STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1.

Store-operated Ca(2+) channels activated by the depletion of Ca(2+) from the endoplasmic reticulum (ER) are a major Ca(2+) entry pathway in nonexcitable cells and are essential for T cell activation and adaptive immunity. After store depletion, the ER Ca(2+) sensor STIM1 and the CRAC channel protein Orai1 redistribute to ER-plasma membrane (PM) junctions, but the fundamental issue of how STIM1 activates the CRAC channel at these sites is unresolved. Here, we identify a minimal, highly conserved 107-aa CRAC activation domain (CAD) of STIM1 that binds directly to the N and C termini of Orai1 to open the CRAC channel. Purified CAD forms a tetramer that clusters CRAC channels, but analysis of STIM1 mutants reveals that channel clustering is not sufficient for channel activation. These studies establish a molecular mechanism for store-operated Ca(2+) entry in which the direct binding of STIM1 to Orai1 drives the accumulation and the activation of CRAC channels at ER-PM junctions.

Escalating costs of self-injury mortality in the 21st century United States: an interstate observational study.

BACKGROUND: Estimating the economic costs of self-injury mortality (SIM) can inform health planning and clinical and public health interventions, serve as a basis for their evaluation, and provide the foundation for broadly disseminating evidence-based policies and practices. SIM is operationalized as a composite of all registered suicides at any age, and 80% of drug overdose (intoxication) deaths medicolegally classified as 'accidents,' and 90% of corresponding undetermined (intent) deaths in the age group 15 years and older. It is the long-term practice of the United States (US) Centers for Disease Control and Prevention (CDC) to subsume poisoning (drug and nondrug) deaths under the injury rubric. This study aimed to estimate magnitude and change in SIM and suicide costs in 2019 dollars for the United States (US), including the 50 states and the District of Columbia. METHODS: Cost estimates were generated from underlying cause-of-death data for 1999/2000 and 2018/2019 from the US Centers for Disease Control and Prevention's (CDC's) Wide-ranging ONline Data for Epidemiologic Research (WONDER). Estimation utilized the updated version of Medical and Work Loss Cost Estimation Methods for CDC's Web-based Injury Statistics Query and Reporting System (WISQARS). Exposures were medical expenditures, lost work productivity, and future quality of life loss. Main outcome measures were disaggregated, annual-averaged total and per capita costs of SIM and suicide for the nation and states in 1999/2000 and 2018/2019. RESULTS: 40,834 annual-averaged self-injury deaths in 1999/2000 and 101,325 in 2018/2019 were identified. Estimated national costs of SIM rose by 143% from $0.46 trillion to $1.12 trillion. Ratios of quality of life and work losses to medical spending in 2019 US dollars in 2018/2019 were 1,476 and 526, respectively, versus 1,419 and 526 in 1999/2000. Total national suicide costs increased 58%-from $318.6 billion to $502.7 billion. National per capita costs of SIM doubled from $1,638 to $3,413 over the observation period; costs of the suicide component rose from $1,137 to $1,534. States in the top quintile for per capita SIM, those whose cost increases exceeded 152%, concentrated in the Great Lakes, Southeast, Mideast and New England. States in the bottom quintile, those with per capita cost increases below 70%, were located in the Far West, Southwest, Plains, and Rocky Mountain regions. West Virginia exhibited the largest increase at 263% and Nevada the smallest at 22%. Percentage per capita cost increases for suicide were smaller than for SIM. Only the Far West, Southwest and Mideast were not represented in the top quintile, which comprised states with increases of 50% or greater. The bottom quintile comprised states with per capita suicide cost increases below 24%. Regions represented were the Far West, Southeast, Mideast and New England. North Dakota and Nevada occupied the extremes on the cost change continuum at 75% and - 1%, respectively. CONCLUSION: The scale and surge in the economic costs of SIM to society are large. Federal and state prevention and intervention programs should be financed with a clear understanding of the total costs-fiscal, social, and personal-incurred by deaths due to self-injurious behaviors.

Length and colonization rates of roots associated with arbuscular or ectomycorrhizal fungi decline differentially with depth in two northern hardwood forests.

Ectomycorrhizal (EM) and arbuscular mycorrhizal (AM) fungi are often studied independently, and thus little is known regarding differences in vertical distribution of these two groups in forests where they co-occur. We sampled roots at two soil depths in two northern hardwood stands in Bartlett, New Hampshire, co-dominated by tree species that associate with AM or EM fungi. Root length of both groups declined with depth. More importantly, root length of EM plant species exceeded that of AM plants at 0-10-cm depth, while AM exceeded EM root length at 30-50-cm depth. Colonization rates were similar between mineral and organic portions of the shallow (0-10 cm) samples for EM and AM fungi and declined dramatically with depth (30-50 cm). The ratio of EM to AM fungal colonization declined with depth, but not as much as the decline in root length with depth, resulting in greater dominance by EM fungi near the surface and by AM fungi at depth. The depth distribution of EM and AM roots may have implications for soil carbon accumulation as well as for the success of the associated tree species.

Human papillomavirus detection in oral rinses and history of tonsillectomy in U.S. adults.

PURPOSE: This study aims to elucidate any relationship between prior tonsillectomy and the presence of oropharyngeal HPV DNA found in screening mouth rinses. MATERIALS AND METHODS: A cross sectional study was conducted using the 2011-2014 National Health and Nutrition Examination Survey (NHANES). Participants between 40 and 69 were included in the study and medical, surgical, and sexual health history were recorded. Multivariable analyses were conducted to examine factors associated with HPV prevalence in oral rinse samples. RESULTS: A total of 4825 participants were recorded with 21.1 % having a history of tonsillectomy. In the no tonsillectomy group, 8.6 % of respondents had a positive oral rinse for HPV, while 7.2 % of those with a tonsillectomy had a positive rinse sample. There was no association between age and HPV prevalence (OR = 1.04, 95 % CI: [1.00-1.07]). When controlling for demographics, medical history, and sexual behaviors, tonsillectomy history was not shown to have an association with HPV (OR = 0.86, 95 % CI: [0.53-1.40]). However, men, Hispanics, smokers, and those with higher lifetime sexual partners had increased odds of having a positive HPV oral rinse sample which was statistically significant. CONCLUSION: Our data showed that a history of tonsillectomy was not significantly associated with the presence of HPV in an oral rinse. However, a significant relationship was seen between the presence of HPV in oral rinses and certain demographic factors such as male gender, Hispanic race, smoking history, and increased sexual partners.

Spatio-temporal variation of nitrate based on Landsat 8 in Playa Colorada bay, Sinaloa, Mexico.

Characterizing water quality in coastal waters through spatial observations is challenging, due to spatial and temporal variations in water composition. Nitrate, an important compound for water quality assessment, has received little attention in estimates made from satellite measurements, even though it can be estimated using models generated from multispectral images. Since nitrate is a non-optically active parameter that can be correlated with optically active parameters, it was related to bands of the visible and infrared spectrum, captured in Landsat-8 images, and used to generate empirical models to estimate the spatio-temporal variation of nitrate concentration in the Playa Colorada Bay, in the state of Sinaloa Northwest Mexico. Four sampling campaigns were performed, two in spring and two in fall. Nitrate nitrogen (NO3-N) concentration ranged between 0.69 and 1.80 mg/L, values higher than those recommended in the Mexican ecological criteria of water quality for the protection of marine aquatic life in coastal areas. Generated models showed a significant relationship (P < 0.05) between NO3-N and band reflectance in the infrared (band 5) and short-wave infrared (band 6 and band 7) spectra of Landsat-8 imagery. The B6 band appeared in all models selected to estimate NO3-N in the bay. These results evidence the potential of Landsat-8 images for the estimation of nitrate in the coastal waters of Sinaloa, México.

Cryoablation is associated with shorter length of stay and reduced opioid use in pectus excavatum repair.

PURPOSE: The use of intercostal nerve cryoablation (INC) is becoming increasingly common in patients undergoing pectus excavatum (PE) repair. This study sought to evaluate the use of INC compared to traditional use of thoracic epidural (TE). METHODS: A retrospective review of 79 patients undergoing PE repair with either INC or TE from May 2009 to December 2019 was conducted. The operations were performed by four surgeons who worked together at four different hospitals and have the same standardized practice. The primary outcome measure was hospital length of stay (LOS). Secondary variables included surgical time, total operating room time, operating room time cost, total hospital cost, inpatient opioid use, long-term opioid use after discharge, and postoperative complications. RESULTS: LOS decreased to 2.5 days in the INC group compared to 5 days in the TE group (p < 0.0001). Surgical time was increased in the INC group, but there was no difference in total OR time. The INC group experienced significantly lower hospital costs. Total hospital opioid administration was significantly lower in INC group, and there was a significant decrease in long-term opioid use in the INC group. CONCLUSIONS: INC is a newer modality that decreases LOS, controls pain, and results in overall cost savings. We recommend that INC be included in the current practice for postoperative pain control in PE patients undergoing Nuss procedure.

Zinc toxicity in seedlings of three trees from the Fabaceae associated with arbuscular mycorrhizal fungi.

Due to diverse human activities zinc (Zn) may reach phytotoxic levels in the soil. Here, we evaluated the differential sensibility of three Brazilian tree species from the Fabaceae to increasing soil Zn concentrations and its physiological response to cope with excess Zn. A greenhouse experiment was conducted with the species: Mimosa caesalpiniaefolia, Erythrina speciosa and Schizolobium parahyba, and the addition of 0, 200, 400 and 600 mg Zn kg-1 to the soil. Plants were harvested after three months of cultivation, and growth, root symbiosis, biochemical markers and elemental composition were analyzed. Soil Zn addition reduced seedling growth, irrespective of the species, with a strong reduction in M. caesalpiniaefolia. Regarding root symbiosis, in N2-fixing species, nitrogenase activity was reduced by the highest Zn concentrations. Zn addition caused plants nutritional imbalances, mainly in roots. The content of photosynthetic pigments in leaves decreased up to 40%, suggesting that high Zn contents interfered with its biosynthesis, and altered the content of foliar polyamines and free amino acids, depending on the species and the soil Zn concentration. Zn toxicity in M. caesalpiniaefolia plants was observed at available soil Zn concentrations greater than 100 mg kg-1 (DTPA-extractable), being the most sensitive species and E. speciosa was moderately sensitive. S. parahyba was a moderately tolerant species, which seems to be related to polyamines accumulation and to mycorrhizal association. This last species has the potential for revegetation of areas with moderately high soil Zn concentration and for phytostabilization purposes. Future research evaluating the tolerance to multiple metal stress under field conditions should confirm S. parayba suitability in Zn contaminated areas of tropical regions.

Particulate Air Pollutants, Brain Structure, and Neurocognitive Disorders in Older Women.

Introduction: An increasing number of studies have suggested that exposure to particulate matter (PM) may represent a novel - and potentially amendable - environmental determinant of brain aging. The current longitudinal environmental epidemiological study addressed some important knowledge gaps in this emerging field, which combines the study of air pollution and neuroepidemiology. The investigators hypothesized that long-term PM exposure adversely influences global brain volume and brain regions (e.g., frontal lobe or hippocampus) that are critical to memory and complex cognitive processing or that are affected by neuropathological changes in dementia. It was also hypothesized that long-term PM exposure results in neurovascular damage and may increase the risk of mild cognitive impairment (MCI) and -dementia. Methods: The investigators selected a well-characterized and geographically diverse population of older women (N = 7,479; average age = 71.0 ± 3.8 years at baseline) in the Women's Health Initiative (WHI) Memory Study (WHIMS) cohort (1996-2007), which included a subcohort (n = 1,403) enrolled in the WHIMS-Magnetic Resonance Imaging (WHIMS-MRI) study (2005-2006). Residence-specific yearly exposures to PM ≤ 2.5 µm in aerodynamic diameter (PM2.5) were estimated using a Bayesian maximum entropy spatiotemporal model of annual monitoring data (1999-2007) recorded in the U.S. Environmental Protection Agency (U.S. EPA) Air Quality System (AQS). Annual exposures (1996-2005) to diesel PM (DPM) were assigned to each residential census tract in a nationwide spatiotemporal mapping, based on a generalized additive model (GAM), to conduct census tract-specific temporal interpolation of DPM on-road estimates given by the U.S. EPA National-Scale Air Toxics Assessment Program. Multiple linear regression and multicovariate-adjusted Cox models were used to examine the associations, with statistical adjustment for multiple potential confounders. Results: The investigators found that participants had smaller brain volumes, especially in the normal-appearing white matter (WM), if they lived in locations with higher levels of cumulative exposure (1999-2006) to PM 2.5 before the brain MRI scans were performed. The associations were not explained by sociodemographic factors, socioeconomic status, lifestyle factors, or other clinical characteristics. Analyses showed that the adverse effect on brain structure in the participants was driven primarily by the smaller WM volumes associated with cumulative PM2.5 exposures, which were present in the WM divisions of the association brain area (frontal, parietal, and temporal lobes) and corpus callosum. Increased DPM exposures were associated with larger ventricular volume, suggesting an overall atrophic effect on the aging brains. The participants tended to have smaller gray matter (GM) volumes if they lived in areas with the highest (i.e., fourth quartile) estimated cumulative DPM exposure in the 10 years before the brain MRI scans, compared with women in the first to third quartiles. This observed association was present in the total brain GM and in the association brain cortices. The associations with normal-appearing WM varied by DPM exposure range. For women with estimated cumulative exposure below that of the fourth quartile, increased DPM estimates were associated with smaller WM volumes. However, for women with increased cumulative DPM exposures estimates in the fourth quartile, WM volumes were larger. This pattern of association was found consistently in the association brain area; no measurable difference was found in the volume of the corpus callosum. These observed adverse effects of cumulative exposure to PM2.5 (linking exposure with smaller WM volumes) and to DPM (linking exposure in the highest quartile with smaller GM volumes) were not significantly modified by existing cardiovascular diseases, diabetes mellitus, obesity, or measured white blood cell (WBC) count. MRI measurements of the structural brain showed no differences in small-vessel ischemic diseases (SVID) in participants with varying levels of cumulative exposure to PM2.5 (1999-2006) or DPM (1996-2005), and no associations between PM exposures and SVID volumes were noted for total brain, association brain area, GM, or WM. For neurocognitive outcomes followed until 2007, the investigators found no evidence for increased risk of MCI/dementia associated with long-term PM exposures. Although exploratory secondary analyses showed different patterns of associations linking PM exposures separately with MCI and dementia, none of the -results was statistically significant. A similar lack of associations between PM exposures and MCI/dementia was found across the subgroups, with no strong indications for effect modification by cardiovascular diseases, diabetes mellitus, obesity, or WBC count. Conclusions: The investigators concluded that their study findings support the hypothesized brain-structure neurotoxicity associated with PM exposures, a result that is in line with emerging neurotoxicological data. However, the investigators found no evidence of increased risk of MCI/dementia associated with long-term PM exposures.To better test the neurovascular effect hypothesis in PM-associated neurotoxic effects on the aging brain, the investigators recommend that future studies pay greater attention to selecting optimal populations with repeated measurements of cerebrovascular damage and address the possibility of selection biases accordingly. To further investigate the long-term consequence of brain-structure neurotoxicity on pathological brain aging, future researchers should take the pathobiologically heterogeneous neurocognitive outcomes into account and design adequately powered prospective cohort studies with improved exposure estimation and valid outcome ascertainment to assess whether PM-associated neurotoxicity increases the risks of pathological brain aging, including MCI and dementia.

Examining the Psychometric Properties of the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire in Two Samples of Youth with OCD.

Researchers have demonstrated that quality of life (QOL) is an important construct to measure in individuals with mental health disorders, yet only a small amount of research has been dedicated to examining QOL and its response to treatment in children and adolescents with obsessive-compulsive disorder (OCD). The current study explored the psychometric properties of a measure of QOL, the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), by examining the reliability, validity, and treatment sensitivity of this measure delivered in two separate RCTs for OCD (total N = 251 across both studies). Our results provide evidence for the reliability and validity of the PQ-LES-Q in adolescents with OCD (all Cronbach's alphas >.89, convergent validity correlations significant at the p < .05 level), but that an adaptation of the measure many be necessary for valid use in younger children with OCD.

Action potential amplitude as a noninvasive indicator of motor unit-specific hypertrophy.

Skeletal muscle fibers hypertrophy in response to strength training, with type II fibers generally demonstrating the greatest plasticity in regards to cross-sectional area (CSA). However, assessing fiber type-specific CSA in humans requires invasive muscle biopsies. With advancements in the decomposition of surface electromyographic (sEMG) signals recorded using multichannel electrode arrays, the firing properties of individual motor units (MUs) can now be detected noninvasively. Since action potential amplitude (APSIZE) has a documented relationship with muscle fiber size, as well as with its parent MU's recruitment threshold (RT) force, our purpose was to examine if MU APSIZE, as a function of its RT (i.e., the size principle), could potentially be used as a longitudinal indicator of MU-specific hypertrophy. By decomposing the sEMG signals from the vastus lateralis muscle of 10 subjects during maximal voluntary knee extensions, we noninvasively assessed the relationship between MU APSIZE and RT before and immediately after an 8-wk strength training intervention. In addition to significant increases in muscle size and strength (P < 0.02), our data show that training elicited an increase in MU APSIZE of high-threshold MUs. Additionally, a large portion of the variance (83.6%) in the change in each individual's relationship between MU APSIZE and RT was explained by training-induced changes in whole muscle CSA (obtained via ultrasonography). Our findings suggest that the noninvasive, electrophysiological assessment of longitudinal changes to MU APSIZE appears to reflect hypertrophy specific to MUs across the RT continuum.

Characteristics of Young Children with Obsessive-Compulsive Disorder: Baseline Features from the POTS Jr. Sample.

Pediatric obsessive-compulsive disorder (OCD) is a chronic and impairing condition that can emerge early in childhood and persist into adulthood. The primary aim of this paper is to examine the characteristics of a large sample of young children with OCD (age range from 5 to 8). The sample will be described with regard to: demographics, OCD symptoms/severity, family history and parental psychopathology, comorbidity, and global and family functioning. The sample includes 127 youth with a primary diagnosis of OCD who participated in a multi-site, randomized control clinical trial of family-based exposure with response prevention. Key findings include moderate to severe OCD symptoms, high rates of impairment, and significant comorbidity, despite the participants' young age. Discussion focuses on how the characteristics of young children compare with older youth and with the few other samples of young children with OCD. Considerations regarding generalizability of the sample and limitations of the study are discussed.

Longer Interset Rest Periods Enhance Muscle Strength and Hypertrophy in Resistance-Trained Men.

Schoenfeld, BJ, Pope, ZK, Benik, FM, Hester, GM, Sellers, J, Nooner, JL, Schnaiter, JA, Bond-Williams, KE, Carter, AS, Ross, CL, Just, BL, Henselmans, M, and Krieger, JW. Longer interset rest periods enhance muscle strength and hypertrophy in resistance-trained men. J Strength Cond Res 30(7): 1805-1812, 2016-The purpose of this study was to investigate the effects of short rest intervals normally associated with hypertrophy-type training versus long rest intervals traditionally used in strength-type training on muscular adaptations in a cohort of young, experienced lifters. Twenty-one young resistance-trained men were randomly assigned to either a group that performed a resistance training (RT) program with 1-minute rest intervals (SHORT) or a group that employed 3-minute rest intervals (LONG). All other RT variables were held constant. The study period lasted 8 weeks with subjects performing 3 total body workouts a week comprised 3 sets of 8-12 repetition maximum (RM) of 7 different exercises per session. Testing was performed prestudy and poststudy for muscle strength (1RM bench press and back squat), muscle endurance (50% 1RM bench press to failure), and muscle thickness of the elbow flexors, triceps brachii, and quadriceps femoris by ultrasound imaging. Maximal strength was significantly greater for both 1RM squat and bench press for LONG compared to SHORT. Muscle thickness was significantly greater for LONG compared to SHORT in the anterior thigh, and a trend for greater increases was noted in the triceps brachii (p = 0.06) as well. Both groups saw significant increases in local upper body muscle endurance with no significant differences noted between groups. This study provides evidence that longer rest periods promote greater increases in muscle strength and hypertrophy in young resistance-trained men.

Workforce perspective on racial and ethnic equity in early childhood autism evaluation and treatment: "The cornerstone of everything we do".

LAY ABSTRACT: Black and non-White Latinx children tend to receive autism diagnoses later in life and with a higher degree of impairment than White children. The purpose of this study was to learn what is currently helping as well as preventing Black and non-White Latinx children from getting access to autism evaluation and services. We held virtual interviews with 26 experts who work with autistic children and their families, including clinical providers, researchers, advocates, and policymakers/government representatives. From these interviews, we identified four themes that have an impact on equity in autism services: (1) who makes up the workforce, (2) workforce capacity and accessibility, (3) workforce payment structure, and (4) changes due to the COVID-19 pandemic. These findings show the need for improved workforce diversity, autism-specific education, payment structures, and additional support for workforce members to avoid burnout. To make childhood autism services more equitable, diversity in recruitment across training levels, cultural awareness, increased autism education for all pediatric providers, and partnerships with caregivers as experts must be prioritized. These investments in the autism workforce will allow professionals in the field to better meet the needs of children and families from Black and non-White Latinx communities and achieve equity in early childhood autism services.

New Medical Device and Therapeutic Approvals in Otolaryngology: State of the Art Review of 2022.

Objective: To review new drugs and devices relevant to otolaryngology approved by the Food and Drug Administration (FDA) in 2022. Data Sources: Publicly available FDA data on drugs and devices approved in 2022. Review Methods: A preliminary screen was conducted to identify drugs and devices relevant to otolaryngology. A secondary screen by members of the American Academy of Otolaryngology-Head and Neck Surgery's (AAO-HNS) Medical Devices and Drugs Committee differentiated between minor updates and new approvals. The final list of drugs and devices was sent to members of each subspecialty for review and analysis. Conclusion: A total of 1251 devices and 37 drugs were identified on preliminary screening. Of these, 329 devices and 5 drugs were sent to subspecialists for further review, from which 37 devices and 2 novel drugs were selected for further analysis. The newly approved devices spanned all subspecialties within otolaryngology. Many of the newly approved devices aimed to enhance patient experience, including over-the-counter hearing aids, sleep monitoring devices, and refined CPAP devices. Other advances aimed to improve surgical access, convenience, or comfort in the operating room and clinic. Implications for Practice: Many new devices and drugs are approved each year to improve patient care and care delivery. By staying up to date with these advances, otolaryngologists can leverage new innovations to improve the safety and quality of care. Given the recent approval of these devices, further studies are needed to assess long-term impact within the field of otolaryngology.

Natural orifice specimen extraction in laparoscopic colorectal surgery: transanal and transvaginal approaches.

BACKGROUND: This study was designed to evaluate the outcomes of patients who underwent various laparoscopic colorectal procedures with natural orifice specimen extraction (NOSE) at our institute over a 20-year period. Specifically, the study aimed to investigate whether transanal and transvaginal approaches are safe and effective alternatives for extracting the specimen during laparoscopic colorectal surgeries. METHODS: We analyzed a prospectively designed database of a consecutive series of patients who underwent various laparoscopic colorectal surgeries for different rectal pathologies between April 1991 and May 2011 at the Texas Endosurgery Institute. The selection criteria for the NOSE approach were based on disease entities, site and size of tumors, and distance of colorectal lesions from the anal verge. RESULTS: A total of 303 patients underwent laparoscopic colorectal procedures with the NOSE approach for specimen extraction, including 277 transanal and 26 transvaginal extractions. The operative time for procedures with transanal specimen extraction was 164.7 ± 47.5 min, the estimated blood loss was 87.5 ± 46.7 ml, and the rate of postoperative complications was 3.6 %. For laparoscopic right hemicolectomy with transvaginal specimen extraction, the operative time was 159 ± 27.1 min and the estimated blood loss was 83.5 ± 14.4 ml. Intraoperatively, transvaginal extraction was associated with 2 complications (7.7 %); however, this procedure was not associated with any postoperative complications. The length of hospital stay was 6.9 ± 2.8 and 5.5 ± 2.5 days for patients who underwent transanal extraction and transvaginal extraction, respectively. CONCLUSIONS: Both transanal and transvaginal specimen extractions in laparoscopic colorectal surgeries are safe and effective approaches with comparable postoperative complication rates. In comparison with transanal specimen extraction, transvaginal extraction is more complicated due to the anatomy of the pouch of Douglas. The transvaginal approach thus needs more effective extraction devices for preventing injury to adjacent organs, especially the sigmoid colon and rectum.

Geographic Variation in Otolaryngologist Intranasal Steroid Prescribing Patterns Among Medicare Beneficiaries.

BACKGROUND: Intranasal corticosteroids (INCS) are a commonly prescribed medication to treat various rhinological conditions. However, no prior studies have looked at factors and patterns that influence the rates of INCS prescriptions among Medicare beneficiaries in the United States. OBJECTIVE: This study aims to describe the patterns of INCS prescriptions by otolaryngologists for Medicare beneficiaries in the United States between 2013 and 2017. METHODS: Data on the most common INCS prescriptions by otolaryngologists for Medicare beneficiaries were obtained from the 2013 to 2017 Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (PUF) and the Part D Public Use Files from the Centers for Medicare and Medicaid Services (CMS). INCS prescriptions were analyzed by cost, state, provider, and regional temperature. State temperature data was collected through the National Centers for Environmental Information. RESULTS: From 2013 to 2017, the total claims per beneficiary for fluticasone, mometasone, and triamcinolone combined increased from 2.31 to 2.39. Combined cost/beneficiary was similar for mometasone and triamcinolone at 102.47 and 103.60 respectively, while it was much lower for fluticasone at 39.12. There was a strong correlation between otolaryngology providers per beneficiary in each state and total claims per state with a correlation coefficient of .79. Additionally, comparing the average state temperature to the claims/beneficiary yielded a moderately strong correlation coefficient of .44, suggesting that temperature was a possible factor for INCS prescription patterns. CONCLUSIONS: INCS prescriptions by otolaryngologists and the number of INCS beneficiaries have increased between 2013 and 2017. Over the same time period, the costs of fluticasone and triamcinolone have decreased while the cost of mometasone increased. Total providers by state correlated with claims per state. Additionally, average annual temperature was positively correlated with INCS claims per beneficiary in each state.

Virtual Versus In-Person Head and Neck Physical Examination Training in Medical Students: A Pilot Assessment.

OBJECTIVE: To compare the effect of virtual and in-person head and neck physical examination training events on medical student confidence in performing examination maneuvers and seeking mentorship from otolaryngology faculty and residents. METHODS: Training events were held with first-year medical student volunteers in 2020 (in-person) and 2021 (virtual). Participants in both cohorts were given didactics on head and neck cancer, trained to perform a head and neck physical examination, and demonstrated their clinical skills to otolaryngology faculty and residents. Pre- and post-training surveys were utilized to assess the following outcomes: participant head and neck cancer knowledge, confidence in performing examination maneuvers, and confidence in seeking mentorship in otolaryngology. Differences in outcomes between training settings were assessed by comparing participant survey responses pre- and post- training. RESULTS: Both in-person and virtual training modalities improved participant confidence in performing the physical examination. There was no significant difference in the degree of improvement between training types. In-person training significantly increased participant confidence in seeking mentorship from otolaryngology faculty and residents (P = .003), while virtual training did not (P = .194). CONCLUSION: Virtual training modalities are feasible methods of teaching the head and neck physical examination. Instruction through a video conferencing platform has the potential to be incorporated into traditional in-person medical education in a permanent fashion. This pilot study can inform future studies directly comparing in-person and virtual physical examination training modalities.

Pediatric trichotillomania.

Trichotillomania (TTM) is an impulse control disorder characterized by chronic hair-pulling, distress, and impairment. Although the negative effects of TTM are documented and often readily evident, there remains a paucity of psychopathology and treatment research on this disorder, particularly in pediatric populations. In an effort to improve assessment of pediatric TTM, several TTM-specific instruments for youth have now been developed to reliably identify symptoms and examine related phenomenology. Instrument development has now yielded instruments to evaluate TTM and related symptoms in the context of clinical trials of youth, and the first randomized controlled trial of any treatment for pediatric TTM was recently published. Using the initial pediatric TTM studies as building blocks, future research is now needed to create a stronger body of knowledge about the relative and combined efficacy of potential interventions for TTM in youth, as well as to examine the effects of TTM phenomenology and comorbidity on treatment outcome. Dissemination efforts must also be heightened for this knowledge to best reach these vulnerable populations.

STIM1 and calmodulin interact with Orai1 to induce Ca2+-dependent inactivation of CRAC channels.

Ca(2+)-dependent inactivation (CDI) is a key regulator and hallmark of the Ca(2+) release-activated Ca(2+) (CRAC) channel, a prototypic store-operated Ca(2+) channel. Although the roles of the endoplasmic reticulum Ca(2+) sensor STIM1 and the channel subunit Orai1 in CRAC channel activation are becoming well understood, the molecular basis of CDI remains unclear. Recently, we defined a minimal CRAC activation domain (CAD; residues 342-448) that binds directly to Orai1 to activate the channel. Surprisingly, CAD-induced CRAC currents lack fast inactivation, revealing a critical role for STIM1 in this gating process. Through truncations of full-length STIM1, we identified a short domain (residues 470-491) C-terminal to CAD that is required for CDI. This domain contains a cluster of 7 acidic amino acids between residues 475 and 483. Neutralization of aspartate or glutamate pairs in this region either reduced or enhanced CDI, whereas the combined neutralization of six acidic residues eliminated inactivation entirely. Based on bioinformatics predictions of a calmodulin (CaM) binding site on Orai1, we also investigated a role for CaM in CDI. We identified a membrane-proximal N-terminal domain of Orai1 (residues 68-91) that binds CaM in a Ca(2+)-dependent manner and mutations that eliminate CaM binding abrogate CDI. These studies identify novel structural elements of STIM1 and Orai1 that are required for CDI and support a model in which CaM acts in concert with STIM1 and the N terminus of Orai1 to evoke rapid CRAC channel inactivation.