 69%), with ≥3 comorbidities (70% vs. 23%), had Medicare insurance (83% vs. 34%) compared with patients without dementia (P < 0.0001). Overall, 38% of patients had complications after spine fusions compared with 21% of patients without dementia during the study period. Median LOS was significantly longer in patients with dementia compared with patients without dementia (6 vs. 4 days). Patients with dementia were less likely to be discharged home (19% vs. 40%) and incurred higher in-hospitalization charges ($139,101 vs. $101,629) compared with patients without dementia. No differences in terms of in-hospital mortality were noted across the cohorts (1.4% vs. 1.6%). CONCLUSIONS: Patients with dementia had 1.5 times longer LOS and 1.4 times higher index hospitalization charges and were 2.5 times more likely to have complications and 71% less likely to be discharged home, with no difference in mortality compared with patients without dementia after spine fusions.

A scoping review of the evaluation and effectiveness of technical assistance.

BACKGROUND: Although the benefits of evidence-based practices (EBPs) for advancing community outcomes are well-recognized, challenges with the uptake of EBPs are considerable. Technical assistance (TA) is a core capacity building strategy that has been widely used to support EBP implementation and other community development and improvement efforts. Yet despite growing reliance on TA, no reviews have systematically examined the evaluation of TA across varying implementation contexts and capacity building aims. This study draws on two decades of peer-reviewed publications to summarize the evidence on the evaluation and effectiveness of TA. METHODS: Guided by Arksey and O'Malley's six-stage methodological framework, we used a scoping review methodology to map research on TA evaluation. We included peer-reviewed articles published in English between 2000 and 2020. Our search involved five databases: Business Source Complete, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC), PsycInfo, and PubMed. RESULTS: A total of 125 evaluation research studies met the study criteria. Findings indicate that publications have increased over the last two decades, signaling a growth in the recognition and reporting of TA. Technical assistance is being implemented across diverse settings, often serving socially vulnerable and under-resourced populations. Most evaluation research studies involved summative evaluations, with TA outcomes mostly reported at the organizational level. Only 5% of the studies examined sustainability of TA outcomes. This review also demonstrates that there is a lack of consistent standards regarding the definition of TA and the level of reporting across relevant TA evaluation categories (e.g., cadence of contact, and directionality). CONCLUSIONS: Advances in the science and practice of TA hinge on understanding what aspects of TA are effective and when, how, and for whom these aspects of TA are effective. Addressing these core questions requires (i) a standard definition for TA; (ii) more robust and rigorous evaluation research designs that involve comparison groups and assessment of direct, indirect, and longitudinal outcomes; (iii) increased use of reliable and objective TA measures; and (iv) development of reporting standards. We view this scoping review as a foundation for improving the state of the science and practice of evaluating TA.

Cytokine induced 3-D organotypic psoriasis skin model demonstrates distinct roles for NF-κB and JAK pathways in disease pathophysiology.

Psoriasis vulgaris is an inflammatory skin disease that affects 2%-3% of the population worldwide. One of the major challenges in discovering novel therapies is the poor translatability of animal models to human disease. Therefore, it is imperative to develop human preclinical models of psoriasis that are amenable to pharmacological intervention. Here, we report a 3-D reconstituted human epidermis (RHE) culture system treated with cytokines commonly associated with psoriasis (TNFα, IL-17A and IL-22) that reproduced some key features of the human disease. The effects on epidermal morphology, gene transcription and cytokine production, which are dysregulated in psoriasis were assessed. Certain morphological features of psoriatic epidermis were evident in cytokine-stimulated RHEs, including hypogranulosis and parakeratosis. In addition, RHEs responded to a cytokine mix in a dose-dependent manner by expressing genes and proteins associated with impaired keratinocyte differentiation (keratin 10/K10, loricrin), innate immune responses (S100A7, DEFB4, elafin) and inflammation (IL-1α, IL-6, IL-8, IL-10, IL-12/23p40, IL-36γ, GM-CSF and IFNγ) typical of psoriasis. These disease-relevant changes in morphology, gene transcription and cytokine production were robustly attenuated by pharmacologically blocking TNFα/IL-17A-induced NF-κB activation with IKK-2 inhibitor IV. Conversely, inhibition of IL-22-induced JAK1 signalling with ABT-317 strongly attenuated morphological features of the disease but had no effect on NFκB-dependent cytokine production, suggesting distinct mechanisms of action by the cytokines driving psoriasis. These data support the use of cytokine-induced RHE models for identifying and targeting keratinocyte signalling pathways important for disease progression and may provide translational insights into novel keratinocyte mechanisms for novel psoriasis therapies.

Noninvasive Tape-Stripping with High-Resolution RNA Profiling Effectively Captures a Preinflammatory State in Nonlesional Psoriatic Skin.

Tape stripping is a minimally invasive, nonscarring method that can be utilized to assess gene expression in the skin but is infrequently used given technical constraints. By comparing different tape stripping technologies and full-thickness skin biopsy results of lesional and nonlesional psoriatic skin from the same patients, we demonstrate that tape stripping with optimized high-resolution transcriptomic profiling can be used to effectively assess and characterize inflammatory responses in the skin. Upon comparison with single-cell RNA-sequencing data from psoriatic full-thickness skin biopsies, we illustrate that tape-stripping efficiently captures the transcriptome of the upper layers of the epidermis with sufficient resolution to assess the molecular components of the feed-forward immune amplification pathway in psoriasis. Notably, nonlesional psoriatic skin sampled by tape stripping demonstrates activated, proinflammatory changes when compared to healthy control skin, suggesting a prepsoriatic state, which is not captured on full-thickness skin biopsy transcriptome profiling. This work illustrates an approach to assess inflammatory response in the epidermis by combining noninvasive sampling with high throughput RNA-sequencing, providing a foundation for biomarker discoveries and mechanism of action studies for inflammatory skin conditions.

Supracervical Hysterectomy Is Protective against Mesh Complications after Minimally Invasive Abdominal Sacrocolpopexy: A Population-Based Cohort Study of 12,189 Patients.

PURPOSE: Although minimally invasive (robotic or laparoscopic) abdominal sacrocolpopexy (MISC) has become the new gold standard for durable pelvic organ prolapse repair after the vaginal mesh controversy, current literature is limited. Our objective was to study reoperation for mesh complications after MISC. MATERIALS AND METHODS: All women undergoing MISC in California from January 2012 to December 2018 were identified from Office of Statewide Health Planning and Development data sets using appropriate ICD-9/10 (International Classification of Diseases 9th/10th Revision) and CPT® (Current Procedural Terminology) codes. Univariate and multivariable analyses were performed to assess associations between patient demographics, surgical details and our primary outcomes: rates of reoperation for a mesh complication. RESULTS: Of 12,189 women undergoing MISC 8,398 (68.9%) had concomitant hysterectomy. Total hysterectomy (TH) and supracervical hysterectomy (SCH) were performed in 5,027 (41.2%) and 3,371 (27.6%) cases, respectively. Reoperation rates for mesh complications were lower after SCH vs TH (overall: 0.7%, mean followup time 1,111 days vs 3.1%, mean followup time 1,095 days, p <0.001; subcohort with at least 4 years of followup: 2.1% vs 8.9%, p <0.001). Additionally, mesh complication rates were higher even if TH was performed remotely, as compared to concomitant SCH (5.2% vs 0.7%, p <0.001). The increased risk for reoperation due to mesh complications after TH was preserved on multivariable analysis (OR 4.20, 95% CI 2.72‒6.50, p <0.001). CONCLUSIONS: Concomitant TH at time of MISC is associated with a significantly higher rate of mesh complication as compared to SCH. The increased risk of a mesh complication associated with TH is present even if the TH was performed prior to the MISC.

Thermal stress induces a positive phenotypic and molecular feedback loop in zebrafish embryos.

Aquatic organisms must cope with both rising and rapidly changing temperatures. These thermal changes can affect numerous traits, from molecular to ecological scales. Biotic stressors are already known to induce the release of chemical cues which trigger behavioural responses in other individuals. In this study, we infer whether fluctuating temperature, as an abiotic stressor, may similarly induce stress-like responses in individuals not directly exposed to the stressor. To test this hypothesis, zebrafish (Danio rerio) embryos were exposed for 24 h to fluctuating thermal stress, to medium in which another embryo was thermally stressed before ("stress medium"), and to a combination of these. Growth, behaviour, expression of molecular markers, and of whole-embryo cortisol were used to characterise the thermal stress response and its propagation between embryos. Both fluctuating high temperature and stress medium significantly accelerated development, by shifting stressed embryos from segmentation to pharyngula stages, and altered embryonic activity. Importantly, we found that the expression of sulfide:quinone oxidoreductase (SQOR), the antioxidant gene SOD1, and of interleukin-1ß (IL-1ß) were significantly altered by stress medium. This study illustrates the existence of positive thermal stress feedback loops in zebrafish embryos where heat stress can induce stress-like responses in conspecifics, but which might operate via different molecular pathways. If similar effects also occur under less severe heat stress regimes, this mechanism may be relevant in natural settings as well.

Phospholipase A2 enzymes represent a shared pathogenic pathway in psoriasis and pityriasis rubra pilaris.

Altered epidermal differentiation along with increased keratinocyte proliferation is a characteristic feature of psoriasis and pityriasis rubra pilaris (PRP). However, despite this large degree of overlapping clinical and histologic features, the molecular signatures these skin disorders share are unknown. Using global transcriptomic profiling, we demonstrate that plaque psoriasis and PRP skin lesions have high overlap, with all differentially expressed genes in PRP relative to normal skin having complete overlap with those in psoriasis. The major common pathway shared between psoriasis and PRP involves the phospholipases PLA2G2F, PLA2G4D, and PLA2G4E, which were found to be primarily expressed in the epidermis. Gene silencing each of the 3 PLA2s led to reduction in immune responses and epidermal thickness both in vitro and in vivo in a mouse model of psoriasis, establishing their proinflammatory roles. Lipidomic analyses demonstrated that PLA2s affect mobilization of a phospholipid-eicosanoid pool, which is altered in psoriatic lesions and functions to promote immune responses in keratinocytes. Taken together, our results highlight the important role of PLA2s as regulators of epidermal barrier homeostasis and inflammation, identify PLA2s as a shared pathogenic mechanism between PRP and psoriasis, and as potential therapeutic targets for both diseases.

Physician Interpretation of Data of Uncertain Clinical Utility in Oncology Prescription Drug Promotion.

BACKGROUND: Little is known about how physicians interpret data displays that depict preliminary or exploratory clinical data in physician-targeted sales aids for oncology drugs. Using three factorial experiments, we examined whether disclosures of data limitations and clinical uncertainty adequately communicate the limitations and practical utility of this type of data. SUBJECTS, MATERIALS, AND METHODS: The studies used a 2 (disclosure of data limitations: technical, nontechnical) × 2 (disclosure of clinical uncertainty: present, absent) + 1 (control: no disclosure) between-subjects experimental design to examine the impact of disclosures as they relate to presentations of preliminary or exploratory data in promotional communications for oncology products. In each experiment, we randomized oncologists and primary care physicians with oncology experience to view one version of a two-page sales aid. Following this exposure, physicians completed a web-based survey. The design was replicated in three concurrently conducted experiments using sales aids for different fictitious oncology drugs, each featuring one of three common data displays: a forest plot (n = 495), a Kaplan-Meier curve (n = 504), or a bar chart (n = 532). RESULTS: Results provide initial evidence that in some contexts disclosures can improve understanding of the clinical utility of certain information about a drug and the limitations of results presented in a data display. Disclosures can also temper perceptions of how much evidence is presented that supports a conclusion that the drug is an appropriate treatment. In terms of the language used in the disclosure of data limitations, physicians in all three experiments strongly preferred the nontechnical disclosures. CONCLUSION: The findings from the three experiments in this study suggest that disclosures have the potential to increase relevant knowledge, but more research is needed to establish best practice recommendations for using disclosures to convey contextual information relevant for interpreting data displays in promotional communications. IMPLICATIONS FOR PRACTICE: This article reports the results from three large, online experimental studies that address a growing concern that drug companies often share favorable clinical trial results with physicians in promotional materials that lack important context for physicians to interpret the data. This series of studies investigates whether strategic use of two types of disclosures (disclosure of data limitations and a disclosure of clinical uncertainty) improves understanding and reduces misinterpretations among physicians. The results from these studies help identify communication factors that impact how physicians critically appraise preliminary or exploratory clinical trial data to inform policy and regulatory efforts.