Risk of SARS-CoV-2 Transmission During Flexible Laryngoscopy: A Systematic Review.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reportedly infected otolaryngologists disproportionately in the early parts of the coronavirus disease 2019 pandemic. Recommendations from national and international health organizations suggest minimizing the use of flexible laryngoscopy as a result. OBJECTIVE: To review evidence on the risks of aerosolization and transmission of SARS-CoV-2 from patients to health care personnel during endoscopy of the upper aerodigestive tract. EVIDENCE REVIEW: A comprehensive review of literature was performed on April 19, 2020, using the PubMed/MEDLINE (1966-April 2020), Embase (1975-April 2020), and Web of Science (1900-April 2020) databases. All English-language primary research studies were included if they assessed the transmission of SARS-CoV-2 or SARS-CoV-1 during procedures in the upper aerodigestive tract. The primary outcome measure was disease transmission among health care workers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for accuracy of reporting. FINDINGS: The queries for SARS-CoV-2 and SARS-CoV-1 identified 6 articles for systematic review. No studies included in this review provided data for SARS-CoV-2 transmission during flexible laryngoscopy. A total of 204 of 1264 health care workers (16.1%) had procedure-specific infections of SARS-CoV-1 or SARS-CoV-2. Among those, 53 of 221 (24.0%) were exposed during intubation, 1 of 15 (6.7%) during bronchoscopy, and 1 of 1 (100%) during endoscopy-assisted intubation. CONCLUSIONS AND RELEVANCE: A substantial lack of research precludes formal conclusions about the safety of flexible laryngoscopy and transmission of SARS-CoV-2 from patients to health care workers. The use of appropriate precautionary measures and personal protective equipment appears to reduce the risk of transmission. Given the uncertainty in transmission and the known benefits of safety precautions, upper airway endoscopy may be reasonable to perform if precautionary steps are taken

Divergent amino acid and sphingolipid metabolism in patients with inherited neuro-retinal disease

OBJECTIVES: The non-essential amino acids serine, glycine, and alanine, as well as diverse sphingolipid species, are implicated in inherited neuro-retinal disorders and are metabolically linked by serine palmitoyltransferase (SPT), a key enzyme in membrane lipid biogenesis. To gain insight into the pathophysiological mechanisms linking these pathways to neuro-retinal diseases we compared patients diagnosed with two metabolically intertwined diseases: macular telangiectasia type II (MacTel), hereditary sensory autonomic neuropathy type 1 (HSAN1), or both. METHODS: We performed targeted metabolomic analyses of amino acids and broad sphingolipids in sera from a cohort of MacTel (205), HSAN1 (25) and Control (151) participants. RESULTS: MacTel patients exhibited broad alterations of amino acids, including changes in serine, glycine, alanine, glutamate, and branched-chain amino acids reminiscent of diabetes. MacTel patients had elevated 1-deoxysphingolipids but reduced levels of complex sphingolipids in circulation. A mouse model of retinopathy indicates dietary serine and glycine restriction can drive this depletion in complex sphingolipids. HSAN1 patients exhibited elevated serine, lower alanine, and a reduction in canonical ceramides and sphingomyelins compared to controls. Those patients diagnosed with both HSAN1 and MacTel showed the most significant decrease in circulating sphingomyelins. CONCLUSIONS: These results highlight metabolic distinctions between MacTel and HSAN1, emphasize the importance of membrane lipids in the progression of MacTel, and suggest distinct therapeutic approaches for these two neurodegenerative diseases

Buffy the vampire slayer: what being Jewish has to do with it

This article examines the whiteness in the television series Buffy the Vampire Slayer. The author argues that the show’s overwhelming whiteness is a product of a generalized white anxiety about the numerical loss of white dominance across the United States and, in particular, in California. The article goes on to think through the role that Jewishness plays in the program, discussing the relationship between the apparently Anglo-American Buffy, played by a Jewish actor, and her sidekick, Willow, who is characterized as Jewish but is played by a non-Jewish actor. The evil master in the first series is given Nazi characteristics and the destruction that he wants to inflict carries connotations of the Holocaust. Structurally, Buffy is produced as the Jew who saves the United States from this demonic destruction. In this traumatic renarrativising, the Holocaust comes to stand for the white-experienced crisis of the loss of white supremacy in the United States. With this reading we can begin to understand the show’s popularity among early adult, predominantly white Americans

Structure and Functions of Pediatric Aerodigestive Programs: A Consensus Statement

Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients

Human Polycomb 2 Protein Is a SUMO E3 Ligase and Alleviates Substrate-Induced Inhibition of Cystathionine β-Synthase Sumoylation

Human cystathionine β-synthase (CBS) catalyzes the first irreversible step in the transsulfuration pathway and commits homocysteine to the synthesis of cysteine. Mutations in CBS are the most common cause of severe hereditary hyperhomocysteinemia. A yeast two-hybrid approach to screen for proteins that interact with CBS had previously identified several components of the sumoylation pathway and resulted in the demonstration that CBS is a substrate for sumoylation. In this study, we demonstrate that sumoylation of CBS is enhanced in the presence of human polycomb group protein 2 (hPc2), an interacting partner that was identified in the initial yeast two-hybrid screen. When the substrates for CBS, homocysteine and serine for cystathionine generation and homocysteine and cysteine for H2S generation, are added to the sumoylation mixture, they inhibit the sumoylation reaction, but only in the absence of hPc2. Similarly, the product of the CBS reaction, cystathionine, inhibits sumoylation in the absence of hPc2. Sumoylation in turn decreases CBS activity by ∼28% in the absence of hPc2 and by 70% in its presence. Based on these results, we conclude that hPc2 serves as a SUMO E3 ligase for CBS, increasing the efficiency of sumoylation. We also demonstrate that γ-cystathionase, the second enzyme in the transsulfuration pathway is a substrate for sumoylation under in vitro conditions. We speculate that the role of this modification may be for nuclear localization of the cysteine-generating pathway under conditions where nuclear glutathione demand is high

Recent Region-wide Declines in Caribbean Reef Fish Abundance

Profound ecological changes are occurring on coral reefs throughout the tropics, with marked coral cover losses and concomitant algal increases, particularly in the Caribbean region. Historical declines in the abundance of large Caribbean reef fishes likely reflect centuries of overexploitation. However, effects of drastic recent degradation of reef habitats on reef fish assemblages have yet to be established. By using meta-analysis, we analyzed time series of reef fish density obtained from 48 studies that include 318 reefs across the Caribbean and span the time period 1955–2007. Our analyses show that overall reef fish density has been declining significantly for more than a decade, at rates that are consistent across all subregions of the Caribbean basin (2.7% to 6.0% loss per year) and in three of six trophic groups. Changes in fish density over the past half-century are modest relative to concurrent changes in benthic cover on Caribbean reefs. However, the recent significant decline in overall fish abundance and its consistency across several trophic groups and among both fished and nonfished species indicate that Caribbean fishes have begun to respond negatively to habitat degradation

Gene expression profiling of mucinous ovarian tumors and comparison with upper and lower gastrointestinal tumors identifies markers associated with adverse outcomes.

PURPOSE: Advanced-stage mucinous ovarian carcinoma (MOC) has poor chemotherapy response and prognosis and lacks biomarkers to aid stage I adjuvant treatment. Differentiating primary MOC from gastrointestinal (GI) metastases to the ovary is also challenging due to phenotypic similarities. Clinicopathologic and gene-expression data were analyzed to identify prognostic and diagnostic features. EXPERIMENTAL DESIGN: Discovery analyses selected 19 genes with prognostic/diagnostic potential. Validation was performed through the Ovarian Tumor Tissue Analysis consortium and GI cancer biobanks comprising 604 patients with MOC (n = 333), mucinous borderline ovarian tumors (MBOT, n = 151), and upper GI (n = 65) and lower GI tumors (n = 55). RESULTS: Infiltrative pattern of invasion was associated with decreased overall survival (OS) within 2 years from diagnosis, compared with expansile pattern in stage I MOC [hazard ratio (HR), 2.77; 95% confidence interval (CI), 1.04–7.41, P = 0.042]. Increased expression of THBS2 and TAGLN was associated with shorter OS in MOC patients (HR, 1.25; 95% CI, 1.04–1.51, P = 0.016) and (HR, 1.21; 95% CI, 1.01–1.45, P = 0.043), respectively. ERBB2 (HER2) amplification or high mRNA expression was evident in 64 of 243 (26%) of MOCs, but only 8 of 243 (3%) were also infiltrative (4/39, 10%) or stage III/IV (4/31, 13%). CONCLUSIONS: An infiltrative growth pattern infers poor prognosis within 2 years from diagnosis and may help select stage I patients for adjuvant therapy. High expression of THBS2 and TAGLN in MOC confers an adverse prognosis and is upregulated in the infiltrative subtype, which warrants further investigation. Anti-HER2 therapy should be investigated in a subset of patients. MOC samples clustered with upper GI, yet markers to differentiate these entities remain elusive, suggesting similar underlying biology and shared treatment strategies

Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?

Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease

Homologous Recombination Deficiency Should Be Tested for in Patients With Advanced Stage High-Grade Serous Ovarian Cancer Aged 70 Years and Over

OBJECTIVE: Due to limited data on homologous recombination deficiency (HRD) in older patients (≥ 70 years) with advanced stage high grade serous ovarian cancer (HGSC), we aimed to determine the rates of HRD at diagnosis in this age group. METHODS: From the Phase 3 trial VELIA the frequency of HRD and BRCA1/2 pathogenic variants (PVs) was compared between younger (\u3c 70 years) and older participants. HRD and somatic(s) BRCA1/2 pathogenic variants (PVs) were determined at diagnosis using Myriad myChoice® CDx and germline(g) BRCA1/2 PVs using Myriad BRACAnalysis CDx®. HRD was defined if a BRCA PV was present, or the genomic instability score (GIS) met threshold (GIS ≥ 33 & ≥ 42 analyzed). RESULTS: Of 1140 participants, 21% were ≥ 70 years. In total, 26% (n = 298) had a BRCA1/2 PV and HRD, 29% (n = 329) were HRD/BRCA wild-type, 33% (n = 372) non-HRD, and 12% HR-status unknown (n = 141). HRD rates were higher in younger participants, 59% (n = 476/802), compared to 40% (n = 78/197) of older participants (GIS ≥ 42) [p \u3c 0.001]; similar rates demonstrated with GIS ≥ 33, 66% vs 48% [p \u3c 0.001]. gBRCA PVs observed in 24% younger vs 8% of older participants (p \u3c 0.001); sBRCA in 8% vs 10% (p = 0.2559), and HRD (GIS ≥ 42) not due to gBRCA was 35% vs 31% (p = 0.36). CONCLUSIONS: HRD frequency was similar in participants aged \u3c 70 and ≥ 70 years (35% vs 31%) when the contribution of gBRCA was excluded; rates of sBRCA PVs were also similar (8% v 10%), thus underscoring the importance of HRD and BRCA testing at diagnosis in older patients with advanced HGSC given the therapeutic implications