mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state.

Survival in the wild requires organismal adaptations to the availability of nutrients. Endosomes and lysosomes are key intracellular organelles that couple nutrition and metabolic status to cellular responses, but how they detect cytosolic ATP levels is not well understood. Here, we identify an endolysosomal ATP-sensitive Na(+) channel (lysoNa(ATP)). The channel is a complex formed by two-pore channels (TPC1 and TPC2), ion channels previously thought to be gated by nicotinic acid adenine dinucleotide phosphate (NAADP), and the mammalian target of rapamycin (mTOR). The channel complex detects nutrient status, becomes constitutively open upon nutrient removal and mTOR translocation off the lysosomal membrane, and controls the lysosome's membrane potential, pH stability, and amino acid homeostasis. Mutant mice lacking lysoNa(ATP) have much reduced exercise endurance after fasting. Thus, TPCs make up an ion channel family that couples the cell's metabolic state to endolysosomal function and are crucial for physical endurance during food restriction.

Analysis of Cephalometric Differences of the Midface and Upper Face in Males and Females: A Radiographic Study.

Gender affirmation facial surgery (GAFS) is an important component in treating gender dysphoria among transgender individuals by addressing gender incongruence of the face. There is a paucity of literature describing objective characterizations of the anatomic differences between male and female faces. In this study, cephalometric measurements were taken on routine CT imaging performed on cisgender patients between 2017 and 2020. Specifically defined cephalometric landmarks of the upper and midface were measured and compared between male and female cohorts. Thirty-eight patients, 19 male and 19 female, were identified for this study. Significant differences were identified in the frontal prominence, orbital size, malar height, bizygomatic width, nose, and upper lip, with moderate rates of specificity for each gender. Some important ratios are also presented. Differences in the malar region and the orbit highlight the importance of these areas as a point of focus for GAFS. These cephalometric findings provide objective evidence and parameters for perceived anatomic differences in male and female faces. In addition, they help both corroborate current surgical techniques as well as guide future approaches to GAFS.

Survival outcomes of patients with subglottic squamous cell carcinoma : a study of the National Cancer Database.

BACKGROUND: Subglottic squamous cell carcinoma (SCC) represents less than 5% of all laryngeal cancers. Our objective was to better characterize survival using the National Cancer Database (NCDB) registry from 2004 to 2015. RESULTS: 403 patients met inclusion criteria. 63.8% presented with advanced-stage disease. Treatment regimens were as follows: 15.9% underwent surgery alone, 16.9% underwent surgery followed by adjuvant therapy, and 67.2% underwent primary chemo/radiation (C/RT). Five-year overall survival (OS) was 58.6% for Stage I and II patients, 49.1% for Stage III, and 36.3% for stage IV. Adjusted OS for all-stage patients was worse with C/RT compared to upfront surgery (40.6% vs. 58.4%; HR 1.83 [95%CI 1.29-2.61] p < 0.001) and adjusted OS for stage 4 disease was significantly worse with C/RT compared to surgery (26.0% vs. 45.2%, HR 1.79 [95%CI 1.17-2.73] p = 0.007). CONCLUSION: Majority of patients were treated with primary C/RT. Adjusted survival favors upfront surgery versus C/RT, especially in patients with Stage IV disease.

Betel Quid Use and Oral Cancer in a High-Risk Refugee Community in the USA: The Effectiveness of an Awareness Initiative.

Betel nut (BN) is a psychoactive oral carcinogen that is commonly used among Asian communities. This study aims to investigate BN usage patterns and the effectiveness of a visually guided educational initiative in a high-risk refugee population. All adult patients presenting to a private practice clinic, free community clinic, or health fair in the refugee community of Clarkston, Georgia during days when survey staff were present were approached for the study. Participants were first categorized into a familiar and unfamiliar cohort depending on participant-reported familiarity with BN. Depending on familiarity, subjects were then administered a pre-intervention test surveying health awareness for BN and usage patterns where relevant; subsequently, a visually guided educational brochure was reviewed, and a post-intervention test was administered. Results were statistically analyzed (STATA 12). Forty-eight participants were surveyed for the familiar cohort and 25 for the unfamiliar cohort. Among the familiar cohort, South and Southeast Asians comprised 91% of participants. On frequency of use, 42.8% reported social, 28.6% reported usage during celebrations only, and 28.6% reported daily. The most common reasons for use were for taste (40.9%), enjoyment (38.6%), and addiction (25%). Among the familiar cohort, 75% believed BN was harmful for health compared to 8% among the unfamiliar (p < 0.0001). In the familiar cohort, 52.3% believed BN alone could cause cancer compared to 4% among the unfamiliar (p < 0.0001). Following the educational intervention, 100% of participants believed BN mastication is harmful in both cohorts (p < 0.01), while 87.5% of participants in both cohorts recognized that BN alone could cause cancer (p < 0.0007). This study illustrates gaps in understanding regarding oral cancer and the health consequences of chronic BN mastication, as well as the efficacy of a visually guided educational brochure to improve participant knowledge among a high-risk refugee population.

Treatment and survival vary by race/ethnicity in patients with anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is the rarest type of thyroid cancer and has the lowest overall survival. To the authors' knowledge, the impact of socioeconomic status and race/ethnicity has not yet been described. METHODS: Data regarding 719 patients diagnosed with their first primary malignant ATC from January 1, 1998 to December 31, 2011 in the Surveillance, Epidemiology, and End Results program registries were examined. Differences in receipt of thyroidectomy, radiotherapy, and lymph node examination were examined by race/ethnicity. Survival also was examined by race/ethnicity. RESULTS: Nearly 70% of patients were non-Hispanic white, and 55.4% of patients received treatment. Tumor size (P = .13), lymph node involvement (P = .60), and residence in high poverty neighborhoods (P = .08) did not vary by race/ethnicity. Nonwhite patients were more likely to receive no treatment (adjusted odds ratio, 0.29; 95% confidence interval [95% CI], 0.16-0.54). When receipt of radiotherapy was adjusted for, nonwhite patients had a higher risk of overall death (adjusted hazards ratio [aHR], 1.24; 95% CI, 1.01-1.54), although not disease-specific death (aHR, 1.14; 95% CI, 0.92-1.42). Patients living in areas of high poverty had lower overall survival (aHR, 1.54; 95% CI, 1.09-2.18) and disease-specific survival (aHR, 1.68; 95% CI, 1.19-2.36). CONCLUSIONS: In this population-based study of patients with ATC, nonwhite patients were found to be less likely to receive treatment. Furthermore, nonwhite patients had poorer overall survival, and patients living in areas of high poverty had both worse overall and disease-specific survival. Racial/ethnic and socioeconomic disparities appear to exist in the treatment and survival of patients with ATC. Cancer 2018;124:1780-90. © 2018 American Cancer Society.

Future growth of physicians and non-physician providers within the U.S. Dermatology workforce.

Trends in the training, supply, availability, career decisions, and retirement of US dermatology physicians are not well delineated. The current study evaluates whether growth in the dermatology workforce will keep pace with population expansion in the United States. A dermatologist supply model was projected to 2030 drawing on data from the American Academy of Dermatology, American Medical Association, Bureau of Labor Statistics, American Association of Medical Colleges, and other associations. The clinically active dermatologist workforce in 2015 was 36 per capita (1,000,000); entry following postgraduate training was age 30 with career separation at age 65 on average. Added to the provider model are physician assistants and nurse practitioners in dermatology practices. A linear regression micro simulation model based on age cohorts produced a per capita supply of dermatology providers of 61 (±3) per 1,000,000 by 2030, up from 47 in 2016. The dermatology workforce is growing faster than population expansion. Workforce estimates could be affected by changing trends in retirement and training of dermatology providers. Investments in training of nurse practitioners and physician assistants, in addition to training more doctors, may be an effective strategy for increasing access to care in populations with low dermatologist density.

Effective local anesthesia for onabotulinumtoxin A injections to treat hyperhidrosis associated with traumatic amputation.

BACKGROUND: Botulinum toxin type A (BTX-A) injections are an effective treatment for controlling hyperhidrosis at sites of amputation. Hyperesthesia associated with amputated limbs is a major barrier to performing this procedure under local anesthesia. OBJECTIVE: To present a novel method for improving local anesthesia with BTX-A injections. Methods & RESULTS: A 29-year-old military veteran with a below-the-knee amputation of his right leg was suffering from amputation site hyperhidrosis, which was impeding his ability to comfortably wear a prosthesis. Prior to presenting to our clinic, the patient received one treatment of BTX-A injections to his amputation stump while under general anesthesia for surgical repair of trauma-related injuries. In our dermatology clinic, we repeated the procedure using topical lidocaine-prilocaine (30 gm total) for local anesthesia. This provided effective relief of hyperhidrosis for 6 months, but the procedure was very painful (9/10 intensity). We repeated the same procedure 6 months later, using ice in addition to topical lidocaine-prilocaine (30 gm) for local anesthesia; this resulted in reduced pain (3/10 intensity) for the patient. CONCLUSIONS: We suggest using ice in combination with a topical anesthetic as an effective method for pain control that avoids general anesthesia in treating amputation-associated hyperhidrosis.

Role of semaphorin-1a in the developing visual system of the disease vector mosquito Aedes aegypti.

BACKGROUND: Despite the devastating impact of mosquito-borne illnesses on human health, very little is known about mosquito developmental biology, including development of the mosquito visual system. Mosquitoes possess functional adult compound eyes as larvae, a trait that makes them an interesting model in which to study comparative developmental genetics. Here, we functionally characterize visual system development in the dengue and yellow fever vector mosquito Aedes aegypti, in which we use chitosan/siRNA nanoparticles to target the axon guidance gene semaphorin-1a (sema1a). RESULTS: Immunohistochemical analyses revealed the progression of visual sensory neuron targeting that results in generation of the retinotopic map in the mosquito optic lobe. Loss of sema1a function led to optic lobe phenotypes, including defective targeting of visual sensory neurons and failed formation of the retinotopic map. These sema1a knockdown phenotypes correlated with behavioral defects in larval photoavoidance. CONCLUSIONS: The results of this investigation indicate that Sema1a is required for optic lobe development in A. aegypti and highlight the behavioral importance of a functioning visual system in preadult mosquitoes.

Student-run free clinics may enhance medical students' self-confidence in their clinical skills and preparedness for clerkships.

INTRODUCTION: Student-run free clinics (SRFCs) offer medical students a unique opportunity to develop their clinical, diagnostic, and social skills while providing care to medically underserved communities. This study aims to evaluate the value of SRFC involvement on students' self-reported confidence in various clinical domains and satisfaction with their medical education. METHODS: We conducted a single-center retrospective pre-post assessment at an urban academic institution among second- to fourth-year medical students. We administered a 25-item questionnaire capturing the scope of clinic involvement and assessing self-reported confidence in multiple clinical domains following a one-year-long participation in student-run free clinics. RESULTS: Fifty-six students completed the survey. Participation in SRFCs significantly increased self-reported confidence in patient history-taking (p < 0.001), performing oral presentations (p < 0.001) and physical exams (p < 0.001). Students also reported significantly greater confidence in working with translators (p < 0.001) or as part of an interprofessional team (p < 0.001) and understanding the needs of the population served (p < 0.001). Students also found SRCs to significantly improve their confidence in preparedness for clerkships (p < 0.001). SRFC involvement can improve medical students' confidence in their clinical and interpersonal skills and enhance preparedness for clerkships and working with diverse patient groups. CONCLUSION: SRFCs are a useful tool in the medical school curriculum that help bridge the gap between classroom learning and clinic and may encourage practice in medically underserved communities. SRFCs also integrate classroom material and clinical practice, although standardized evaluation metrics need to be developed. SRFCs should be incorporated as a learning experience by medical schools nationwide.

Head & Neck Trauma in the Geriatric Population.

Craniofacial trauma in the geriatric population is increasing as our population ages. Due to loss of bone quality and medical comorbidities, injuries for minor trauma can be severe. A more extensive medical evaluation is usually warranted in this population before proceeding with surgery. In addition, unique surgical considerations exist in the repair of atrophic and edentulous bony fractures. Some quality improvement measures have already been undertaken but more is needed to help standardize care in this vulnerable population.

Bone Union of Osseous Microvascular Free Tissue Transfer in Mandibular Reconstruction.

OBJECTIVES: Osseous microvascular free tissue transfer (MFTT) is the gold standard for reconstruction for most segmental mandibulectomy defects. The most common osseous MFTT utilized in reconstruction is the fibular, scapular, and osteocutaneous radial forearm (OCRF) free flap. We evaluated postoperative bone union as well as clinical complications following MFTT and the impact of various patient and reconstructive characteristics, including type of osseous MFTT. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care academic hospital. METHODS: This study examined patients who underwent osseous MFTT for mandibular defects from January 2017 to January 2019. RESULTS: An overall 144 osteotomies in 58 patients were evaluated. Of the 144 junctions, 28 (19.4%) showed radiographic nonunion. Patients who underwent preoperative (odds ratio [OR] = 0.30, P = .027) and postoperative (OR = 0.28, P = .003) radiation had a significantly lower bone union score. Time from surgery to postoperative imaging was associated with higher bone union scores (OR = 1.07, P = .024). When bone union scores were compared among types of MFTT, fibular (OR = 5.62, P = .008) and scapular (OR = 4.69, P = .043) MFTT had significantly higher scores than OCRF MFTT. Twelve (20.7%) patients had postoperative complications. There was no statistically significant correlation between clinical complications and various variables, including type of osseous MFTT. CONCLUSION: Pre- and postoperative radiation and time from surgery have an impact on bone union. Regarding the type of MFTT, fibular and scapular MFTT appeared to have higher bone union when compared with OCRF. There was no impact of bone union or type of osseous MFTT on clinical complications.

A Brief Executive Language Screen for Frontal Aphasia.

Aphasia assessment tools have primarily focused on classical aphasia type and severity, with minimal incorporation of recent findings that suggest a significant role of executive control operations in language generation. Assessment of the interface between language and executive functions is needed to improve detection of spontaneous speech difficulties. In this study we develop a new Brief Executive Language Screen (BELS), a brief tool specifically designed to assess core language and executive functions shown to be involved in spontaneous generation of language. Similar to other measures of aphasia, the BELS assesses articulation and core language skills (repetition, naming and comprehension). Unique additions to the BELS include assessments of spontaneous connected speech, word fluency (phonemic/semantic) and sentence completion (verbal initiation, inhibition and selection). One-hundred and eight healthy controls and 136 stroke patients were recruited. Confirmatory factor analysis was used to determine construct validity and logistic regression was used to evaluate the discriminative validity, informing the final version of the BELS. The results showed that the BELS is sensitive for articulation and nominal language deficits, and it measures executive aspects of spontaneous language generation, which is a hallmark of frontal dynamic aphasia. The results have encouraging theoretical and practical implications.

Pharyngeal Dystonia Mimicking Spasmodic Dysphonia.

OBJECTIVE: The aim of this study was to describe the presentation of pharyngeal dystonia (PD), which can occur as a focal or segmental dystonia with a primarily pharyngeal involvement for the discussion of treatment methods for controlling consequent symptoms. PD is specific to speech-related tasks. METHODS: A retrospective medical record review of four patients with PD was performed. RESULTS: All patients were initially misdiagnosed with adductor spasmodic dysphonia and failed standard treatment with botulinum toxin type A (BTX). On laryngoscopy, the patients were discovered to have segmental or focal dystonia primarily affecting the pharyngeal musculature contributing to their vocal manifestations. A novel treatment regimen was designed, which involved directing BTX injections into the muscles involved in spasmodic valving at the oropharyngeal level. After titrating to an optimal dose, all patients showed improvement in their voice and speech with only mild dysphagia. These patients have maintained favorable results with repeat injections at 6- to 12-week intervals. CONCLUSIONS: PD, or dystonia with predominant pharyngeal involvement, is a rare entity with vocal manifestations that are not well described. It can be easily mistaken for spasmodic dysphonia. PD is specific to speech-related tasks. A novel method of BTX injections into the involved muscles results in a significant improvement in voice without significant dysphagia.

Changes in thyroid cancer incidence, post-2009 American Thyroid Association guidelines.

BACKGROUND: The thyroid cancer incidence rate has tripled in the United States since the 1980s, especially among women and small-sized tumors. This trend has been attributed to increased detection due to the availability of ultrasound and fine-needle aspiration technology. In 2009, the American Thyroid Association (ATA) released revisions to their guidelines for well-differentiated thyroid cancers. OBJECTIVE: To examine trends in thyroid cancer incidence rates by tumor size and gender following the 2009 ATA guideline revisions. METHODS: Cases of differentiated thyroid cancer diagnosed from 2000 to 2012 were analyzed from the National Cancer Institute Surveillance Epidemiology and End Results program, 18 registries. Trends in incidence rates based on gender (males, females) and tumor size (< 1.0 cm, 1.0-2.9 cm, 3.0-3.9 cm, ≥ 4.0 cm) were analyzed using Joinpoint Regression and reported as the annual percentage change (APC). RESULTS: From 2000 to 2009, overall thyroid cancer incidence rates increased rapidly by about 8% per year in both sexes. Incidence rates increased across all tumor sizes, but especially in tumors 1.0 to 2.9 cm (men, APC = 7.7; women, APC = 7.8) and < 1.0 cm (men, APC = 7.8; women = 10.9) for both genders. Since 2009, the trend slowed in men (APC = 3.0) and women (APC = 2.8). The deceleration among females was confined to tumors less than 2.9 cm. Trends for all size groups in males remained constant from 2000 to 2012. CONCLUSION: The rapid increase in thyroid cancer incidence rates over the past three decades has recently slowed, especially among small-sized cancers and women, which coincides with the 2009 ATA guideline revisions. LEVEL OF EVIDENCE: 2c. Laryngoscope, 127:2437-2441, 2017.

The Risk of Vocal Fold Atrophy after Serial Corticosteroid Injections of the Vocal Fold.

OBJECTIVE: The aim of this study was to illustrate the risk of vocal fold atrophy in patients who receive serial subepithelial steroid injections for vocal fold scar. METHODS: This study is a retrospective case report of two patients who underwent a series of weekly subepithelial infusions of 10 mg/mL dexamethasone for benign vocal fold lesion. Shortly after the procedures, both patients developed a weak and breathy voice. The first patient was a 53-year-old man with radiation-induced vocal fold stiffness. Six injections were performed unilaterally, and 1 week later, he developed unilateral vocal fold atrophy with new glottal insufficiency. The second patient was a 67-year-old woman with severe vocal fold inflammation related to laryngitis and calcinosis, Raynaud's phenomenon, esophagean dysmotility, sclerodactyly, and telangiectasia (CREST) syndrome. Five injections were performed bilaterally, and 1 week later, she developed bilateral vocal fold atrophy with a large midline glottal gap during phonation. In both cases, the steroid-induced vocal atrophy resolved spontaneously after 4 months. OUTCOMES & IMPORTANCE: Serial subepithelial steroid infusions of the vocal folds, although safe in the majority of patients, carry the risk of causing temporary vocal fold atrophy when given at short intervals.

Coupling Underwater Superoleophobic Membranes with Magnetic Pickering Emulsions for Fouling-Free Separation of Crude Oil/Water Mixtures: An Experimental and Theoretical Study.

Oil/water separations have become an area of great interest, as growing oil extraction activities are increasing the generation of oily wastewaters as well as increasing the risk of oil spills. Here, we demonstrate a membrane-based and fouling-free oil/water separation method that couples carbon nanotube-poly(vinyl alcohol) underwater superoleophobic ultrafiltration membranes with magnetic Pickering emulsions. We demonstrate that this process is insensitive to low water temperatures, high ionic strength, or crude oil loading, while allowing operation at high permeate fluxes and producing high quality permeate. Furthermore, we develop a theoretical framework that analyzes the stability of Pickering emulsions under filtration mechanics, relating membrane surface properties and hydrodynamic conditions in the Pickering emulsion cake layer to membrane performance. Finally, we demonstrate the recovery and recyclability of the nanomagnetite used to form the Pickering emulsions through a magnetic separation step, resulting in an environmentally friendly, continuous process for oil/water separation.