Genetic analysis of daf-18/PTEN missense mutants for starvation resistance and developmental regulation during Caenorhabditis elegans L1 arrest.

Mutations in the well-known tumor suppressor PTEN are observed in many cancers. PTEN is a dual-specificity phosphatase that harbors lipid and protein-phosphatase activities. The Caenorhabditis elegans PTEN ortholog is daf-18, which has pleiotropic effects on dauer formation, aging, starvation resistance, and development. Function of 3 daf-18 point-mutants, G174E, D137A, and C169S, had previously been investigated using high-copy transgenes in a daf-18 null background. These alleles were generated based on their mammalian counterparts and were treated as though they specifically disrupt lipid or protein-phosphatase activity, or both, respectively. Here, we investigated these alleles using genome editing of endogenous daf-18. We assayed 3 traits relevant to L1 starvation resistance, and we show that each point mutant is essentially as starvation-sensitive as a daf-18 null mutant. Furthermore, we show that G174E and D137A do not complement each other, suggesting overlapping effects on lipid and protein-phosphatase activity. We also show that each allele has strong effects on nucleocytoplasmic localization of DAF-16/FoxO and dauer formation, both of which are regulated by PI3K signaling, similar to a daf-18 null allele. In addition, each allele also disrupts M-cell quiescence during L1 starvation, though D137A has a weaker effect than the other alleles, including the null. Our results confirm that daf-18/PTEN is important for promoting starvation resistance and developmental arrest and that it is a potent regulator of PI3K signaling, and they highlight challenges of using genetic analysis to link specific DAF-18/PTEN enzymatic activities to particular phenotypes.

Burnett's "Cocaine" for dandruff.

Joseph Burnett manufactured the diethyl ether used for William T.G. Morton's public demonstration of inhaled surgical anesthesia on October 16, 1846 (Ether Day). A later Burnett product was a hairdressing oil claimed to prevent baldness and dandruff. It contained cocoa-nut oil and was called Cocoaine. In 1902 and 1903, it was sometimes advertised as Burnett's Cocaine (rather than Cocoaine), possibly to emulate the economic success of coca-based beverages such as Vin Mariani and Coca-Cola. Coca leaves are now decocainized before use in preparation of Coca-Cola, and the recovered cocaine is used for scientific and dwindling medical purposes.

Kety-Schmidt Application of Nitrous Oxide to Determine Cerebral Blood Flow.

In the 1940s, Seymour S. Kety and Carl F. Schmidt measured cerebral blood flow in awake humans by means of subanesthetic doses of inhaled nitrous oxide. The inhalation route obviated the need for an arterial injection of the indicator, and nitrous oxide had virtues of metabolic inertness, rapid diffusion through the blood-brain barrier, comparable blood and brain solubility, and ease of analytical detection. The technique was also applied to the heart. Follow-up work by Kety contributed to the development of brain scanning methods.

Anesthesia and COVID-19: What We Should Know and What We Should Do.

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.

Utility of fecal and serum anti-Saccharomyces cerevisiae antibodies in the diagnosis of Crohn's disease-like condition of the pouch.

BACKGROUND: Fecal antibodies against bacterial products may directly reflect the interaction between luminal bacteria and mucosal immunity, and assays for these antibodies may be clinically useful in the diagnosis and differential diagnosis of Crohn's disease-like (CDL) condition of the pouch. AIMS: This study aims to evaluate stool and serum anti-Saccharomyces cerevisiae antibodies (ASCA) in normal and diseased pouches, to assess the correlation between ASCA levels and endoscopic disease activity, and to ascertain the diagnostic utility of ASCA for CDL of the pouch. METHODS: One hundred eighty-nine patients with ileal pouches were prospectively enrolled and corresponding serum and pouch aspirate samples were collected. Fecal and serum ASCA levels were measured with enzyme-linked immunosorbent assay in a blinded fashion. Statistical analysis was then conducted using the signed rank test, Spearman correlation coefficients, and analysis of variance. RESULTS: Forty-three patients (22.8 %) had irritable pouch syndrome or normal pouches, 74 (39.2 %) had pouchitis/cuffitis, 52 (27.5 %) had CDL, 9 (4.8 %) had familial adenomatous polyposis, and 11 (5.8 %) had surgical complications of the pouch. Receiver operating characteristic curves to distinguish CDL from other categories of pouch dysfunction had an area under the curve (AUC) of 0.608 for fecal ASCA and an AUC of 0.517 for serum ASCA. Neither fecal nor serum ASCA correlated with endoscopic disease activity scores. There was a significant difference in the mean values of fecal ASCA between inflammatory and fistulizing CDL (0.27 vs. 0.03 ELISA units/ml, P < 0.05). CONCLUSIONS: Fecal ASCA appears to be better than serum ASCA in differentiating CDL from other pouch disorders, although this distinction may be of limited clinical utility.

A comparison of self-perceived health status in inflammatory bowel disease and irritable bowel syndrome patients from a Canadian national population survey.

OBJECTIVE: To determine whether differences exist in perceptions of physical health, mental health and stress levels between patients with inflammatory bowel disease (IBD) and patients with irritable bowel syndrome (IBS). METHODS: Data were obtained from the 2005 Canadian Community Health Survey, which had a sample size of 132,947 Canadians. Information on 4441 participants aged 19 years or older who reported that they had been diagnosed with Crohn's disease (n=474), ulcerative colitis (n=637) or IBS (n=3330) was analyzed regarding perceptions of their physical health, mental health, stress levels and activity levels. RESULTS: Overall, IBD patients reported being in fair to poor health (P<0.01) more often than IBS patients. In addition, IBS patients were more likely than IBD patients to report poor mental health status (P<0.01) and greater stress levels (P<0.01). In multivariate analyses, having IBS or IBD along with another chronic disease significantly increased the odds of reporting poorer health status. CONCLUSIONS: People with IBD were more likely to experience fair or poor general health. IBS patients reported higher levels of stress and poorer mental health than IBD patients. When IBS or IBD coexisted with another chronic condition, activity participation at home and at work was significantly more likely to be impaired.

Are perineal and luminal fistulas associated in Crohn's disease? A population-based study.

BACKGROUND & AIMS: We aimed to determine the frequency of fistulizing Crohn's disease (CD) and the relationship between perineal and luminal fistulas. METHODS: A population-based retrospective study was conducted by using the University of Manitoba Inflammatory Bowel Disease Research Registry. In 2003 there were 3192 IBD patients, 1595 had (CD), and 398 patients reported stricturing or fistulizing disease. Patients were interviewed and medical records were reviewed for phenotype assessment. Perineal fistulas were defined as those exiting in the perineum or fistulizing to sexual organs. Luminal fistulas were defined as arising from the bowel to organs other than the perineum. RESULTS: The prevalence of fistulizing CD was at most 22.1%. Of the 398 patients, 280 CD patients were eligible for full phenotype verification. Of these, 50 patients had both perineal and luminal fistulas, 151 had only perineal fistulas, and 79 had only luminal fistulas. Odds ratio (OR) for likelihood of having luminal fistula disease if perineal disease was present was 5.02 (95% confidence interval [CI], 3.40-7.42; P < .0001). Fistula patients were more likely to be diagnosed younger; 20-29 years (OR, 1.37; 95% CI, 1.02-1.85; P = .048). Compared with luminal fistulas, perineal fistulas had a higher likelihood to have colonic (OR, 3.32; 95% CI, 1.59-6.90; P = .002) rather than isolated ileal involvement (OR, 0.39; 95% CI, 0.21-0.72; P = .004). The comparison of fistulizing CD to non-fistulizing disease revealed a predisposition to colonic (OR, 1.41; 95% CI, 1.04-1.90; P = .032), ileocolonic (OR, 2.49; 95% CI, 1.91-3.26; P < .001), and upper gastrointestinal (OR, 3.87; 95% CI, 1.93-7.74; P < .0001) disease versus isolated ileal involvement (OR, 0.25; 95% CI, 0.19-0.34; P < .0001). CONCLUSIONS: There is a lower prevalence of fistulizing CD in this population than previously published. Perineal and luminal fistula diseases are highly related to one another but typically have distinct clinical associations.

Prenatal detection of a de novo Yqh-acrocentric translocation.

OBJECTIVES: To identify the extra chromosomal material on 46,XX,21p+ for prenatal diagnosis. DESIGN AND METHODS: Conventional cytogenetic studies using GTG (G bands by trypsin using Giemsa) and CBG (C bands by barium hydroxide using Giemsa) techniques were performed on chromosomes at metaphase obtained from cultured amniocytes and parental blood lymphocytes. Molecular cytogenetic techniques, QF-PCR (quantitative fluorescent polymerase chain reaction), FISH (fluorescent in-situ hybridization), and DA-DAPI (Distamycin A and 4,6-diamino-2-phenylindole) staining, were then used to clarify the extra material present on fetal chromosome 21 p. RESULTS: The extra material on fetal chromosome 21 p has originated from Yqh, most likely at PAR2 (the secondary pseudoautosomal region). The karyotype should be 46,XX,der(21)t(Y;21)(q12;p13)de novo.ish der(21)t(Y;21)(q12;p13) (EST Cdy16c07+). CONCLUSION: This case demonstrates the usefulness of molecular techniques in the investigation of rare chromosomal rearrangements.