Physicians' attitude toward identification and management of childhood obesity in Israel

Obesity is a serious health problem, and is becoming increasingly common in affluent societies. In 1998, an Expert Committee published guidelines regarding obesity evaluation and treatment. The purpose of this study was to assess the attitude of primary care physicians in Israel toward diagnosis and treatment of childhood obesity, as related to the recommended guidelines. Primary physicians caring for children and adolescents were asked to complete an anonymous questionnaire including personal and professional details, methods of diagnosis, documentation and treatment of childhood obesity, and familiarity with and implementation of the Expert Committee recommendations. One hundred forty-four physicians, treating approximately 100,000 children monthly, completed the questionnaire. Ninety-four percent were considered to have diagnosed obesity properly. Furthermore, only 19% reported weighing all children examined, while 99% of the physicians suggested some treatment for obesity. The most frequent recommendations for managing obesity were referral to a dietitian (92%), physical exercise (85%), and group treatment (27%). The majority of physicians (78%) were not familiar with the new Expert Committee recommendations regarding obesity treatment. This study suggests that the majority of primary physicians diagnose obesity properly and recommend accepted modalities to manage obesity. A comprehensive program to prevent and treat obesity is recommended to improve the health status of the population.     

Enhanced bioavailability of polyaromatic hydrocarbons in the form of mucin complexes

Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical shield against a range of toxic materials. However, in this work, we demonstrate, for the first time, that, upon complexation of polyaromatic hydrocarbons with mucins, enhanced bioavailability and, therefore, toxicity are obtained. This work was aimed to demonstrate how complexation of various highly hydrophobic polycyclic aromatic hydrocarbons with representative mucin glycoprotein could lead to the formation of previously undescribed materials, which exhibit increased toxicity versus pristine polycyclic aromatic hydrocarbons. In the present work, we show that a representative mucin glycoprotein, bovine submaxillary mucin, has impressive and unprecedented capabilities of binding and solubilizing water-insoluble materials in physiological solution. The complexes formed between the mucin and a series of polycyclic aromatic hydrocarbons were comprehensively characterized, and their toxicity was evaluated by both in vivo and in vitro assays. In addition, the bioavailability and membrane-penetration capabilities were tested using an internalization assay. Our results provide, for the first time, evidence of an unknown route by which hydrophobic materials may achieve higher bioavailability, penetrating some of the biological defense systems, in the form of water-soluble complexes with mucosal proteins.     

The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production

HIV type 1 (HIV-1) was shown to assemble either at the plasma membrane or in the membrane of late endosomes. Now, we report an essential role for human ubiquitin ligase POSH (Plenty of SH3s; hPOSH), a trans-Golgi network-associated protein, in the targeting of HIV-1 to the plasma membrane. Small inhibitory RNA-mediated silencing of hPOSH ablates virus secretion and Gag plasma membrane localization. Reintroduction of native, but not a RING finger mutant, hPOSH restores virus release and Gag plasma membrane localization in hPOSH-depleted cells. Furthermore, expression of the RING finger mutant hPOSH inhibits virus release and induces accumulation of intracellular Gag in normal cells. Together, our results identify a previously undescribed step in HIV biogenesis and suggest a direct function for hPOSH-mediated ubiquitination in protein sorting at the trans-Golgi network. Consequently, hPOSH may be a useful host target for therapeutic intervention.     

Healthcare associated infective endocarditis: a distinct entity

The terms hospital- and community-acquired infections do not cover any longer the full spectrum of acquisition of infection. Consequently, the term healthcare associated infection (HCA) has been recently introduced. In order to examine the applicability of 'HCA infection' to patients with infective endocarditis (IE), 125 episodes of culture-positive IE were categorized into 3 groups of acquisition. 14 (11%) of 125 episodes were defined as hospital acquired (HA) IE (onset of more than 72 h after admission), 52 (42%) as HCA (IE on admission in patients with significant previous healthcare contact), and 59 (47%) as community acquired (CA) (IE on admission in people without recent healthcare contact). 41 (77%) of the 53 causative agents in the HCA IE group were typical nosocomial pathogens, whereas these types of pathogens constituted only 22% (14/64) of the microorganisms in the group of CA IE (p<0.0001). Mortality in the HA and HCA groups combined was significantly higher than that in the CA group (19/62, 31%, vs 6/59, 10%, p=0.01). HCA IE should be recognized as a distinct category that constitutes a large proportion of all cases of IE. HCA IE is significantly different from CA IE and, therefore, may require a different therapeutic approach.     

Staphylolysin is an effective therapeutic agent for <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> experimental keratitis

Background  

Therapy of S. aureus keratitis is increasingly challenging due to emerging resistant strains. Staphylolysin (LasA protease) is a staphylolytic endopeptidase secreted by Pseudomonas aeruginosa. The purpose of the current study was to study the effect of treatment with staphylolysin on experimental keratitis caused by various Staphylococcus aureus strains.     

Epidemiology of carbapenem resistant Klebsiella pneumoniae colonization in an intensive care unit

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged during recent years in several intensive care units. The objective of our study was to determine the incidence of CRKP and the risk factors associated with acquisition during intensive care unit (ICU) stay. This prospective cohort study was conducted between May 2007 and April 2008 in a medical-surgical ICU at a tertiary medical center. Rectal surveillance cultures were obtained from patients on admission and twice weekly. Of screened patients, 7.0% (21/299) were CRKP colonized on admission to the ICU. One hundred eighty (81%) patients were screened at least twice. Of these, 48 (27%) patients acquired CRKP during ICU stay. Of the 69 CRKP colonized patients (both imported and ICU acquired), 29% (20/69) were first identified by microbiologic cultures, while screening cultures identified 49 patients (71%). Of these, 23 (47%) subsequently developed clinical microbiological cultures. Independent risk factors for CRKP acquisition included recent surgery (OR 7.74; CI 3.42-17.45) and SOFA score on admission (OR 1.17; CI 1-1.22). In conclusion, active surveillance cultures detected a sizable proportion of CRKP colonized patients that were not identified by clinical cultures. Recent surgical procedures and patient severity were independently associated with CRKP acquisition.     

Inhibition of metastatic outgrowth from single dormant tumor cells by targeting the cytoskeleton

Metastatic breast cancer may emerge from latent tumor cells that remain dormant at disseminated sites for many years. Identifying mechanisms regulating the switch from dormancy to proliferative metastatic growth has been elusive due to the lack of experimental models of tumor cell dormancy. We characterized the in vitro growth characteristics of cells that exhibit either dormant (D2.0R, MCF-7, and K7M2AS1.46) or proliferative (D2A1, MDA-MB-231, and K7M2) metastatic behavior in vivo. Although these cells proliferate readily in two-dimensional culture, we show that when grown in three-dimensional matrix, distinct growth properties of the cells were revealed that correlate to their dormant or proliferative behavior at metastatic sites in vivo. In three-dimensional culture, cells with dormant behavior in vivo remained cell cycle arrested with elevated nuclear expression of p16 and p27. The transition from quiescence to proliferation of D2A1 cells was dependent on fibronectin production and signaling through integrin beta1, leading to cytoskeletal reorganization with filamentous actin (F-actin) stress fiber formation. We show that phosphorylation of myosin light chain (MLC) by MLC kinase (MLCK) through integrin beta1 is required for actin stress fiber formation and proliferative growth. Inhibition of integrin beta1 or MLCK prevents transition from a quiescent to proliferative state in vitro. Inhibition of MLCK significantly reduces metastatic outgrowth in vivo. These studies show that the switch from dormancy to metastatic growth may be regulated, in part, through epigenetic signaling from the microenvironment, leading to changes in the cytoskeletal architecture of dormant cells. Targeting this process may provide therapeutic strategies for inhibition of the dormant-to-proliferative metastatic switch.