ATP-dependent citrate lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling of the Heart.

Background: Metabolic remodeling is a hallmark of the failing heart. Oncometabolic stress during cancer increases the activity and abundance of the ATP-dependent citrate lyase (ACL, Acly ), which promotes histone acetylation and cardiac adaptation. ACL is critical for the de novo synthesis of lipids, but how these metabolic alterations contribute to cardiac structural and functional changes remains unclear. Methods: We utilized human heart tissue samples from healthy donor hearts and patients with hypertrophic cardiomyopathy. Further, we used CRISPR/Cas9 gene editing to inactivate Acly in cardiomyocytes of MyH6-Cas9 mice. In vivo, positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to the loss of ACL. We conducted a multi-omics analysis using RNA-sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. Results: Here, we show that in mice, ACL drives metabolic adaptation in the heart to sustain contractile function, histone acetylation, and lipid modulation. Notably, we show that loss of ACL increases glucose oxidation while maintaining fatty acid oxidation. Ex vivo isotope tracing experiments revealed a reduced efflux of glucose-derived citrate from the mitochondria into the cytosol, confirming that citrate is required for reductive metabolism in the heart. We demonstrate that YAP inactivation facilitates ACL deficiency. Computational flux analysis and integrative multi-omics analysis indicate that loss of ACL induces alternative isocitrate dehydrogenase 1 flux to compensate. Conclusions: This study mechanistically delineates how cardiac metabolism compensates for suppressed citrate metabolism in response to ACL loss and uncovers metabolic vulnerabilities in the heart.

Genetic modifiers of somatic expansion and clinical phenotypes in Huntington's disease reveal shared and tissue-specific effects.

Huntington's disease (HD), due to expansion of a CAG repeat in HTT , is representative of a growing number of disorders involving somatically unstable short tandem repeats. We find that overlapping and distinct genetic modifiers of clinical landmarks and somatic expansion in blood DNA reveal an underlying complexity and cell-type specificity to the mismatch repair-related processes that influence disease timing. Differential capture of non-DNA-repair gene modifiers by multiple measures of cognitive and motor dysfunction argues additionally for cell-type specificity of pathogenic processes. Beyond trans modifiers, differential effects are also illustrated at HTT by a 5'-UTR variant that promotes somatic expansion in blood without influencing clinical HD, while, even after correcting for uninterrupted CAG length, a synonymous sequence change at the end of the CAG repeat dramatically hastens onset of motor signs without increasing somatic expansion. Our findings are directly relevant to therapeutic suppression of somatic expansion in HD and related disorders and provide a route to define the individual neuronal cell types that contribute to different HD clinical phenotypes.

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-ß0-thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

Prediction of Listeria monocytogenes Clonal Complexes from Multilocus Variable Number Tandem Repeat Analysis Patterns Using a Machine Learning Approach.

Multilocus variable number tandem repeat analysis (MLVA) is a molecular subtyping technique that remains useful for those without the resources to access whole genome sequencing for the tracking and tracing of bacterial contaminants. Unlike techniques such as multilocus sequence typing (MLST) and pulsed-field gel electrophoresis, MLVA did not emerge as a standardized subtyping method for Listeria monocytogenes, and as a result, there is no reference database of virulent or food-associated MLVA subtypes as there is for MLST-based clonal complexes (CCs). Having previously shown the close congruence of a 5-loci MLVA scheme with MLST, a predictive model was created using the XGBoost machine learning (ML) technique, which enabled the prediction of CCs from MLVA patterns with ∼85% (±4%) accuracy. As well as validating the model on existing data, a straightforward update protocol was simulated for if and when previously unseen subtypes might arise. This article illustrates how ML techniques can be applied with elementary coding skills to add value to previous-generation molecular subtyping data in-built food processing environments.

UW Supplementation with AP39 Improves Liver Viability Following Static Cold Storage.

Static cold storage of donor livers at 4°C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H2S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H2S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H2S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.

Identifying novel data-driven subgroups in congenital heart disease using multi-modal measures of brain structure.

Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.

Packaging of disposable vaping products and e-liquids in England, Canada and the United States: A content analysis.

BACKGROUND AND AIMS: Vaping product packaging is varied and often features bright colours and novel designs, particularly among recently marketed disposable vapes. This study provides an overview of attributes found on the packaging of popular disposable vapes and e-liquid bottles in England, Canada and the United States (US) and assesses compliance with local packaging regulations. DESIGN: Content analysis. SETTING: Brick-and-mortar and online shops in England (London), Canada (Ontario) and the US (New Hampshire and South Carolina). CASES: 108 vaping products (including packaging) from 76 brands in a range of flavours and nicotine levels. Specifically, 48 disposable vapes (15 from England, 16 from Canada, 17 from the US) and 60 e-liquid bottles (20 per country). MEASUREMENTS: Textual and graphic branding and marketing elements, independently coded by two researchers and checked by a third. FINDINGS: Compliance with local packaging regulations varied across countries. Health warnings were present on the packaging of all but one nicotine-containing product, although 33% of disposables and 17% of e-liquids featuring the warning did not adhere to formatting requirements. Leaflets were seldom included with e-liquid bottles, even in England (45%) where mandatory, and omitted elsewhere. Labelling of nicotine type and batch numbers was inconsistent. Vaping product packaging featured claims relating to sensory perceptions (41%), most often flavours, and some (32%) featured youth-appealing content. Common graphic elements included stylised brand fonts (80%), brand logos (54%), product representations on the external packaging (47%) and abstract graphic elements (64%). Colours on packaging, disposable vapes and e-liquid bottles were associated with product flavour. CONCLUSIONS: In England, Canada and the United States, popular disposable vapes and e-liquid bottles appear to have varying compliance with local packaging regulations and inconsistent labelling of nicotine and product characteristics. The use of colourful designs, evocative descriptors and appealing graphics to promote flavours underscores the need for comprehensive packaging regulations and enforcement.

Molecular signatures of longissimus dorsi differ between dairy cattle based on prepartum muscle reserves and branched-chain volatile fatty acid supplementation.

Dairy cattle with high (HM) versus low muscle (LM) reserves exhibit distinct temporal changes in longissimus dorsi muscle depth (LDD) in late gestation. Branched-chain volatile fatty acids (BCVFA) supplementation increased blood glucose levels. We hypothesized that differences in HM and LM reflect distinct muscle metabolism and BCVFA supplementation altered metabolic pathways. At 42 d before expected calving (BEC) Holstein dairy cows were enrolled in a 2 x 2 factorial study of diet and muscle reserves, by assigning to control (CON) or BCVFA supplemented diets and LDD of HM (>4.6 cm) or LM (≤4.6 cm) groups: HM-CON (n=13), HM-BCVFA (n=10), LM-CON (n=9), and LM-BCVFA (n=9). Longisumus dorsi was biopsied at 21 d BEC, total RNA isolated and protein coding gene expression measured with RNA-seq. Between HM and LM 713 genes were differentially expressed and 481 between BCVFA and CON (P<0.05). Transcriptional signatures indicated differential distribution of Type II fibers between groups, with MYH1 greater in LM and MYH2 greater in HM cattle (P<0.05). Signatures of LM cattle relative to HM indicated greater activation of autophagy, ubiquitin-proteasome, and Ca2+-calpain pathways. HM cattle displayed greater expression of genes that encode extracellular matrix proteins and factors that regulate their proteolysis and turnover. BCVFA modified transcriptomes by increasing expression of genes that regulate fatty acid degradation and flux of carbons into the TCA cycle as acetyl CoA. Molecular signatures support distinct metabolic strategies between LM and HM cattle, and that BCVFA supplementation increased substrates for energy generation.

An adjustable acoustic metamaterial cell using a magnetic membrane for tunable resonance.

Acoustic metamaterials are growing in popularity for sound applications including noise control. Despite this, there remain significant challenges associated with the fabrication of these materials for the sub-100 Hz regime, because acoustic metamaterials for such frequencies typically require sub-mm scale features to control sound waves. Advances in additive manufacturing technologies have provided practical methods for rapid fabrication of acoustic metamaterials. However, there is a relatively high sensitivity of their resonant characteristics to sub-mm deviations in geometry, pushing the limits of additive manufacturing. One way of overcoming this is via active control of device resonance. Here, an acoustic metamaterial cell with adjustable resonance is demonstrated for the sub-100 Hz regime. A functionally superparamagnetic membrane-devised to facilitate the fabrication process by eliminating magnetic poling requirements-is engineered using stereolithography, and its mechanical and acoustic properties are experimentally measured using laser Doppler vibrometry and electret microphone testing, with a mathematical model developed to predict the cell response. It is demonstrated that an adjustable magnetic acoustic metamaterial can be fabricated at ultra-subwavelength dimensions ( ≤ λ /77.5), exhibiting adjustable resonance from 88.73 to 86.63 Hz. It is anticipated that this research will drive new innovations in adjustable metamaterials, including wider frequency ranges.

Examining the Role of Aguas Frescas in Assessment of Sugary-Drink Intake among Mexican and Mexican American Adults.

BACKGROUND: Aguas frescas are Mexican drinks that are typically made with water, sugar, and fruit. Aguas frescas may be a significant component of sugary-drink intake among Mexican and Mexican-American (MA) adults. However, it is unclear whether survey respondents report aguas frescas consumption when it is not specifically queried in standardized beverage frequency instruments. OBJECTIVES: This study examined the prevalence of aguas frescas consumption, the sociodemographic correlates of aguas frescas intake, and how specifically querying aguas frescas intake affects sugary-drink estimates among Mexican and MA adults. METHODS: Cross-sectional, online surveys were conducted in 2021 with 5377 Mexican and 3073 MA adults as part of the International Food Policy Study. Past 7-d consumption of sugar-sweetened beverages (SSBs), sugary drinks, and aguas frescas were assessed along with relevant covariates. Weighted analyses included logistic and linear regression, including models with correlation structure. RESULTS: An estimated 61.7% of Mexican and 28.7% of MA adults consumed aguas frescas. In Mexico, consumption was associated with females, low education, perceiving oneself as having about the right weight, being good to excellent health, and consuming an unhealthy amount of sugary drinks. For MAs, intake was associated with being younger, speaking Spanish, and perceiving oneself as being underweight or about the right weight. Among Mexican adults who consumed aguas frescas but did not report them unless specifically queried, the volume of SSB intake was 67.9% higher for females and 64.3% higher for males when aguas frescas were included. Among MAs, SSB intake was 56.9% higher for females and 44.1% higher for males. Most participants (79.9%-85.2%) remained in the same sugary-drink tertiles when including compared with excluding aguas frescas. CONCLUSIONS: Aguas frescas should be queried during beverage intake assessments, as they contribute a nontrivial amount of added sugars to the diets of many Mexican and MA adults.

Identification of genetic modifiers of Huntington's disease somatic CAG repeat instability by in vivo CRISPR-Cas9 genome editing.

Huntington's disease (HD), one of >50 inherited repeat expansion disorders (Depienne and Mandel, 2021), is a dominantly-inherited neurodegenerative disease caused by a CAG expansion in HTT (The Huntington's Disease Collaborative Research Group, 1993). Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the property driving disease is the CAG length-dependent propensity of the repeat to further expand in brain (Swami et al ., 2009; GeM-HD, 2015; Hensman Moss et al ., 2017; Ciosi et al ., 2019; GeM-HD, 2019; Hong et al ., 2021). Routes to slowing somatic CAG expansion therefore hold great promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair (MMR) pathway, modify somatic expansion in HD mouse models (Wheeler and Dion, 2021). To identify novel modifiers of somatic expansion, we have used CRISPR-Cas9 editing in HD knock-in mice to enable in vivo screening of expansion-modifier candidates at scale. This has included testing of HD onset modifier genes emerging from human genome-wide association studies (GWAS), as well as interactions between modifier genes, thereby providing new insight into pathways underlying CAG expansion and potential therapeutic targets.

Scientometric trends and knowledge maps of global polychlorinated naphthalenes research over the past four decades.

Polychlorinated naphthalenes (PCNs) were included in the banned list of the Stockholm Convention due to their potential to provoke a wide range of adverse effects on living organisms and the environment. Many reviews have been written to clarify the state of knowledge and identify the research needs of this pollutant class. However, studies have yet to analyse the scientometric complexities of PCN literature. In this study, we used bibliometric R and vosviewer programs as a scientometric tool to fill this gap by focusing on articles indexed on Web of Science and Scopus databases and those published between 1973 and 2022. A total of 707 articles were published within this period with a publication/author, author/publication, and co-authors/publication ratios of 0.45, 2.19, and 4.86, respectively. Developed countries dominated most scientometric indices (number of publications, citations, and collaboration networks) in the survey period. Lotka's inverse square rule of author productivity showed that Lotka's laws do not fit PCN literature. An annual percentage growth rate of 7.46% and a Kolmogorov-Smirnoff goodness-of-fit of 0.88 suggests that more output on PCNs is likely in years to come. More research is needed from scholars from developing countries to measure the supremacy of the developed nations and to effectively comply with the Stockholm Convention agreement.

Outcomes of Six Specific Types of Post-Hospital Brain Injury Rehabilitation Programs.

OBJECTIVE: Evaluate outcomes of intensive posthospital brain injury rehabilitation programs compared to supported living (SL) programs; explore variations in outcome by diagnostic category (traumatic brain injury, stroke, and other acquired brain injury [ABI]) and specific program type. SETTING: Data were obtained from Residential Neurobehavioral, Residential Neurorehabilitation, Home and Community Neurorehabilitation, Day Treatment, Outpatient Neurorehabilitation, and SL programs serving individuals with ABI. PARTICIPANTS: A total of 2120 individuals with traumatic brain injury, stroke, or other ABI participated in this study. MAIN MEASURES: The main measures are sex, age, time since injury, and Mayo-Portland Adaptability Inventory (4th edition; MPAI-4). DESIGN: Retrospective analyses of demographic variables and MPAI-4 Total, index, and subscale Rasch-derived T-scores on admission and discharge. RESULTS: Gains on MPAI-4  Total T-scores were significantly greater for the intensive rehabilitation (IR) group in comparison to stable functioning in the SL group (F = 236.69, P < .001, partial η2 = .101) while controlling for admission/time 1 scores; similar results were found for MPAI-4 indices and subscales. For the IR cohort, discharge scores differed by diagnostic category after controlling for admission scores for the Total MPAI-4 T-score (F = 22.65, P < .001, partial η2 = .025), as well as all indices and subscales. A statistically significant interaction between program type and diagnostic group on discharge MPAI-4 Total T-scores (F = 2.55, P = .018, partial η2 = .01) after controlling for admission scores indicated that differing outcomes across diagnoses also varied by program type. Varying significant main effects and interactions were apparent for MPAI-4 indices and subscales with generally small effect sizes. CONCLUSIONS: Significant gains on MPAI-4 variables across IR program types compared to no change over a comparable period of time for SL programs supports the effectiveness of posthospital brain injury rehabilitation. This finding in the presence of small effect sizes on outcome variables for program type and for significant interactions between program type and diagnostic category suggests that participants generally were appropriately matched to program type and benefited from interventions provided through specific program types.

Diverse Fgfr1 signaling pathways and endocytic trafficking regulate mesoderm development.

The fibroblast growth factor (FGF) pathway is a conserved signaling pathway required for embryonic development. Activated FGF receptor 1 (FGFR1) drives multiple intracellular signaling cascade pathways, including ERK/MAPK and PI3K/AKT, collectively termed canonical signaling. However, unlike Fgfr1-null embryos, embryos containing hypomorphic mutations in Fgfr1 lacking the ability to activate canonical downstream signals are still able to develop to birth but exhibit severe defects in all mesodermal-derived tissues. The introduction of an additional signaling mutation further reduces the activity of Fgfr1, leading to earlier lethality, reduced somitogenesis, and more severe changes in transcriptional outputs. Genes involved in migration, ECM interaction, and phosphoinositol signaling were significantly downregulated, proteomic analysis identified changes in interactions with endocytic pathway components, and cells expressing mutant receptors show changes in endocytic trafficking. Together, we identified processes regulating early mesoderm development by mechanisms involving both canonical and noncanonical Fgfr1 pathways, including direct interaction with cell adhesion components and endocytic regulation.

Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease.

Anti-amyloid treatments for early symptomatic Alzheimer disease have recently become clinically available in some countries, which has greatly increased the need for biomarker confirmation of amyloid pathology. Blood biomarker (BBM) tests for amyloid pathology are more acceptable, accessible and scalable than amyloid PET or cerebrospinal fluid (CSF) tests, but have highly variable levels of performance. The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to consider the minimum acceptable performance of BBM tests for clinical use. Amyloid PET status was identified as the reference standard. For use as a triaging test before subsequent confirmatory tests such as amyloid PET or CSF tests, the BBM Workgroup recommends that a BBM test has a sensitivity of ≥90% with a specificity of ≥85% in primary care and ≥75-85% in secondary care depending on the availability of follow-up testing. For use as a confirmatory test without follow-up tests, a BBM test should have performance equivalent to that of CSF tests - a sensitivity and specificity of ~90%. Importantly, the predictive values of all biomarker tests vary according to the pre-test probability of amyloid pathology and must be interpreted in the complete clinical context. Use of BBM tests that meet these performance standards could enable more people to receive an accurate and timely Alzheimer disease diagnosis and potentially benefit from new treatments.

Stereodynamical control of cold HD + D2 collisions.

We report full-dimensional quantum calculations of stereodynamic control of HD(v = 1, j = 2) + D2 collisions that has been probed experimentally by Perreault et al. using the Stark-induced adiabatic Raman passage (SARP) technique. Computations were performed on two highly accurate full-dimensional H4 potential energy surfaces. It is found that for both potential surfaces, rotational quenching of HD from with concurrent rotational excitation of D2 from is the dominant transition with cross sections four times larger than that of elastically scattered D2 for the same quenching transition in HD. This process was not considered in the original analysis of the SARP experiments that probed ΔjHD = -2 transitions in HD(vHD = 1, jHD = 2) + D2 collisions. Cross sections are characterized by an l = 3 resonance for ortho-D2(jD2 = 0) collisions, while both l = 1 and l = 3 resonances are observed for the para-D2(jD2 = 1) partner. While our results are in excellent agreement with prior measurements of elastic and inelastic differential cross sections, the agreement is less satisfactory with the SARP experiments, in particular for the transition for which the theoretical calculations indicate that D2 rotational excitation channel is the dominant inelastic process.

Status Epilepticus Identification and Treatment Among Emergency Medical Services Agencies.

This cross-sectional study examines the association between unidentified status epilepticus and prehospital benzodiazepine treatment.

Differential responses to cigarette package labeling alternatives among adults who smoke: Results from a randomized trial.

INTRODUCTION: Little experimental research has evaluated whether the effects of cigarette package inserts with efficacy messages and/or pictorial health warning labels (PHWLs) differ across key subgroups of adults who smoke. METHODS: Adults who reported currently smoking (n=367) were randomly assigned to one of four groups: small text-only health warning labels (HWLs) on pack sides (control); inserts with efficacy messages and small HWLs (inserts-only); PHWLs showing harms of smoking (PHWLs-only); both (inserts+PHWLs). Participants received a 14-day supply of cigarettes labeled to reflect their group. Every evening over two weeks, participants reported forgoing and stubbing out cigarettes before they finished smoking over the prior 24 hours, combined into a binary indicator of either behavior (e.g., forgoing/stubbing). Separate mixed-effects logistic models were estimated to evaluate moderation of labeling group contrasts (i.e., PHWLs vs not; inserts vs. not; inserts-only vs. inserts+PHWLs; PHWLs-only vs. inserts+PHWLs) by baseline covariates (self-efficacy to quit, intention to quit, education, health literacy, time discounting), predicting day-level forgoing/stubbing. RESULTS: Education moderated PHWL effects, with PHWLs predicting more forgoing/stubbing only among those with low education (OR=4.68, p<0.001). Time discounting moderated insert effects, with inserts promoting fogoing/stubbing only among those with low time discounting (i.e., lower impulsivity; OR=4.35, p<0.001). CONCLUSIONS: Inserts with efficacy messages appear effective mostly among people with low time discounting, whereas PHWLs appear most effective amongst those with low education, suggesting their potential to address education-related disparities. Labeling strategies appeared equally effective across subgroups defined by self-efficacy to quit, quit intention, and health literacy. Combining inserts with PHWLs did not appear to mitigate moderation effects. IMPLICATIONS: This randomized trial with adults who smoke suggests that cigarette packs with inserts describing cessation benefits and tips can promote cessation-related behaviors (i.e., forgoing or stubbing out cigarettes) among those with low time discounting (i.e., low impulsivity). Alternative interventions may be needed for people with high time discounting, as found in cessation trials. Pictorial health warning labels (PHWLs) appear most effective among those with low education, potentially addressing education-related disparities. No differential effects were found for those with different levels of self-efficacy to quit, quit intentions, or health literacy. Combining inserts and PHWLs may not be more effective than either alone.

The Prevalence of Hip Dysplasia on Radiographs for Adolescent Idiopathic Scoliosis.

BACKGROUND: During radiographic assessment of adolescent idiopathic scoliosis (AIS), upright images frequently capture the hip. The purpose of this study was to assess the prevalence of radiographic hip dysplasia on postero-anterior (PA) scoliosis radiographs, as defined as a lateral center edge angle (LCEA) ≤25 degrees. METHODS: All patients with upright PA scoliosis radiographs over a one-year study period at a single tertiary academic medical center (2020 to 2021) were included in the study. Radiographs containing the hip joints were annotated by 3 reviewers for left and right LCEA, and triradiate cartilage (TRC) status. Inter-rater reliability was determined among the 3 reviewers. RESULTS: Two hundred fifty patients {500 hips, 75.6% female, median age 14 [interquartile range (IQR)=3]} had PA scoliosis radiographs that captured the hip, which qualified for analysis. Seventy-four hips (14.8%) demonstrated evidence of dysplasia (LCEA ≤25 deg) in 55/250 patients (22%). The median LCEA was significantly lower in the dysplastic hip cohort (23.9 deg, IQR=4.8 deg), compared with those without dysplasia (33 deg IQR=7.3 deg; P=0.001). A higher percentage of dysplastic hip patients were female than male (72.7% vs. 27.3%). Patients with bilateral dysplasia had a similar LCEA ( 22.9 deg) [to those with unilateral dysplasia (22.9 deg left, 23.9 deg right, P=0.689)]. CONCLUSIONS: In a cohort of 250 AIS patients, 22% demonstrated evidence of hip dysplasia, as defined as an LCEA ≤2 degrees. The dysplastic patients were more likely to be female. Screening for hip symptomatology in AIS patients may be of benefit, considering the frequency of radiographic hip dysplasia in this population. LEVEL OF EVIDENCE: III. Type of Evidence: diagnostic.

"The ban is there, but it is not there": perceptions of cigarette users and tobacco vendors regarding ban on the sale of loose cigarettes in India.

Introduction: Banning the sales of loose cigarettes is recommended by Article 16 of the World Health Organization - Framework Convention on Tobacco Control. This study aims to understand the perceptions of cigarette users and tobacco vendors regarding such a ban. Methods: Using a systematic recruitment and interview protocol, we interviewed cigarette users (n = 28) and tobacco vendors (n = 28) from two Indian cities where sales of loose cigarettes were banned (Mumbai) or not banned (Delhi). Separate semi-structured interview guides were used for users and vendors. Interview questions focused on reasons for purchasing loose cigarettes, preference for buying and selling loose vs. packs, thoughts on the necessity of banning loose cigarettes, and the perceived impact of the policy ban for vendors and cigarette users. We performed thematic analysis and used NVivo for organizing transcript coding. Results: The main reasons users cited for purchasing loose cigarettes were financial constraints, social restrictions (fear of getting caught), and limiting cigarette consumption. In Mumbai, awareness of the existing ban was poor among both users and vendors. Those who were aware did not think the policy had been implemented. Users thought that loose cigarettes promoted smoking initiation and prevented them from quitting. Both users and vendors reported that a ban on loose cigarettes would reduce cigarette consumption and promote quit attempts as it would not be possible for everyone to purchase packs because of financial and social reasons. Conclusion: Users in both cities reported easy access to and widespread availability of loose cigarettes. Low awareness of the ban in Mumbai suggested inadequate enforcement. A country-wide ban on the sale of loose cigarettes could be highly effective in preventing smoking initiation and promoting quitting.