Key

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

Sotagliflozin: a dual sodium-glucose co-transporter-1 and -2 inhibitor for the management of Type 1 and Type 2 diabetes mellitus.

AIMS: To evaluate the evidence for the novel dual sodium-glucose co-transporter-1 (SGLT1) and -2 (SGLT2) inhibitor, sotagliflozin, which may enhance the efficacy of SGLT2 inhibitors by additionally reducing intestinal glucose absorption. METHODS: The search terms 'sotagliflozin', 'LX4211', 'SGLT' and 'diabetes' were entered into PubMed. Evidence for the pharmacokinetics, pharmacodynamics, safety and efficacy of sotagliflozin in Type 1 and 2 diabetes was extracted from the retrieved literature, critically evaluated, and contextualized in relation to data on existing SGLT2 inhibitors. RESULTS: There is convincing evidence from a range of phase II and III clinical trials that sotagliflozin significantly improves glycaemic control in both Type 1 and Type 2 diabetes. Additional benefits, such as smaller postprandial plasma glucose excursions, lower insulin requirements, appetite suppression and weight loss have been documented. While this is encouraging, several safety concerns remain; a dose-dependent increase in the rate of diabetic ketoacidosis, diarrhoea and genital mycotic infection is apparent, although statistical exploration of the data regarding such events is currently lacking. Speculatively, use of a 200-mg rather than a 400-mg dose may help to limit unwanted effects. CONCLUSIONS: The current evidence for sotagliflozin in diabetes appears promising. Further studies sufficiently powered to assess present and emerging safety concerns, as well as to identify individuals for whom sotagliflozin may be of particular benefit/harm would now be informative for regulatory decision-making. Direct comparisons with existing SGLT2 inhibitors are also needed to determine relative safety/efficacy profiles for the different indications.

Workplace Environment Microaggressions in Otolaryngology-Head and Neck Surgery: An International Survey.

OBJECTIVE: To survey members of the otolaryngology community about their personal and observed experiences of being treated differently because of one's physical attributes, cultural norms, or preferences in the workplace. STUDY DESIGN: Cross-sectional survey. SETTING: International Electronic Survey. METHODS: We invited members of the international otolaryngology community including 3 European or American otorhinolaryngological Societies to complete a survey about personal/observed experience of differential treatment in the workplace related to age, biological sex; disability, gender identity, language proficiency, military experience, citizenship, ethnicity/race, political belief, and sexual orientation. Results were analyzed according to participant ethnicity/race (white vs non-white) and gender (male vs female) RESULTS: Four hundred seven participants completed the evaluations: 301 white (74%) and 106 non-white (26%) participants. Non-white participants reported significantly more experiences of differential treatment (microaggressions) than white participants (p < .05). Non-white participants more frequently felt that they needed to work harder for the same opportunities as their peers and were more likely to consider leaving a position because of an unsupportive environment. In general, females reported more frequent experiences with differential treatment related to sexual orientation, biological sex, and gender identity than males. CONCLUSION: We recognized reports of differential treatment as a proxy for microaggressions. Non-white members of the otolaryngology community self-report experiencing or observing more microaggressions than white members in the workplace. Acknowledging the existence and impact of microaggressions in the field of Otolaryngology is the first step towards cultivating an inclusive, diverse workforce where all members feel supported, validated, and welcomed.

Microaggressions in European versus American Workplace Environments of Otolaryngology-Head and Neck Surgery.

Objective: To compare the workplace experience of European and U.S. members of the otolaryngology community. Methods: European and U.S. otolaryngologists-head and neck surgeons (OTO-HNS) were surveyed through three otorhinolaryngological societies. We inquired about personal and observed experiences of differential treatment in the workplace related to age, biological sex, ethnicity, disability, gender identity, political belief, and sexual orientation. Results were compared according to the world region. Differential treatment was used as a proxy for microaggressions. Results: A total of 348 practitioners participated in the survey: 148 American and 230 European OTO-HNS. European OTO-HNS reported significantly higher proportions of observed or personal experiences of differential treatment based on age (p = .049), language proficiency (p = .027), citizenship (p = .001), hair texture (p = .017), height/weight (p = .002), clothing (p = .011), and professionalism (p = .002) compared with U.S. OTO-HNS. Differential treatment related to political belief (p = .043), socioeconomic status (p = .018), and ethnicity (p = .001) were higher in the United States compared with Europe. Feelings of exclusion (p = .027) and consideration of leaving their position (p = .001) were significantly higher in the United States compared with Europe. In both the United States and Europe, female OTO-HNS reported more frequent differential treatment related to biological sex than males. Conclusion: Differential treatment, or microaggressions, related to personal characteristics or behavior varied in the United States and Europe with more ethnicity-based microaggressions in the United States and physical characteristic-based microaggressions in Europe. In both regions, females were more subject to microaggressions than males. More efforts are needed to tackle microaggressions and discrimination in the clinical and academic workplace of the Western otolaryngology community. Level of Evidence: 4.

Laryngeal Trauma.

Laryngeal trauma is rare but potentially fatal. Initial evaluation includes efficient history and physical examination, imaging, bedside flexible laryngoscopy, and if necessary, operative endoscopic evaluation. Multiple classification systems exist for laryngeal trauma, and each has its merits. We recommend a patient-centered approach, rather than using the classification alone. Secure airways are the primary goal of acute management, with awake tracheostomy more often indicated over oral intubation compared with traumas not involving the larynx. More severe injuries typically require surgical intervention. Early intervention results in optimal voice and airway outcomes.

Prevalence of Laryngopharyngeal Reflux Symptoms, Dysphonia, and Vocal Tract Discomfort in Amateur Choir Singers.

INTRODUCTION: Vocal tract discomfort (VTD), dysphonia, and laryngopharyngeal reflux (LPR) symptoms are complaints frequently reported by amateur singers. There are two aims of this study. The first is to evaluate the prevalence of these symptoms using validated questionnaires. The second is to correlate singing-related variables with the questionnaire responses. METHODS: A total of 392 amateur choir singers (ACS) and 514 control subjects completed an online survey divided into four parts: (1) clinical and demographic characteristics, (2) training in singing and singing experience, (3) history of gastroesophageal reflux disease and LPR symptoms, (4) validated questionnaires. Specifically, the reflux symptom index (RSI), the vocal tract discomfort scale (VTDS), and the voice symptom scale (VoiSS) were included to analyze the actual burden related to LPR symptoms, VTD, and dysphonia. RESULTS: ACS demonstrated a healthier lifestyle and a lower prevalence of gastroesophageal reflux disease symptoms in comparison with control subjects. ACS scored significantly higher in VTDS and VoiSS than control subjects, while no differences in the RSI results were found. Significant correlations among the questionnaires' results were demonstrated. Occasional professional singing was the variable influencing VTDS and VoiSS results the most. CONCLUSION: ACS do not evidently manifest a higher impairment connected to LPR (RSI score), while they do report higher levels of voice (VoiSS score) and vocal tract (VTDS score) impairments, in comparison with control subjects. The relevant correlations among the PRO measures suggest that LPR symptoms, VTD, and dysphonia are related to each other. Given the relevant repercussion on the severity of VTD and dysphonia, providers should specifically ask about occasional professional singing when treating amateur singers.

ProEx C stain analysis in recurrent respiratory papillomatosis.

OBJECTIVES: We evaluated the presence and pattern of ProEx C stain, a marker for the proliferative capacity of cells, in laryngeal tissues, including benign, malignant, and recurrent respiratory papilloma (RRP) specimens, and compared it to hematoxylin and eosin staining for the presence of dysplasia. METHODS: We performed a retrospective study with chart review. RESULTS: A total of 26 specimens (9 benign, 7 malignant, 10 RRP) representing 21 patients were stained. ProEx C stained positive in the nuclei of laryngeal tissue, consistent with its localization in cervical cytology specimens. Seven of 9 benign and 7 of 10 RRP specimens stained positive. The benign specimens were mostly polyps. The malignant specimens were either well or moderately differentiated squamous cell carcinoma, and they stained strongly and diffusely. In benign and RRP specimens, the basal layer typically stained positive. Other areas of epithelium stained weakly in benign specimens and variably in RRP specimens. Current analysis of hematoxylin and eosin-stained RRP specimens revealed that 30% of specimens had at least moderate dysplasia and 80% exhibited viral changes (koilocytosis). CONCLUSIONS: ProEx C is a clean and reliable stain in laryngeal tissue, and stains positive in RRP. This study could not definitively correlate positive ProEx C staining in areas of greater dysplasia, although a trend was observed. Further studies are necessary to determine whether ProEx C can be used in triage of cases of clinically aggressive RRP for closer follow-up or frequent operative intervention.

Trauma-informed care improves management of paradoxical vocal fold movement patients.

OBJECTIVES: Vocal cord dysfunction (VCD) has been used by clinicians, primarily pulmonologists, to describe a variety of conditions in which the regulation and coordination of vocal fold movements are part of the explanation of cough or difficulty breathing, mainly paradoxical vocal fold motion disorder (PVFM). Prior studies show an intersection of mental health issues, primarily anxiety, and PVFM. We began incorporating mental health screening tools using the Life Events Checklist-5 (LEC-5) and the Posttraumatic Stress Disorder (PTSD) Checklist for Civilians (PCL-C) to assess symptomatology that may be related to traumatic life events. We seek to review the utility of these questionnaires for identifying patients who have experienced emotional trauma and use the principles of trauma-informed care currently lacking for PVFM. METHODS: We incorporated mental health screening tools using the PCL-C and LEC-5 for anyone referred to the Chicago Institute for Voice Care for VCD from the pulmonology clinic at our institution. Each patient underwent a comprehensive strobovideolaryngoscopy including provocative maneuvers to provoke paradoxical movements. RESULTS: A total of 16 subjects were analyzed; of those, seven (43.8%) screened positive for PTSD with the PCL-C. Overall, 58 traumatic events occurred among the 16 patients, with 31 (61.7%) of the traumatic events occurring in the seven positively screened for PTSD. CONCLUSIONS: Using the PCL-C and LEC-5, the principles of trauma-informed care principles were applied to patients initially referred for VCD who were found to have prior traumatic events. We recommend early mental health screening to establish a multidisciplinary team in PVFM. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:1508-1513, 2020.

Laryngeal electromyography findings in a patient with HIV, John Cunningham virus and bilateral true vocal fold motion impairment.

We present the findings from laryngeal electromyography (EMG) on a 33-year-old HIV-positive male who presented with decreased vocal endurance and a breathy voice. Management considerations were broadened by the history of John Cunningham (JC) virus recovered from his cerebrospinal fluid and the consequent diagnosis of progressive multifocal leukoencephalopathy. We reviewed the available literature on neuropathy, HIV, JC virus and how all these factors relate to voice disturbances. We present laryngeal EMG findings, discuss the benefit of electrodiagnostic studies, and offer an algorithm for interpreting this information and applying it to create the optimal care plan for these patients. As medical management of HIV-related diseases continues to improve, more patients may present with similar circumstances.

Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.

Human trifunctional protein catalyzes three steps in mitochondrial beta-oxidation of fatty acids, including the long chain 3-hydroxyacyl-CoA dehydrogenase step. Deficiency of this heterocomplex, which contains 4 alpha and 4 beta subunits, causes sudden unexplained infant death, a Reye-like syndrome, cardiomyopathy, or skeletal myopathy. We determined the molecular basis of this deficiency in a patient with neonatal presentation and later sudden death using reverse transcription and PCR amplification of his alpha subunit mRNA. We demonstrated a universal deletion of exon 3 (71 bp) in his mRNA. This deletion causes a frameshift and very early premature termination. Amplification of genomic DNA demonstrated that the patient was a compound heterozygote with two different mutations in the 5' donor splice site following exon 3: a paternally inherited G to A transversion at the invariant position +1 and a maternally inherited A to G mutation at position +3. Both allelic mutations apparently cause exon 3 skipping, resulting in undetectable levels of alpha subunit protein, and complete loss of trifunctional protein. This is the initial molecular characterization of trifunctional protein deficiency.

A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden neonatal death.

Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common known genetic disorder of fatty acid oxidation. Most (approximately 80%) cases are homozygous for a single mutation: A to G replacement at nucleotide 985 (A985G). MCAD deficiency typically presents in the second year of life as hypoketotic hypoglycemia associated with fasting and may progress to liver failure, coma, and death. Prompt diagnosis and management may prevent long-term sequelae. MCAD deficiency was verified by analysis of urinary acylglycine and serum acylcarnitine species from two neonates referred for diagnosis. Full-length cDNA and MCAD exon 7 and 11 genomic clones were prepared for sequence analysis. Normal and mutant cDNAs were expressed in bacteria, and enzymatic activity was assayed by the ferricenium hexaflurophosphate method. Four compound heterozygote individuals from two unrelated families with A985G on one allele and a novel G to A mutation at nucleotide 583 (G583A) as the second mutant allele presented with MCAD deficiency in the first week of life. The expressed G583A mutant protein lacks enzymatic activity. This novel mutation, G583A, is associated with severe MCAD deficiency causing hypoglycemia or sudden, unexpected neonatal death. This previously unrecognized phenotype of MCAD deficiency may contribute significantly to preventable infant deaths.

Special airway concerns in patients with mucopolysaccharidoses.

The mucopolysaccharidoses are comprised of hereditary disorders joined by errant degradation of mucopolysaccharides. The relatively infrequent opportunity to care for these patients is evidenced by a fairly small number of case reports and anecdotal information. Though lifespan is increasing, onset of respiratory pathology or involvement remains portentous. We present two cases that punctuate the need for insightful decision making while managing the airway for these patients.

Airway involvement and obstruction from granulomas in African-American patients with sarcoidosis.

Sarcoidosis is a global disorder whose breadth of organ involvement can often be underappreciated. Head and neck manifestations include involvement of the skin, salivary glands, sinonasal cavity, and larynx. Of cases of upper airway sarcoidosis, laryngeal sarcoidosis and airway compromise portend a greater risk of fatal outcomes. People representing all racial groups have been diagnosed with sarcoidosis. Although many studies have evaluated incidence and manifestations of sarcoidosis in multiple ethnicities, few studies have explored racial predilection for laryngeal involvement. However, assertions that disease severity and poor outcome may be tied to the African diaspora as well as related socio-economic and cultural realities have been recognized. We present our case series of six African-American patients diagnosed with sarcoidosis and presented with complaints of voice change and increased shortness of breath. Four of them required expeditious, surgical management of the airway. Two had limited supraglottic involvement and have avoided tracheotomy with aggressive and timely pharmacotherapeutic intervention and close clinical surveillance. Early recognition of laryngeal manifestations of sarcoidosis and airway compromise is essential to provide patients with conservative management without the need for aggressive surgical intervention.

Pneumomediastinum and retroperitoneal air after removal of papillomas with the microdebrider and jet ventilation.

OBJECTIVE: To discuss the complication of pneumothorax from alveolar rupture after transtracheal high-frequency jet ventilation and to present a case of pneumothorax, pneumomediastinum and pneumoperitoneum after jet ventilation coupled with use of the microdebrider. METHOD: Detailed case report. RESULTS: Unilateral pnuemothorax, subcutaneous emphysema, pneumomediastinum and retroperitoneal air discovered after jet ventilation for removal of airway papillomas resolved with conservative management. DISCUSSION: We discuss the difference between the respective patterns of air seepage in a peripheral alveolar injury versus a probable microperforation in the trachea. We also review the epidemiology of this rare disorder and its incidence in the African-American community. CONCLUSION: The recurrent nature of this disorder mandates multiple surgical procedures. Great care must be taken to eradicate disease and avoid complications. Pneumomediastinum in this setting can be managed conservatively.

Comparative Analysis of Characteristics of Voice Use Amidst Clergy.

The development of "Care of the Professional Voice" as a subspecialty of Otolaryngology-Head and Neck Surgery has expanded the concept of professional voice users. Although sometimes uncompensated, the clergy represents a unique group of voice users who are required to perform at a professional level. Additionally, cultural norms create great diversity in terms of style of delivery and typical venues, adding to the interest in this subset of professional voice users. We surveyed 403 respondents and found certain factors predictive of voice problems for members of the clergy. Age, length of sermon, and ethnicity were all found to be statistically significant indicators. Further investigations are needed.

The human pancreatic lipase-encoding gene: structure and conservation of an Alu sequence in the lipase gene family.

The isolation and characterization of the human gene (hPL) encoding pancreatic lipase is reported. The gene has 13 exons dispersed in about 20 kb of genomic DNA. A pseudogene of hPL was also partially characterized. An Alu sequence is conserved in the homologous introns of hPL and the lipoprotein lipase-encoding gene.

Deletion of the N-terminus of murine map2 by gene targeting disrupts hippocampal ca1 neuron architecture and alters contextual memory.

Microtubule-associated protein-2 (MAP2) is a brain specific A-kinase anchoring protein that targets the cyclic AMP-dependent protein kinase holoenzyme (PKA) to microtubules. Phosphorylation of MAP2 by different protein kinases is crucial for neuronal growth. The N-terminus of MAP2 contains the binding site for regulatory subunit II of cAMP-dependent protein kinase (PKA-RIIbeta). Using homologous recombination, we created a mutant line of mice (delta1-158) that express truncated MAP2 lacking the N-terminal peptide and the PKA binding site. Deletion of the PKA binding site from the MAP2 gene resulted in decreased efficiency of MAP2 phosphorylation. Biochemical and immunohistochemical studies demonstrate major changes in the morphology of hippocampal neurons in delta1-158 mice. Behavioral tests indicate that delta1-158 mice were impaired (exhibited less conditioned freezing) relative to Wild-Type (WT) controls during a test of contextual, but not during auditory cue, fear conditioning when tested at 8 weeks or 8 months of age. The delta1-158 mice displayed a heightened sensitivity to shock at 8 weeks, but not at 8 months of age. We conclude that PKA binding to MAP2 and MAP2 phosphorylation is essential for the selective development of contextual memory.

Nosocomial infections on nursing units with floors cleaned with a disinfectant compared with detergent.

Nosocomial infections on eight acute care nursing units in a tertiary care hospital was compared between two 3-month periods in which floors were cleaned with either disinfectant or detergent. Personnel performing infection surveillance were unaware of the cleaning product used. Surface cultures from selected floor sites were obtained at 3 and 6 months to assess microbial contamination. The combined nosocomial infection rate for the eight wards did not differ between disinfectant (8.0/100 patient discharges) and detergent (7.1/100). For individual wards, a significant difference in nosocomial infection rate between the two periods was observed in only one ward, favouring the detergent. No differences in floor contamination were observed.

Inherited long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency and a fetal-maternal interaction cause maternal liver disease and other pregnancy complications.

Fetal-maternal interactions are critical determinants of maternal health during pregnancy and perinatal outcome. This review explores the causative relationship of a fetal disorder of mitochondrial fatty acid oxidation, long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, and the serious maternal liver diseases of pregnancy-preeclampsia, the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet counts), and acute fatty liver of pregnancy. Features of the metabolic adaptation necessitated during the fetal-neonatal transition; common phenotypes of pediatric fatty acid oxidation disorders, including neonatal hypoketotic, hypoglycemia and hepatic crisis; and clinical abnormalities of HELLP and acute fatty liver of pregnancy are presented. Evidence that a common mutation in the alpha-subunit (LCHAD) of trifunctional protein, E474Q, is always one of the mutant alleles in fetal isolated LCHAD deficiency associated with these disorders of pregnancy that cause high maternal, fetal, and newborn morbidity and mortality is reviewed. Recommendations for molecular testing for LCHAD deficiency in families with life-threatening maternal liver disease are given.