ZBP1 promotes inflammatory responses downstream of TLR3/TLR4 via timely delivery of RIPK1 to TRIF.

ZBP1 is widely recognized as a mediator of cell death for its role in initiating necroptotic, apoptotic, and pyroptotic cell death pathways in response to diverse pathogenic infection. Herein, we characterize an unanticipated role for ZBP1 in promoting inflammatory responses to bacterial lipopolysaccharide (LPS) or double-stranded RNA (dsRNA). In response to both stimuli, ZBP1 promotes the timely delivery of RIPK1 to the Toll-like receptor (TLR)3/4 adaptor TRIF and M1-ubiquitination of RIPK1, which sustains activation of inflammatory signaling cascades downstream of RIPK1. Strikingly, ZBP1-mediated regulation of these pathways is important in vivo, as Zbp1−/− mice exhibited resistance to LPS-induced septic shock, revealed by prolonged survival and delayed onset of hypothermia due to decreased inflammatory responses and subsequent cell death. Further findings revealed that ZBP1 promotes sustained inflammatory responses by mediating the kinetics of proinflammatory "TRIFosome" complex formation, thus having a profound impact downstream of TLR activation. Given the well-characterized role of ZBP1 as a viral sensor, our results exemplify previously unappreciated crosstalk between the pathways that regulate host responses to bacteria and viruses, with ZBP1 acting as a crucial bridge between the two.

Treatment for Opioid Use Disorder: Population Estimates - United States, 2022.

In 2022, 81,806 opioid-involved overdose deaths were reported in the United States, more than in any previous year. Medications for opioid use disorder (OUD), particularly buprenorphine and methadone, substantially reduce overdose-related and overall mortality. However, only a small proportion of persons with OUD receive these medications. Data from the 2022 National Survey on Drug Use and Health were applied to a cascade of care framework to estimate and characterize U.S. adult populations who need OUD treatment, receive any OUD treatment, and receive medications for OUD. In 2022, 3.7% of U.S. adults aged ≥18 years needed OUD treatment. Among these, only 25.1% received medications for OUD. Most adults who needed OUD treatment either did not perceive that they needed it (42.7%) or received OUD treatment without medications for OUD (30.0%). Compared with non-Hispanic Black or African American and Hispanic or Latino adults, higher percentages of non-Hispanic White adults received any OUD treatment. Higher percentages of men and adults aged 35-49 years received medications for OUD than did women and younger or older adults. Expanded communication about the effectiveness of medications for OUD is needed. Increased efforts to engage persons with OUD in treatment that includes medications are essential. Clinicians and other treatment providers should offer or arrange evidence-based treatment, including medications, for patients with OUD. Pharmacists and payors can work to make these medications available without delays.

Differential effects of high-fat diet on endocrine, metabolic and depressive-like behaviors in male and female rats.

The complications of obesity extend beyond the periphery to the central nervous system (CNS) and include an increased risk of developing neuropsychiatric co-morbidities like depressive illness. Preclinical studies support this concept, including studies that have examined the effects of a high-fat diet (HFD) on depressive-like behaviors. Although women are approximately two-fold more likely to develop depressive illness compared to men, most preclinical studies have focused on the effects of HFD in male rodents. Accordingly, the goal of this study was to examine depressive-like behaviors in male and female rats provided access to a HFD. In agreement with prior studies, male and female rats provided a HFD segregate into an obesity phenotype (i.e., diet-induced obesity; DIO) or a diet resistant (DR) phenotype. Upon confirmation of the DR and DIO phenotypes, behavioral assays were performed in control chow, DR, and DIO rats. In the sucrose preference test, male DIO rats exhibited significant decreases in sucrose consumption (i.e., anhedonia) compared to male DR and male control rats. In the forced swim test (FST), male DIO rats exhibited increases in immobility and decreases in climbing behaviors in the pre-test sessions. Interestingly, male DR rats exhibited these same changes in both the pre-test and test sessions of the FST, suggesting that consumption of a HFD, even in the absence of the development of an obesity phenotype, has behavioral consequences. Female rats did not exhibit differences in sucrose preference, but female DIO rats exhibited increases in immobility exclusively in the test session of the FST, behavioral changes that were not affected by the stage of the estrous cycle. Collectively, these studies demonstrate that access to a HFD elicits different behavioral outcomes in male and female rats.

RETRACTED: Changes in Tobacco Dependence and Association With Onset and Progression of Use by Product Type From Wave 1 to Wave 3 of the Population Assessment of Tobacco and Health (PATH) Study.

INTRODUCTION: This study examined trajectories of tobacco dependence (TD) in relation to changes in tobacco product use and explored the effects of product-specific adding, switching, or discontinued use on dependence over time. AIMS AND METHODS: Data were analyzed from the first three waves of the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative, longitudinal study of adults and youth in the United States. Data included 9556 Wave 1 (2013/2014) adult current established tobacco users who completed all three interviews and had established use at ≥2 assessments. Groups included cigarettes-only users, e-cigarettes-only users, cigars-only users, hookah-only users, any smokeless-only users, cigarette + e-cigarette dual users, and multiple product users. A validated 16-item scale assessed TD across product users. RESULTS: Wave 1 e-cigarette-only users' who maintained exclusive e-cigarette use increased levels of TD through Wave 3 as did those who added or switched to another product. Wave 1 multiple product users' TD decreased across waves. TD for all other Wave 1 user groups remained about the same. For Wave 1 cigarette-only smokers, switching to another product or moving to a pattern of no established use was associated with lower levels of TD than smokers whose use stayed the same. Movement to no established use of any tobacco product was consistently associated with lower TD for all other product users. CONCLUSIONS: Except for Wave 1 e-cigarette-only users, TD among US tobacco product users was stable over time, with daily users less likely to vary from baseline. IMPLICATIONS: The level of TD among most US tobacco users was stable over the first three waves of the PATH Study and trends in levels of TD were predominantly unrelated to changes in patterns of continued product use. Stable levels of TD suggest a population at persistent risk of health impacts from tobacco. Wave 1 e-cigarette users, including those maintaining exclusive e-cigarette use, experienced increasing levels of TD over time, perhaps because of increases in quantity or frequency of their e-cigarette product use or increasing efficiency of nicotine delivery over time.

Predictors of E-cigarette and Cigarette Use Trajectory Classes from Early Adolescence to Emerging Adulthood Across Four Years (2013-2017) of the PATH Study.

INTRODUCTION: This study examines predictors of trajectories of cigarette and e-cigarette use among a cohort of US adolescents transitioning into young adulthood. Comparing trajectories of each tobacco product is important to determine if different intervention targets are needed to prevent progression to daily use. METHODS: Latent trajectory class analyses identified cigarette and e-cigarette use (never, ever excluding past 12-month, past 12-month (excluding past 30-day (P30D)), P30D 1-5 days, P30D 6+ days) trajectory classes, separately, among US youth (12-17; N = 10,086) using the first 4 waves (2013-2017) of data from the nationally representative PATH Study. Weighted descriptive analyses described the class characteristics. Weighted multinomial logistic regression analyses examined demographic, psychosocial, and behavioral predictors of class membership. RESULTS: Younger adolescents 12-15 years had lower tobacco use compared to 16-17 year olds and less stable classes. In the 16-17 year group, there were five unique trajectories of cigarette smoking, including a Persistent High Frequency class. Four e-cigarette use trajectories were identified; but not a persistent use class. Shared predictors of class membership for cigarettes and e-cigarettes included mental health problems, other tobacco use, marijuana use, and poorer academic achievement. Male sex and household tobacco use were unique e-cigarette trajectory class predictors. CONCLUSIONS: There was no evidence that initiation with e-cigarettes as the first product tried was associated with cigarette progression (nor cigarettes as first product and e-cigarette progression). Interventions should focus on well-established risk factors such as mental health and other substance use to prevent progression of use for both tobacco products. IMPLICATIONS: Using nationally representative data and definitions of use that take into account frequency and recency of use, longitudinal 4-year trajectories of e-cigarette and cigarette use among US adolescents transitioning into young adulthood were identified. Results among 16-17-year olds revealed a class of persistent high frequency cigarette smoking that was not identified for e-cigarette use. Cigarette use progression was not associated with e-cigarettes as the first product tried. Risk factors for progression of use of both products included mental health and other substance use, which are important prevention targets for both tobacco products.

Changes in Tobacco Dependence and Association With Onset and Progression of Use by Product Type From Waves 1 to 3 of the Population Assessment of Tobacco and Health (PATH) Study.

INTRODUCTION: This study examined trajectories of tobacco dependence (TD) in relationship to changes in tobacco product use, and explored the effects of product-specific adding, switching, or discontinued use on dependence over time. AIMS AND METHODS: Data were analyzed from the first three waves from the Population Assessment of Tobacco and Health (PATH) Study, a nationally representative, longitudinal study of adults and youth in the United States. Data included 9556 wave 1 (2013-2014) adult current established tobacco users aged 18 or older who completed all three interviews and had established use at ≥2 assessments. Mutually exclusive groups included: users of cigarettes only, e-cigarettes only, cigars only, hookah only, any smokeless only, cigarette + e-cigarette dual users, and other multiple product users. A validated 16-item scale assessed TD across product users. RESULTS: People who used e-cigarettes exclusively at wave 1 had small increases in TD through wave 3. Wave 1 multiple product users' TD decreased across waves. TD for all other wave 1 user groups remained about the same. For wave 1 cigarette only smokers, switching to another product was associated with lower levels of TD than smokers whose use stayed the same. Movement to no established use of any tobacco product was consistently associated with lower TD for all product users. CONCLUSIONS: Except for wave 1 e-cigarette only users (who experienced small increases in TD), TD among U.S. tobacco product users was stable over time, with daily users less likely to vary from baseline. IMPLICATIONS: The level of TD among most U.S. tobacco users was stable over the first three waves of the PATH Study and trends in levels of TD were predominantly unrelated to changes in patterns of continued product use. Stable levels of TD suggest a population at persistent risk of health impacts from tobacco. Wave 1 e-cigarette users experienced small increases in levels of TD over time, perhaps due to increases in quantity or frequency of their e-cigarette use or increasing efficiency of nicotine delivery over time.

Incidental maternal findings on fetal MRI.

AIM: To evaluate the type and frequency of maternal findings incidentally identified during fetal magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective single-centre study was undertaken which included all consecutive fetal MRI studies performed between July 2017 and May 2021 at a tertiary institution. Two fellowship-trained radiologists reviewed the studies independently to determine the type and frequency of incidental maternal findings of both no clinical significance (requiring no further follow-up) and of clinical significance (requiring further follow-up, work-up, and/or management). Differences in acquisition were resolved by two-reader consensus. Non-diagnostic MRI examinations or abdominal MRI examinations indicated for maternal complications were excluded from review. RESULTS: A total of 455 consecutive fetal MRI examinations performed in 429 women were included. Mean age was 30 years (SD 5.5 years). At least one incidental maternal finding was identified in 58% (265/455) of studies. Umbilical hernias (35%), maternal hydronephrosis (19%), and maternal hydro-ureter (15%) were the most common. Only two studies (0.5%) showed clinically significant incidental maternal findings (pancreatic pseudocyst and ovarian cyst). CONCLUSIONS: Incidental maternal findings are common on fetal MRI but rarely require further follow-up, work-up, and/or management.

Public health infection prevention: An analysis of existing training during the COVID-19 pandemic.

OBJECTIVES: In response to the COVID-19 pandemic, agencies and organizations required trainings to support the needs of the public health workforce. To better understand the training resources available, this study identified, organized, and classified infection prevention and control (IPC) training and educational opportunities. STUDY DESIGN: Environmental scan. METHODS: A total of 306 IPC training resources were compiled between January and April 2021. Key themes and topics were identified and compared to the Healthcare Infection Control Practices Advisory Committee's (HICPAC) core IPC practices. RESULTS: Three hundred and six training resources, including webinars, fact sheets, module-based learning activities, infographics, and professional practice guidance materials, were identified. Common themes included proper use of personal protective equipment (e.g., masks, gloves), community reopening guidance, and mass vaccination resources. A large proportion (74.9%) of trainings were under 60 min. Using the HICPAC framework, the most frequently addressed content included standard precautions (40%), leadership support (31.6%), and transmission-based precautions (25.8%). Few trainings addressed performance monitoring and feedback (17.1%). CONCLUSIONS: A wide range of organizations developed IPC-specific content during the pandemic. However, these resources did not address the breadth of knowledge required to implement IPC concepts effectively. The creation of universally applicable IPC core competencies and the development of high-quality IPC education and trainings for public health and the overall responder workforces should be prioritized. Accessible high-quality online and just-in-time trainings are critical for future pandemic and disaster preparedness.

Exercise, diet, and sleep habits of nurses working full-time during the COVID-19 pandemic: An observational study.

BACKGROUND: Healthy diet, exercise, and sleep practices may mitigate stress and prevent illness. However, lifestyle behaviors of acute care nurses working during stressful COVID-19 surges are unclear. PURPOSE: To quantify sleep, diet, and exercise practices of 12-hour acute care nurses working day or night shift during COVID-19-related surges. METHODS: Nurses across 10 hospitals in the United States wore wrist actigraphs and pedometers to quantify sleep and steps and completed electronic diaries documenting diet over 7-days. FINDINGS: Participant average sleep quantity did not meet national recommendations; night shift nurses (n = 23) slept significantly less before on-duty days when compared to day shift nurses (n = 34). Proportionally more night shift nurses did not meet daily step recommendations. Diet quality was low on average among participants. DISCUSSION: Nurses, especially those on night shift, may require resources to support healthy sleep hygiene, physical activity practices, and diet quality to mitigate stressful work environments.

Opioid Use and Its Relationship to Cardiovascular Disease and Brain Health: A Presidential Advisory From the American Heart Association.

The misuse of opioids continues to be epidemic, resulting in dependency and a recent upsurge in drug overdoses that have contributed to a significant decrease in life expectancy in the United States. Moreover, recent data suggest that commonly used opioids for the management of pain may produce undesirable pharmacological actions and interfere with critical medications commonly used in cardiovascular disease and stroke; however, the impact on outcomes remains controversial. The American Heart Association developed an advisory statement for health care professionals and researchers in the setting of cardiovascular and brain health to synthesize the current literature, to provide approaches for identifying patients with opioid use disorder, and to address pain management and overdose. A literature and internet search spanning from January 1, 2012, to February 15, 2021, and limited to epidemiology studies, reviews, consensus statements, and guidelines in human subjects was conducted. Suggestions and considerations listed in this document are based primarily on published evidence from this review whenever possible, as well as expert opinion. Several federal and institutional consensus documents and clinical resources are currently available to both patients and clinicians; however, none have specifically addressed cardiovascular disease and brain health. Although strategic tools and therapeutic approaches for recognition of opioid use disorder and safe opioid use are available for health care professionals who manage patients with cardiovascular disease and stroke, high-quality evidence does not currently exist. Therefore, there is an urgent need for more research to identify the most effective approaches to improve care for these patients.

Association of tobacco product use with chronic obstructive pulmonary disease (COPD) prevalence and incidence in Waves 1 through 5 (2013-2019) of the Population Assessment of Tobacco and Health (PATH) Study.

BACKGROUND: We examined the association of non-cigarette tobacco use on chronic obstructive pulmonary disease (COPD) risk in the Population Assessment of Tobacco and Health (PATH) Study. METHODS: There were 13,752 participants ≥ 40 years with Wave 1 (W1) data for prevalence analyses, including 6945 adults without COPD for incidence analyses; W1-5 (2013-2019) data were analyzed. W1 tobacco use was modeled as 12 mutually-exclusive categories of past 30-day (P30D) single and polyuse, with two reference categories (current exclusive cigarette and never tobacco). Prevalence and incidence ratios of self-reported physician-diagnosed COPD were estimated using weighted multivariable Poisson regression. RESULTS: W1 mean (SE) age was 58.1(0.1) years; mean cigarette pack-years was similar for all categories involving cigarettes and exclusive use of e-cigarettes (all > 20), greater than exclusive cigar users (< 10); and COPD prevalence was 7.7%. Compared to P30D cigarette use, never tobacco, former tobacco, and cigar use were associated with lower COPD prevalence (RR = 0.33, (95% confidence interval-CI) [0.26, 0.42]; RR = 0.57, CI [0.47, 0.70]; RR = 0.46, CI [0.28, 0.76], respectively); compared to never tobacco use, all categories except cigar and smokeless tobacco use were associated with higher COPD prevalence (RR former = 1.72, CI [1.33, 2.23]; RR cigarette = 3.00, CI [2.37, 3.80]; RR e-cigarette = 2.22, CI [1.44, 3.42]; RR cigarette + e-cigarette = 3.10, CI [2.39, 4.02]; RR polycombusted = 3.37, CI [2.44, 4.65]; RR polycombusted plus noncombusted = 2.75, CI]1.99, 3.81]). COPD incidence from W2-5 was 5.8%. Never and former tobacco users had lower COPD risk compared to current cigarette smokers (RR = 0.52, CI [0.35, 0.77]; RR = 0.47, CI [0.32, 0.70], respectively). Compared to never use, cigarette, smokeless, cigarette plus e-cigarette, and polycombusted tobacco use were associated with higher COPD incidence (RR = 1.92, CI [1.29, 2.86]; RR = 2.08, CI [1.07, 4.03]; RR = 1.99, CI [1.29, 3.07]; RR = 2.59, CI [1.60, 4.21], respectively); exclusive use of e-cigarettes was not (RR = 1.36, CI [0.55, 3.39]). CONCLUSIONS: E-cigarettes and all use categories involving cigarettes were associated with higher COPD prevalence compared to never use, reflecting, in part, the high burden of cigarette exposure in these groups. Cigarette-but not exclusive e-cigarette-use was also strongly associated with higher COPD incidence. Compared to cigarette use, only quitting tobacco was protective against COPD development.

Identifying Interaction Partners of Yeast Protein Disulfide Isomerases Using a Small Thiol-Reactive Cross-Linker: Implications for Secretory Pathway Proteostasis.

Protein disulfide isomerases (PDIs) function in forming the correct disulfide bonds in client proteins, thereby aiding the folding of proteins that enter the secretory pathway. Recently, several PDIs have been identified as targets of organic electrophiles, yet the client proteins of specific PDIs remain largely undefined. Here, we report that PDIs expressed in Saccharomyces cerevisiae are targets of divinyl sulfone (DVSF) and other thiol-reactive protein cross-linkers. Using DVSF, we identified the interaction partners that were cross-linked to Pdi1 and Eug1, finding that both proteins form cross-linked complexes with other PDIs, as well as vacuolar hydrolases, proteins involved in cell wall biosynthesis and maintenance, and many ER proteostasis factors involved ER stress signaling and ER-associated protein degradation (ERAD). The latter discovery prompted us to examine the effects of DVSF on ER quality control, where we found that DVSF inhibits the degradation of the ERAD substrate CPY*, in addition to covalently modifying Ire1 and blocking the activation of the unfolded protein response. Our results reveal that DVSF targets many proteins within the ER proteostasis network and suggest that these proteins may be suitable targets for covalent therapeutic development in the future.

Sexual violence history predicts changes in vaginal immune parameters during sexual arousal.

OBJECTIVE: To examine the influence of sexual arousal on vaginal mucosal inflammatory cytokine and antibody production in healthy women with and without histories of childhood and/or adult sexual violence. METHODS: Ninety-one premenopausal healthy women (ages 18-42) attended a single laboratory session in which they provided vaginal fluid samples before and after viewing one neutral and one erotic film. While viewing the films, participants' vaginal sexual arousal was recorded using vaginal photoplethysmography. RESULTS: Of the 91 participants, 41 (45%) reported no history of sexual violence, 17 (19%) reported a history of childhood sexual abuse (CSA) only, 19 (21%) reported a history of adult sexual assault (ASA) only, and 10 (11%) reported a history of both CSA and ASA, with 4 participants choosing not to provide information on their sexual violence history. For women with a history of ASA but not CSA, there was a significant increase in vaginal IL-1ß following arousal, while for women with a history of CSA (with or without ASA), there was a significant decrease. Women without CSA histories had a significant increase in vaginal IgA following sexual arousal, while women with CSA histories had a decrease. CONCLUSION: Sexual arousal possibly plays a role in modifying vaginal immune responses in young, healthy women. Moreover, these effects may vary depending upon sexual assault histories, such that relative to women without assault histories, women with a history of early life sexual trauma showed significantly altered vaginal immune responses following sexual arousal. If replicated, these findings may help explain the increased risk for sexually transmitted infections observed among women with sexual assault histories.

Polysubstance use in the U.S. opioid crisis.

Interventions to address the U.S. opioid crisis primarily target opioid use, misuse, and addiction, but because the opioid crisis includes multiple substances, the opioid specificity of interventions may limit their ability to address the broader problem of polysubstance use. Overlap of opioids with other substances ranges from shifts among the substances used across the lifespan to simultaneous co-use of substances that span similar and disparate pharmacological categories. Evidence suggests that nonmedical opioid users quite commonly use other drugs, and this polysubstance use contributes to increasing morbidity and mortality. Reasons for adding other substances to opioids include enhancement of the high (additive or synergistic reward), compensation for undesired effects of one drug by taking another, compensation for negative internal states, or a common predisposition that is related to all substance consumption. But consumption of multiple substances may itself have unique effects. To achieve the maximum benefit, addressing the overlap of opioids with multiple other substances is needed across the spectrum of prevention and treatment interventions, overdose reversal, public health surveillance, and research. By addressing the multiple patterns of consumption and the reasons that people mix opioids with other substances, interventions and research may be enhanced.

Lack of Evidence for a Relationship Between Salivary CRP and Women's Sexual Desire: An Investigation Across Clinical and Healthy Samples.

BACKGROUND: Inflammation has been linked to a variety of mental and physical health outcomes that disproportionately impact women, and which can impair sexual function; thus, there is reason to expect a link between inflammation and women's sexual functioning. AIM: To test the hypothesis that higher concentrations of C-reactive protein (CRP), a general biomarker of inflammation, would predict women's lower sexual desire. METHOD: As 2 independent research teams, we conducted 3 separate studies (total n = 405) that assessed salivary CRP and various measurements of sexual desire in different women populations. OUTCOMES: Female Sexual Function Index, Sexual Desire Inventory-2, Decreased Sexual Desire Screener, and Sexual Interest and Desire Inventory. RESULTS: Regardless of the way sexual desire was measured (e.g., state vs trait; general desire vs. desire functioning) and the population sampled (i.e., healthy vs. clinically diagnosed with sexual dysfunction), all the studies revealed null results. CLINICAL IMPLICATIONS: While exploratory, the convergence of these null results across studies and researchers suggests that if there is an association between inflammation and women's sexual desire, it is likely very subtle. STRENGTHS & LIMITATIONS: Across 2 independent research teams, 3 unrelated studies, and various measurements of sexual desire, results were consistent. These points lend to the generalizability of the results. However, study designs were cross-sectional. CONCLUSIONS: Future research may reveal (i) a non-linear threshold effect, such that inflammation does not begin to impact women's sexual desire until it is at a high level, (ii) inflammatory biomarkers other than CRP might be more sensitive in detecting associations between inflammation and desire, should they exist, or (iii) the mechanisms underlying sexual dysfunction may differ between sexes. Clephane K, et al. Lack of Evidence for a Relationship Between Salivary CRP and Women's Sexual Desire: An Investigation Across Clinical and Healthy Samples. J Sex Med 2022;19:745-760.

Role of the Trifluoropropynyl Ligand in Blue-Shifting Charge-Transfer States in Emissive Pt Diimine Complexes and an Investigation into the PMMA-Imposed Rigidoluminescence and Rigidochromism.

Square-planar PtII complexes are of interest as dopants for the emissive layer of organic light-emitting diodes. Herein, the photophysics of three Pt bipyridyl complexes with the strongly e- withdrawing, high-field, 3,3,3-trifluoropropynyl ligand has been investigated. One complex, (phbpy)PtC2CF3 (phbpy = 6-phenyl-2,2'-dipyridyl), has also been characterized by single-crystal X-ray diffraction. All complexes reported are emissive in both RT CH2Cl2 solution (ΦPL = 0.007 to 0.027) and PMMA film (ΦPL = 0.25 to 0.42). The trifluoropropynyl ligand elevates the energy of the MLCT and LL'CT states above that of the IL π-π* state, resulting in IL emission in all cases. The emission energies of the trifluoropropynyl compounds are also blue-shifted relative to the analogous pentafluorophenylethynyl compounds, suggesting that the trifluoropropynyl ligand is one of the most electron-withdrawing alkynyl ligands. Rate constants for radiative and nonradiative deactivation were determined from experimentally determined values of ΦPL and excited-state lifetimes in both solution and PMMA films. The increase in ΦPL upon incorporation into PMMA film (rigidoluminescence) results from a decrease in the rate constant for non-radiative relaxation. Experimental activation energies for excited-state decay in combination with TDDFT are consistent with the rigidoluminescence resulting from an increase in the energy of the non-emissive triplet metal-centered state. Two of the complexes investigated, (Ph2bpy)Pt(C2CF3)2 and (t-Bu2bpy)Pt(C2CF3)2, where t-Bu2bpy = 4,4'-di-tert-butyl-2,2'-dipyridyl and Ph2bpy = 4,4'-diphenyl-2,2'-dipyridyl, exhibit concentration-dependent excimer emission (orange) along with monomer emission (blue), enabling fine-tuning of the emission color. However, excimer emission was absent in cured PMMA films up to the solubility limit for solution processing of (Ph2bpy)Pt(C2CF3)2 in CH2Cl2, demonstrating the diffusional nature of excimer formation.

Validation of the Wave 1 and Wave 2 Population Assessment of Tobacco and Health (PATH) Study Indicators of Tobacco Dependence Using Biomarkers of Nicotine Exposure Across Tobacco Products.

INTRODUCTION: This study examined the predictive relationships between biomarkers of nicotine exposure and 16-item self-reported level of tobacco dependence (TD) and subsequent tobacco use outcomes. AIMS AND METHODS: The Population Assessment of Tobacco and Health (PATH) Study surveyed adult current established tobacco users who provided urine biospecimens at Wave 1 (September 2013-December 2014) and completed the Wave 2 (October 2014-October 2015) interview (n = 6872). Mutually exclusive user groups at Wave 1 included: Cigarette Only, E-cigarette Only, Cigar Only, Hookah Only, Smokeless Tobacco Only, Cigarette Plus E-cigarette, multiple tobacco product users who smoked cigarettes, and multiple tobacco product users who did not smoke cigarettes. Total Nicotine Equivalents (TNE-2) and TD were measured at Wave 1. Approximate one-year outcomes included frequency/quantity used, quitting, and adding/switching to different tobacco products. RESULTS: For Cigarette Only smokers and multiple tobacco product users who smoked cigarettes, higher TD and TNE-2 were associated with: a tendency to smoke more, smoking more frequently over time, decreased likelihood of switching away from cigarettes, and decreased probability of quitting after one year. For other product user groups, Wave 1 TD and/or TNE-2 were less consistently related to changes in quantity and frequency of product use, or for adding or switching products, but higher TNE-2 was more consistently predictive of decreased probability of quitting. CONCLUSIONS: Self-reported TD and nicotine exposure assess common and independent aspects of dependence in relation to tobacco use behaviors for cigarette smokers. For other product user groups, nicotine exposure is a more consistent predictor of quitting than self-reported TD. IMPLICATIONS: This study suggests that smoking cigarettes leads to the most coherent pattern of associations consistent with a syndrome of TD. Because cigarettes continue to be prevalent and harmful, efforts to decrease their use may be accelerated via conventional means (eg, smoking cessation interventions and treatments), but also perhaps by decreasing their dependence potential. The implications for noncombustible tobacco products are less clear as the stability of tobacco use patterns that include products such as e-cigarettes continue to evolve. TD, nicotine exposure measures, and consumption could be used in studies that attempt to understand and predict product-specific tobacco use behavioral outcomes.

Evaluating opioid analgesic prescribing limits: A narrative review.

PURPOSE: In response to the opioid crisis, opioid analgesic guidelines and prescribing limits have proliferated. The purpose of this narrative review is to examine evidence from studies evaluating the patient or public health impact of federal and state opioid analgesic prescribing guidelines and laws, describe gaps and challenges in current research, and highlight opportunities for improving future research. METHODS: We focused on evidence from a literature review covering 2013 through 2019. We identified 30 studies evaluating opioid analgesic thresholds based on federal policies and guidelines, state laws, and Medicaid state plans that attempt to influence the course of patient care at or when the limit is exceeded (e.g., prior authorization). RESULTS: Most studies evaluated changes in prescribing or dispensing patterns of opioid analgesics, largely finding decreases in prescribing after policy enactment. Fewer studies evaluated patient or public health outcomes beyond changes in prescribing and dispensing patterns; results were infrequently stratified by potentially important sociodemographic and clinical factors. No studies assessed the potential for adverse patient outcomes for which we have emerging evidence of harms. CONCLUSIONS: We describe knowledge gaps and propose opportunities for future research to sufficiently assess the potential impact and unintended consequences of opioid analgesic prescribing laws, regulations, guidelines, and policies.

Development and preliminary evaluation of the Neurofibromatosis Type 1 Adult Quality of Life (NF1-AdQoL) questionnaire.

BACKGROUND: Neurofibromatosis Type 1 (NF1) is a variable and unpredictable multisystem genetic disorder that predisposes to medical complications, cognitive impairment and disfigurement, of all which can impact negatively upon the health-related quality of life (HRQoL) of affected adults. AIMS: To develop and validate a disease-specific HRQoL adult questionnaire to evaluate effects of NF1 from the patient's viewpoint. METHODS: The Neurofibromatosis Type 1 Adult Health-related Quality of Life questionnaire (NF1-AdQoL) was based on patient interviews (n = 8), clinician survey and questionnaire pilot study. Adults with NF1 (n = 114, aged 18-40 years) were recruited from three Australian genetics clinics and completed the NF1-AdQoL, the 29-item Skindex (Skindex-29) and the 36-item Short Form, version 2 (SF-36v2) questionnaires. An exploratory factor analysis of the NF1-AdQoL was conducted to assess construct validity. Convergent and discriminant validity of the NF1-AdQoL was determined by using multitrait multimethod analysis with Skindex-29 and SF-36v2 scores. RESULTS: Factor analysis indicated that 62.7% of the common variance between the questionnaires could be explained by three factors: 'emotions associated with cosmetic appearance' (12 items), 'functioning - social and learning' (11 items) and 'physical symptoms' (8 items). NF1-AdQoL had good internal consistency (Cronbach α = 0.96). Convergent validity was confirmed by moderate associations with similarly named scales of the Skindex-29 and SF-36v2. Results from all three HRQoL questionnaires indicated overall healthy HRQoL for young to early middle-aged adults with NF1. CONCLUSION: The NF1-AdQoL is a relatively valid, feasible and fairly easy to read tool to measure the HRQoL of adults with NF1. Further evaluation is required to determine the test-retest reliability, responsiveness and validity of the NF1-AdQoL in larger adult NF1 cohorts.

Global core indicators for measuring WHO's paediatric quality-of-care standards in health facilities: development and expert consensus.

BACKGROUND: There are currently no global recommendations on a parsimonious and robust set of indicators that can be measured routinely or periodically to monitor quality of hospital care for children and young adolescents. We describe a systematic methodology used to prioritize and define a core set of such indicators and their metadata for progress tracking, accountability, learning and improvement, at facility, (sub) national, national, and global levels. METHODS: We used a deductive methodology which involved the use of the World Health Organization Standards for improving the quality-of-care for children and young adolescents in health facilities as the organizing framework for indicator development. The entire process involved 9 complementary steps which included: a rapid literature review of available evidence, the application of a peer-reviewed systematic algorithm for indicator systematization and prioritization, and multiple iterative expert consultations to establish consensus on the proposed indicators and their metadata. RESULTS: We derived a robust set of 25 core indicators and their metadata, representing all 8 World Health Organization quality standards, 40 quality statements and 520 quality measures. Most of these indicators are process-related (64%) and 20% are outcome/impact indicators. A large proportion (84%) of indicators were proposed for measurement at both outpatient and inpatient levels. By virtue of being a parsimonious set and given the stringent criteria for prioritizing indicators with "quality measurement" attributes, the recommended set is not evenly distributed across the 8 quality standards. CONCLUSIONS: To support ongoing global and national initiatives around paediatric quality-of-care programming at country level, the recommended indicators can be adopted using a tiered approach that considers indicator measurability in the short-, medium-, and long-terms, within the context of the country's health information system readiness and maturity. However, there is a need for further research to assess the feasibility of implementing these indicators across contexts, and the need for their validation for global common reporting.