Antisense oligonucleotides targeting the miR-29b binding site in the GRN mRNA increase progranulin translation.

Heterozygous GRN (progranulin) mutations cause frontotemporal dementia (FTD) due to haploinsufficiency, and increasing progranulin levels is a major therapeutic goal. Several microRNAs, including miR-29b, negatively regulate progranulin protein levels. Antisense oligonucleotides (ASOs) are emerging as a promising therapeutic modality for neurological diseases, but strategies for increasing target protein levels are limited. Here, we tested the efficacy of ASOs as enhancers of progranulin expression by sterically blocking the miR-29b binding site in the 3' UTR of the human GRN mRNA. We found 16 ASOs that increase progranulin protein in a dose-dependent manner in neuroglioma cells. A subset of these ASOs also increased progranulin protein in iPSC-derived neurons and in a humanized GRN mouse model. In FRET-based assays, the ASOs effectively competed for miR-29b from binding to the GRN 3' UTR RNA. The ASOs increased levels of newly synthesized progranulin protein by increasing its translation, as revealed by polysome profiling. Together, our results demonstrate that ASOs can be used to effectively increase target protein levels by partially blocking miR binding sites. This ASO strategy may be therapeutically feasible for progranulin-deficient FTD as well as other conditions of haploinsufficiency.

Evaluation of the relationship between occupational-specific task performance and measures of physical fitness, cardiovascular and musculoskeletal health in firefighters.

INTRODUCTION: Firefighters are required to perform physically strenuous tasks such as hose drags, victim rescues, forcible entries and stair climbs to complete their public safety mission. Occupational-specific tasks are often used to evaluate the ability of firefighters to adequately/safely perform their duties. Depending on the regions, occupational-specific tasks include six to eight individual tasks, which emphasize distinct aspects of their physical fitness, while also requiring different levels of cardiovascular (CVH) and musculoskeletal health (MSH). Therefore, the aim of this study was to evaluate the relationship between specific occupational task performance and measures of physical fitness, cardiovascular and musculoskeletal health. METHODS: Using a cross-sectional design, 282 full-time male and female firefighters were recruited. A researcher-generated questionnaire and physical measures were used to collect data on sociodemographic characteristics, CVH, MSH and weekly physical activity habits. Physical measures were used to collect data on physical fitness and occupational-specific task performance. RESULTS: Absolute cardiorespiratory fitness (abV̇O2max), grip strength, leg strength, push-ups, sit-ups and lean body mass (all p < 0.001) had an inverse association with completion times on all occupational-specific tasks. Age was positively related to the performance of all tasks (all p < 0.05). Higher heart rate variability (HRV) was associated with better performance on all tasks (all p < 0.05). Bodyfat percentage (BF%) and diastolic blood pressure were positively associated with the step-up task (p < 0.05). Lower back musculoskeletal injury (LoBMSI), musculoskeletal discomfort (MSD), and lower limb MSD were associated with a decreased odds of passing the step-up. Upper body MSIs (UBMSI), LoBMSIs and Lower back MSD were associated with decreased odds of passing the rescue drag. CONCLUSION: Firefighters that were taller, leaner, stronger and fitter with a more favourable CVH profile, higher HRV and less musculoskeletal discomfort performed best on all occupational-specific tasks.

Inferior Outcomes for Patients Transferred Between Surgical Stages for Knee Periprosthetic Joint Infection.

BACKGROUND: Periprosthetic joint infection (PJI) in total knee arthroplasty may result in 2-stage revision surgery. There are limited data describing outcomes when the first stage is completed at an outside hospital and the patient is referred to a tertiary center. We hypothesized that patients have greater success when both surgeries occur at a single center. METHODS: There were 25 knee PJI patients who presented with an antibiotic spacer and had a minimum 2-year follow-up who were retrospectively identified at a single tertiary referral center from 2014 to 2021. A cohort matched for age, sex, body mass index, Elixhauser comorbidity measure, spacer type, infectious organism, and year of surgery was established with patients who had both stages completed at the investigating institution. Modified Delphi success criteria of no subsequent surgery or reinfection with any species were compared. RESULTS: The transferred group demonstrated a treatment success of 40% compared to 84% in the continuous group (P < .01). The transferred group was more likely to have an additional procedure between stages (44 versus 8%, P < .01), with a higher number of surgeries after primary total knee arthroplasty (4.8 versus 3.0, P < .01), between stages (1.4 versus 0.2, P < .01), and after second stage (0.8 versus 0.2, P = .03). The transferred group had longer durations between stages (20.1 versus 7.0 weeks, P < .01). CONCLUSION: Patients who have PJIs transferred between stages demonstrated higher treatment failure. Surgeons should consider transfer early with a goal of continuous management by a single institution.

Evaluating workplace protection factors (WPFs) of different firefighter PPE interface control measures for select volatile organic compounds (VOCs).

Structural firefighters are exposed to a complex set of contaminants and combustion byproducts, including volatile organic compounds (VOCs). Additionally, recent studies have found structural firefighters' skin may be exposed to multiple chemical compounds via permeation or penetration of chemical byproducts through or around personal protective equipment (PPE). This mannequin-based study evaluated the effectiveness of four different PPE conditions with varying contamination control measures (incorporating PPE interface design features and particulate blocking materials) to protect against ingress of several VOCs in a smoke exposure chamber. We also investigated the effectiveness of long-sleeve base layer clothing to provide additional protection against skin contamination. Outside gear air concentrations were measured from within the smoke exposure chamber at the breathing zone, abdomen, and thigh heights. Personal air concentrations were collected from mannequins under PPE at the same general heights and under the base layer at abdomen and thigh heights. Sampled contaminants included benzene, toluene, styrene, and naphthalene. Results suggest that VOCs can readily penetrate the ensembles. Workplace protection factors (WPFs) were near one for benzene and toluene and increased with increasing molecular weight of the contaminants. WPFs were generally lower under hoods and jackets compared to under pants. For all PPE conditions, the pants appeared to provide the greatest overall protection against ingress of VOCs, but this may be due in part to the lower air concentrations toward the floor (and cuffs of pants) relative to the thigh-height outside gear concentrations used in calculating the WPFs. Providing added interface control measures and adding particulate-blocking materials appeared to provide a protective benefit against less-volatile chemicals, like naphthalene and styrene.

Measuring midwives' perceptions of their practice climate across racial-ethnic identities: An invariance analysis of the Midwifery Practice Climate Scale.

Diversification of the midwifery workforce is key to addressing disparities in maternal health in the United States. Midwives who feel supported in their practice environments report less burnout and turnover; therefore, creating positive practice environments for midwives of color is an essential component of growing and retaining midwives of color in the workforce. The Midwifery Practice Climate Scale (MPCS) is a 10-item instrument developed through multiphase empirical analysis to measure midwives' practice environments, yet the MPCS had not been independently tested with midwives of color. We conducted invariance analyses to test whether latent means can be compared between midwives of color and non-Hispanic White samples. A step-up approach applied a series of increasingly stringent constraints to model estimations with multiple group confirmatory factor analyses with two pooled samples. A configural model was estimated as the basis of multiple group comparisons where all parameters were allowed to freely vary. Metric invariance was estimated by constraining item factor loadings to be equal. Scalar invariance was estimated by constraining intercepts of indicators to be equal. Each model was compared to the baseline model. The findings supported scalar invariance of MPCS across midwives of color and non-Hispanic White midwives, indicating that the MPCS is measuring the same intended construct across groups, and that differences in scores between these two groups reflect true group differences and are not related to measurement error. Additionally, in this sample, there was no statistically significant difference in perceptions of the practice environments across midwives of color and non-Hispanic White midwives (p > 0.05).

Comparing Cesarean Birth Utilization Between US Hospitals: A Demonstration of the Robson Ten-Group Classification System for Use in Quality Improvement and Benchmarking.

BACKGROUND: The World Health Organization-endorsed Robson Ten-Group Classification System (TGCS) is a standard reporting mechanism for cesarean birth, yet this approach is not widely adopted in the United States. OBJECTIVE: To describe the application and utility of the TGCS to compare hospital-level cesarean births rates, for use in quality improvement and benchmarking. METHODS: We conducted a descriptive, secondary data analysis of the Consortium on Safe Labor dataset using data from 228 438 women's births, from 2002 to 2008, in 12 sites across the United States. We stratified births into 10 mutually exclusive groups and calculated within-group proportions of group size and cesarean birth rates for between-hospital comparisons of cesarean birth, trial of labor after cesarean (TOLAC), and labor induction utilization. RESULTS: There is variation in use of cesarean birth, labor induction, and TOLAC across the 12 sites. CONCLUSION: The TGCS provides a method for between-hospital comparisons, particularly for revealing usage patterns of labor induction, TOLAC, and cesarean birth. Adoption of the TGCS in the United States would provide organizations and quality improvement leaders with an effective benchmarking tool to assist in reducing the use of cesarean birth and increasing the support of TOLAC.

Contemporary Nurse-Midwifery Care in Colorado: A Survey of Certified Nurse-Midwife Practices in Hospital and Community Settings.

Lack of access to birth facilities and maternity care providers has contributed to rising US maternal mortality and morbidity rates, especially among women in rural areas. Evidence supports the increased use of midwives as a potential solution for access-to-care issues. This observational survey was conducted to identify the practice environment for Certified Nurse-Midwives® in Colorado for the purpose of informing future workforce expansion. Study results indicate that midwives provide services aligned with the midwifery model of care and have mostly autonomous practice in hospitals where midwifery practices are already established. However, there is limited use of midwives, as fewer than half of Colorado's 69 birthing hospitals have midwifery practices, and financial constraint created by low Medicaid reimbursement could be a limiting factor in establishing new midwifery practices. Policy recommendations based on survey results include (a) support for midwifery education and workforce development, (b) removal of hospital-level restrictions for privileges of midwives, and (c) consideration for public payment models that promote expansion of midwifery practices.

Establishing a health profession: What oncology patient navigators can learn from the National Association of Community Health Workers.

Persons who identify as community health workers (CHWs) may hold other titles and/or certifications, including the title of patient navigator (PN). PN roles first emerged from Dr. Harold Freeman's initiative at Harlem Hospital as a strategy to reduce disparities in access to health care, whereas CHW roles extend beyond health systems and are predominantly found in community-based organizations and nonprofits. Although CHWs' origins in the United States predate those of PNs, the growth of CHWs' professional identity and national representation trails that of PNs despite evidence of CHWs' effectiveness since the 1960s. Barriers to progress have included a pattern of short-term and inequitable funding for CHW positions, a lack of employer support for participation in association business, and broad diversity in CHW roles and work settings. The National Association of Community Health Workers (NACHW) was launched in 2019 and built on earlier organizing efforts by multisector, multicultural CHWs and allies in the CHW section of the American Public Health Association and on efforts to create the American Association of Community Health Workers (2006-2009). Trends in health care financing, increasing calls for racial equity, and the coronavirus disease 2019 (COVID-19) pandemic have amplified the unique abilities and trust that CHWs apply to underresourced, marginalized, and multiethnic populations to address both the social determinants of health and health system access, cost, and quality. As a result, the NACHW has been at the forefront of efforts to improve federal funding for COVID responses, to sustain funding for CHWs and their organizations beyond the pandemic, and to drive equity in the rebuilding of public health infrastructure and the transformation of payment models and health systems. Lessons learned from this process that have implications for the oncology patient navigation field include the persistent need to reinforce the value of self-determination for the profession in matters of policy; the importance of actively cultivating unity among diverse cultural and practice groups within the profession; the essential roles of active volunteer leadership, early staffing, and substantial financial support over an extended startup period; the ongoing need for leadership development within a workforce with limited exposure to a professional association culture; the vital importance of ongoing efforts to collaborate with and build capacity among state-level CHW networks; and the value of opportunistic national collaborations in a rapidly evolving policy environment.

Clinical outcomes of brain metastasectomy from soft tissue and bone sarcomas: a systematic review.

BACKGROUND: Brain metastasis in sarcomas is associated with a poor prognosis. Data regarding prognostic factors and clinical outcomes of surgical resection of brain metastasis from sarcomas are limited. The objective of this systematic review was to evaluate survival outcomes post-brain metastasectomy for patients with soft tissue and bone sarcomas. METHODS: A systematic review was conducted examining survival outcomes among adults and children with soft tissue and bone sarcoma undergoing brain metastasectomy, in the English language from inception up to May 31, 2021. Two reviewers independently evaluated and screened the literature, extracted the data, and graded the included studies. The body of evidence was evaluated and graded according to the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Results were synthesized using descriptive methods. A meta-analysis was not possible due to the low quality and heterogeneity of studies. RESULTS: Ten studies published between 1994 and 2020 were included: three were retrospective cohort studies and seven were case series. 507 patients were included, of whom 269 underwent brain metastasectomy. The median follow-up period ranged between 14 and 29 months. The median survival period after metastasectomy ranged from 7 to 25 months. The most common prognostic factors associated with survival included presenting performance status, age, number of brain metastases, presence of lung metastases, and peri-operative radiation therapy administration. DISCUSSION: Although the level of evidence is low, retrospective studies support that brain metastasectomy can be performed with reasonable post-operative survival in selected individuals.

Effect of live-fire training on ventricular-vascular coupling.

INTRODUCTION: Cardiovascular events are a leading cause of firefighter duty-related death, with the greatest risk occurring during or shortly after fire suppression activity. Increased cardiovascular risk potentially manifests from detrimental changes in ventricular function, vascular load, and their interaction, described as ventricular-vascular coupling. PURPOSE: To determine the effect of live-fire training on ventricular-vascular coupling. METHODS: Sixty-eight male (28 [Formula: see text] 7 years, 26.9 [Formula: see text] 3.9 kg/m2) and fifteen female (36 [Formula: see text] 8 years, 24.3 [Formula: see text] 3.9 kg/m2) firefighters completed hemodynamic and cardiac measures before and after 3 h of intermittent live-fire training. Left ventricular function was assessed as ejection fraction (EF) and ventricular elastance (ELV: end systolic pressure [ESP]/end systolic volume) via echocardiography and applanation tonometry-estimated ESP. Vascular load was assessed as arterial elastance (EA: ESP/stroke volume [SV]). Ventricular-vascular coupling (VVC) was quantified as the ratio of EA to ELV and indexed to body surface area (EAI, ELVI). RESULTS: Following firefighting EF decreased (p < 0.01) with no change in ELVI (p = 0.34). SV decreased (p < 0.01) with no change in ESP (p = 0.09), driving a significant increase in EAI (p < 0.01). These changes resulted in a significant increase in the VVC ratio (p < 0.01). CONCLUSION: The findings suggest that firefighting does not alter ventricular elastance but increases arterial elastance in healthy firefighters, resulting in a mismatch between ventricular and vascular systems. This increase in ventricular-vascular coupling ratio and concomitant reduction in ventricular systolic function may contribute to increased cardiovascular risk following live firefighting.

A Systematic Review and Meta-Analysis of Advanced Biomarkers for Predicting Incident Cardiovascular Disease among Asymptomatic Middle-Aged Adults.

Cardiovascular disease (CVD) continues as the most important cause of mortality. Better risk screening and prediction are needed to reduce the cardiovascular disease burden. The aim of the study was to assess the role of serum biomarkers in the prediction of CVD among asymptomatic middle-aged adults with no prior CVD history. A systematic review and meta-analysis were carried out using literature from PubMed and following PRISMA reporting guidelines. Twenty-five studies met our inclusion criteria and were included in the systematic review. The most commonly studied biomarker was high-sensitivity C reactive protein (hs-CRP) (10 studies), which showed that higher hs-CRP levels are associated with an increased risk of subsequent CVD events and mortality. In addition, several less-studied biomarkers (N-terminal pro-brain natriuretic peptide (NT-proBNP), fibrinogen, gamma-glutamyl transferase (GGT), and others) also showed significant associations with greater future risk of CVD. A meta-analysis was possible to perform for hs-CRP and NT-proBNP, which showed statistically significant results for the ability of hs-CRP (hazard ratio (HR) 1.19, (95% CI: 1.09−1.30), p < 0.05) and NT-proBNP (HR 1.22, (1.13−1.32), p < 0.05) to predict incident CVD among middle-aged adults without a prior CVD history or symptoms. Several serum biomarkers, particularly hs-CRP and NT-proBNP, have the potential to improve primary CVD risk prevention among asymptomatic middle-aged adults.

Hierarchy of contamination control in the fire service: Review of exposure control options to reduce cancer risk.

The international fire service community is actively engaged in a wide range of activities focused on development, testing, and implementation of effective approaches to reduce exposure to contaminants and the related cancer risk. However, these activities are often viewed independent of each other and in the absence of the larger overall effort of occupational health risk mitigation. This narrative review synthesizes the current research on fire service contamination control in the context of the National Institute for Occupational Safety and Health (NIOSH) Hierarchy of Controls, a framework that supports decision making around implementing feasible and effective control solutions in occupational settings. Using this approach, we identify evidence-based measures that have been investigated and that can be implemented to protect firefighters during an emergency response, in the fire apparatus and at the fire station, and identify several knowledge gaps that remain. While a great deal of research and development has been focused on improving personal protective equipment for the various risks faced by the fire service, these measures are considered less effective. Administrative and engineering controls that can be used during and after the firefight have also received increased research interest in recent years. However, less research and development have been focused on higher level control measures such as engineering, substitution, and elimination, which may be the most effective, but are challenging to implement. A comprehensive approach that considers each level of control and how it can be implemented, and that is mindful of the need to balance contamination risk reduction against the fire service mission to save lives and protect property, is likely to be the most effective.

Firefighter hemodynamic responses to different fire training environments.

Firefighting is associated with an increased risk for a cardiovascular (CV) event, likely due to increased CV strain. The increase in CV strain during firefighting can be attributed to the interaction of several factors such as the strenuous physical demand, sympathetic nervous system activation, increased thermal burden, and the environmental exposure to smoke pollutants. Characterizing the impact of varying thermal burden and pollutant exposure on hemodynamics may help understand the CV burden experienced during firefighting. The purpose of this study was to examine the hemodynamic response of firefighters to training environments created by pallets and straw; oriented strand board (OSB); or simulated fire/smoke (fog). Twenty-three firefighters had brachial blood pressure measured and central blood pressure and hemodynamics estimated from the pressure waveform at baseline, and immediately and 30 minutes after each scenario. The training environment did not influence the hemodynamic response over time (interaction, p > 0.05); however, OSB scenarios resulted in higher pulse wave velocity and blood pressure (environment, p < 0.05). In conclusion, conducting OSB training scenarios appears to create the largest arterial burden in firefighters compared to other scenarios in this study. Environmental thermal burden in combination with the strenuous exercise, and psychological and environmental stress placed on firefighters should be considered when designing fire training scenarios and evaluating CV risk.

Differences in 5-year weight change between younger and older US firefighters.

BACKGROUND: Research consistently finds that, on average, firefighters gain weight over time and some data indicate that younger firefighters are more likely to gain weight than older firefighters. The purpose of this study was to estimate the 5-year weight change among younger and older US firefighters. METHODS: Data from two occupational medical exams separated by 5 years (2009-2016) were examined from a cohort of US career firefighters in Virginia (males, n = 589; females, n = 67). The cohort was grouped into two age categories (< 45 years and ≥ 45 years). Weight change subgroups were Loss (decrease of > 3% body weight), Stable (within ±3% body weight) and Gain (increase of > 3% body weight). Multinomial logistic regression models and linear regression models were conducted to examine differences in the probability of being in a particular weight change category, weight change overall and by weight change category between younger and older firefighters. RESULTS: At baseline, 25 and 35% of younger (< 45 years) and older (≥ 45 years) were obese, respectively. Younger firefighters gained significantly (P < 0.05) more weight (3.0 ± 0.2 kg) than older firefighters (0.8 ± 0.5 kg). Younger firefighters were more likely to gain weight (53% versus 39%) and less likely (10% versus 20%) to lose weight as compared to older firefighters. Smaller weight gains were associated with age and BMI with the smallest increases observed in overweight and obese firefighters ≥45 years of age. CONCLUSIONS: Health care providers should be attentive to weight gain, even among young non-obese firefighters, and counsel firefighters to avoid the additive risks of being older and heavier. In addition, weight loss/management programs should be promoted in the fire service to encourage healthy body weight and to prevent unhealthy weight gain among both young and old firefighters alike.

First Report of Diplodia Shoot Blight and Canker Disease caused by Diplodia sapinea on Ponderosa Pine in Wyoming, USA.

Diplodia sapinea is a common fungal pathogen that causes shoot blight and canker of naturally occurring and planted pines and other conifers throughout the world. Damage can be severe severe, affectingand affect needles, new shoots, branches, and main stems, often leading to mortality. In August 2018, aerial surveys revealed 1,659 ha of ponderosa pine (Pinus ponderosa) displaying varying degrees of crown necrosis in Crook County, Wyoming (WY). In May 2019, ground surveys of this area, which was previously affected by hail the previous spring, identified typical Diplodia shoot blight and canker signs and symptoms (e.g., pycnidia, crooked shoots, discolored needles, resinous cankers). Symptoms were observed in thousands of seedlings, saplings, and mature ponderosa pine trees over the large area. Because D. sapinea had not been previously reported in WY, this study was conducted to confirm the presence and aggressiveness of D. sapinea isolates from WY on this commercially and ecologically important host tree. Pycnidia and conidia (size 34 to 39 µm × 12 to 13 µm) consistent with D. sapinea were confirmed in 19 trees from three locations in the county. Three isolates were confirmed as D. sapinea using species-specific PCR (Smith and Stanosz 2006) and are retained at the Rocky Mountain Research Station, Moscow, ID and Colorado State University, Fort Collins, CO. To confirm isolate aggressiveness, 3-year-old potted ponderosa pine seedlings were inoculated in greenhouses from March to April 2020 at the Charles E. Bessey Nursery, Halsey, NE using similar methods as previously described (Blodgett and Stanosz 1997). Wounding was conducted using a scalpel to excise a single needle fascicle from a recently expanded shoot. Cuts were made flush to the stem at 2 to 2.5 cm below an apical bud-tip. A 1.5% water-agar plug with cultured mycelia of one of the three DNA-confirmed isolates was placed over the stem wound, or sterile water-agar plugs were used as negative controls. Parafilm® (4-cm wide) was wrapped around the inoculated stems, centered at the wound for 4 weeks. Two independent trials were conducted consecutively, 3 hrs apart, in different greenhouses with five seedlings per isolate or control. Symptoms first appeared 5 days post-inoculation. All seedlings inoculated with the three isolates developed typical D. sapinea symptoms, including cankers (mean length 5.98.7 ± 1.13.0 cm standard error and 5.5 ± 0.8 cm standard error, trial 1 and 2 respectively) at 4-weeks post-inoculation, while mock-inoculated seedlings developed no symptoms. Stem segments (2-cm long) were excised, centered at canker margins (or centered 3 cm below wounds for controls), and surface disinfested for 30 sec in 70% ethanol and 5 min in 1.05% sodium hypochlorite, then placed in Petri plates containing tannic acid agar (Blodgett et al. 2003). After 3 weeks, isolates were subcultured from colony margins to Petri plates containing 1.5% water agar and autoclaved ponderosa pine needles. Pycnidia and conidia consistent with D. sapinea were confirmed after another month from all seedlings inoculated with each isolate, but not from control seedlings. This report confirms that D. sapinea is present in WY, and WY isolates can be aggressive pathogens of ponderosa pine. Reducing host water stress (Blodgett et al. 1997a, Blodgett et al. 1997b) may be the best option to manage Diplodia shoot blight and canker disease in forested sites. This can be accomplished by stand thinning and/or managing competing vegetation. Favoring non-host species might be an alternative management option in areas with severe disease. References: J. T. Blodgett et al. 2003. For. Pathology 33:395. J. T. Blodgett and G. R. Stanosz. 1997. Plant Dis. 81:143. J. T. Blodgett et al. 1997a. Phytopathology 87:429. J. T. Blodgett et al. 1997b. Phytopathology 87:422. D. R. Smith and G. R. Stanosz. Plant Dis. 90:307, 2006.

Effects of firefighting hood design, laundering and doffing on smoke protection, heat stress and wearability.

Firefighter hoods must provide protection from elevated temperatures and products of combustion (e.g. particulate) while simultaneously being wearable (comfortable and not interfering with firefighting activities). The purpose of this study was to quantify the impact of (1) hood design (traditional knit hood vs particulate-blocking hood), (2) repeated laundering, and (3) hood removal method (traditional vs overhead doffing) on (a) protection from soot contamination on the neck, (b) heat stress and (c) wearability measures. Using a fireground exposure simulator, 24 firefighters performed firefighting activities in realistic smoke and heat conditions using a new knit hood, new particulate-blocking hood and laundered particulate-blocking hood. Overall, soot contamination levels measured from neck skin were lower when wearing the laundered particulate-blocking hoods compared to new knit hoods, and when using the overhead hood removal process. No significant differences in skin temperature, core temperature, heart rate or wearability measures were found between the hood conditions. Practitioner Summary: The addition of a particulate-blocking layer to firefighters' traditional two-ply hood was found to reduce the PAH contamination reaching the neck but did not affect heat stress measurements or thermal perceptions. Modifying the process for hood removal resulted in a larger reduction in neck skin contamination than design modification. Abbreviations: ANOVA: analysis of variance; B: new particulate-blocking hood and PPE (PPE configuration); FES: fireground exposure simulator; GI: gastrointestinal; K: new knit hood and PPE (PPE configuration); L: laundered particulate-blocking hood and PPE (PPE configuration); LOD: limit of detection; MLE: maximum likelihood estimation; NFPA: National fire protection association; PAH: polycyclic aromatic hydrocarbon; PPE: personal protective equipment; SCBA: self-contained breathing apparatus; THL: total heat loss; TPP: thermal protective performance.

Correlation Between Heart Rate Characteristic Index Score and Severity of Brain Injury in Neonates With Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains devastating for neonates despite widespread treatment with therapeutic hypothermia (TH). The heart rate characteristic (HRC) index score, a measure of heart rate variability, could prove useful in the management of neonates with HIE as new therapies emerge or when withdrawal-of-support decisions are being considered. PURPOSE: The main purpose was to describe correlation between HRC index scores and brain magnetic resonance imaging (MRI) severity of injury for neonates with HIE. METHODS/ANALYSIS: Low/high HRC index scores retrieved at initiation of TH (baseline), 24, 48, 72, and 96 hours, brain MRI severity of injury, and National Institute of Child Health and Human Development Death/Disability and Death scores were collected and analyzed retrospectively. Independent t tests and linear regression were used to examine relationships for each outcome measure. RESULTS: Twenty-seven neonates were stratified into 2 groups: noninjury (n = 11) and injury (n = 16). Statistically significant relationships were observed. Strikingly, mean low HRC index score for the noninjury group ranged between 0.37 and 0.65 and was between 0.61 and 0.86 for the injury group. Mean high HRC index score for the noninjury group ranged between 0.66 and 1.02 and was between 1.04 and 1.41 for the injury group. IMPLICATIONS FOR PRACTICE: HRC index score may be a useful guide in the future management of neonates with HIE. IMPLICATIONS FOR RESEARCH: This study established correlations between HRC index and MRI injury scores in neonates treated with TH. Further research is warranted to establish important relationships between brain injury and HRC index scores before this tool can be used clinically for this purpose.

Are we underestimating overweight and obesity prevalence in children?

OBJECTIVE: To objectively determine the prevalence of overweight and obesity in elementary school children in two rural counties in Vermont prior to implementing a community-based intervention. METHODS: School-based objective measures of body mass index (BMI) were obtained from 1,688 public school children in first, third, and fifth grades in two Northern Vermont counties in the Fall of 2017. RESULTS: Forty-one percentage of elementary school children were either overweight or obese, nearly double the estimated Vermont prevalence rate of 22.2%. Schools located in more rural areas showed higher levels of overweight and obesity in children than schools in less rural areas in these northern counties (p < .005). CONCLUSIONS: Indirect and self-reported measures of BMI may be underestimating the true prevalence of overweight and obesity particularly in more rural communities. POLICY IMPLICATIONS: Data presented here in which children were measured directly by trained study staff demonstrate that the prevalence of obesity among children in elementary school is alarmingly high. Accurate, ongoing BMI measurement surveillance is one tool to better understand both the current trends in childhood overweight and obesity and the effect of community and state interventions.

Impact of select PPE design elements and repeated laundering in firefighter protection from smoke exposure.

As the Fire Service becomes more aware of the potential health effects from occupational exposure to hazardous contaminants, personal protective equipment (PPE) manufacturers, and fire departments have responded by developing and implementing improved means of firefighter protection, including more frequent laundering of PPE after exposures. While laboratory testing of new PPE designs and the effect of laundering on PPE fabric provides a useful way to evaluate these approaches, laboratory scale testing does not necessarily translate to full garment protection. Utilizing a fireground smoke exposure simulator, along with air and/or filter-substrate sampling for polycyclic aromatic hydrocarbons (PAHs) and benzene, this pilot study tested the chemical-protective capabilities of firefighting PPE of different designs (knit hood vs. particulate-blocking hood, turnout jacket with zipper closure vs. hook & dee closure), including the impact of repeatedly exposing and cleaning (through laundering or decontamination on-scene) PPE 40 times. Overall, PAH contamination on filters under hoods in the neck region were higher (median PAHs = 14.7 µg) than samples taken under jackets in the chest region (median PAHs = 7.05 µg). PAH levels measured under particulate-blocking hoods were lower than levels found under knit hoods. Similarly, zippered closures were found to provide a greater reduction in PAHs compared to hook & dee closures. However, neither design element completely eliminated contaminant ingress. Measurements for benzene under turnout jackets were similar to ambient chamber air concentrations, indicating little to no attenuation from the PPE. The effect of laundering or on-scene decontamination on contaminant breakthrough appeared to depend on the type of contaminant. Benzene breakthrough was negatively associated with laundering, while PAH breakthrough was positively associated. More research is needed to identify PPE features that reduce breakthrough, how targeted changes impact exposures, and how fireground exposures relate to biological absorption of contaminants.

TEAD-YAP Interaction Inhibitors and MDM2 Binders from DNA-Encoded Indole-Focused Ugi Peptidomimetics.

DNA-encoded combinatorial synthesis provides efficient and dense coverage of chemical space around privileged molecular structures. The indole side chain of tryptophan plays a prominent role in key, or "hot spot", regions of protein-protein interactions. A DNA-encoded combinatorial peptoid library was designed based on the Ugi four-component reaction by employing tryptophan-mimetic indole side chains to probe the surface of target proteins. Several peptoids were synthesized on a chemically stable hexathymidine adapter oligonucleotide "hexT", encoded by DNA sequences, and substituted by azide-alkyne cycloaddition to yield a library of 8112 molecules. Selection experiments for the tumor-relevant proteins MDM2 and TEAD4 yielded MDM2 binders and a novel class of TEAD-YAP interaction inhibitors that perturbed the expression of a gene under the control of these Hippo pathway effectors.