A common single nucleotide variant in the cytokine receptor-like factor-3 (CRLF3) gene causes neuronal deficits in human and mouse cells.

Single nucleotide variants in the general population are common genomic alterations, where the majority are presumed to be silent polymorphisms without known clinical significance. Using human induced pluripotent stem cell (hiPSC) cerebral organoid modeling of the 1.4 megabase Neurofibromatosis type 1 (NF1) deletion syndrome, we previously discovered that the cytokine receptor-like factor-3 (CRLF3) gene, which is co-deleted with the NF1 gene, functions as a major regulator of neuronal maturation. Moreover, children with NF1 and the CRLF3L389P variant have greater autism burden, suggesting that this gene might be important for neurologic function. To explore the functional consequences of this variant, we generated CRLF3L389P-mutant hiPSC lines and Crlf3L389P-mutant genetically engineered mice. While this variant does not impair protein expression, brain structure, or mouse behavior, CRLF3L389P-mutant human cerebral organoids and mouse brains exhibit impaired neuronal maturation and dendrite formation. In addition, Crlf3L389P-mutant mouse neurons have reduced dendrite lengths and branching, without any axonal deficits. Moreover, Crlf3L389P-mutant mouse hippocampal neurons have decreased firing rates and synaptic current amplitudes relative to wild type controls. Taken together, these findings establish the CRLF3L389P variant as functionally deleterious and suggest that it may be a neurodevelopmental disease modifier.

Maternal depression, parenting, and child psychological outcomes in the context of maternal pain.

Parental chronic pain is associated with adverse outcomes in children, but the mechanisms of transmission are largely untested. Mothers with chronic pain (N = 400, Mage = 40.3 years, 90.5% White) and their children (Mage = 10.33 years, 83.3% White, 50.2% female) were recruited in 2016-2018 to test longitudinal pathways of risk transmission from maternal chronic pain to children's psychological symptoms, examining roles of parenting, maternal depression, and child distress tolerance. Maternal pain was associated with positive (ß = .28) and pain-specific (ß = .10) parenting behaviors. Maternal depression was associated with lower child distress tolerance (ß = -.03), which was associated with greater child psychological symptoms (ß = -.62). Parenting and maternal pain were not prospectively associated with child outcomes. When considering the dual-generational impacts of chronic pain, physical and psychological functioning should be examined.

Examining the acceptability and feasibility of the Compassionate Mindful Resilience (CMR) programme in adults living with chronic kidney disease: the COSMIC study findings.

BACKGROUND: Individuals with chronic kidney disease experience difficult physical and psychological symptoms, that impact quality of life, and are at increased risk of anxiety and depression. Access to specialist psychological support is limited. This study aimed to support a new service development project, in collaboration with Kidney Care UK, to implement the Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, which provides accessible mindfulness techniques and practices to enhance compassion and resilience, and explore its feasibility for people living with stage 4 or 5 kidney disease and transplant. METHODS: A multi-method feasibility design was utilised. Participants over 18 years, from the UK, with stage 4 or 5 kidney disease or post-transplant, and who were not currently undergoing psychotherapy, were recruited to the four-week CMR programme. Data was collected at baseline, post-intervention and three-months post to measure anxiety, depression, self-compassion, mental wellbeing, resilience, and mindfulness. The acceptability of the intervention for a kidney disease population was explored through qualitative interviews with participants, and the Mindfulness Teacher. RESULTS: In total, 75 participants were recruited to the study, with 65 completing the CMR programme. The majority were female (66.2%) and post-transplant (63.1%). Analysis of completed outcome measures at baseline and post-intervention timepoints (n = 61), and three-months post intervention (n = 45) revealed significant improvements in participant's levels of anxiety (p < .001) and depression (p < .001), self-compassion (p = .005), mental wellbeing (p < .001), resilience (p.001), and mindfulness (p < .001). Thematic analysis of interviews with participants (n = 19) and Mindfulness Teacher (n = 1) generated three themes (and nine-subthemes); experiences of the CMR programme that facilitated subjective benefit, participants lived and shared experiences, and practicalities of programme participation. All participants interviewed reported that they found programme participation to be beneficial. CONCLUSION: The findings suggest that the CMR programme has the potential to improve psychological outcomes among people with chronic kidney disease. Future randomized controlled trials are required to further test its effectiveness.

Tailored vs. General COVID-19 prevention for adults with mental disabilities residing in group homes: a randomized controlled effectiveness-implementation trial.

BACKGROUND: People with serious mental illness (SMI) and people with intellectual disabilities/developmental disabilities (ID/DD) are at higher risk for COVID-19 and more severe outcomes. We compare a tailored versus general best practice COVID-19 prevention program in group homes (GHs) for people with SMI or ID/DD in Massachusetts (MA). METHODS: A hybrid effectiveness-implementation cluster randomized control trial compared a four-component implementation strategy (Tailored Best Practices: TBP) to dissemination of standard prevention guidelines (General Best-Practices: GBP) in GHs across six MA behavioral health agencies. GBP consisted of standard best practices for preventing COVID-19. TBP included GBP plus four components including: (1) trusted-messenger peer testimonials on benefits of vaccination; (2) motivational interviewing; (3) interactive education on preventive practices; and (4) fidelity feedback dashboards for GHs. Primary implementation outcomes were full COVID-19 vaccination rates (baseline: 1/1/2021-3/31/2021) and fidelity scores (baseline: 5/1/21-7/30/21), at 3-month intervals to 15-month follow-up until October 2022. The primary effectiveness outcome was COVID-19 infection (baseline: 1/1/2021-3/31/2021), measured every 3 months to 15-month follow-up. Cumulative incidence of vaccinations were estimated using Kaplan-Meier curves. Cox frailty models evaluate differences in vaccination uptake and secondary outcomes. Linear mixed models (LMMs) and Poisson generalized linear mixed models (GLMMs) were used to evaluate differences in fidelity scores and incidence of COVID-19 infections. RESULTS: GHs (n=415) were randomized to TBP (n=208) and GBP (n=207) including 3,836 residents (1,041 ID/DD; 2,795 SMI) and 5,538 staff. No differences were found in fidelity scores or COVID-19 incidence rates between TBP and GBP, however TBP had greater acceptability, appropriateness, and feasibility. No overall differences in vaccination rates were found between TBP and GBP. However, among unvaccinated group home residents with mental disabilities, non-White residents achieved full vaccination status at double the rate for TBP (28.6%) compared to GBP (14.4%) at 15 months. Additionally, the impact of TBP on vaccine uptake was over two-times greater for non-White residents compared to non-Hispanic White residents (ratio of HR for TBP between non-White and non-Hispanic White: 2.28, p = 0.03). CONCLUSION: Tailored COVID-19 prevention strategies are beneficial as a feasible and acceptable implementation strategy with the potential to reduce disparities in vaccine acceptance among the subgroup of non-White individuals with mental disabilities. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04726371, 27/01/2021. https://clinicaltrials.gov/study/NCT04726371 .

Volatile chemical product emissions enhance ozone and modulate urban chemistry.

Decades of air quality improvements have substantially reduced the motor vehicle emissions of volatile organic compounds (VOCs). Today, volatile chemical products (VCPs) are responsible for half of the petrochemical VOCs emitted in major urban areas. We show that VCP emissions are ubiquitous in US and European cities and scale with population density. We report significant VCP emissions for New York City (NYC), including a monoterpene flux of 14.7 to 24.4 kg ⋅ d-1 ⋅ km-2 from fragranced VCPs and other anthropogenic sources, which is comparable to that of a summertime forest. Photochemical modeling of an extreme heat event, with ozone well in excess of US standards, illustrates the significant impact of VCPs on air quality. In the most populated regions of NYC, ozone was sensitive to anthropogenic VOCs (AVOCs), even in the presence of biogenic sources. Within this VOC-sensitive regime, AVOCs contributed upwards of ∼20 ppb to maximum 8-h average ozone. VCPs accounted for more than 50% of this total AVOC contribution. Emissions from fragranced VCPs, including personal care and cleaning products, account for at least 50% of the ozone attributed to VCPs. We show that model simulations of ozone depend foremost on the magnitude of VCP emissions and that the addition of oxygenated VCP chemistry impacts simulations of key atmospheric oxidation products. NYC is a case study for developed megacities, and the impacts of VCPs on local ozone are likely similar for other major urban regions across North America or Europe.

Use of SPY angiography in tissue assessment for wound healing outcomes after breast reconstruction.

OBJECTIVE: The objective of this study was to evaluate whether a systematic image assessment protocol using SPY Elite images (LifeCell Corp., US) of viable tissue at the periphery of the surgical field was associated with positive wound healing outcomes following mastectomy and breast reconstruction. METHOD: Patients undergoing mastectomy and subsequent breast reconstruction surgery at a single tertiary medical centre were included. SPY images were prospectively analysed using a systematic image assessment protocol, and an absolute value of mean fluorescence was calculated by measuring peripheral, in-situ tissue from each image. Patient medical records were retrospectively reviewed for demographics, surgical characteristics and postoperative outcomes. These variables were statistically tested for associations with mean fluorescence. RESULTS: A total of 63 patients were included in the final analysis. We found that objectively determined mean fluorescence values were not statistically significantly associated with postoperative complications. CONCLUSION: In this study, objectively measured mean fluorescence values representing breast tissue remaining after dissection showed little utility in the assessment of postoperative wound healing outcomes as they did not identify patients who would later have complications of wound healing. DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

COVID-19-Related Outcomes Among Group Home Residents with Serious Mental Illness in Massachusetts in the First Year of the Pandemic.

This study examined COVID-19 infection and hospitalizations among people with serious mental illness who resided in residential care group homes in Massachusetts during the first year of the COVID-19 pandemic. The authors analyzed data on 2261 group home residents and COVID-19 data from the Massachusetts Department of Public Health. Outcomes included positive COVID-19 tests and COVID-19 hospitalizations March 1, 2020-June 30, 2020 (wave 1) and July 1, 2020-March 31, 2021 (wave 2). Associations between hazard of outcomes and resident and group home characteristics were estimated using multi-level Cox frailty models including home- and city-level frailties. Between March 2020 and March 2021, 182 (8%) residents tested positive for COVID-19, and 51 (2%) had a COVID-19 hospitalization. Compared with the Massachusetts population, group home residents had age-adjusted rate ratios of 3.0 (4.86 vs. 1.60 per 100) for COVID infection and 13.5 (1.99 vs. 0.15 per 100) for COVID hospitalizations during wave 1; during wave 2, the rate ratios were 0.5 (4.55 vs. 8.48 per 100) and 1.7 (0.69 vs. 0.40 per 100). In Cox models, residents in homes with more beds, higher staff-to-resident ratios, recent infections among staff and other residents, and in cities with high community transmission risk had greater hazard of COVID-19 infection. Policies and interventions that target group home-specific risks are needed to mitigate adverse communicable disease outcomes in this population.Clinical Trial Registration Number This study provides baseline (i.e., pre-randomization) data from a clinical trial study NCT04726371.

Meaning and Purpose (MaP) therapy in advanced cancer patients: a randomised controlled trial.

PURPOSE: We aimed to examine the efficacy of Meaning and Purpose (MaP) Therapy in promoting posttraumatic growth and meaningful life attitudes (choices and goal seeking) in people living with advanced cancer. METHODS: Patients with a prognosis ≥ 1 year were stratified across two sites and randomised to receive MaP therapy and regular oncology/palliative care (Intervention) or usual care (Control). They completed measures at baseline (t0), post-intervention (12 weeks, t1) and 12 weeks later (t2). Our primary outcome was posttraumatic growth (PTGI); secondary outcome measures included life attitudes (LAPR), spiritual wellbeing (FACIT-Sp), anxiety, demoralization and depression. TRIAL REGISTRATION NUMBER: ACTRN12618001751268, 7 January 2019. RESULTS: We consented 107 from 404 eligible patients (26.5%) and randomised 55 to MaP Invention (35 completing t1, 25 t2) and 52 to Control (32 completing t1, 25 t2). Fidelity of the intervention was sustained. PTGI mean scores were significantly higher post-intervention on analysis by covariance (Cohen's d = 0.7 at t1 & d = 0.5 at t2). Secondary measures were significant, including LAPR (d = 0.4) and FACIT-Sp (meaning subscale d = 0.4; total d = 0.4). Participants completing six sessions achieved more noteworthy effect sizes. CONCLUSION: This brief, structured individual intervention shows promise for sustaining sense of coherence, meaning and choices in life despite living with advanced cancer.

Topical Review: Acute and Chronic Pain Experiences in Transgender and Gender-Diverse Youth.

OBJECTIVE: To provide an overview of the existing literature on gender diversity in pediatric acute and chronic pain, propose an ecological systems model of understanding pain in transgender and gender-diverse (TGD) youth, and identify a direction for future work that will address the key knowledge gaps identified. METHODS: Relevant literature on pain and gender diversity was reviewed, drawing from adult literature where there was insufficient evidence in pediatric populations. Existing relevant models for understanding minority stress, gender and pain, and pain experiences within marginalized groups were considered with the reviewed literature to develop a pain model in TGD youth. RESULTS: While there is an abundance of literature pointing to increased risk for pain experiences amongst TGD youth, there is comparably little empirical evidence of the rates of pain amongst TGD youth, prevalence of TGD identities in pain care settings, effective pain treatments for TGD youth and unique considerations for their care, and the role intersectional factors in understanding TGD youth identities and pain. CONCLUSION: Pediatric psychologists are well-positioned to advance the research on acute and chronic pain in TGD youth, make evidence-based adaptations to clinical care for TGD youth with pain, including pain related to gender affirmation, and support colleagues within the medical system to provide more inclusive care.

Median canaliform nail dystrophy in a 2-year-old boy: Case report and review of the literature.

Median canaliform nail dystrophy (MCD) is a rare nail abnormality with an unknown etiology. We report the case of MCD of both great toenails in a 2-year-old boy presenting with a fir tree nail pattern and longitudinal splits. MCD was treated with topical marigold therapy (Tagetes sp.). By 15 weeks, the proximal 50% of the MCD had normalized. The report highlights a potential new treatment of marigold therapy for MCD.

Cardiac myosin-binding protein C interaction with actin is inhibited by compounds identified in a high-throughput fluorescence lifetime screen.

Cardiac myosin-binding protein C (cMyBP-C) interacts with actin and myosin to modulate cardiac muscle contractility. These interactions are disfavored by cMyBP-C phosphorylation. Heart failure patients often display decreased cMyBP-C phosphorylation, and phosphorylation in model systems has been shown to be cardioprotective against heart failure. Therefore, cMyBP-C is a potential target for heart failure drugs that mimic phosphorylation or perturb its interactions with actin/myosin. Here we have used a novel fluorescence lifetime-based assay to identify small-molecule inhibitors of actin-cMyBP-C binding. Actin was labeled with a fluorescent dye (Alexa Fluor 568, AF568) near its cMyBP-C binding sites; when combined with the cMyBP-C N-terminal fragment, C0-C2, the fluorescence lifetime of AF568-actin decreases. Using this reduction in lifetime as a readout of actin binding, a high-throughput screen of a 1280-compound library identified three reproducible hit compounds (suramin, NF023, and aurintricarboxylic acid) that reduced C0-C2 binding to actin in the micromolar range. Binding of phosphorylated C0-C2 was also blocked by these compounds. That they specifically block binding was confirmed by an actin-C0-C2 time-resolved FRET (TR-FRET) binding assay. Isothermal titration calorimetry (ITC) and transient phosphorescence anisotropy (TPA) confirmed that these compounds bind to cMyBP-C, but not to actin. TPA results were also consistent with these compounds inhibiting C0-C2 binding to actin. We conclude that the actin-cMyBP-C fluorescence lifetime assay permits detection of pharmacologically active compounds that affect cMyBP-C-actin binding. We now have, for the first time, a validated high-throughput screen focused on cMyBP-C, a regulator of cardiac muscle contractility and known key factor in heart failure.

Characterization of Baseline Temperature Characteristics Using Thermography in The Clinical Setting.

BACKGROUND: Thermography is a diagnostic method based on the ability to record infrared radiation emitted by the skin and is unique in its ability to accurately show physiological and/or pathological cutaneous temperature changes in a non-invasive way. This method can be used to indirectly assess changes or impairments in cutaneous perfusion. Significant technological advancements have allowed thermography to be more commonly utilized by clinicians, yet a basic consensus of patient characteristics that may affect temperature recordings is not established. MATERIALS AND METHODS: We evaluated cutaneous temperature in a cohort of outpatients to understand what factors, including tobacco use and other high-risk characteristics, contribute to cutaneous tissue perfusion as measured by thermography. Participants were prospectively enrolled if they were a combustible cigarette smoker, an electronic cigarette (e-cigarette) user, or a never smoker. Standardized thermographic images of the subject's facial profiles, forearms, and calves were taken and demographic characteristics, medical comorbidities, and tobacco product use were assessed. These variables were statistically tested for associations with temperature at each anatomic site. RESULTS: We found that gender had a significant effect on thermographic temperature that differed by anatomic site, and we found a lack of significant difference in thermographic temperature by race. Our regression analysis did not support significant differences in thermographic temperatures across smoking groups, while there was a trend for decreased perfusion in smokers relative to non-smokers and e-cigarette users relative to non-smokers. CONCLUSION: Thermographic imaging is a useful tool for clinical and research use with consideration of sex and other perfusion-affecting characteristics.

Clinical features of chronic bullous dermatosis of childhood.

BACKGROUND: Chronic bullous dermatosis of childhood (CBDC) is a rare autoimmune subepidermal blistering disease, which can develop following vaccination or medication, or with an autoimmune condition or illness, among other causes. AIM: To identify and better understand the clinical features of CBDC by performing a systematic review, in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. METHODS: Eligible studies included publication since 1980, CBDC diagnosis, case studies, subjects aged < 18 years, clinical features and no language restriction. A database search was conducted including Embase, MEDLINE and Scopus on 14 July 2021 (see Appendix for search terms). Data were assessed for risk of bias. Jamovi was used for statistical analysis. Age and sex were compared with mucocutaneous involvement, cutaneous involvement, other symptoms, human leucocyte antigen type and lesion descriptions. RESULTS: After removing duplicate references using Endnote, 351 papers were identified, of which 91 met the inclusion criteria. These papers included 130 cases of CBDC: 110 children and 20 neonates. The ratio of male : female patients was 19 : 1 for neonates and 74:55 for children. χ² analysis with 1 degree of freedom showed that CBDC in neonates was associated with facial (χ²(1) = 9.67, P < 0.01), mouth (χ²(1) = 31.0, P < 0.001), upper airway (χ²(1) = 52.7, P < 0.001), oesophageal (χ²(1) = 34.6, P < 0.001), ophthalmic (χ²(1) = 6.27, P = 0.01) involvement and with respiratory distress (χ²(1) = 22.7 P < 0.001). CBDC in children was associated with genital (χ²(1) = 3.96, P < 0.05), arm (χ²(1) = 6.99, P < 0.01) and leg (χ²(1) = 7.03, P < 0.01) involvement. CBDC in male patients was associated with facial (χ²(1) = 7.01, P < 0.01), scalp (χ²(1) = 5.96, P < 0.02) and perianal (χ²(1) = 7.22, P < 0.01) involvement. CONCLUSION: Neonates with CBDC are more likely to have a mucocutaneous distribution of lesions, whereas children are more likely to have cutaneous lesions. The limitations of this study include selection bias, and the small neonate sample size makes the study unrepresentative of the population. The review highlights the need for further research into the clinical features of CBDC in neonates.

Psoriasis and osteoporosis: a literature review.

Psoriasis is a chronic inflammatory skin disease with complex comorbidities. Recent evidence has revealed how the inflammatory nature of psoriasis affects bone mineral density and may lead to osteoporosis. This review outlines the current understanding and advances on the association between psoriasis and osteoporosis. The current literature suggests an increased risk of osteopenia and osteoporosis in patients with extensive and chronic psoriasis, compounded by other lifestyle and genetic factors. It suggests that prophylactic measures such as vitamin D supplementation and increasing weight-bearing exercises can help, but in patients with extensive psoriasis, prolonged systemic inflammation may require long-term management. Although there have been many short-term RCTs on the efficacy and safety of biologics in psoriasis, clinical studies looking at the long-term effects of biologics, such as whether they might improve bone mineral density in these patients with psoriasis are yet to be conducted.

Trajectories and biopsychosocial predictors of daily acute pain in adolescents receiving treatment for pain: a daily diary study.

Research regarding daily acute pain and its correlates has primarily been conducted with adolescents who have had major surgery or musculoskeletal pain, restraining efforts towards adapting interventions for adolescents with other sources of acute pain. We explored the trajectories and correlates of pain intensity. Adolescents with an opioid prescription to treat acute pain (N = 157) completed demographic questions, and the PROMIS pediatric depression and anxiety subscales. A 10-day daily diary assessed pain intensity, pain interference, sleep quality, and opioid use. Three trajectories of pain intensity emerged: (1) slow decreases in pain, (2) rapid decreases in pain, and (3) stable or slight increases in pain. Teens with stable pain demonstrated the greatest anxiety levels. Higher sleep quality predicted lower next day pain intensity and pain interference, when controlling for opioid use. Future research should employ intensive longitudinal methodology to further guide intervention development and prevent the transition to chronic pain.

Defining the incidence of cutaneous squamous cell carcinoma in coastal NSW Australia.

BACKGROUND/OBJECTIVES: To describe the incidence of primary cutaneous squamous cell carcinoma in coastal NSW Australia. METHODS: The design is a case-controlled study of reported cSCC from 2016 to 2019 within a defined region of coastal southern NSW. Participants include all reported pathological diagnoses of cSCC in patients greater than 20 years of age. The main outcome measures the incidence and relative risk of cSCC. RESULTS: The age-adjusted incidence rate of primary cSCC was 856/105 /year. Men over 60 years of age had an age-adjusted incidence rate of 2875/106 /year. Histologically diagnosed invasive SCC samples were included using SNOMED clinical term codes. Keratoacanthomas and SCC in situ SNOWMED codes were not included. SCC in situ results was found within the sample analysis and was offset by including one SCC per annum per person. CONCLUSIONS: The rates of cSCC are far higher than previously reported and demand a reappraisal of our national management of this disease.

Parental Cannabis Use, Negative Parenting, and Behavior Problems of Young Children.

Introduction: Cannabis use in the United States is increasingly accepted and legal. Rise in use among childbearing aged adults is potentially concerning, as the impacts of parental cannabis use on children are largely unknown, especially for young children. This study examined whether cannabis use is associated with increased risk for negative parenting and child emotional and behavioral problems among the parents of young children. Methods: We conducted a cross-sectional survey of parents and child behavior, recruited through five primary care practices in three states. Parents of children aged 1.5-5 years reported on family demographics, last 6-months cannabis use, negative parenting, parent mental health, parents' adverse childhood experiences (ACEs), and child emotional/behavioral problems. We conducted hierarchical regressions to determine if parental cannabis use predicts negative parenting and/or child emotional/behavioral problems when controlling for other risk factors. Results: Of 266 responding parents, 34 (13%) reported cannabis use in the last 6 months. Parents who endorsed cannabis use reported significantly more negative parenting, ACEs, anxiety, depression, and child emotional/behavioral problems. Adjusting for the effects of other risk factors, cannabis use significantly predicted more negative parenting, but was not uniquely and significantly associated with child emotional/behavioral problems. Conclusion: Parental cannabis predicted negative parenting, which in turn predicted early childhood emotional/behavioral problems; however, parental cannabis use did not predict child emotional/behavioral problems when other risk factors were considered. Further research is needed to elucidate the nature and direction of relationships between parent cannabis use, negative parenting, child psychological outcomes, and other risk factors.

Actin-binding compounds, previously discovered by FRET-based high-throughput screening, differentially affect skeletal and cardiac muscle.

Actin's interactions with myosin and other actin-binding proteins are essential for cellular viability in numerous cell types, including muscle. In a previous high-throughput time-resolved FRET (TR-FRET) screen, we identified a class of compounds that bind to actin and affect actomyosin structure and function. For clinical utility, it is highly desirable to identify compounds that affect skeletal and cardiac muscle differently. Because actin is more highly conserved than myosin and most other muscle proteins, most such efforts have not targeted actin. Nevertheless, in the current study, we tested the specificity of the previously discovered actin-binding compounds for effects on skeletal and cardiac α-actins as well as on skeletal and cardiac myofibrils. We found that a majority of these compounds affected the transition of monomeric G-actin to filamentous F-actin, and that several of these effects were different for skeletal and cardiac actin isoforms. We also found that several of these compounds affected ATPase activity differently in skeletal and cardiac myofibrils. We conclude that these structural and biochemical assays can be used to identify actin-binding compounds that differentially affect skeletal and cardiac muscles. The results of this study set the stage for screening of large chemical libraries for discovery of novel compounds that act therapeutically and specifically on cardiac or skeletal muscle.

Racial/Ethnic Differences in Associations of Non-cigarette Tobacco Product Use With Subsequent Initiation of Cigarettes in US Youths.

INTRODUCTION: Understanding which non-cigarette tobacco products precede smoking in youth across different racial/ethnic groups can inform policies that consider tobacco-related health disparities. METHODS: We used nationally representative, longitudinal data from the Population Assessment of Tobacco and Health Study waves 1-4. The sample was a dynamic cohort of cigarette-naïve youth aged 12-17 years. Mixed-effects models were used to assess non-cigarette product (e-cigarette, cigar product, or other product) use with cigarette use over 1-year intervals. RESULTS: Of the 28 788 observations pooled across waves 1-4, respondents were 48.7% non-Hispanic white, 13.9% non-Hispanic black, and 23.1% Hispanic. Odds of cigarette initiation over 1-year follow-up were higher among youth with prior use of e-cigarettes (odds ratio [OR], 2.76; 95% confidence interval [CI], 2.21-3.45), cigars (OR, 2.00; 95% CI, 1.42-2.80), or other products (OR, 1.66; 95% CI, 1.28-2.14) compared to never users. At the population level, 20.6% of cigarette initiation was attributable to e-cigarette use among white youth and 21.6% among Hispanic youth, while only 3.5% of cigarette initiation was attributable to e-cigarette use among black youth. In contrast, 9.1% of cigarette initiation for black youth was attributable to cigar use compared to only 3.9% for both white and Hispanic youth. CONCLUSIONS: Prior use of e-cigarettes, cigars, and other non-cigarette products were all associated with subsequent cigarette initiation. However, white and Hispanic youth were more likely to initiate cigarettes through e-cigarette use (vs. cigar or other product use), while black youth were more likely to initiate cigarettes through cigar use (vs. e-cigarette or other product use). IMPLICATIONS: Our findings suggest that previous studies on effects of non-cigarette tobacco products may overlook the critical role of cigar products as a pathway into cigarette smoking among US youth, particularly black youth. While our data support the importance of e-cigarette use as a pathway into smoking, regulatory actions aimed at addressing youth e-cigarette use alone may contribute to disparities in black versus white tobacco use and further exacerbate inequities in tobacco-related disease. Thus, contemporary policy development and discourse about the effects of non-cigarette tobacco products on cigarette initiation should consider cigar and other non-cigarette products as well as e-cigarettes.

The effect of nanoparticulate PdO co-catalysts on the faradaic and light conversion efficiency of WO3 photoanodes for water oxidation.

WO3 photoanodes offer rare stability in acidic media, but are limited by their selectivity for oxygen evolution over parasitic side reactions, when employed in photoelectrochemical (PEC) water splitting. Herein, this is remedied via the modification of nanostructured WO3 photoanodes with surface decorated PdO as an oxygen evolution co-catalyst (OEC). The photoanodes and co-catalyst particles are grown using an up-scalable aerosol assisted chemical vapour deposition (AA-CVD) route, and their physical properties characterised by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM) and UV-vis absorption spectroscopy. Subsequent PEC and transient photocurrent (TPC) measurements showed that the use of a PdO co-catalyst dramatically increases the faradaic efficiency (FE) of water oxidation from 52% to 92%, whilst simultaneously enhancing the photocurrent generation and charge extraction rate. The Pd oxidation state was found to be critical in achieving these notable improvements to the photoanode performance, which is primarily attributed to the higher selectivity towards oxygen evolution when PdO is used as an OEC and the formation of a favourable junction between WO3 and PdO, that drives band bending and charge separation.