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Karrie M Butler,1 Joyce S Ramos,2 Christina A Buchanan,1 Lance C Dalleck1,2 1Department of Recreation, Exercise, and Sport Science, Western State Colorado University, Gunnison, CO, USA; 2SHAPE Research Centre, Exercise Science and Clinical Exercise Physiology, College of Nursing and Health Sciences, Flinders University, Adelaide, SA, Australia Purpose: The high prevalence of metabolic syndrome (MetS), prediabetes, and increased risk of cardiovascular diseases linked with prolonged sitting has created a need to identify options to limit sedentary behaviors. A potentially simple approach to achieve this goal in the university setting is to provide students the option to stand during courses rather than sit. The purpose of the present study was to examine the effects of standing in the college classroom setting on cardiometabolic risk factors in a cohort of college students.Patients and methods: Healthy college students (n=21) who attended at least two courses per week (a minimum of 5 hours) in a specified university building with standing desks participated in a 7-week intervention that was divided into three phases: 3 weeks of standing, 1 week of washout (sitting), and 3 weeks of sitting. The participants (mean ± SD: age, height, weight, body mass index, and waist-to-hip ratio were 22.7±6.4 years, 174.3±10.0 cm, 70.6±14.3 kg, 23.0±3.0 kg/m2, and 0.76±0.05, respectively) were randomly assigned to the phase of intervention of which they should start (sitting or standing), and all participants engaged in sitting during the washout phase. Cardiometabolic risk factors and metabolic equivalents (METs) were measured at baseline and weekly throughout the intervention.Results: Paired t-tests revealed significant differences (P

An implementation intention is a planning technique that involves specifying a situation for initiating an intended action and linking these specific cues to the intention. In two experiments with young adults, we found significant increases in prospective memory with implementation intentions. With an implementation intention, but not with standard instructions, prospective memory performance was maintained under demanding attentional conditions (Experiment 2). Ongoing task performance did not decline, however, in relation with a no prospective memory control. Positive effects were not observed when the imagery component of the implementation intention was isolated from the verbal component. We suggest that implementation intention planning (relative to standard instructions) increases the likelihood that people will encode a robust associative link between the target cue and the intended action, thereby promoting reflexive triggering of the intended action on presentation of the target cue. [ABSTRACT FROM AUTHOR]

This article describes an innovative, evidence-based approach to community healthcare: the creation of toolkits to address health problems. The exemplar used is the development of an evidence-based meningococcal disease prevention toolkit, with action plans for dissemination, implementation, and evaluation, to be used by healthcare providers in developing comprehensive programs on college campuses. Qualitative research methods were used to develop the content. Formative and summative evaluations were conducted. Anticipated outcomes of such toolkits when implemented as designed are provision of evidence-based healthcare, improved health status of individuals, populations, and communities, fewer hospitalizations, and reduction of healthcare costs. [ABSTRACT FROM AUTHOR]

After stroke, persistent gait deficits cause debilitating falls and poor functional mobility. Gait restoration can preclude these outcomes. Sixteen subjects (>12 months poststroke) were randomized to two gait training groups. Group 1 received 12 weeks of treatment, 4 times a week, 90 min per session, including 30 min strengthening and coordination, 30 min over-ground gait training, and 30 min weight-supported treadmill training. Group 2 received the same treatment, but also used functional neuromuscular stimulation (FNS) with intramuscular (IM) electrodes (FNS-IM) for each aspect of treatment. Outcome measures were kinematics of gait swing phase. Both groups showed no significant pre-/posttreatment gains in peak swing hip flexion. Group 1 (no FNS) had no significant gains in other gait components at posttreatment or at follow-up. Group 2 (FNS-IM) had significant gains in peak swing knee flexion and mid-swing ankle dorsiflexion (p < 0.05) that were maintained for 6 months. [ABSTRACT FROM AUTHOR]

Inhibitory control of prepotent responses has been examined by using the antisaccade task, during which a reflexive saccade toward a peripheral onset must be suppressed before an eye movement in the opposite direction from the onset can be executed. In the present experiments, we sought to determine whether older and younger adults would perform similarly on this task. Older adults had a harder time suppressing their reflexive responses, as measured by an increase in the proportion of saccade direction errors. Despite an age-related decline in saccade direction accuracy, the increase in saccade latency associated with the antisaccade condition was the same for both younger and older adults. These results support the view that the effectiveness of inhibitory control declines with age (Hasher & Zacks, 1988; Hasher, Zacks, & May, 1999). [ABSTRACT FROM AUTHOR]

Background: Heterozygous variants in Transient receptor potential melastatin type 7 ( TRPM7 ), encoding an essential and ubiquitously expressed cation channel, may cause hypomagnesemia, but current evidence is insufficient to draw definite conclusions and it is unclear whether any other phenotypes can occur., Methods: Individuals with unexplained hypomagnesemia underwent whole-exome sequencing which identified TRPM7 variants. Pathogenicity of the identified variants was assessed by combining phenotypic, functional and in silico analyses., Results: We report three new heterozygous missense variants in TRPM7 (p.Met1000Thr, p.Gly1046Arg, p.Leu1081Arg) in individuals with hypomagnesemia. Strikingly, autism spectrum disorder and developmental delay, mainly affecting speech and motor skills, was observed in all three individuals, while two out of three also presented with seizures. The three variants are predicted to be severely damaging by in silico prediction tools and structural modeling. Furthermore, these variants result in a clear loss-of-function of TRPM7-mediated magnesium uptake in vitro , while not affecting TRPM7 expression or insertion into the plasma membrane., Conclusions: This study provides additional evidence for the association between heterozygous TRPM7 variants and hypomagnesemia and adds developmental delay to the phenotypic spectrum of TRPM7 -related disorders. Considering that the TRPM7 gene is relatively tolerant to loss-of-function variants, future research should aim to unravel by what mechanisms specific heterozygous TRPM7 variants can cause disease., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: We previously described the KINSSHIP syndrome, an autosomal dominant disorder associated with intellectual disability (ID), mesomelic dysplasia and horseshoe kidney, caused by de novo variants in the degron of AFF3. Mouse knock-ins and overexpression in zebrafish provided evidence for a dominant-negative mode of action, wherein an increased level of AFF3 resulted in pathological effects., Methods: Evolutionary constraints suggest that other modes-of-inheritance could be at play. We challenged this hypothesis by screening ID cohorts for individuals with predicted-to-be damaging variants in AFF3. We used both animal and cellular models to assess the deleteriousness of the identified variants., Results: We identified an individual with a KINSSHIP-like phenotype carrying a de novo partial duplication of AFF3 further strengthening the hypothesis that an increased level of AFF3 is pathological. We also detected seventeen individuals displaying a milder syndrome with either heterozygous Loss-of-Function (LoF) or biallelic missense variants in AFF3. Consistent with semi-dominance, we discovered three patients with homozygous LoF and one compound heterozygote for a LoF and a missense variant, who presented more severe phenotypes than their heterozygous parents. Matching zebrafish knockdowns exhibit neurological defects that could be rescued by expressing human AFF3 mRNA, confirming their association with the ablation of aff3. Conversely, some of the human AFF3 mRNAs carrying missense variants identified in affected individuals did not rescue these phenotypes. Overexpression of mutated AFF3 mRNAs in zebrafish embryos produced a significant increase of abnormal larvae compared to wild-type overexpression further demonstrating deleteriousness. To further assess the effect of AFF3 variation, we profiled the transcriptome of fibroblasts from affected individuals and engineered isogenic cells harboring + / + , KINSSHIP/KINSSHIP, LoF/ + , LoF/LoF or KINSSHIP/LoF AFF3 genotypes. The expression of more than a third of the AFF3 bound loci is modified in either the KINSSHIP/KINSSHIP or the LoF/LoF lines. While the same pathways are affected, only about one third of the differentially expressed genes are common to the homozygote datasets, indicating that AFF3 LoF and KINSSHIP variants largely modulate transcriptomes differently, e.g. the DNA repair pathway displayed opposite modulation., Conclusions: Our results and the high pleiotropy shown by variation at this locus suggest that minute changes in AFF3 function are deleterious., (© 2024. The Author(s).)

Group B Streptococcus (GBS) vaccines, designed to be given to pregnant women, are in clinical trials. There is an opportunity to conduct preparatory research now to understand the drivers of and barriers to GBS vaccine acceptance. This will enable targeted interventions so that delays in vaccine uptake might be avoided. A multicenter, mixed-methodology, cross-sectional study evaluated the acceptability of a hypothetical GBS vaccine among pregnant women in two countries with differing health systems. Pregnant women in Philadelphia, US, and Dublin, Ireland, completed an electronic survey and a Discrete Choice Experiment. Five hundred and two women were included in the final analysis. Fifty-three percent of US and 30% of Irish participants reported both awareness and understanding of GBS. The median likelihood score for vaccine receipt (measured on a 10-point scale) was 9 (US: 9 (IQR 7-10), IRL: 9 (IQR 6-10)). Among the US participants, identifying as Black or African American was associated with a lower likelihood of vaccine receipt. Possession of a college degree was associated with increased likelihood of vaccine receipt. Perceived infant benefit was the most important driver of GBS vaccine acceptance. Safety concerns about a novel vaccine was the most prominent barrier identified. Good GBS vaccine uptake is achievable through strong messaging that highlights vaccine safety and the potential infant benefits. Preparation for vaccine implementation should include efforts to increase awareness among pregnant women about GBS infection and a continued focus on improving acceptability of currently recommended maternal vaccines, particularly in population subgroups with low uptake of maternal immunizations.

Importance: Older patients using many prescription drugs (hyperpolypharmacy) may be at increased risk of adverse drug effects., Objective: To test the effectiveness and safety of a quality intervention intended to reduce hyperpolypharmacy., Design, Setting, and Participants: This randomized clinical trial allocated patients 76 years or older who used 10 or more prescription medications to a deprescribing intervention or to usual care (1:1 ratio) at an integrated health system with multiple preexisting deprescribing workflows. Data were collected from October 15, 2020, to July 29, 2022., Intervention: Physician-pharmacist collaborative drug therapy management, standard-of-care practice recommendations, shared decision-making, and deprescribing protocols administered by telephone over multiple cycles for a maximum of 180 days after allocation., Main Outcomes and Measures: Primary end points were change in the number of medications and in the prevalence of geriatric syndrome (falls, cognition, urinary incontinence, and pain) from 181 to 365 days after allocation compared with before randomization. Secondary outcomes were use of medical services and adverse drug withdrawal effects., Results: Of a random sample of 2860 patients selected for potential enrollment, 2470 (86.4%) remained eligible after physician authorization, with 1237 randomized to the intervention and 1233 to usual care. A total of 1062 intervention patients (85.9%) were reached and agreed to enroll. Demographic variables were balanced. The median age of the 2470 patients was 80 (range, 76-104) years, and 1273 (51.5%) were women. In terms of race and ethnicity, 185 patients (7.5%) were African American, 234 (9.5%) were Asian or Pacific Islander, 220 (8.9%) were Hispanic, 1574 (63.7%) were White (63.7%), and 257 (10.4%) were of other (including American Indian or Alaska Native, Native Hawaiian, or >1 race or ethnicity) or unknown race or ethnicity. During follow-up, both the intervention and usual care groups had slight reductions in the number of medications dispensed (mean changes, -0.4 [95% CI, -0.6 to -0.2] and -0.4 [95% CI, -0.6 to -0.3], respectively), with no difference between the groups (P = .71). There were no significant changes in the prevalence of a geriatric condition in the usual care and intervention groups at the end of follow-up and no difference between the groups (baseline prevalence: 47.7% [95% CI, 44.9%-50.5%] vs 42.9% [95% CI, 40.1%-45.7%], respectively; difference-in-differences, 1.0 [95% CI, -3.5 to 5.6]; P = .65). No differences in use of medical services or adverse drug withdrawal effects were observed., Conclusions and Relevance: In this randomized clinical trial from an integrated care setting with various preexisting deprescribing workflows, a bundled hyperpolypharmacy deprescribing intervention was not associated with reduction in medication dispensing, prevalence of geriatric syndrome, utilization of medical services, or adverse drug withdrawal effects. Additional research is needed in less integrated settings and in more targeted populations., Trial Registration: ClinicalTrials.gov Identifier: NCT05616689.

This investigation examined whether the mode of locomotion matters in how 8-, 10-, 12-, and 14-year-old children ( N = 91) judge dynamic affordances in a complex perception-action task with significant safety risks. The primarily European American children in the sample came from the area of Iowa City, Iowa and were balanced for gender. The same children crossed a single lane of continuous traffic on foot and on bike (order counterbalanced) in identical immersive virtual environments. We found that although 8-year-olds chose significantly larger gaps when crossing on bike than on foot, these gaps were not large enough to compensate for their delay in entering the gap and their slowness in crossing the road. As a result, they ended up with less time to spare when exiting the roadway on bike than on foot. In contrast, 14-year-olds exhibited no difference in their gap choices on bike than on foot, nor did they exhibit a difference in their timing of entry into the gap. However, they crossed the road much more quickly on bike, resulting in significantly more time to spare when crossing on bike than on foot. The 10- and 12-year-olds' performance fit neatly between that of the 8- and 14-year-olds. We conclude that as children gained better control over the bike with age, they were better able to match their gap decisions with their crossing movements such that bicycling afforded even safer road-crossing than walking for 14-year-olds. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The vacuolar H+-ATPase is an enzymatic complex that functions in an ATP-dependent manner to pump protons across membranes and acidify organelles, thereby creating the proton/pH gradient required for membrane trafficking by several different types of transporters. We describe heterozygous point variants in ATP6V0C, encoding the c-subunit in the membrane bound integral domain of the vacuolar H+-ATPase, in 27 patients with neurodevelopmental abnormalities with or without epilepsy. Corpus callosum hypoplasia and cardiac abnormalities were also present in some patients. In silico modelling suggested that the patient variants interfere with the interactions between the ATP6V0C and ATP6V0A subunits during ATP hydrolysis. Consistent with decreased vacuolar H+-ATPase activity, functional analyses conducted in Saccharomyces cerevisiae revealed reduced LysoSensor fluorescence and reduced growth in media containing varying concentrations of CaCl2. Knockdown of ATP6V0C in Drosophila resulted in increased duration of seizure-like behaviour, and the expression of selected patient variants in Caenorhabditis elegans led to reduced growth, motor dysfunction and reduced lifespan. In summary, this study establishes ATP6V0C as an important disease gene, describes the clinical features of the associated neurodevelopmental disorder and provides insight into disease mechanisms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aims of this study were to explore the health of nurse leaders and assess intentions to integrate workplace mental health/wellness practices., Background: National efforts address high rates of poor mental health and lifestyle behaviors among nurses. Few studies describe the extent to which nurse leaders in academic and clinical environments can influence a strategic mission for health/well-being among the nursing workforce., Methods: Two hundred seventeen email invitations were distributed to nurse leaders from 5 Kentucky nursing organizations to complete a 1-time 46-item online survey assessing individual health behaviors and intentions to build a culture of workplace health/well-being., Results: Most respondents reported positive physical health (86%), positive mental health/intentions for action to change behaviors (80%), improved self-care practices (86%), integration of self-care practices in the workplace (79%), and commitment to integrate suicide prevention training (55%)., Conclusions: Overall, nurse leaders reported positive healthy behaviors. The finding that the highest intentions were reported to integrate, sustain, and/or advance lifestyle behaviors for self-care practices as well as to integrate practices for mental health and well-being in the work environment is encouraging. Enhanced strategies and efforts are needed to prioritize workplace cultures of wellness to benefit nurses and further promote well-being among nurse leaders., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: There are vaccines in clinical trials that target the bacterium Group B Streptococcus (GBS). When approved, GBS vaccines will be intended for administration to pregnant women to prevent infection in their infants. The success of any vaccine will depend on its' uptake in the population. Experience with prior maternal vaccines, e.g. influenza, Tdap and COVID-19 vaccines, teaches us that acceptance of vaccines, especially if novel, is challenging for pregnant women, and that provider recommendation is a key driver of vaccine uptake., Methods: This study investigated attitudes of maternity care providers towards the introduction of a GBS vaccine in three countries (the United States (US), Ireland, and the Dominican Republic (DR)) with different GBS prevalence and prevention practices. Semi-structured interviews with maternity care providers were transcribed and coded for themes. The constant comparative method, and inductive theory building were used to develop conclusions., Results: Thirty-eight obstetricians, 18 general practitioners and 14 midwives participated. There was variability in provider attitudes towards a hypothetical GBS vaccine. Responses ranged from enthusiasm to doubts over the need for a vaccine. Attitudes were influenced by perceived additional benefits of a vaccine over current strategy and confidence in the safety of vaccines during pregnancy. Knowledge, experience and approaches to GBS prevention differed geographically and according to provider type, and influenced how participants assessed the risks and benefits of a GBS vaccine., Conclusion: Maternity care providers are engaged in the topic of GBS management and there is opportunity to leverage attitudes and beliefs that will support a strong recommendation for a GBS vaccine. However, knowledge of GBS, and of the limitations of current prevention strategies vary among providers in different regions, and between different provider types. Targeted educational efforts with antenatal providers should focus on highlighting safety data the potential benefits of vaccination over current strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Witteveen-Kolk syndrome (WITKOS) is a rare, autosomal dominant neurodevelopmental disorder caused by heterozygous loss-of-function alterations in the SIN3A gene. WITKOS has variable expressivity that commonly overlaps with other neurodevelopmental disorders. In this study, we characterized a distinct DNA methylation epigenetic signature (episignature) distinguishing WITKOS from unaffected individuals as well as individuals with other neurodevelopmental disorders with episignatures and described 9 previously unpublished individuals with SIN3A haploinsufficiency., Methods: We studied the phenotypic characteristics and the genome-wide DNA methylation in the peripheral blood samples of 20 individuals with heterozygous alterations in SIN3A. A total of 14 samples were used for the identification of the episignature and building of a predictive diagnostic biomarker, whereas the diagnostic model was used to investigate the methylation pattern of the remaining 6 samples., Results: A predominantly hypomethylated DNA methylation profile specific to WITKOS was identified, and the classifier model was able to diagnose a previously unresolved test case. The episignature was sensitive enough to detect individuals with varying degrees of phenotypic severity carrying SIN3A haploinsufficient variants., Conclusion: We identified a novel, robust episignature in WITKOS due to SIN3A haploinsufficiency. This episignature has the potential to aid identification and diagnosis of individuals with WITKOS., Competing Interests: Conflict of Interest The authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Introduction: Vaccines are being developed against Group B Streptococcus and respiratory syncytial virus. These vaccines are designed to be given to pregnant women to protect infants; thus, their success depends on uptake in this population. Maternal immunization programs have struggled to achieve target coverage rates. This systematic narrative synthesis aims to define the most important barriers and facilitators for maternal immunization and to identify priority areas for future research., Methods: A search strategy was developed in Medline and adapted according to the requirements of additional search engines. Two reviewers independently reviewed the studies, using pre-specified inclusion and exclusion criteria. Results sections of included studies were coded, and thematic analysis was used to identify prominent themes., Results: 321 studies were included in the final review. Most studies came from North America (37%), Europe (26%) or East Asia, Australia and New Zealand (22%). Low-and middle-income countries were under-represented. Five percent of studies came from Sub-Saharan Africa, and 2% came from South Asia. The prominent factors impacting maternal immunization were provider recommendation, perceived risks and benefits of maternal vaccines for the infant, race, birthplace, and access to healthcare. Few studies explored reasons behind racial and socioeconomic disparities in maternal immunization rates., Discussion: A strong provider recommendation, equitable access to prenatal care and messaging that focuses on vaccine safety and infant benefits emerged as the key components for optimising vaccine uptake among pregnant women. Research among healthcare providers, minority groups and in low- and-middle-income countries was lacking. In anticipation of the expansion of maternal immunization programmes, focused research is needed to address these gaps and inform a successful public health strategy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: The purpose of Cultivating Practices for Resilience (CPR) was to develop, implement, and evaluate college-wide strategic initiatives to promote wellness and resilience and improve mental health outcomes in baccalaureate nursing students., Design and Methods: Six hundred and fifty-four students were invited to complete a 24-item survey over 3 weeks in 2021. Descriptive statistics/logistic regression were used for data analysis., Findings: One hundred and thirty-one students completed the survey; 61% were sophomores. White students (p = 0.024) and males (p = 0.023) had higher intentions to refer colleagues to mental health services. Those perceiving CPR programming more helpful had higher intentions to refer (p < 0.001) and embrace the ANA's Healthy Nurse Healthy Nation™ campaign (p < 0.001)., Practice Implications: Stronger strategic efforts are needed to help shape an academic culture for cultivating practices for resilience among baccalaureate nursing students, especially females and underrepresented population groups., (© 2021 Wiley Periodicals LLC.)

Background: Rett syndrome (RTT) is a rare neurodevelopmental disorder associated with pathogenic MECP2 variants. Because the MECP2 gene is subject to X-chromosome inactivation (XCI), factors including MECP2 genotypic variation, tissue differences in XCI, and skewing of XCI all likely contribute to the clinical severity of individuals with RTT., Methods: We analyzed the XCI patterns from blood samples of 320 individuals and their mothers. It includes individuals with RTT (n = 287) and other syndromes sharing overlapping phenotypes with RTT (such as CDKL5 Deficiency Disorder [CDD, n = 16]). XCI status in each proband/mother duo and the parental origin of the preferentially inactivated X chromosome were analyzed., Results: The average XCI ratio in probands was slightly increased compared to their unaffected mothers (73% vs. 69%, p = .0006). Among the duos with informative XCI data, the majority of individuals with classic RTT had their paternal allele preferentially inactivated (n = 180/220, 82%). In sharp contrast, individuals with CDD had their maternal allele preferentially inactivated (n = 10/12, 83%). Our data indicate a weak positive correlation between XCI skewing ratio and clinical severity scale (CSS) scores in classic RTT patients with maternal allele preferentially inactivated XCI (r s  = 0.35, n = 40), but not in those with paternal allele preferentially inactivated XCI (r s  = -0.06, n = 180). The most frequent MECP2 pathogenic variants were enriched in individuals with highly/moderately skewed XCI patterns, suggesting an association with higher levels of XCI skewing., Conclusion: These results extend our understanding of the pathogenesis of RTT and other syndromes with overlapping clinical features by providing insight into the both XCI and the preferential XCI of parental alleles., (© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Purpose: Gabriele-de Vries syndrome (GADEVS) is a rare genetic disorder characterized by developmental delay and/or intellectual disability, hypotonia, feeding difficulties, and distinct facial features. To refine the phenotype and to better understand the molecular basis of the syndrome, we analyzed clinical data and performed genome-wide DNA methylation analysis of a series of individuals carrying a YY1 variant., Methods: Clinical data were collected for 13 individuals not yet reported through an international call for collaboration. DNA was collected for 11 of these individuals and 2 previously reported individuals in an attempt to delineate a specific DNA methylation signature in GADEVS., Results: Phenotype in most individuals overlapped with the previously described features. We described 1 individual with atypical phenotype, heterozygous for a missense variant in a domain usually not involved in individuals with YY1 pathogenic missense variations. We also described a specific peripheral blood DNA methylation profile associated with YY1 variants., Conclusion: We reported a distinct DNA methylation episignature in GADEVS. We expanded the clinical profile of GADEVS to include thin/sparse hair and cryptorchidism. We also highlighted the utility of DNA methylation episignature analysis for classification of variants of unknown clinical significance., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Numerous SCN8A mutations have been identified, of which, the majority are de novo missense variants. Most mutations result in epileptic encephalopathy; however, some are associated with less severe phenotypes. Mouse models generated by knock-in of human missense SCN8A mutations exhibit seizures and a range of behavioral abnormalities. To date, there are only a few Scn8a mouse models with in-frame deletions or insertions, and notably, none of these mouse lines exhibit increased seizure susceptibility. In the current study, we report the generation and characterization of two Scn8a mouse models (ΔIRL/+ and ΔVIR/+) carrying overlapping in-frame deletions within the voltage sensor of domain 4 (DIVS4). Both mouse lines show increased seizure susceptibility and infrequent spontaneous seizures. We also describe two unrelated patients with the same in-frame SCN8A deletion in the DIV S5-S6 pore region, highlighting the clinical relevance of this class of mutations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wong, Butler, Shapiro, Thelin, Mattison, Garber, Goldenberg, Kubendran, Schaefer and Escayg.)

Background: The massive transfusion protocol (MTP) is designed to quickly provide blood products at a fixed ratio for the exsanguinating patient. At our academic medical center, the frequency of MTP activation increased over 10-fold between 2008 and 2015, putting inordinate stress on our transfusion service., Study Design and Methods: Gathering a large number of relevant stakeholders, we performed a multidisciplinary root cause analysis (RCA) in response to the acute clinical need to reform our MTP., Results: Through the RCA, we identified four principal opportunities for improvement (OFI) associated with our MTP: education, stewardship, process improvement, and communication. Through the deployment of new approaches to each of these OFI, we reduced MTP activations, blood product waste, and transfusion service technologist stress., Conclusion: The MTP is amenable to improvement, and, although time intensive, the RCA process yields significant favorable effects: improving communication with colleagues, reducing stress within the transfusion service, and improving resource utilization. Activation of the MTP at our institution is now more aligned with its primary purpose: rapidly providing large quantities of blood products to exsanguinating patients., (© 2021 AABB.)

Report back is active sharing of research findings with participants to prompt behavior change. Research on theory-driven report back for environmental risk reduction is limited. The study aim is to evaluate the impact of a stage-tailored report back process with participants who had high home radon and/or air nicotine levels. An observational one-group pre-post design was used, with data collection at 3, 9, and 15 months post intervention. Participants from the parent study ( N = 515) were randomized to the treatment or control group and this sample included all 87 treatment participants who: (1) had elevated radon and/or air nicotine at baseline; and (2) received stage-tailored report back of their values. Short-term test kits measured radon; passive airborne nicotine samplers assessed secondhand smoke (SHS) exposure. Stage of action was categorized as: (1) ' Unaware ', (2) ' Unengaged ', (3) ' Deciding ', (4) ' Action ', and (5) ' Maintenance '. Interventions were provided for free, such as in-person radon and SHS test kits and a brief telephonic problem-solving consultation. Stage of action for radon mitigation and smoke-free policy increased from baseline to 3 months and remained stable between 3 and 9 months. Stage of action for radon was higher at 15 months than baseline. Among those with high baseline radon, observed radon decreased by 15 months ( p < 0.001). Tailored report back of contaminant values reduced radon exposure and changed the health behavior necessary to remediate radon and SHS exposure.

Public health experts agree that pregnant women who fall into priority groups may be offered a Coronavirus Disease 2019 (COVID-19) vaccine. However, little is known about attitudes of pregnant women toward COVID-19 vaccination. We surveyed 300 pregnant women during the roll out of the Pfizer-BioNTech vaccine in Ireland. Women rated likelihood of receipt of a vaccine during pregnancy, on a 1-10 scale (1 = very unlikely, 10 = very likely). One hundred and thirteen (38%) women responded with a score of ≥8, while a similar proportion (36%) selected a score of ≤2. Safety of their unborn infant was the primary driver of decision making among survey participants, but specific safety concerns differed according to likely acceptance of a vaccine. Communication about COVID-19 vaccines to pregnant women must explicitly address safety. Pregnant women and their health-care providers should be supported with accessible interpretations of data so that they can make the best choice for their individual risk profile.

Tenorio syndrome (TNORS) (OMIM #616260) is a relatively recent disorder with very few cases described so far. Clinical features included macrocephaly, intellectual disability, hypotonia, enlarged ventricles and autoimmune diseases. Molecular underlying mechanism demonstrated missense variants and a large deletion encompassing RNF125, a gene that encodes for an U3 ubiquitin ligase protein. Since the initial description of the disorder in six patients from four families, several new patients were diagnosed, adding more evidence to the clinical spectrum. In this article, we described 14 additional cases with deep phenotyping and make an overall review of all the cases with pathogenic variants in RNF125. Not all patients presented with overgrowth, but instead, most patients showed a common pattern of neurodevelopmental disease, macrocephaly and/or large forehead. Segregation analysis showed that, though the variant was inherited in some patients from an apparently asymptomatic parent, deep phenotyping suggested a mild form of the disease in some of them. The mechanism underlying the development of this disease is not well understood yet and the report of further cases will help to a better understanding and clinical characterization of the syndrome., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Objectives: Pathogenic missense variants in the potassium channel tetramerization domain-containing 1 (KCTD1) gene are associated with autosomal dominant Scalp-Ear-Nipple syndrome (SENS), a type of ectodermal dysplasia characterized by aplasia cutis congenita of the scalp, hairless posterior scalp nodules, absent or rudimentary nipples, breast aplasia and external ear anomalies. We report a child with clinical features of an ectodermal dysplasia, including sparse hair, dysmorphic facial features, absent nipples, 2-3 toe syndactyly, mild atopic dermatitis and small cupped ears with overfolded helices. We also review the published cases of SENS with molecularly confirmed KCTD1 variants., Methods and Results: Using whole-exome sequencing, we identified a novel, de novo in-frame insertion in the broad-complex, tramtrack and bric-a-brac (BTB) domain of the KCTD1 gene. By comparing to the previously reported patients, we found that our patient's clinical features and molecular variant are consistent with a diagnosis of SENS., Conclusions: This is only the 13th KCTD1 variant described and the first report of an in-frame insertion causing clinical features, expanding the mutational spectrum of KCTD1 and SENS., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Mutations in the voltage-gated sodium channel gene SCN8A cause a broad range of human diseases, including epilepsy, intellectual disability, and ataxia. Here we describe three mouse lines on the C57BL/6J background with novel, overlapping mutations in the Scn8a DIIS4 voltage sensor: an in-frame 9 bp deletion (Δ9), an in-frame 3 bp insertion (∇3) and a 35 bp deletion that results in a frameshift and the generation of a null allele (Δ35). Scn8a Δ9/+ and Scn8a ∇3/+ heterozygous mutants display subtle motor deficits, reduced acoustic startle response, and are resistant to induced seizures, suggesting that these mutations reduce activity of the Scn8a channel protein, Na v 1.6. Heterozygous Scn8a Δ35/+ mutants show no alterations in motor function or acoustic startle response, but are resistant to induced seizures. Homozygous mutants from each line exhibit premature lethality and severe motor impairments, ranging from uncoordinated gait with tremor (Δ9 and ∇3) to loss of hindlimb control (Δ35). Scn8a Δ9/Δ9 and Scn8a ∇3/∇3 homozygous mutants also exhibit impaired nerve conduction velocity, while normal nerve conduction was observed in Scn8a Δ35/Δ35 homozygous mice. Our results suggest that hypomorphic mutations that reduce Na v 1.6 activity will likely result in different clinical phenotypes compared to null alleles. These three mouse lines represent a valuable opportunity to examine the phenotypic impacts of hypomorphic and null Scn8a mutations without the confound of strain-specific differences., (© 2019 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Introduction: Tobacco smoke and radon are the leading causes of lung cancer. The FRESH intervention was a randomized controlled trial of 515 homeowners to promote stage of action to reduce radon and air nicotine levels., Methods: We studied 515 participants, 257 in a treatment group and 258 in a control group. Treatment participants received free radon and air nicotine test kits, report back, and telephone support, and those participants whose homes had high radon levels received a voucher for $600 toward mitigation. Both groups were asked to retest 15 months post intervention. We examined differences in stage of action to test for and mitigate radon and adopt a smoke-free-home policy and in observed radon and air nicotine values by study group over time., Results: Homeowners in the treatment group scored higher on stage of action to test for radon and air nicotine and to mitigate for radon during follow-up than those in the control group at 3 months and 9 months, but the effect of the intervention diminished after 9 months. We saw no difference between groups or over time in observed radon or air nicotine values. Of homeowners in the treatment group with high radon levels at baseline, 17% mitigated, and 80% of them used the voucher we provided., Conclusion: The null finding of no significant change in observed radon or air nicotine values from baseline to 15 months may reflect the low proportion of radon mitigation systems installed and the decline in stage of action to adopt a smoke-free home policy. Including a booster session at 9 months post intervention may improve the remediation rate.

Aim The aim of this study was to evaluate trends in admissions for patients with primary varicella infection in Irish hospitals. Methods The Hospital Inpatient Enquiry System was evaluated from Irish hospitals from 2005-2016 for patients with primary varicella infection. Results There were 2717 admissions with primary varicella infection. The average annual number of admissions was 226 for an incidence of 4.87/100,000. Average length of stay (ALOS) was 5-days. Sixty-two (2.5%) patients required intensive-care with an ALOS of 26-days. The most common secondary diagnoses were cellulitis, volume-depletion and streptococcal infection. The number of admissions due to streptococcal infection and cellulitis significantly increased over the period. Conclusion Chickenpox places a consistent burden on Irish healthcare, accounting for in excess of 1100 acute and 160 intensivecare bed days annually. This study adds weight to the argument that universal varicella vaccine should be considered and provides baseline epidemiology to determine vaccine effectiveness in the future., Competing Interests: The authors have no conflicts of interest to declare.

Purpose: To examine the short-term impact of a personalized environmental report-back intervention to reduce home exposure to tobacco smoke and radon on perception of synergistic risk for lung cancer. Radon-induced lung cancer is more common among those exposed to tobacco smoke., Design: Randomized controlled trial., Setting: Primary care clinics and a pharmacy waiting area at a University Medical Center in the Southeastern United States and community events., Participants: Five hundred sixty adult homeowners and renters (3-month follow-up, n = 334)., Intervention: Personalized environmental report back., Measures: Single-item synergistic risk perception measure using 5-point Likert-type scale., Analysis: Change in synergistic risk from baseline to 3 months was evaluated using a generalized estimating equation model containing main effects of treatment group and time. Covariates in the model included age, gender, education, and home smoking status., Results: For treatment and control groups combined, there was a significant increase in perception of synergistic risk from baseline to 3 months, but the study groups did not differ. There was no association between perceived synergistic risk and whether or not there were smokers at home., Conclusion: Learning about combined risks for lung cancer, with or without dual home screening for secondhand smoke and radon and environmental report-back, may enhance perceived risk for combined environmental exposures. Evaluation of perceived synergistic risk with a single item is a study limitation.

Background: More radon-related lung cancers occur among those exposed to tobacco smoke., Objectives: To test the effects of a personalized environmental report back intervention on change in stage of action for air nicotine testing and adopting a smoke-free home and radon testing and mitigation from baseline to 3 months postintervention., Methods: The study design used a two-arm parallel groups randomized controlled trial with stratified quota sampling. The treatment group received free air nicotine and radon home test kits and a brief problem-solving phone intervention; the control group received a coupon for free test kits. A sample of 515 homeowners were enrolled; 319 completed the 3-month follow-up. Stage of action to test and remediate the home was measured consistent with the precaution adoption process model. Linear mixed modeling assessed whether the main and interaction effects of treatment and time were associated with the testing and remediation outcomes; multiple covariates were included in the models., Results: The models for the four stages of action outcomes (testing and remediating for radon and secondhand smoke) each had a significant treatment-by-time effect. The general pattern was an increase in stage of action from baseline to 3 months. The degree of change was generally larger among the treatment group participants relative to the controls, indicating that those in the treatment group were more ready to take action. For all the models, participants with higher self-efficacy for radon/air nicotine testing and radon/secondhand smoke remediation were more ready to take action to test and remediate. Synergistic risk perception was associated with stage of action for radon mitigation., Conclusions: Homeowners who were provided free radon and air nicotine test kits, given their results, and engaged in a brief telephonic problem-solving consultation tended to show a greater increase in readiness to take action to test and remediate by 3 months compared with those who received standard public health practice. Both groups showed an increase in stage of action for all four outcomes over time.

Previous reports have identified SLC6A1 variants in patients with generalized epilepsies, such as myoclonic-atonic epilepsy and childhood absence epilepsy. However, to date, none of the identified SLC6A1 variants has been functionally tested for an effect on GAT-1 transporter activity. The purpose of this study was to determine the incidence of SLC6A1 variants in 460 unselected epilepsy patients and to evaluate the impact of the identified variants on γ-aminobutyric acid (GABA)transport. Targeted resequencing was used to screen 460 unselected epilepsy patients for variants in SLC6A1. Five missense variants, one in-frame deletion, one nonsense variant, and one intronic splice-site variant were identified, representing a 1.7% diagnostic yield. Using a [ 3 H]-GABA transport assay, the seven identified exonic variants were found to reduce GABA transport activity. A minigene splicing assay revealed that the splice-site variant disrupted canonical splicing of exon 9 in the mRNA transcript, leading to premature protein truncation. These findings demonstrate that SLC6A1 is an important contributor to childhood epilepsy and that reduced GAT-1 function is a common consequence of epilepsy-causing SLC6A1 variants., (Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.)

GABAA receptors are ligand-gated anion channels that are important regulators of neuronal inhibition. Mutations in several genes encoding receptor subunits have been identified in patients with various types of epilepsy, ranging from mild febrile seizures to severe epileptic encephalopathy. Using whole-genome sequencing, we identified a novel de novo missense variant in GABRA5 (c.880G > C, p.V294L) in a patient with severe early-onset epilepsy and developmental delay. Targeted resequencing of 279 additional epilepsy patients identified 19 rare variants from nine GABAA receptor genes, including a novel de novo missense variant in GABRA2 (c.875C > A, p.T292K) and a recurrent missense variant in GABRB3 (c.902C > T, p.P301L). Patients with the GABRA2 and GABRB3 variants also presented with severe epilepsy and developmental delay. We evaluated the effects of the GABRA5, GABRA2 and GABRB3 missense variants on receptor function using whole-cell patch-clamp recordings from human embryonic kidney 293T cells expressing appropriate α, β and γ subunits. The GABRA5 p.V294L variant produced receptors that were 10-times more sensitive to GABA but had reduced maximal GABA-evoked current due to increased receptor desensitization. The GABRA2 p.T292K variant reduced channel expression and produced mutant channels that were tonically open, even in the absence of GABA. Receptors containing the GABRB3 p.P301L variant were less sensitive to GABA and produced less GABA-evoked current. These results provide the first functional evidence that de novo variants in the GABRA5 and GABRA2 genes contribute to early-onset epilepsy and developmental delay, and demonstrate that epilepsy can result from reduced neuronal inhibition via a wide range of alterations in GABAA receptor function.

Little is known about polytobacco use in college students. One nationally representative survey indicated 51.3% of tobacco-using college students used more than one product, which may increase risk of tobacco-related disease and premature death. The purpose of this study was to examine the association of intention to quit smoking (ITQS) cigarettes with polytobacco use status, controlling for frequency of tobacco product use and cigarette smoking intensity as measured by cigarettes per day (CPD). Data are from a larger quasi-experimental study conducted at a large state university in the Southeastern United States. Analysis is based on the combined sample of current smokers from two randomly selected cohorts surveyed two months apart. Polytobacco users ( n  = 52) were as likely as cigarette-only users ( n  = 81) to intend to quit smoking. Compared to students who used tobacco products 1-9 days per month, students using 10-29 days per month or daily reported higher ITQS. Higher intensity smokers (>10 CPD) were 71% less likely to indicate ITQS, compared to lower intensity smokers (≤10 CPD) ( p  = .025). College student polytobacco users were as likely as those using only cigarettes to intend to quit smoking. Interventions are needed to target college student polytobacco users as well as cigarette smokers as both groups may intend to quit. Smokers using 10 or fewer CPD and those who use tobacco products daily or 10-29 days per month may be more motivated to quit than college students who smoke with more intensity but who use tobacco products less frequently.

Diagnosis of Kawasaki Disease (KD) can be challenging due to lack of a diagnostic test, and some children present with 'incomplete' KD when not all diagnostic criteria are met. Treatment with intravenous immunoglobulin (IVIG) and aspirin reduces the risk of coronary artery complications. There is sub-group of patients who are resistant to IVIG/aspirin therapy and are at increased risk of complications. Recent evidence suggests that additional treatment of this high-risk group with corticosteroids is beneficial in reducing this risk. We examine the treatment and coronary artery outcomes, by retrospective review of medical records, of a cohort of 32 paediatric patients with KD admitted to a single Irish tertiary centre from January 2010-December 2014. Twenty-eight percent of patients (9/32) had an incomplete diagnosis of KD; these patients received IVIG later compared to those with a complete KD diagnosis. 15/32 (47%) had abnormal echocardiogram findings in the acute phase, 8/32 (25%) had echocardiogram abnormalities at 6-week follow-up, and 4/32 (12.5%) had persisting abnormalities. This study highlights the potential for adverse outcome in KD, the difficulty in diagnosis in 'incomplete' cases, and the need to identify children at higher risk for adverse outcome where adjunctive therapies would be most beneficial.

Passive enhanced safety surveillance (ESS) was implemented in the United Kingdom and in the Republic of Ireland for Vaxigrip and Intanza 15 µg influenza vaccines during the 2016/17 influenza season. Lessons learned during 2015/16 ESS implementation were integrated and applied towards the current ESS. The primary objective was to estimate the reporting rates of suspected adverse reactions (ARs) occurring within 7 days of vaccination with Vaxigrip or Intanza 15 µg. For Vaxigrip (N = 962), 17 vaccinees (1.8%) reported 59 suspected ARs (6.1%) within 7 days of vaccination. For Intanza 15 µg (N = 1000), 21 vaccinees (2.1%) reported 101 (10.1%) suspected ARs within 7 days of vaccination. No obvious pattern in the type of suspected ARs or their frequency was observed for either vaccine. None of the frequencies of suspected ARs were above the 2015/16 ESS frequencies for Vaxigrip, whereas for Intanza 15 µg only one AR (oropharyngeal pain) crossed the historical threshold. There was no change in reactogenicity and data was consistent with the safety profiles of the two vaccines. The passive ESS experience gained from season to season will help to contribute to a sustainable safety surveillance system of seasonal influenza vaccines early in the season.

Background: The contribution of genetic factors to epilepsy has long been recognized and has been estimated to play a role in 70% to 80% of cases. Identification of a pathogenic variant can help families to better cope with the disorder, allows for genetic counseling to determine recurrence risk, and in some cases, can directly influence treatment options. In this study, we determined the diagnostic yield of a clinical gene panel applied to an unselected cohort of epilepsy patients., Methods: Variant reports from 339 clinically referred epilepsy patients screened using a 110-gene panel were retrospectively reviewed. Variants were classified using the American College of Medical Genetics and Genomics guidelines., Results: Pathogenic or likely pathogenic variants were identified in 62 individuals (18%) and potentially causative variants were identified in an additional 21 individuals (6%). Causative and potentially causative variants were most frequently identified in SCN1A (n = 15) and KCNQ2 (n = 10). Other genes in which disease-causing variants were identified in multiple individuals included CDKL5, SCN2A, SCN8A, SCN1B, STXBP1, TPP1, PCDH19, CACNA1A, GABRA1, GRIN2A, SLC2A1, and TSC2. Sixteen additional genes had variants identified in single individuals., Conclusions: We identified 87 variants in 30 different genes that could explain disease, of which 54% were not previously reported. This study confirms the utility of targeted gene panel analysis in epilepsy and highlights several factors to improve the yield of diagnostic genetic testing, including the critical need for clinical phenotype information and parental samples, microarray analysis for whole exon deletions and duplications, and frequent update of panels to incorporate new disease genes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this retrospective study was to review the diagnostic accuracy of real-time polymerase chain reaction (PCR) testing of cerebrospinal fluid (CSF) samples for Streptococcus pneumoniae DNA in comparison with traditional bacterial culture. The hypothesis was that PCR is more sensitive than culture and would detect more cases of pneumococcal meningitis, particularly in children treated with antimicrobials before CSF sampling occurred. Patients younger than 16 years of age who had a CSF sample tested for S. pneumoniae DNA by PCR between 2004 and 2015 were included. A total of 2025 samples were included, and the PCR had a sensitivity of 100% and specificity of 98% for the detection of S. pneumoniae DNA in comparison with culture. Of the 28 culture negative/PCR positive cases, 25 (89%) were probable meningitis cases and only 3 (11%) were suspected false positive results. Nineteen (76%) of the 25 probable cases required ICU admission, and 3 died (12%). Six different serotypes were found in the culture positive patients (18C, 6B, 14, 22F, 7F and 33F). This study demonstrates that PCR testing of CSF samples for S. pneumoniae is sensitive and specific when compared with culture. PCR is particularly useful in detecting those cases where culture is negative, perhaps relating to pre-CSF sampling administration of antimicrobials.

Emerging tobacco product use is increasing. We evaluated factors associated with perceived risk of and intention to use waterpipe tobacco by surveying students at a large university in the southeastern U.S. (N = 667). Proportional odds modeling assessed whether demographic characteristics and social acceptability are associated with perceived risk of waterpipe tobacco use; and if these factors and perceived risk are related to intention to use waterpipe tobacco. Participants who perceived waterpipe tobacco to be more socially acceptable had lower odds of perceiving it as risky (95% confidence interval [CI] 0.50-0.68). Compared with never users, former tobacco users and current users had lower odds of perceiving waterpipe tobacco use as risky (95% CI 0.38-0.80 and 0.28-0.63, respectively). Similarly, students with greater perceived social acceptability scores had higher odds of intending to use waterpipe tobacco (95% CI 1.41-2.63), while those who perceived greater risk had lower odds of intending to use it (95% CI 0.34-0.64). Compared with never users, former users had higher odds of intending to use waterpipe tobacco (95% CI 1.42-7.21). Among those who had ever used waterpipe tobacco, 90% reported 'to socialize' as the most frequent reason for deciding to do so. Findings underscore the need for future prevention efforts., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose/objectives: To examine the association of smoking in the home with lung cancer worry, perceived risk, and synergistic risk, controlling for sociodemographics, family history of lung cancer, and health-related self-concept. The hypothesis is that participants with smoking in the home would have higher scores for lung cancer worry, perceived risk, and synergistic risk.
., Design: Cross-sectional baseline survey. 
., Setting: Participants recruited from an outpatient clinic and pharmacy at University of Kentucky HealthCare, an academic medical center.
., Sample: 515 homeowners from a larger randomized, controlled trial aimed at reducing exposure to radon and secondhand smoke (SHS).
., Methods: Homeowners were selected via quota sampling so that about half would have a smoker or smokers in the home.
., Main Research Variables: Lung cancer worry and perceived risk; perception of synergistic risk of radon and SHS exposure; demographics.
., Findings: Participants with smoking in the home had higher rates of lung cancer worry and perceived risk. In addition, those with less education and a family history of lung cancer and who were current smokers had higher lung cancer worry and perceived lung cancer risk scores. Predictors of perception of synergistic risk were marital status and health-related self-concept.
., Conclusions: Homeowners with smoking in the home, less education, and a family history of lung cancer had greater lung cancer worry and perceived lung cancer risk. Lung cancer risk reduction interventions with vulnerable populations are needed. 
., Implications for Nursing: Nurses are in a unique position to target high-risk populations and identify opportunities to create teachable moments to reduce environmental risks of radon and tobacco smoke exposure.

Purpose: To examine frequency, prominence, and content of local print media after a 4-year policy advocacy intervention., Design: This was a controlled community-based trial., Setting: The study took place in 39 rural counties (22 intervention, 17 comparison)., Subjects: Subjects consisted of 2525 newspaper articles monitored over 18 quarters (July 2007 to December 2011)., Intervention: One key element of the tailored policy advocacy intervention delivered by community advisors was building demand for smoke-free policy via media advocacy strategies., Measures: Media clips were coded to assess number of articles; percent of tobacco-related articles on the front page or bold heading section; percent of pro-health articles; and percent of articles with secondhand smoke (SHS)-relevant topics or themes., Analysis: Coded data were entered into Atlas.ti software. Article frequencies and attributes were compared between groups and over time using negative binomial regression for longitudinal data, with county-level demographics as covariates., Results: In the last 3 years, there were approximately twice as many articles in intervention than in comparison counties. Media clips from newspapers in intervention counties were between 1.4 and 2 times more likely to have front page placement and percent of relevant topic or theme than were those in comparison counties. There was no difference in rate of pro-health articles by group., Conclusion: The policy advocacy intervention to promote smoke-free policy increased media attention to SHS and may have increased public awareness of issues related to smoke-free policy.