Providing alcohol-related screening and brief interventions to adolescents through health care systems: Obstacles and solutions

Duncan Clark and Howard Moss identify obstacles to alcohol-related screening and treatment for adolescents and propose policy solutions

Verbal short-term memory deficits in Down syndrome: phonological, semantic, or both?

The current study examined the phonological and semantic contributions to the verbal short-term memory (VSTM) deficit in Down syndrome (DS) by experimentally manipulating the phonological and semantic demands of VSTM tasks. The performance of 18 individuals with DS (ages 11–25) and 18 typically developing children (ages 3–10) matched pairwise on receptive vocabulary and gender was compared on four VSTM tasks, two tapping phonological VSTM (phonological similarity, nonword discrimination) and two tapping semantic VSTM (semantic category, semantic proactive interference). Group by condition interactions were found on the two phonological VSTM tasks (suggesting less sensitivity to the phonological qualities of words in DS), but not on the two semantic VSTM tasks. These findings suggest that a phonological weakness contributes to the VSTM deficit in DS. These results are discussed in relation to the DS neuropsychological and neuroanatomical phenotype

Anthrax Lethal Toxin Disrupts Intestinal Barrier Function and Causes Systemic Infections with Enteric Bacteria

A variety of intestinal pathogens have virulence factors that target mitogen activated protein kinase (MAPK) signaling pathways, including Bacillus anthracis. Anthrax lethal toxin (LT) has specific proteolytic activity against the upstream regulators of MAPKs, the MAPK kinases (MKKs). Using a murine model of intoxication, we show that LT causes the dose-dependent disruption of intestinal epithelial integrity, characterized by mucosal erosion, ulceration, and bleeding. This pathology correlates with an LT-dependent blockade of intestinal crypt cell proliferation, accompanied by marked apoptosis in the villus tips. C57BL/6J mice treated with intravenous LT nearly uniformly develop systemic infections with commensal enteric organisms within 72 hours of administration. LT-dependent intestinal pathology depends upon its proteolytic activity and is partially attenuated by co-administration of broad spectrum antibiotics, indicating that it is both a cause and an effect of infection. These findings indicate that targeting of MAPK signaling pathways by anthrax LT compromises the structural integrity of the mucosal layer, serving to undermine the effectiveness of the intestinal barrier. Combined with the well-described immunosuppressive effects of LT, this disruption of the intestinal barrier provides a potential mechanism for host invasion via the enteric route, a common portal of entry during the natural infection cycle of Bacillus anthracis

Restaurant outbreak of Legionnaires' disease associated with a decorative fountain: an environmental and case-control study

BACKGROUND: From June to November 2005, 18 cases of community-acquired Legionnaires' disease (LD) were reported in Rapid City South Dakota. We conducted epidemiologic and environmental investigations to identify the source of the outbreak. METHODS: We conducted a case-control study that included the first 13 cases and 52 controls randomly selected from emergency department records and matched on underlying illness. We collected information about activities of case-patients and controls during the 14 days before symptom onset. Environmental samples (n = 291) were cultured for Legionella. Clinical and environmental isolates were compared using monoclonal antibody subtyping and sequence based typing (SBT). RESULTS: Case-patients were significantly more likely than controls to have passed through several city areas that contained or were adjacent to areas with cooling towers positive for Legionella. Six of 11 case-patients (matched odds ratio (mOR) 32.7, 95% CI 4.7-infinity) reported eating in Restaurant A versus 0 controls. Legionella pneumophila serogroup 1 was isolated from four clinical specimens: 3 were Benidorm type strains and 1 was a Denver type strain. Legionella were identified from several environmental sites including 24 (56%) of 43 cooling towers tested, but only one site, a small decorative fountain in Restaurant A, contained Benidorm, the outbreak strain. Clinical and environmental Benidorm isolates had identical SBT patterns. CONCLUSION: This is the first time that small fountain without obvious aerosol-generating capability has been implicated as the source of a LD outbreak. Removal of the fountain halted transmission

Improving phylogeny reconstruction at the strain level using peptidome datasets

Typical bacterial strain differentiation methods are often challenged by high genetic similarity between strains. To address this problem, we introduce a novel in silico peptide fingerprinting method based on conventional wet-lab protocols that enables the identification of potential strain-specific peptides. These can be further investigated using in vitro approaches, laying a foundation for the development of biomarker detection and application-specific methods. This novel method aims at reducing large amounts of comparative peptide data to binary matrices while maintaining a high phylogenetic resolution. The underlying case study concerns the Bacillus cereus group, namely the differentiation of Bacillus thuringiensis, Bacillus anthracis and Bacillus cereus strains. Results show that trees based on cytoplasmic and extracellular peptidomes are only marginally in conflict with those based on whole proteomes, as inferred by the established Genome-BLAST Distance Phylogeny (GBDP) method. Hence, these results indicate that the two approaches can most likely be used complementarily even in other organismal groups. The obtained results confirm previous reports about the misclassification of many strains within the B. cereus group. Moreover, our method was able to separate the B. anthracis strains with high resolution, similarly to the GBDP results as benchmarked via Bayesian inference and both Maximum Likelihood and Maximum Parsimony. In addition to the presented phylogenomic applications, whole-peptide fingerprinting might also become a valuable complementary technique to digital DNA-DNA hybridization, notably for bacterial classification at the species and subspecies level in the future.This research was funded by Grant AGL2013-44039-R from the Spanish “Plan Estatal de I+D+I”, and by Grant EM2014/046 from the “Plan Galego de investigación, innovación e crecemento 2011-2015”. BS was recipient of a Ramón y Cajal postdoctoral contractfrom the Spanish Ministry of Economyand Competitiveness. This work was also partially funded by the [14VI05] Contract-Programme from the University of Vigo and the Agrupamento INBIOMED from DXPCTSUG-FEDER unha maneira de facer Europa (2012/273).The research leading to these results has also received funding from the European Union’s Seventh Framework Programme FP7/REGPOT-2012-2013.1 under grant agreement n˚ 316265, BIOCAPS. This document reflects only the authors’ views and the European Union is not liable for any use that may be made of the information contained herein. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Temporary Closure of the Open Abdomen: A Systematic Review on Delayed Primary Fascial Closure in Patients with an Open Abdomen

Background This study was designed to systematically review the literature to assess which temporary abdominal closure (TAC) technique is associated with the highest delayed primary fascial closure (FC) rate. In some cases of abdominal trauma or infection, edema or packing precludes fascial closure after laparotomy. This "open abdomen'' must then be temporarily closed. However, the FC rate varies between techniques. Methods The Cochrane Register of Controlled Trials, MEDLINE, and EMBASE databases were searched until December 2007. References were checked for additional studies. Search criteria included (synonyms of) "open abdomen,'' "fascial closure,'' "vacuum,'' "reapproximation,'' and "ventral hernia.'' Open abdomen was defined as "the inability to close the abdominal fascia after laparotomy.'' Two reviewers independently extracted data from original articles by using a predefined checklist. Results The search identified 154 abstracts of which 96 were considered relevant. No comparative studies were identified. After reading them, 51 articles, including 57 case series were included. The techniques described were vacuum-assisted closure (VAC; 8 series), vacuum pack (15 series), artificial burr (4 series), Mesh/sheet (16 series), zipper (7 series), silo (3 series), skin closure (2 series), dynamic retention sutures (DRS), and loose packing (1 series each). The highest FC rates were seen in the artificial burr (90%), DRS (85%), and VAC (60%). The lowest mortality rates were seen in the artificial burr (17%), VAC (18%), and DRS (23%). Conclusions These results suggest that the artificial burr and the VAC are associated with the highest FC rates and the lowest mortality rate

The Peter Pan paradigm

Genetic and environmental agents that disrupt organogenesis are numerous and well described. Less well established, however, is the role of delay in the developmental processes that yield functionally immature tissues at birth. Evidence is mounting that organs do not continue to develop postnatally in the context of these organogenesis insults, condemning the patient to utilize under-developed tissues for adult processes. These poorly differentiated organs may appear histologically normal at birth but with age may deteriorate revealing progressive or adult-onset pathology. The genetic and molecular underpinning of the proposed paradigm reveals the need for a comprehensive systems biology approach to evaluate the role of maternal-fetal environment on organogenesis

Bacillus anthracis Peptidoglycan Stimulates an Inflammatory Response in Monocytes through the p38 Mitogen-Activated Protein Kinase Pathway

We hypothesized that the peptidoglycan component of B. anthracis may play a critical role in morbidity and mortality associated with inhalation anthrax. To explore this issue, we purified the peptidoglycan component of the bacterial cell wall and studied the response of human peripheral blood cells. The purified B. anthracis peptidoglycan was free of non-covalently bound protein but contained a complex set of amino acids probably arising from the stem peptide. The peptidoglycan contained a polysaccharide that was removed by mild acid treatment, and the biological activity remained with the peptidoglycan and not the polysaccharide. The biological activity of the peptidoglycan was sensitive to lysozyme but not other hydrolytic enzymes, showing that the activity resides in the peptidoglycan component and not bacterial DNA, RNA or protein. B. anthracis peptidoglycan stimulated monocytes to produce primarily TNFα; neutrophils and lymphocytes did not respond. Peptidoglycan stimulated monocyte p38 mitogen-activated protein kinase and p38 activity was required for TNFα production by the cells. We conclude that peptidoglycan in B. anthracis is biologically active, that it stimulates a proinflammatory response in monocytes, and uses the p38 kinase signal transduction pathway to do so. Given the high bacterial burden in pulmonary anthrax, these findings suggest that the inflammatory events associated with peptidoglycan may play an important role in anthrax pathogenesis

Functional clustering of yeast proteins from the protein-protein interaction network

BACKGROUND: The abundant data available for protein interaction networks have not yet been fully understood. New types of analyses are needed to reveal organizational principles of these networks to investigate the details of functional and regulatory clusters of proteins. RESULTS: In the present work, individual clusters identified by an eigenmode analysis of the connectivity matrix of the protein-protein interaction network in yeast are investigated for possible functional relationships among the members of the cluster. With our functional clustering we have successfully predicted several new protein-protein interactions that indeed have been reported recently. CONCLUSION: Eigenmode analysis of the entire connectivity matrix yields both a global and a detailed view of the network. We have shown that the eigenmode clustering not only is guided by the number of proteins with which each protein interacts, but also leads to functional clustering that can be applied to predict new protein interactions