AuTomaTed Alcohol Misuse INterventions in a Bariatric Surgery Population: The ATTAIN Bariatric Pilot.

Introduction Alcohol screening and brief intervention has been shown to reduce unhealthy alcohol use, although widespread adoption into primary care practice has been slow. Patients undergoing bariatric surgery are at an increased risk of unhealthy alcohol use. The authors compared a novel, web-based screening tool called ATTAIN to usual care for real-world effectiveness and accuracy among bariatric surgery registry patients. Methods The authors analyzed the results of a quality improvement project that tested ATTAIN among bariatric surgery registry patients. Participants were stratified into 3 groups by surgery status (preoperative vs postoperative) and prior screening for unhealthy alcohol use (screened vs not screened in the past year). Participants in these 3 groups were divided into intervention plus usual care (n = 2249) and control (n = 2130) groups, with intervention being an email to complete ATTAIN, and control being usual care (eg, office-based screening). Primary outcomes included screening and positivity rates for unhealthy drinking behavior between groups. Secondary outcomes included positivity rates via ATTAIN vs usual care for individuals who were screened by both modalities. Chi-square test was used for statistical analysis. Results The overall screening rates were 67.4% (intervention arm) and 38.6% (control). The ATTAIN response rate was 47% of those invited. The overall positive screen rate was 7.7% (intervention) and 2.6% (control); p < .001 for both. For dual screened intervention participants, the positive screen rate was 10% (ATTAIN) vs 2% (usual care) with p < .001. Conclusion ATTAIN is a promising method of increasing screening and detection rates for unhealthy drinking behavior.

Latex Anaphylaxis Caused by Occupational Exposure to Balloons.

Latex allergies often develop by sensitization to latex allergens by repeated exposure. Because in recent years latex has been ubiquitous in medical equipment, health workers have a higher prevalence of latex allergies than the general population, and care must be taken to ensure workers' safety. We report a case of a female health care worker in her 20s who experienced a severe, biphasic anaphylactic reaction within minutes after being exposed to rubber balloons at a latex-free children's hospital. After being stabilized with epinephrine, dexamethasone, and fluid resuscitation, over a six-hour period, she was discharged home. En route home, her symptoms recurred, and she was admitted to the ICU for observation for impending respiratory failure. She was hospitalized for about 48 hours before being discharged home. She presented to the occupational medicine clinic a few days later for further management. No acute care was required and she was discharged. This case is consistent with occupational latex-induced anaphylaxis. Health personnel should be educated about the importance of compliance with latex allergy mitigation procedures, as well as the severe nature of hypersensitivity reactions that may occur in sensitized persons. It may be beneficial to address the social pressures that can contribute to noncompliance, as balloons are a common gift for children and may be viewed as an acceptable way to cheer up a sick child, tempting some staff to turn a blind eye to policy. The reasons for the policy, and for strict adherence, should be communicated clearly.

TFIID and Spt-Ada-Gcn5-acetyltransferase functions probed by genome-wide synthetic genetic array analysis using a Saccharomyces cerevisiae taf9-ts allele.

TAF9 is a TATA-binding protein associated factor (TAF) conserved from yeast to humans and shared by two transcription coactivator complexes, TFIID and SAGA. The essentiality of the TAFs has made it difficult to ascertain their roles in TFIID and SAGA function. Here we performed a genomic synthetic genetic array analysis using a temperature-sensitive allele of TAF9 as a query. Results from this experiment showed that TAF9 interacts genetically with: (1) genes for multiple transcription factor complexes predominantly involving Mediator, chromatin modification/remodeling complexes, and regulators of transcription elongation; (2) virtually all nonessential genes encoding subunits of the SWR-C chromatin-remodeling complex and both TAF9 and SWR-C required for expressing the essential housekeeping gene RPS5; and (3) key genes for cell cycle control at the G1/S transition, as well as genes involved in cell polarity, cell integrity, and protein synthesis, suggesting a link between TAF9 function and cell growth control. We also showed that disruption of SAGA by deletion of SPT20 alters histone-DNA contacts and phosphorylated forms of RNA polymerase II at coding sequences. Our results raise the possibility of an unappreciated role for TAF9 in transcription elongation, perhaps in the context of SAGA, and provide further support for TAF9 involvement in cell cycle progression and growth control.

A genomic screen for yeast vacuolar membrane ATPase mutants.

V-ATPases acidify multiple organelles, and yeast mutants lacking V-ATPase activity exhibit a distinctive set of growth defects. To better understand the requirements for organelle acidification and the basis of these growth phenotypes, approximately 4700 yeast deletion mutants were screened for growth defects at pH 7.5 in 60 mm CaCl(2). In addition to 13 of 16 mutants lacking known V-ATPase subunits or assembly factors, 50 additional mutants were identified. Sixteen of these also grew poorly in nonfermentable carbon sources, like the known V-ATPase mutants, and were analyzed further. The cwh36Delta mutant exhibited the strongest phenotype; this mutation proved to disrupt a previously uncharacterized V-ATPase subunit. A small subset of the mutations implicated in vacuolar protein sorting, vps34Delta, vps15Delta, vps45Delta, and vps16Delta, caused both Vma- growth phenotypes and lower V-ATPase activity in isolated vacuoles, as did the shp1Delta mutation, implicated in both protein sorting and regulation of the Glc7p protein phosphatase. These proteins may regulate V-ATPase targeting and/or activity. Eight mutants showed a Vma- growth phenotype but no apparent defect in vacuolar acidification. Like V-ATPase-deficient mutants, most of these mutants rely on calcineurin for growth, particularly at high pH. A requirement for constitutive calcineurin activation may be the predominant physiological basis of the Vma- growth phenotype.

DEAD-box RNA helicase Sub2 is required for expression of lacZ fusions in Saccharomyces cerevisiae and is a dosage-dependent suppressor of RLR1 (THO2).

RLR1 (THO2) encodes a novel, phylogenetically-conserved KEKE motif protein involved in transcription and transcription-associated recombination in Saccharomyces cerevisiae. One characteristic aspect of RLR1 function is its requirement for expression of the Escherichia coli lacZ reporter gene regardless of the yeast promoter to which it is fused. rlr1-1 was originally isolated (employing lacZ as a transcriptional reporter) as a suppressor of a mutation in the gene encoding Sin4, a subunit of the Mediator subcomplex of the RNA polymerase II (PolII) transcriptional machinery. To clarify the function of Rlr1, we performed a genetic screen for dosage-dependent suppressors of the cold-sensitive phenotype of rlr1-1. From this screen we isolated SUB2, encoding a conserved DEAD-box RNA helicase family member having roles in both pre-mRNA splicing and mRNA export in yeast, flies, and humans. We demonstrate that Sub2, like Rlr1, is required for lacZ to be expressed in yeast, and that sub2 mutants manifest rlr1-like growth defects. Our results are consistent with a hypothesis where expression of lacZ fusions in yeast preferentially requires a Sub2-mediated mRNP assembly/export pathway linked to transcription via Rlr1.

The RAVE complex is an isoform-specific V-ATPase assembly factor in yeast.

The regulator of ATPase of vacuoles and endosomes (RAVE) complex is implicated in vacuolar H(+)-translocating ATPase (V-ATPase) assembly and activity. In yeast, rav1 mutants exhibit a Vma(-) growth phenotype characteristic of loss of V-ATPase activity only at high temperature. Synthetic genetic analysis identified mutations that exhibit a full, temperature-independent Vma(-) growth defect when combined with the rav1 mutation. These include class E vps mutations, which compromise endosomal sorting. The synthetic Vma(-) growth defect could not be attributed to loss of vacuolar acidification in the double mutants, as there was no vacuolar acidification in the rav1 mutant. The yeast V-ATPase a subunit is present as two isoforms, Stv1p in Golgi and endosomes and Vph1p in vacuoles. Rav1p interacts directly with the N-terminal domain of Vph1p. STV1 overexpression suppressed the growth defects of both rav1 and rav1vph1, and allowed RAVE-independent assembly of active Stv1p-containing V-ATPases in vacuoles. Mutations causing synthetic genetic defects in combination with rav1 perturbed the normal localization of Stv1-green fluorescent protein. We propose that RAVE is necessary for assembly of Vph1-containing V-ATPase complexes but not Stv1-containing complexes. Synthetic Vma(-) phenotypes arise from defects in Vph1p-containing complexes caused by rav1, combined with defects in Stv1p-containing V-ATPases caused by the second mutation. Thus RAVE is the first isoform-specific V-ATPase assembly factor.