Acute moderate normobaric hypoxia does not modify circulating thyroid hormone concentrations induced by one hour of head out cold-water immersion.

This study tested the hypothesis that acute moderate normobaric hypoxia augments circulating thyroid hormone concentrations during and following one hour of cold head out water immersion (HOWI), compared to when cold HOWI is completed during normobaric normoxia. In a randomized crossover single blind design, 12 healthy adults (27 ± 2 y, 2 women) completed one hour of cold (22.0±0.1°C) HOWI breathing either normobaric normoxia (FiO2 = 0.21) or normobaric hypoxia (FiO2 = 0.14). Free and total thyroxine (T3) and triiodothyronine (T4), and thyroid stimulating hormone (TSH) concentrations were measured in venous blood samples obtained before (baseline), during (15-, 30-, and 60-min), and 15 min following HOWI (post-), and were corrected for changes in plasma volume. Arterial oxyhemoglobin saturation and core (rectal) temperature were measured continuously. Arterial oxyhemoglobin saturation was lower during hypoxia (90 ± 3%) compared to normoxia (98 ± 1%, p<0.001). Core temperature fell from baseline (normoxia: 37.2 ± 0.4°C, hypoxia: 37.2 ± 0.4°C) to post- cold HOWI (normoxia: 36.4 ± 0.5°C, hypoxia: 36.3 ± 0.5°C, p<0.001) in both conditions but did not change differently between conditions (condition x time: p=0.552). Circulating TSH, Total T3, Free T4, Total T3, and Free T4 concentrations demonstrated significant main effects of time (all p≤0.024), but these changes did not differ between normoxic and hypoxic conditions (condition x time: all p³0.163). These data indicate that acute moderate normobaric hypoxia does not modify the circulating thyroid hormone response during one hour of cold HOWI.

Standardized indolent systemic mastocytosis evaluations across a healthcare system: implications for screening accuracy.

Timely diagnosis of systemic mastocytosis (SM) remains challenging due to care heterogeneity. We implemented a standardized approach for SM screening and diagnosis utilizing a novel healthcare system-wide international screening registry. A retrospective analysis assessed rates of SM, cutaneous mastocytosis (CM), and molecular diagnoses before and two years after care standardization. Accuracy of individual and combined SM screening tests - basal serum tryptase (BST) ≥11.5 and ≥20.0 ng/mL, REMA ≥2, monomorphic maculopapular CM, and elevated BST based upon tryptase genotype - was analyzed. Tryptase genotyping and high-sensitivity KIT p.D816V testing increased substantially two years following care standardization. SM diagnoses doubled from 47 to 94 and KIT p.D816V molecular diagnoses increased from 24 to 79. Mean BST and KIT p.D816V variant allele frequency (VAF) values were significantly lower in patients diagnosed after standardization. Hereditary-alpha tryptasemia prevalence was increased in SM prior to care standardization at 4/30 (13.3%) but reflected the general population prevalence two years later at 5/76 (6.6%). Elevated BST based upon genotype and BST ≥11.5 ng/mL had the highest sensitivities at 84.2% and 88.3%, respectively. Presence of monomorphic MPCM, elevated BST based upon tryptase genotype, and the combination of REMA ≥2 with elevated BST based upon tryptase genotype had specificities >90%. BST >20.0 ng/mL had low sensitivity and specificity and was not required to establish any indolent SM diagnosis. Care standardization increased SM diagnosis rates, particularly in patients with low BSTs. Stratifying BST based upon genotype had the best overall sensitivity and specificity of any indolent SM screening test and improved the REMA score specificity.

Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians.

DESCRIPTION: The American College of Physicians (ACP) developed this clinical guideline to update recommendations on newer pharmacologic treatments of type 2 diabetes. This clinical guideline is based on the best available evidence for effectiveness, comparative benefits and harms, consideration of patients' values and preferences, and costs. METHODS: This clinical guideline is based on a systematic review of the effectiveness and harms of newer pharmacologic treatments of type 2 diabetes, including glucagon-like peptide-1 (GLP-1) agonists, a GLP-1 agonist and glucose-dependent insulinotropic polypeptide agonist, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, and long-acting insulins, used either as monotherapy or in combination with other medications. The Clinical Guidelines Committee prioritized the following outcomes, which were evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach: all-cause mortality, major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for congestive heart failure, progression of chronic kidney disease, serious adverse events, and severe hypoglycemia. Weight loss, as measured by percentage of participants who achieved at least 10% total body weight loss, was a prioritized outcome, but data were insufficient for network meta-analysis and were not rated with GRADE. AUDIENCE AND PATIENT POPULATION: The audience for this clinical guideline is physicians and other clinicians. The population is nonpregnant adults with type 2 diabetes. RECOMMENDATION 1: ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control (strong recommendation; high-certainty evidence). • Use an SGLT-2 inhibitor to reduce the risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. • Use a GLP-1 agonist to reduce the risk for all-cause mortality, major adverse cardiovascular events, and stroke. RECOMMENDATION 2: ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality (strong recommendation; high-certainty evidence).

Renal vascular control during normothermia and passive heat stress does not differ between healthy younger men and women.

Men are likely at greater risk for heat-induced acute kidney injury compared with women, possibly due to differences in vascular control. We tested the hypothesis that the renal vasoconstrictor and vasodilator responses will be greater in younger women compared with men during passive heat stress. Twenty-five healthy adults [12 women (early follicular phase) and 13 men] completed two experimental visits, heat stress or normothermic time-control, assigned in a block-randomized crossover design. During heat stress, participants wore a water-perfused suit perfused with 50°C water. Core temperature was increased by ∼0.8°C in the first hour before commencing a 2-min cold pressor test (CPT). Core temperature remained clamped and at 1-h post-CPT, subjects ingested a whey protein shake (1.2 g of protein/kg body wt), and measurements were taken pre-, 75 min, and 150 min post-protein. Beat-to-beat blood pressure (Penaz method) was measured and segmental artery vascular resistance (VR, Doppler ultrasound) was calculated as segmental artery blood velocity ÷ mean arterial pressure. CPT-induced increases in segmental artery VR did not differ between trials (trial effect: P = 0.142) nor between men (heat stress: 1.5 ± 1.0 mmHg/cm/s, normothermia: 1.4 ± 1.0 mmHg/cm/s) and women (heat stress: 1.4 ± 1.2 mmHg/cm/s, normothermia: 2.1 ± 1.1 mmHg/cm/s) (group effect: P = 0.429). Reductions in segmental artery VR following oral protein loading did not differ between trials (trial effect: P = 0.080) nor between men (heat stress: -0.6 ± 0.8 mmHg/cm/s, normothermia: -0.6 ± 0.6 mmHg/cm/s) and women (heat stress: -0.5 ± 0.5 mmHg/cm/s, normothermia: -1.1 ± 0.6 mmHg/cm/s) (group effect: P = 0.204). Renal vasoconstrictor responses to the cold pressor test and vasodilator responses following an oral protein load during heat stress or normothermia do not differ between younger men and younger women in the early follicular phase of the menstrual cycle.NEW & NOTEWORTHY The mechanisms underlying greater heat-induced acute kidney injury risk in men versus women remain unknown. This study examined renal vascular control, including both vasodilatory (oral protein load) and vasoconstrictor (cold presser test) responses, during normothermia and heat stress and compared these responses between men and women. The results indicated that in both conditions neither renal vasodilatory nor vasoconstrictor responses differ between younger men and younger women.

Pneumococcal Perplexity: Improving Awareness of Updated Pneumococcal Vaccination Recommendations in Two Large Military Treatment Facilities.

INTRODUCTION: Vaccinations are an essential aspect of preventive medicine. In October 2021, the pneumococcal conjugate vaccine-20 (PCV-20) and PCV-15 were authorized for use in adults by the U.S. FDA. In 2022, the Advisory Committee on Immunization Practices (ACIP) subsequently published updated pneumococcal vaccination recommendations that incorporate both PCV-20 and PCV-15. Pneumococcal vaccination is effective in reducing pneumococcal disease, particularly in high-risk patient groups such as those with chronic lung disease; however, the updated dosing schedule for pneumococcal vaccinations can be quite confusing, especially if patients have previously received "older" vaccinations, such as pneumococcal polysaccharide vaccine-23 or PCV-13. The purpose of this quality improvement project was to increase providers' knowledge of current ACIP pneumococcal vaccination recommendations, including indications and dosing schedule, and to improve pneumococcal vaccination rates among eligible adults and children. MATERIALS AND METHODS: Focused education sessions were presented to primary care and subspecialty residents, fellows, and staff at Brooke Army Medical Center and Wilford Hall Ambulatory Surgical Center regarding current ACIP pneumococcal vaccination recommendations. Sessions included information about PCV-15 and PCV-20 vaccines, indications for vaccination, and dosing schedules. Subjective knowledge of updated ACIP pneumococcal vaccination recommendations was assessed among primary care and subspecialty residents, fellows, and staff via an anonymous survey both pre- and post-intervention. Number of PCV-20 vaccinations given and estimated vaccination rates of patients aged 19 to 64 years with asthma were assessed pre- and post-intervention over a 6 month time span. RESULTS: Of surveyed providers, only 9% discussed vaccinations at every visit and 11% did not discuss vaccinations at all. There was a statistically significant increase in providers' knowledge of pneumococcal vaccination guidelines for children post-intervention (P = .01) but no statistically significant increase in knowledge for guidelines for adults, for patients that have received prior pneumococcal vaccines, or in overall confidence in recommending pneumococcal vaccines. There was a 17% increase in the number of PCV-20 vaccinations given post-intervention (198 pre-intervention, 232 post-intervention). The estimated PCV-20 vaccination rate for adults aged 19 to 64 years with asthma increased from 14.9% pre-intervention to 19.5% post-intervention (P = .33). CONCLUSIONS: There is a significant knowledge gap regarding ACIP pneumococcal vaccination recommendations among military providers and a low pneumococcal vaccination rate for adults aged 19 to 64 years with asthma at Joint Base-San Antonio MTFs. Focused education sessions were effective in increasing providers' knowledge of updated pneumococcal vaccination recommendations, confidence in recommending vaccines, total number of pneumococcal vaccinations given, and estimated pneumococcal vaccination rate for adults with asthma. The validity of conclusions drawn from our data were limited because of discordant numbers of survey respondents as well as potentially inaccurate estimates of pneumococcal vaccination rates pre- and post-intervention. Despite this, the results warrant continued education of pneumococcal vaccines, indications, and dosing schedules.

Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis.

Objective: To determine whether prenatal cannabis use alone increases the likelihood of fetal and neonatal morbidity and mortality. Study Design: We searched bibliographic databases, such as PubMed, Embase, Scopus, Cochrane reviews, PsycInfo, MEDLINE, Clinicaltrials.gov, and Google Scholar from inception through February 14, 2022. Cohort or case-control studies with prespecified fetal or neonatal outcomes in pregnancies with prenatal cannabis use. Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small-for-gestational-age (SGA), birthweight (grams), and perinatal mortality. Two independent reviewers screened studies. Studies were extracted by one reviewer and confirmed by a second using a predefined template. Risk of bias assessment of studies, using the Newcastle-Ottawa Quality Assessment Scale, and Grading of Recommendations Assessment, Development, and Evaluation for evaluating the certainty of evidence for select outcomes were performed by two independent reviewers with disagreements resolved by a third. Random effects meta-analyses were conducted, using adjusted and unadjusted effect estimates, to compare groups according to prenatal exposure to cannabis use status. Results: Fifty-three studies were included. Except for birthweight, unadjusted and adjusted meta-analyses had similar results. We found very-low- to low-certainty evidence that cannabis use during pregnancy was significantly associated with greater odds of PTB (adjusted odds ratio [aOR], 1.42; 95% confidence interval [CI], 1.19 to 1.69; I2, 93%; p=0.0001), SGA (aOR, 1.76; 95% CI, 1.52 to 2.05; I2, 86%; p<0.0001), and perinatal mortality (aOR, 1.5; 95% CI, 1.39 to 1.62; I2, 0%; p<0.0001), but not significantly different for birthweight (mean difference, -40.69 g; 95% CI, -124.22 to 42.83; I2, 85%; p=0.29). Because of substantial heterogeneity, we also conducted a narrative synthesis and found comparable results to meta-analyses. Conclusion: Prenatal cannabis use was associated with greater odds of PTB, SGA, and perinatal mortality even after accounting for prenatal tobacco use. However, our confidence in these findings is limited. Limitations of most existing studies was the failure to not include timing or quantity of cannabis use. This review can help guide health care providers with counseling, management, and addressing the limited existing safety data. Protocol Registration: PROSPERO CRD42020172343.

Costs of Fatal and Nonfatal Firearm Injuries in the U.S., 2019 and 2020.

INTRODUCTION: Firearm-related injuries are among the five leading causes of death for people aged 1-44 years in the U.S. The immediate and long-term harms of firearm injuries pose an economic burden on society. Fatal and nonfatal firearm injury costs in the U.S. were estimated providing up-to-date economic burden estimates. METHODS: Counts of nonfatal firearm injuries were obtained from the 2019-2020 Healthcare Cost and Utilization Project Nationwide Emergency Department Sample. Data on nonfatal injury intent were obtained from the National Electronic Injury Surveillance System - Firearm Injury Surveillance System. Counts of deaths (firearm as underlying cause) were obtained from the 2019-2020 multiple cause-of-death mortality data from the National Vital Statistics System. Analyses were conducted in 2023. RESULTS: The total cost of firearm related injuries and deaths in the U.S. for 2020 was $493.2 billion, a 16 percent increase compared with 2019. There are significant disparities in the cost of firearm deaths in 2019-2020, with non-Hispanic Black people, males, and young and middle-aged groups being the most affected. CONCLUSIONS: Most of the nonfatal firearm injury-related costs are attributed to hospitalization. These findings highlight the racial/ethnic differences in fatal firearm injuries and the disproportionate cost burden to urban areas. Addressing this important public health problem can help ameliorate the costs to our society from the rising rates of firearm injuries.

Transient Neurologic Deficits Following Intramuscular Epinephrine Administration for the Treatment of Anaphylaxis.

Anaphylaxis is an acute, potentially life-threatening severe allergic reaction commonly caused by foods, insect stings, and medications. Intramuscular epinephrine is the cornerstone of treatment for anaphylaxis in order to reverse immediate symptoms and prevent progression to life-threatening hemodynamic or respiratory collapse. By nature of its mechanism of action, epinephrine may induce a number of neurovascular-related adverse effects; even at usual therapeutic doses. Rarely described adverse events include transient ischemic attacks, ischemic stroke, intracerebral hemorrhage, and myocardial infarction. These events may be observed more frequently in patients with cardiovascular risk factors including hypertension, hyperlipidemia, and diabetes mellitus. We present a case of transient neurologic deficits in a patient with underlying cardiovascular disease related to intramuscular epinephrine use for the treatment of anaphylaxis. This case serves to further highlight serious adverse neurologic events that may result from intramuscular epinephrine administration.

Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults: A Guidance Statement From the American College of Physicians (Version 2).

DESCRIPTION: The purpose of this updated guidance statement is to guide clinicians on screening for colorectal cancer (CRC) in asymptomatic average-risk adults. The intended audience is all clinicians. The population is asymptomatic adults at average risk for CRC. METHODS: This updated guidance statement was developed using recently published and critically appraised clinical guidelines from national guideline developers since the publication of the American College of Physicians' 2019 guidance statement, "Screening for Colorectal Cancer in Asymptomatic Average-Risk Adults." The authors searched for national guidelines from the United States and other countries published in English using PubMed and the Guidelines International Network library from 1 January 2018 to 24 April 2023. The authors also searched for updates of guidelines included in the first version of our guidance statement. The Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument was used to assess the quality of eligible guidelines. Two guidelines were selected for adoption and adaptation by raters on the basis of the highest average overall AGREE II quality scores. The evidence reviews and modeling studies for these 2 guidelines were also used to synthesize the evidence of diagnostic test accuracy, effectiveness, and harms of CRC screening interventions and to develop our guidance statements. GUIDANCE STATEMENT 1: Clinicians should start screening for colorectal cancer in asymptomatic average-risk adults at age 50 years. GUIDANCE STATEMENT 2: Clinicians should consider not screening asymptomatic average-risk adults between the ages of 45 to 49 years. Clinicians should discuss the uncertainty around benefits and harms of screening in this population. GUIDANCE STATEMENT 3: Clinicians should stop screening for colorectal cancer in asymptomatic average-risk adults older than 75 years or in asymptomatic average-risk adults with a life expectancy of 10 years or less. GUIDANCE STATEMENT 4A: Clinicians should select a screening test for colorectal cancer in consultation with their patient based on a discussion of benefits, harms, costs, availability, frequency, and patient values and preferences. GUIDANCE STATEMENT 4B: Clinicians should select among a fecal immunochemical or high-sensitivity guaiac fecal occult blood test every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years as a screening test for colorectal cancer. GUIDANCE STATEMENT 4C: Clinicians should not use stool DNA, computed tomography colonography, capsule endoscopy, urine, or serum screening tests for colorectal cancer.

Engaging youth and parents in clinical pediatric research: A case-based example.

Background: Youth and parent engagement is a key component of clinical research. There are many ways to actively and meaningfully engage youth and parents as integral members of research teams, for example, through ad-hoc committees, advisory councils, or as co-leads on projects. When youth and parents are actively and meaningfully engaged in research projects, they share knowledge from their lived experiences to improve the quality and relevance of research. Methods: We describe a case-based example of engaging youth and parent research partners when co-designing a questionnaire to assess preferences for pediatric headache treatments, from both a researcher and youth/parent perspective. We also summarize best practices in patient and family engagement from the literature and pertinent guidelines to assist researchers with integrating patient and family engagement into their studies. Results: As researchers, we felt that the integration of a youth and parent engagement plan into our study significantly altered and strengthened questionnaire content validity. We encountered challenges throughout the process and detailed these experiences to help educate others about challenge mitigation and best practices in youth and parent engagement. As youth and parent partners, we felt that engaging in the process of questionnaire development was an exciting and empowering opportunity, and that our feedback was valued and integrated. Conclusions: By sharing our experience, we hope to catalyze thought and discussion around the importance of youth and parent engagement in pediatric research, with the goal of stimulating more appropriate, relevant, and high-quality pediatric research and clinical care in the future.

Use of a Guide-wire as an Adjunct for the Safe Removal of a 'Stuck' Indwelling Central Venous Catheter at Risk for Breaking.

Port-based central venous catheters may remain indwelling for years with subsequent fibrosis resulting in a "stuck" catheter. At time of removal, this can lead to complications such as catheter fracture or require additional operative techniques for safe extraction. We present a case utilizing a protocol wherein a J-tip guidewire is placed to assist in removal. We believe this serves the following beneficial functions: Mechanically, as the catheter stretches and collapses upon retraction it distributes the force circumferentially along the length of the catheter as well as reduces angular kinking, mitigating stress points of fracture. Second, in case of fracture, the distal portion should remain intubated by the J-tip guidewire, reducing embolic potential. Third, it allows more facile percutaneous transvenous retrieval if indicated. Though this does not represent a perfect solution to the "stuck" catheter problem, this technique increases safety and efficacy of removal with easy application at minimal additional cost.

Delayed Hyperpigmented Injection Site Reactions Due to Chronic Dupilumab Use.

Dupilumab is a humanized monoclonal antibody approved for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP), asthma, atopic dermatitis, eosinophilic esophagitis, and prurigo nodularis. The most common adverse reactions from dupilumab use are temporary injection site reactions and ocular surface reactions; however, a variety of both acute and delayed cutaneous reactions have also been described. We present a case of delayed hyperpigmented injection site reactions following chronic dupilumab use.

Fluid balance during physical work in the heat is not modified by the menstrual cycle when fluids are freely available.

We tested the hypothesis that women may be more at risk of becoming dehydrated during physical work in the heat in the early follicular phase (EF), compared with the late follicular (LF) and mid-luteal (ML) phases of the menstrual cycle when allowed free access to drink. Twelve healthy, eumenorrheic, unacclimated women (26 ± 5 yr) completed three trials (EF, LF, and ML phases) involving 4 h of exposure to 33.8 ± 0.8 °C, 54 ± 1% relative humidity. Each hour, participants walked on a treadmill for 30 min at a rate of metabolic heat production of 338 ± 9 W. Participants drank a cool, flavor-preferred non-caloric sport drink ad libitum. Nude body weight was measured pre- and post-exposure, and percent changes in body weight loss were interpreted as an index of changes in total body water. Total fluid intake and urine output were measured and sweat rate was estimated from changes in body mass corrected for fluid intake and urine output. Fluid intake was not different between phases (EF: 1,609 ± 919 mL; LF: 1,902 ± 799 mL; ML: 1,913 ± 671; P = 0.202). Total urine output (P = 0.543) nor sweat rate (P = 0.907) differed between phases. Percent changes in body mass were not different between phases (EF: -0.5 ± 0.9%; LF: -0.3 ± 0.9%; ML: -0.3 ± 0.7%; P = 0.417). This study demonstrates that the normal hormonal fluctuations that occur throughout the menstrual cycle do not alter fluid balance during physical work in the heat.NEW & NOTEWORTHY The effect of the menstrual cycle on fluid balance during physical work in the heat when fluids are freely available is unknown. This study demonstrates that fluid balance is not modified in women across three distinct phases of the menstrual cycle during physical work in the heat These results indicate that when women have free access to cool fluid during physical work in the heat, they respond similarly across all three phases to maintain fluid homeostasis across the menstrual cycle.

Transcriptomics secondary analysis of severe human infection with SARS-CoV-2 identifies gene expression changes and predicts three transcriptional biomarkers in leukocytes.

SARS-CoV-2 is the causative agent of COVID-19, which has greatly affected human health since it first emerged. Defining the human factors and biomarkers that differentiate severe SARS-CoV-2 infection from mild infection has become of increasing interest to clinicians. To help address this need, we retrieved 269 public RNA-seq human transcriptome samples from GEO that had qualitative disease severity metadata. We then subjected these samples to a robust RNA-seq data processing workflow to calculate gene expression in PBMCs, whole blood, and leukocytes, as well as to predict transcriptional biomarkers in PBMCs and leukocytes. This process involved using Salmon for read mapping, edgeR to calculate significant differential expression levels, and gene ontology enrichment using Camera. We then performed a random forest machine learning analysis on the read counts data to identify genes that best classified samples based on the COVID-19 severity phenotype. This approach produced a ranked list of leukocyte genes based on their Gini values that includes TGFBI, TTYH2, and CD4, which are associated with both the immune response and inflammation. Our results show that these three genes can potentially classify samples with severe COVID-19 with accuracy of ∼88% and an area under the receiver operating characteristic curve of 92.6--indicating acceptable specificity and sensitivity. We expect that our findings can help contribute to the development of improved diagnostics that may aid in identifying severe COVID-19 cases, guide clinical treatment, and improve mortality rates.

The General Factor of Personality (GFP) is associated with higher salary, having a leadership position, and working in a social job.

Previous studies have suggested that a general factor exists at the top of the hierarchal structure of personality. One interpretation of this General Factor of Personality (GFP) is that it reflects social effectiveness. Accordingly, in a large employee sample (N = 1267), we tested whether the GFP relates to several outcomes assumed to be linked with social effectiveness. Specifically, we examine whether the GFP is positively related to salary and to obtaining a leadership position. Additionally, we test whether high-GFP employees more often work in social occupations. Controlling for demographics and background variables, it was found that the GFP is indeed positively related to monthly (gross) salary. Moreover, employees occupying leadership positions in organizations scored higher on the GFP. GFP scores of employees in more social occupations (e.g., education, health care) were higher than of employees in other types of jobs (e.g., construction). GFP scores were also positively associated with the extent to which one has to relate to others in the job. Overall, the pattern of findings is in line with the notion of the GFP as relating to social effectiveness or adaptiveness, which are assumed to play a significant role in occupational outcomes.

Targeted therapeutic hypothermia protects against noise induced hearing loss.

Introduction: Exposure to occupational or recreational loud noise activates multiple biological regulatory circuits and damages the cochlea, causing permanent changes in hearing sensitivity. Currently, no effective clinical therapy is available for the treatment or mitigation of noise-induced hearing loss (NIHL). Here, we describe an application of localized and non-invasive therapeutic hypothermia and targeted temperature management of the inner ear to prevent NIHL. Methods: We developed a custom-designed cooling neck collar to reduce the temperature of the inner ear by 3-4°C post-injury to deliver mild therapeutic hypothermia. Results: This localized and non-invasive therapeutic hypothermia successfully mitigated NIHL in rats. Our results show that mild hypothermia can be applied quickly and safely to the inner ear following noise exposure. We show that localized hypothermia after NIHL preserves residual hearing and rescues noise-induced synaptopathy over a period of months. Discussion: This study establishes a minimally-invasive therapeutic paradigm with a high potential for rapid translation to the clinic for long-term preservation of hearing health.

Transcriptional response to mild therapeutic hypothermia in noise-induced cochlear injury.

Introduction: Prevention or treatment for acoustic injury has been met with many translational challenges, resulting in the absence of FDA-approved interventions. Localized hypothermia following noise exposure mitigates acute cochlear injury and may serve as a potential avenue for therapeutic approaches. However, the mechanisms by which hypothermia results in therapeutic improvements are poorly understood. Methods: This study performs the transcriptomic analysis of cochleae from juvenile rats that experienced noise-induced hearing loss (NIHL) followed by hypothermia or control normothermia treatment. Results: Differential gene expression results from RNA sequencing at 24 h post-exposure to noise suggest that NIHL alone results in increased inflammatory and immune defense responses, involving complement activation and cytokine-mediated signaling. Hypothermia treatment post-noise, in turn, may mitigate the acute inflammatory response. Discussion: This study provides a framework for future research to optimize hypothermic intervention for ameliorating hearing loss and suggests additional pathways that could be targeted for NIHL therapeutic intervention.

Successful Long-Term Aspirin Desensitization in a Pilot With Aspirin-Exacerbated Respiratory Disease.

Aspirin-exacerbated respiratory disease (AERD) is a triad of asthma, chronic rhinosinusitis with nasal polyposis (CRSwNP), and adverse respiratory reactions to the ingestion of aspirin/non-steroidal anti-inflammatory drugs.1 Patients with AERD are frequently plagued with CRSwNP that is difficult to manage with systemic steroids, nasal steroids, and surgical polypectomy, often requiring multiple endoscopic sinus surgeries and frequent otolaryngology follow-up.2,3 There are an abundance of therapies to treat CRSwNP in the setting of AERD, all with varying costs, efficacies, and indications for treatment.4 While limited by side effect profile, aspirin desensitization remains an effective, low-cost treatment for patients with CRSwNP and non-steroidal anti-inflammatory drug sensitivity.5 We describe a case of an active duty U.S. Air Force pilot with AERD whose CRSwNP was successfully treated with aspirin desensitization without detrimental effect on his flying status.