An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis.

Myeloid cells are known to suppress antitumour immunity1. However, the molecular drivers of immunosuppressive myeloid cell states are not well defined. Here we used single-cell RNA sequencing of human and mouse non-small cell lung cancer (NSCLC) lesions, and found that in both species the type 2 cytokine interleukin-4 (IL-4) was predicted to be the primary driver of the tumour-infiltrating monocyte-derived macrophage phenotype. Using a panel of conditional knockout mice, we found that only deletion of the IL-4 receptor IL-4Rα in early myeloid progenitors in bone marrow reduced tumour burden, whereas deletion of IL-4Rα in downstream mature myeloid cells had no effect. Mechanistically, IL-4 derived from bone marrow basophils and eosinophils acted on granulocyte-monocyte progenitors to transcriptionally programme the development of immunosuppressive tumour-promoting myeloid cells. Consequentially, depletion of basophils profoundly reduced tumour burden and normalized myelopoiesis. We subsequently initiated a clinical trial of the IL-4Rα blocking antibody dupilumab2-5 given in conjunction with PD-1/PD-L1 checkpoint blockade in patients with relapsed or refractory NSCLC who had progressed on PD-1/PD-L1 blockade alone (ClinicalTrials.gov identifier NCT05013450 ). Dupilumab supplementation reduced circulating monocytes, expanded tumour-infiltrating CD8 T cells, and in one out of six patients, drove a near-complete clinical response two months after treatment. Our study defines a central role for IL-4 in controlling immunosuppressive myelopoiesis in cancer, identifies a novel combination therapy for immune checkpoint blockade in humans, and highlights cancer as a systemic malady that requires therapeutic strategies beyond the primary disease site.

Rab8, Rab11, and Rab35 coordinate lumen and cilia formation during zebrafish left-right organizer development.

An essential process during Danio rerio's left-right organizer (Kupffer's Vesicle, KV) formation is the formation of a motile cilium by developing KV cells which extends into the KV lumen. Beating of motile cilia within the KV lumen directs fluid flow to establish the embryo's left-right axis. However, the timepoint at which KV cells start to form cilia and how cilia formation is coordinated with KV lumen formation have not been examined. We identified that nascent KV cells form cilia at their centrosomes at random intracellular positions that then move towards a forming apical membrane containing cystic fibrosis transmembrane conductance regulator (CFTR). Using optogenetic clustering approaches, we found that Rab35 positive membranes recruit Rab11 to modulate CFTR delivery to the apical membrane, which is required for lumen opening, and subsequent cilia extension into the lumen. Once the intracellular cilia reach the CFTR positive apical membrane, Arl13b-positive cilia extend and elongate in a Rab8 dependent manner into the forming lumen once the lumen reaches an area of 300 µm2. These studies demonstrate the need to acutely coordinate Rab8, Rab11, and Rab35-mediated membrane trafficking events to ensure appropriate timing in lumen and cilia formation during KV development.

Comparative feasibility and preliminary efficacy of CBT for insomnia among adults seeking and not seeking addiction treatment.

Two out of three adults seeking treatment for alcohol or other substance use disorders report co-occurring symptoms of insomnia. This study compared the feasibility, acceptability, and preliminary efficacy of cognitive behavioural therapy for insomnia (CBT-I) among adults seeking and not seeking treatment for substance use. Adults with alcohol or other substance use disorders (n = 22, 32% female, 82% White; Mage = 39.5) completed assessments at baseline, post-treatment, and at 6 week follow-up. Of those, 11 were and 11 were not enrolled in substance use treatment. All received CBT-I. Multiple imputation was used for missing data. Data were analysed using repeated measures analyses of variance. In the substance use treatment group, 6/11 completed post and 5/11 completed follow-up. In the non-treatment group, 9/11 completed post and 7/11 completed follow-up. Participants in both groups reported improvements in insomnia severity, sleep onset latency, and dysfunctional beliefs about sleep, with most effects evident at post and follow-up. There was a marginal group-by-time interaction in the change in frequency of substance use, with only participants not in substance use treatment reporting decreases at follow-up. Participants in substance use treatment reported significant reductions in substance-related problems and symptoms of post-traumatic stress disorder over time; however, they also reported more symptoms at baseline. CBT-I produces similar reductions in insomnia but is relatively less feasible among individuals in (versus not in) treatment for substance use disorder. This may be due to the more complex logistics of accessing CBT-I among those in treatment. We speculate that integrating CBT-I into treatment for addictions may improve feasibility in this population. clinicaltrials.gov NCT04198311.

A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

Challenges in management of invasive fungal infections in stem cell transplant.

Invasive fungal infections cause significant morbidity and mortality in hematopoietic stem cell transplant recipients. In order to minimize these infections, prophylaxis has become routine, although the agents used have changed over time. This presents new challenges as we consider an approach to breakthrough infections and recognize the epidemiologic shift toward isolates with higher rates of drug resistance. This review outlines the management of the most common pathogens (Candida, Aspergillus, Mucorales) as well as rarer pathogens that have higher rates of resistance (Trichosporon, Fusarium, Scedosporium, and Lomentospora). We discuss potential approaches to proven or possible breakthrough infections with yeast and pulmonary mold disease. Finally, we outline the role for combination therapy and newer antifungals, acknowledging current knowledge gaps and areas for future exploration.

Moral injury, mental health and behavioural health outcomes: A systematic review of the literature.

Despite a burgeoning of research on moral injury in the past decade, existing reviews have not explored the breadth of consequences and the multitude of pathways through which moral injury and potentially morally injurious experiences (PMIEs) influence mental and behavioural health outcomes. This study aimed to identify associations between moral injury on mental and behavioural health. Literature searches of psychological and medical databases were conducted through April 2020. Eligible studies measured moral injury or PMIEs, and health outcomes (e.g., depression, substance use and suicidality). Fifty-seven publications representing 49 separate samples were included. Studies examined the impact of moral injury on post-traumatic stress disorder (PTSD) (n = 43); depression (n = 32); anxiety (n = 15); suicide (n = 15); substance use (n = 14); and 'other' health outcomes, including pain, burnout, sleep disturbance and treatment-seeking behaviours (n = 11). The majority of studies found significant positive associations between moral injury-related constructs, mental health and behavioural health outcomes; however, the majority were also cross-sectional and focused on military samples. Proposed mediators included lack of social support, negative cognitions and meaning-making. Moderators included self-compassion, pre-deployment mental health education and mindfulness. Moral injury is associated with a variety of negative health outcomes. Research is needed to determine the mechanisms by which moral injury may influence these outcomes over time.

Insomnia treatment effects among young adult drinkers: Secondary outcomes of a randomized pilot trial.

BACKGROUND: Cognitive behavioral therapy for insomnia (CBT-I) has moderate-to-large effects on insomnia among young adult drinkers, with preliminary data indicating that improvements in insomnia may have downstream effects on alcohol-related consequences. However, the mechanism(s) by which insomnia treatment may facilitate reductions in alcohol-related problems is unclear. Secondary outcome data from a randomized pilot trial were used to examine CBT-I effects on four proposed mediators of the insomnia/alcohol link: alcohol craving, delay discounting, negative affect, and difficulties with emotion regulation. METHODS: Young adults (ages 18 to 30 years) with insomnia who reported 1+ binge drinking episode (4/5+ drinks for women/men) in the past month were randomized to receive CBT-I (n = 28) or to a sleep hygiene control (n = 28). Outcomes were assessed at baseline, after 5 weeks of treatment, and at 1-month posttreatment. RESULTS: Relative to those in sleep hygiene, CBT-I participants reported greater decreases in alcohol craving (d = 0.33) at the end of treatment and greater 1-month posttreatment decreases in delay discounting of large rewards (d = 0.42). CBT-I did not have a significant effect on delay discounting of smaller rewards or momentary negative affect. There was also no significant treatment effect on difficulties with emotion regulation, although findings were confounded by a significant group difference at baseline in difficulties with emotion regulation. CONCLUSIONS: Treatment of insomnia may lead to improvements in alcohol craving and delay discounting of large rewards among young adult drinkers with insomnia. Additional research examining whether improvement in insomnia is a mechanism for improvement in addiction domains is warranted.

Improving Transition to Adulthood for Students with Autism: A Randomized Controlled Trial of STEPS.

Emerging adulthood is a period of heightened risk for young people with autism spectrum disorder (ASD). Due in part to a lack of evidence-based services and supports during the transition to adulthood, many emerging adults fail to matriculate into postsecondary education or thrive in productive employment. The Stepped Transition in Education Program for Students with ASD (STEPS) was developed to address the psychosocial, transition-related needs of emerging adults with ASD. Adolescents and emerging adults (n = 59) with ASD were randomly assigned to either STEPS or transition as usual (TAU). Results indicate that STEPS is acceptable to young people with ASD and their parents and that it can be implemented with high fidelity. Among secondary school students, those who completed STEPS exhibited significantly greater gains in transition readiness from high school, and these gains were largely sustained after program completion. Among students enrolled in postsecondary education, STEPS resulted in increased levels of student adaptation to college relative to those in TAU. Programming to address ASD-related challenges can promote successful educational transitions.

The Parent-Child Relationship and Posttreatment Child Outcomes Across Two Treatments for Oppositional Defiant Disorder.

This study examined the degree to which the parent-child relationship uniquely predicted clinical outcomes in externalizing problems and adaptive skills in children meeting diagnostic criteria for oppositional defiant disorder and whether facets of this relationship moderated the effects of two unique psychosocial treatments. We recruited 134 children and their parents (38.06% female; M age = 9.52 years, range = 7-14; 83.58% White). Families were randomly assigned to 1 of 2 treatments: Parent Management Training (PMT) and Collaborative and Proactive Solutions (CPS). We formed principal components from pretreatment reports and behaviors of the parent-child relationship to predict within- and between-family outcomes in children's externalizing problems and adaptive skills. Four principal components were supported (parental warmth, parental monitoring, family hostility, and family permissiveness). Parental monitoring predicted fewer externalizing problems, whereas family permissiveness predicted more externalizing problems. Parental warmth predicted greatest improvements in children's adaptive skills among families receiving PMT. Family hostility predicted more externalizing problems and poorer adaptive skills for children; however, families receiving CPS were buffered from the negative effect of family hostility on adaptive skills. The parent-child relationship can uniquely inform posttreatment outcomes following treatment for oppositional defiant disorder. Certain treatment approaches may better fit unique relationships that emphasize warmth and/or hostility, allowing clinicians to anticipate and tailor treatments to families.

Meta-Analysis of the RDoC Social Processing Domain across Units of Analysis in Children and Adolescents.

OBJECTIVE: This meta-analysis advances a framework to understand correspondence among units of analysis of the social processing construct within Research Domain Criteria (RDoC). METHOD: As requested for this special issue, eligible studies cited an RDoC-initiative paper or mentioned RDoC in the abstract, title, or keywords were empirical and peer reviewed, and described a correlation or regression analysis (r, ß, or odds ratio) between two different units of analysis in the social processing domain in youth. We examined the frequency (descriptive statistics) and magnitude of correspondence between unit-pairs (random effects models), and predefined moderators (meta-regression). RESULTS: Eight of the twenty-eight possible unit-by-unit pairs were identified, with subjective-by-behavior units being the most common. Of those, only subjective-by-circuit had significant correspondence between units. Moderator analysis revealed that the age and diagnosis of generalized anxiety disorder moderated correspondence between subjective-by-circuit units of analysis, and that a diagnosis of autism spectrum disorder moderated correspondence between subjective-by-gene units of analysis. Younger ages and inclusion of either diagnostic group reduced correspondence. CONCLUSIONS: These findings indicate that the RDoC initiative has generated limited research within the social processing domain across units of analysis in youth to date. Moreover, National Institute of Mental Health (NIMH)-funded studies do not appear to be biased toward supporting the RDoC framework. However, the limited number of included studies precludes the generalizability of these findings and underscores the need for further research. Despite this, results suggest that the NIMH model for providing standard batteries of measurement tools may effectively reduce spurious correlations between subjective-by-behavior units of analysis.

Influence of physical variables on the transfer of Salmonella Typhimurium LT2 between potato (Solanum tuberosum) and stainless steel via static and dynamic contact.

Bacterial cross-contamination between foods and contact surfaces can increase food safety risk; however, these processes are not well described in terms of fundamental variables. The objective was to determine the effect of sliding speed (3.75, 5.00, or 7.75 mm/s), contact time (5 or 40 s), normal pressure (~1217 to 8869 Pa), and number of sequential contacts on bacterial transfer to/from potato samples and stainless steel surfaces. Potato samples (~11 g, 3 × 3 × 1 cm) were either pulled across a stainless steel plate inoculated with Salmonella Typhimurium LT2 (~6.23 Log CFU/cm2) (dynamic contact) or placed on the inoculated plate for multiple sequential contacts on uninoculated squares (static contact). Salmonella on the potato and steel plate then were quantified by plating on modified trypticase soy agar. Bacterial transfer increased with increasing sliding speed (P = 0.0098) in dynamic tests and with contact time (P < 0.0001) in static tests. Salmonella on the inoculated potatoes decreased (P < 0.0001) from ~6.5 to ~5.5 Log CFU after 18 sequential static contacts with stainless steel. Reporting transfer results based on fundamental variables will improve the overall impact of bacterial transfer research on equipment design, cleaning/sanitation strategies, and overall food safety.

Variability of attention bias in socially anxious adolescents: differences in fixation duration toward adult and adolescent face stimuli.

Prior research on attention bias in anxious youth, often utilising a visual dot probe task, has yielded inconsistent findings, which may be due to how bias is assessed and/or variability in the phenomenon. The present study utilises eye gaze tracking to assess attention bias in socially anxious adolescents, and explores several methodological and within-subject factors that may contribute to variability in attention bias. Attention bias to threat was measured in forty-two treatment-seeking adolescents (age 12-16 years) diagnosed with Social Anxiety Disorder. Bias scores toward emotional stimuli (vigilant attention) and bias scores away from emotional stimuli (avoidant attention) were explored. Bias scores changed between vigilance and avoidance within individuals and over the course of stimulus presentation. These differences were not associated with participant characteristics nor with self-reported social anxiety symptoms. However, clinician rated severity of social anxiety, explained a significant proportion of variance in the bias scores for adult, but not the adolescent, stimuli. Variability in attention bias among socially anxious adolescents is common and varies as a function of stimulus duration and type. Results may inform stimulus selection for future research.

Change in gaze-based attention bias in adolescents with Social Anxiety Disorder.

Although attention bias (AB) toward threat has been associated with Social Anxiety Disorder (SAD), concerns regarding the ability of current measures to detect change in AB following treatment exist. We sought to examine change in bias, as measured via eye-tracking, in adolescents with SAD receiving either attention-bias modification training (ABMT) or attention-control training (ACT). Gaze-based AB was associated (r = -0.361) with symptoms of social anxiety prior to treatment, whereas there was no association between bias as measured via dot probe and social anxiety. Moreover, gaze-based bias to same-age face stimuli showed change following treatment. Large effects are seen for condition (ABMT or ACT) and for time, independent of treatment condition, in gaze-based AB to same-age stimuli. Findings suggest that further research on gaze-based bias, to assess stability over time outside of treatment and sensitivity to change following intervention, is warranted.

The Influence of Social Communication Impairments on Gaze in Adolescents with Social Anxiety Disorder.

Adolescents with social anxiety disorder (SAD) often present distorted beliefs related to expected social rejection, coupled with avoidance of social stimuli including interpersonal interactions and others' gaze. Social communication (SC) deficits, often seen in SAD, may play a role in avoidance of social stimuli. The present study evaluated whether SC impairment uniquely contributes to diminished or heightened attention to social stimuli. Gaze patterns to social stimuli were examined in a sample of 41 adolescents with SAD (12-16 years of age; 68% female). Unexpectedly, no significant relationship was observed between SC impairment and fixation duration to angry or neutral faces. However, SC impairment did predict greater fixation duration to happy faces, after controlling for social anxiety severity [adjusted R 2 = 0.201, F(2, 38) = 4.536, p = 0.018]. Clinical implications are discussed, focusing on the potential utility of targeting SC impairments directly in light of the role of SC difficulties in youth with SAD.

Positive associations between potentially morally injurious experiences and alcohol outcomes in college students: Results from a dominance analysis.

OBJECTIVE: A novel framework for understanding college students' alcohol use is moral injury-psychological distress that stems from events that violate moral beliefs. Considering the predominantly positive associations between moral injury and alcohol use in military samples, this relationship may extend to students. The purpose of this study was to examine the association between potentially morally injurious experiences (PMIEs), alcohol use, and related consequences. Furthermore, we aimed to determine the relative importance of PMIE subtypes on alcohol outcomes. METHOD: Participants included 604 college students (78% female; 38% Caucasian) with a mean age of 21 years (SD = 4.44). We hypothesized that (a) the composite PMIE score would be positively associated with alcohol consumption and consequences and (b) Commission with Agency would have the strongest association with alcohol outcomes, followed by Betrayal, Omission, Commission under Duress, posttraumatic stress (PTS) symptoms, and Witnessing. RESULTS: Analyses revealed that PMIEs were positively associated with alcohol-related consequences but not drinks per week when controlling for PTS symptoms. Moreover, the dominance analysis showed that Commission with Agency had the strongest association with consumption, followed by Betrayal, PTS symptoms, Commission under Duress, Witnessing, and Omission. PTS symptoms had the strongest association with alcohol-related consequences, followed by Commission with Agency, Commission under Duress, Omission, Betrayal, and Witnessing. CONCLUSIONS: These findings help distinguish moral injury constructs from PTS and highlight the importance of Commission with Agency in analyzing alcohol outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A plug-and-play, easy-to-manufacture fluidic accessory to significantly enhance the sensitivity of electrochemical immunoassays.

Earlier access to patients' biomarker status could transform disease management. However, gold-standard techniques such as enzyme-linked immunosorbent assays (ELISAs) are typically not deployed at the point-of-care due to their cumbersome instrumentation and complexity. Electrochemical immunosensors can be disruptive in this sector with their small size and lower cost but, without further modifications, the performance of these sensors in complex media (e.g., blood) has been limited. This paper presents a low-cost fluidic accessory fabricated using widely accessible materials and processes for boosting sensor sensitivity through confinement of the detection media next to the electrode surface. Liquid confinement first highlighted a spontaneous reaction between the pseudoreference electrode and ELISA detection substrate 3,3',5,5'-tetramethylbenzidine (TMB) that decreases the amount of oxTMB available for detection. Different strategies are investigated to limit this and maximize reliability. Next, flow cell integration during the signal amplification step of sensor preparation was shown to substantially enhance the detection of cytokine interleukin-6 (IL-6) with the best sensitivity boost recorded for fresh human plasma (x7 increase compared to x5.8 in purified serum and x5.5 in PBS). The flow cell requires no specialized equipment and can be seamlessly integrated with commercial sensors, making an ideal companion for electrochemical signal enhancement.

Demonstration of Inappropriate Validation Method for a Cracker Baking Process Using Predictive Modeling.

Validation of baking processes for the inactivation of Salmonella is complicated by the combined effects of product heating and drying. The goal of this study was to quantitatively evaluate a previously disseminated approach to validating baking processes utilizing a predictive model developed using only isothermal and single-moisture inactivation data for the initially formulated dough. A simple cracker dough was formulated using flour inoculated with a five-strain cocktail of Salmonella. Side-by-side isothermal and baking experiments were performed to estimate Salmonella inactivation kinetics and to quantify survivors in a dynamic environment, respectively. Isothermal, single-moisture inactivation experiments were performed with cracker dough (water activity, aw = 0.956 ± 0.002; moisture content = 0.50 ± 0.01 dry basis) at three temperatures (56, 60, or 63°C) with ≥6 time intervals. Baking experiments were performed in a convection oven at 177°C with samples pulled every 30 s up to 360 s, with an endpoint product aw (25°C) of 0.45. The Salmonella isothermal, single-moisture inactivation kinetics in cracker dough resulted in D60°C and z-values of 4.6 min and 4.9°C, respectively; this model was then integrated over the dynamic product temperature profiles from the baking experiments. In the baking experiments, an average of 5-log reductions of Salmonella was achieved by 150 s of treatment; however, >100-log reductions were predicted by the dough-based models at that time point. This fail-dangerous overestimation of Salmonella lethality in crackers explicitly demonstrated that single-level moisture-based prediction models are inappropriate for describing inactivation in a process with both dynamic temperature and moisture, and that model-based validations must incorporate moisture/aw. Furthermore, end-users should exercise caution when utilizing unvalidated models to validate preventive control processes.

Model-Informed Precision Dosing Improves Outcomes in Patients Receiving Vancomycin for Gram-Positive Infections.

Background: Consensus guidelines for dosing and monitoring of vancomycin recommend collection of 2 serum concentrations to estimate an area under the curve/minimum inhibitory concentration ratio (AUC/MIC). Use of Bayesian software for AUC estimation and model-informed precision dosing (MIPD) enables pre-steady state therapeutic drug monitoring using a single serum concentration; however, data supporting this approach are limited. Methods: Adult patients with culture-proven gram-positive infections treated with vancomycin ≥72 hours receiving either trough-guided or AUC-guided therapy were included in this retrospective study. AUC-guided therapy was provided using MIPD and single-concentration monitoring. Treatment success, vancomycin-associated acute kidney injury (VA-AKI), and inpatient mortality were compared using a desirability of outcome ranking analysis. The most desirable outcome was survival with treatment success and no VA-AKI, and the least desirable outcome was death. Results: The study population (N = 300) was comprised of an equal number of patients receiving AUC-guided or trough-guided therapy. More patients experienced the most desirable outcome in the AUC-guided group compared to the trough-guided group (58.7% vs 46.7%, P = .037). Rates of VA-AKI were lower (21.3% vs 32.0%, P = .037) and median hospital length of stay was shorter (10 days [interquartile range {IQR}, 8-20] vs 12 days [IQR, 8-25]; P = .025) among patients receiving AUC-guided therapy. Conclusions: AUC-guided vancomycin therapy using MIPD and single-concentration monitoring improved outcomes in patients with culture-proven gram-positive infections. Safety was improved with reduced incidence of VA-AKI, and no concerns for reduced efficacy were observed. Moreover, MIPD allowed for earlier assessment of AUC target attainment and greater flexibility in the collection of serum vancomycin concentrations.

Overview of Methamphetamine-Associated Pulmonary Arterial Hypertension.

TOPIC IMPORTANCE: The global surge in methamphetamine use is a critical public health concern, particularly due to its robust correlation with methamphetamine-associated pulmonary arterial hypertension (MA-PAH). This association raises urgent alarms about the potential escalation of MA-PAH incidence, posing a significant and imminent challenge to global public health. REVIEW FINDINGS: This comprehensive review meticulously explores MA-PAH, offering insights into its epidemiology, pathophysiology, clinical presentation, diagnostic intricacies, and management strategies. The pathogenesis, yet to be fully described, involves complex molecular interactions, including alterations in serotonin signaling, reduced activity of carboxylesterase 1, oxidative stress, and dysregulation of pulmonary vasoconstrictors and vasodilators. These processes culminate in the structural remodeling of the pulmonary vasculature, resulting in pulmonary arterial hypertension. MA-PAH exhibits a more severe clinical profile in functional class and hemodynamics compared with idiopathic pulmonary arterial hypertension. Management involves a multifaceted approach, integrating pulmonary vasodilators, cessation of methamphetamine use, and implementing social and rehabilitation programs. These measures aim to enhance patient outcomes and detect potential relapses for timely intervention. SUMMARY: This review consolidates our understanding of MA-PAH, pinpointing knowledge gaps for future studies. Addressing these gaps is crucial for advancing diagnostic accuracy, unraveling mechanisms, and optimizing treatment for MA-PAH, thereby addressing the evolving landscape of this complex health concern.

Parent smoker role conflict and planning to quit smoking: a cross-sectional study.

BACKGROUND: Role conflict can motivate behavior change. No prior studies have explored the association between parent/smoker role conflict and readiness to quit. The objective of the study is to assess the association of a measure of parent/smoker role conflict with other parent and child characteristics and to test the hypothesis that parent/smoker role conflict is associated with a parent's intention to quit smoking in the next 30 days. As part of a cluster randomized controlled trial to address parental smoking (Clinical Effort Against Secondhand Smoke Exposure-CEASE), research assistants completed exit interviews with 1980 parents whose children had been seen in 20 Pediatric Research in Office Settings (PROS) practices and asked a novel identity-conflict question about "how strongly you agree or disagree" with the statement, "My being a smoker gets in the way of my being a parent." Response choices were dichotomized as "Strongly Agree" or "Agree" versus "Disagree" or "Strongly Disagree" for the analysis. Parents were also asked whether they were "seriously planning to quit smoking in 30 days." Chi-square and logistic regression were performed to assess the association between role conflict and other parent/children characteristics. A similar strategy was used to determine whether role conflict was independently associated with intention to quit in the next 30 days. METHODS: As part of a RTC in 20 pediatric practices, exit interviews were held with smoking parents after their child's exam. Parents who smoked were asked questions about smoking behavior, smoke-free home and car rules, and role conflict. Role conflict was assessed with the question, "Please tell me how strongly you agree or disagree with the statement: 'My being a smoker gets in the way of my being a parent.' (Answer choices were: "Strongly agree, Agree, Disagree, Strongly Disagree.") RESULTS: Of 1980 eligible smokers identified, 1935 (97%) responded to the role-conflict question, and of those, 563 (29%) reported experiencing conflict. Factors that were significantly associated with parent/smoker role conflict in the multivariable model included: being non-Hispanic white, allowing home smoking, the child being seen that day for a sick visit, parents receiving any assistance for their smoking, and planning to quit in the next 30 days. In a separate multivariable logistic regression model, parent/smoker role conflict was independently associated with intention to quit in the next 30 days [AOR 2.25 (95% CI 1.80-2.18)]. CONCLUSION: This study demonstrated an association between parent/smoker role conflict and readiness to quit. Interventions that increase parent/smoker role conflict might act to increase readiness to quit among parents who smoke.