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Purpose: This study evaluated the role of the Pediatric Sleep Questionnaire (PSQ) and associated subscales in predicting the severity of obstructive sleep apnea (OSA) in children referred for attended polysomnography (PSG)., Methods: This is a retrospective study of children (0-18 years) who completed PSQs the night of their initial diagnostic PSG (2019-2020). We excluded children with previous PSG, positive airway pressure titrations, or underlying genetic or craniofacial syndromes. Area under the receiver operating characteristic curve (AUC [95%CIs]) were estimated for prediction of varying severities of obstructive apnea-hypopnea index (oAHI > 2, 5, 10, and 25/h) by the PSQ's sleep-related breathing disorders (SRBD) scale and subscales., Results: Of 477 children, median (IQR) age at PSG was 5.7 (4.3); 60% of children were male, 21% were obese, and 4% had oAHI > 25/h. SRBD score did not improve discrimination of OSA cases at any oAHI threshold, with AUC CI that crossed 50% at all severities. Snoring subscale scores were predictive at oAHI > 2/h (AUC = 64.5% [59.5-69.5%]), oAHI > 5/h (AUC = 64.3% [59.6-69.0%]), and oAHI > 10 (AUC = 67.2% [62.0-72.4%]) thresholds, but were not predictive at oAHI > 25/h. The addition of demographic data (age and gender) improved the classification of the SRBD scale., Conclusions: When utilized in children referred for attended PSG due to concerns for an underlying sleep disorder, the PSQ snoring subscale was more predictive of OSA at varying thresholds than the SRBD scale. While the original intent of the PSQ was not for the purpose of predicting severity in children referred for PSG, future directions include augmenting the questionnaire with additional clinical variables., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: The increasing availability of clinical imaging tests (especially CT and MRI) that directly quantify adipose tissue has led to a rapid increase in studies examining the relationship of visceral, subcutaneous, and overall adiposity to cancer survival. To summarize this emerging body of literature, we conducted a systematic review and meta-analysis of imaging-measured as well as anthropometric proxies for adipose tissue distribution and cancer survival across a wide range of cancer types., Methods: Using keywords related to adiposity, cancer, and survival, we conducted a systematic search of the literature in PubMed and MEDLINE, Embase, and Web of Science Core Collection databases from database inception to 30 June 2021. We used a random-effect method to calculate pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) within each cancer type and tested for heterogeneity using Cochran's Q test and the I 2 test., Results: We included 203 records for this review, of which 128 records were utilized for quantitative analysis among 10 cancer types: breast, colorectal, gastroesophageal, head and neck, hepatocellular carcinoma, lung, ovarian, pancreatic, prostate, and renal cancer. We found that imaging-measured visceral, subcutaneous, and total adiposity were not significantly associated with increased risk of overall mortality, death from primary cancer, or cancer progression among patients diagnosed with these 10 cancer types; however, we found significant or high heterogeneity for many cancer types. For example, heterogeneity was similarly high when the pooled HRs (95% CI) for overall mortality associated with visceral adiposity were essentially null as in 1.03 (0.55, 1.92; I 2  = 58%) for breast, 0.99 (0.81, 1.21; I 2  = 71%) for colorectal, versus when they demonstrated a potential increased risk 1.17 (0.85, 1.60; I 2  = 78%) for hepatocellular carcinoma and 1.62 (0.90, 2.95; I 2  = 84%) for renal cancer., Conclusion: Greater adiposity at diagnosis (directly measured by imaging) is not associated with worse survival among cancer survivors. However, heterogeneity and other potential limitations were noted across studies, suggesting differences in study design and adiposity measurement approaches, making interpretation of meta-analyses challenging. Future work to standardize imaging measurements and data analyses will strengthen research on the role of adiposity in cancer survival., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The stargazer mouse mutation causes absence seizures that are more prolonged and frequent than any other petit mal mouse model. Stargazer mice also have an ataxic gait and vestibular problems, including a distinctive head-tossing motion. From the genotyping of a large intersubspecific cross, a panel of 53 recombinant DNAs between D15Mit29 and D15Mit2 has been assembled, and a fine genetic map of the stargazer region has been constructed on mouse Chromosome 15. The stargazer locus has been mapped between D15Mit30 and the parvalbumin gene, and six candidate genes have been excluded by genetic linkage analysis. A physical contig of YACs, BACs, and P1s stretching 1.1 Mb from D15Mit30 to the somatostatin receptor 3 gene is reported, and the DNA interval including the stargazer locus has been narrowed to 150 kb.

Cortistatin is a 14-residue putative neuropeptide with strong structural similarity to somatostatin and is expressed predominantly in cortical GABAergic interneurons of rats. Administration of cortistatin into the brain ventricles specifically enhances slow-wave sleep, presumably by antagonizing the effects of acetylcholine on cortical excitability. Here we report the identification of cDNAs corresponding to mouse and human preprocortistatin and the mRNA distribution and gene mapping of mouse cortistatin. Analysis of the nucleotide and predicted amino acid sequences from rat and mouse reveals that the 14 C-terminal residues of preprocortistatin, which make up the sequence that is most similar to somatostatin, are conserved between species. Lack of conservation of other dibasic amino acid residues whose cleavage by prohormone convertases would give rise to additional peptides suggests that cortistatin-14 is the only active peptide derived from the precursor. As in the rat, mouse preprocortistatin mRNA is present in GABAergic interneurons in the cerebral cortex and hippocampus. The preprocortistatin gene maps to mouse chromosome 4, in a region showing conserved synteny with human 1p36. The human putative cortistatin peptide has an arginine for lysine substitution, compared to the rat and mouse products, and is N-terminally extended by 3 amino acids.

Cyanogen (C2N2), a molecule with properties remarkably similar to carbon dioxide, differentially inhibits three of the four carbonic anhydrases reported here. Bovine carbonic anhydrase II shows 97% loss of esterase activity with no concommitant loss in hydratase activity. The hydratase and esterase activities of human carbonic anhydrase I are decreased by 80% and 55% respectively. Canine carbonic anhydrase shows similar results to human carbonic anhydrase I, retaining 29% hydratase and 62% esterase activity. Rabbit carbonic anhydrase sustained no loss of either hydratase or esterase activity. This inhibition occurs by an irreversible modification of the enzymes. The kinetic parameters for modified and unmodified enzymes were altered in a way that reflects the characteristic effect for each carbonic anhydrase.

The irreversible inhibition of carbonic anhydrase by cyanogen occurs by a unique mechanism. Cyanogen is an affinity label: it behaves like a carbodiimide and produces an intra-molecular cross-link without being incorporated. The nucleophile-labile cross-link is formed between a gamma-COOH of a Glu and an imidazole of a His with a 1:1:1 stoichiometry with the enzyme. The deletion of approximately 1 Glu and approximately 1 His was noted by amino acid analysis of enzymatically hydrolyzed carbonic anhydrase. The modified Glu was converted to 2,4-diaminobutanoic acid and quantitated by amino acid analysis. The presence and quantity of modified His was supported through high-resolution proton NMR analysis.