Competence-Associated Peptide BriC Alters Fatty Acid Biosynthesis in Streptococcus pneumoniae.

Membrane lipid homeostasis is required for bacteria to survive in a spectrum of host environments. This homeostasis is achieved by regulation of fatty acid chain length and of the ratio of unsaturated to saturated fatty acids. In the pathogen Streptococcus pneumoniae, fatty acid biosynthesis is carried out by a cluster of fatty acid biosynthesis (fab) genes (FASII locus) whose expression is controlled by the FabT repressor. Encoded immediately downstream of the FASII locus is BriC, a competence-induced, cell-cell communication peptide that promotes biofilm development as well as nasopharyngeal colonization in a murine model of pneumococcal carriage. Here, we demonstrate that briC is cotranscribed with genes of the fab gene cluster and that a reduction of briC levels, caused by decoupling its transcription from fab gene cluster, negatively affects biofilm development. BriC elevates fabT transcription, which is predicted to alter the balance of unsaturated and saturated fatty acids produced by the pathway. We find that briC inactivation results in a decreased production of unsaturated fatty acids. This affects the membrane properties by decreasing the abundance of di-unsaturated phosphatidylglycerol molecular species. We propose that the link between BriC, FabT, and phospholipid composition contributes to the ability of S. pneumoniae to alter membrane homeostasis in response to the production of a quorum-sensing peptide. IMPORTANCE Adaptation of bacteria to their host environment is a key component of colonization and pathogenesis. As an essential component of bacterial membranes, fatty acid composition contributes to host adaptation. Similarly, cell-cell communication, which enables population level responses, also contributes to host adaptation. While much is known about the pathways that control the biosynthesis of fatty acids, many questions remain regarding regulation of these pathways and consequently the factors that affect the balance between unsaturated and saturated fatty acids. We find that BriC, a cell-cell communication peptide implicated in biofilm regulation and colonization, both is influenced by a fatty acid biosynthesis pathway and affects this same pathway. This study identifies a link between cell-cell communication, fatty acid composition, and biofilms and, in doing so, suggests that these pathways are integrated into the networks that control pneumococcal colonization and host adaptation.

Impact of pooling on accuracy of hepatitis B virus surface antigen screening of blood donations.

Expenditure on screening blood donations in developing countries can be reduced by testing donations in pools. This study evaluated serological screening in pools for hepatitis B virus (HBV) at the Israeli national blood bank and a hospital blood bank in Gaza, the Palestinian Authority. The accuracy of HBV surface antigen (HBsAg) enzyme immunoassay performed on pools of 3-24 samples was compared with individual tests. Delay in detecting positive samples due to dilution in pools and the possibility of antibody-antigen neutralization were analyzed. The sensitivity of pooled testing for HBsAg was 93-99%, prolonging the window period by 5 days (8.3%). Neutralization of HBsAg by hepatitis B surface antibodies (anti-HBs) could be minimized by testing immediately after pooling. Serological testing for HBsAg in pools may be performed using manually created pools of up to six samples, with 5% loss in sensitivity and a risk of neutralization by anti-HBs present in the donor population. Pooling can therefore be considered as an option only in countries with a low prevalence of HBV.

[Are narghile smokers different from cigarette smokers?]. / Les fumeurs de narghilé sont-ils différents des fumeurs de cigarettes?

BACKGROUND: The extent of smoking related health and economic problems is causing increasing alarm throughout the world. In the last few years a great number of subjects, especially in the developing world, have been smoking narghile and epidemiological studies on narghile smoking are an essential subject for investigation. The objectives of this study are to describe the social and cultural characteristics of narghile smokers in Lebanon compared to tobacco smokers. MATERIALS AND METHODS: Our sample is based on the data of 37579 subjects who consulted a non-governmental organisation (NGO), the Hariri Foundation, between 2003 and 2005. This NGO comprises 22 specialised centres distributed throughout Lebanon. The following data concerning exclusive narghile and cigarette smokers were collected: age, sex, the type and duration of tobacco addiction and the level of education. RESULTS: 13776 subjects (36.6% of the sample) were smokers of whom 88% smoked mostly cigarettes. 1529 subjects (11.1%) smoked narghile exclusively, a prevalence of 4.06%. The narghile smokers were younger than the cigarette smokers with a mean age of 36.2+/-8.63 years compared to 45.52+/-1.87 years. The majority of narghile smokers were women (56.57%) giving a male/female ratio of 0.77. A large number of narghile smokers were recent consumers with an exposure of less than 5 years. They differed from the cigarette smokers of whom the majority (72.2%) had smoked for more than 10 years. The proportion of illiterate subjects was greater among the narghile smokers (36.2%) than the cigarette smokers (24.2%). CONCLUSION: The consumption of tobacco is a real and frequent problem in Lebanon. The consumption of narghile is scourge that is gaining popularity, notably among women and the young. This problem is becoming a public health issue that needs to be taken into account within the framework of an anti-smoking policy in Lebanon.

Estimation of delay in detecting hepatitis C virus antibodies in pools compared to individual testing on seroconversion panels.

Testing for anti-hepatitis C virus (HCV) antibodies in pools may reduce blood screening costs, making this approach affordable for developing countries, provided that the dilution of infected blood does not significantly increase the number of undetectable viral particles, especially in seroconverters. This study assessed the delay in detection of HCV antibodies in five HCV seroconversion panels, tested in pools of 6-48 samples, and estimated the risk of transfusion-transmitted HCV caused by pooling. The delay in detection of positive samples was 5-12 days for pools of all sizes, adding 7% to the risk of HCV transmission that occurs when blood donors' samples are tested individually.

Gene therapy for collateral vessel development.

Transfer of the cDNA coding for angiogenic factors represents a novel and promising approach to induce therapeutic angiogenesis and enhance blood flow to ischemic tissues which cannot be revascularized otherwise. This review will focus on therapeutic angiogenesis based on gene transfer techniques for the treatment of myocardial and limb ischemia. The experimental studies demonstrating the angiogenic effect of recombinant growth factors in animal models and in humans, as well as the most promising methods for gene transfer, will be described. Further, gene transfer studies to induce therapeutic angiogenesis will be reviewed to identify critical questions that still need to be answered before gene therapy with angiogenic factors may be considered for routine clinical application.

The R-(+)isomer of O-n-hexyl S-methyl phosphorothioamidate causes delayed neuropathy in hens after generation of a form of inhibited neuropathy target esterase (NTE) which can be reactivated ex vivo.

To initiate delayed neuropathy (DN) in adult hens organophosphates and phosphonates must inhibit most neural NTE and the inhibited NTE must undergo an 'aging' reaction. Phosphinates and those chiral isomers of phosphonates which produce non-aging NTE do not cause DN but act as prophylactic agents. Some racemic phosphoramidates cause DN although the inhibited NTE in autopsy samples can be reactivated in vitro (Johnson, Read and Vilanova, 1991, Arch. Toxicol., 65, 618-624). We now report that pure R(+)isomer of O-n-hexyl S-methyl phosphorothioamidate (5-20 mg/kg per os) caused slight acute effects but typical DN associated with high inhibition of NTE in brain, spinal cord and sciatic nerve (maximum by 6-24 h): the inhibited NTE was easily reactivated by KF (presumed not aged). For each dose the average residual NTE activity in the three tissues 24 h after dosing and the clinical ataxia severity on peak days 15-17 (score out of 4) was: 5 mg/kg: 13, 14, 27% (2,2,2,1); 10 mg/kg: 10, 14, 12%, (4,3,2); 15 mg/kg: 10,11,17%, (3,3,4); 20 mg/kg: 6, 10, 8% (3,3,3,2). The ability of this isomer and of other racemic phosphoramidates to initiate DN by covalent reaction at the active site of NTE (inhibition) without subsequent aging suggests that the chemistry (? charge distribution) in the region of the phosphorus atom determines that disturbance in the molecular environment of NTE which initiates DN.

Mutagenic and carcinogenic pesticides used in the agricultural environment of Gaza Strip.

More than 100 metric tons of formulated pesticides (about 75 pesticides) are used annually in Gaza Strip. It was found that 19 of these pesticides, that have been used, are internationally suspended, cancelled and banned pesticides. About 1100 cases of cancer have been registered in Gaza Strip (1979-1983). The distribution of cancer types among those patients are lymphoma and hematological malignancy, breast, head and neck, gastrointestinal malignancy, reproductive system, urinary system, soft tissue tumors, brain tumors and others. Consequently, the introduction and heavy use of pesticides and other toxic substances in the Gaza Strip environment is suspected to correlate with the growing incidence of cancer and other abnormalities in the nation. Precise determination of the effects of chronic exposure is, therefore, urgently needed.

Periconceptional folate deficiency and implications in neural tube defects.

Nutritional deficiencies are preventable etiological and epigenetic factors causing congenital abnormalities, first cause of infant mortality. Folate deficiency has a well-established teratogenic effect, leading to an increasing risk of neural tube defects. This paper highlights the most recent medical literature about folate deficiency, be it maternal or paternal. It then focuses on associated deficiencies as nutritional deficiencies are multiple and interrelated. Observational and interventional studies have all been consistent with a 50-70% protective effect of adequate women consumption of folates on neural tube defects. Since strategies to modify women's dietary habits and vitamin use have achieved little progress, scientific as well as political effort is mandatory in order to implement global preventive public health strategies aimed at improving the alimentation of women in reproductive age, especially folic acid supplementation. Even with the recent breakthrough of fetal surgery for myelomeningocele, the emphasis should still be on prevention as the best practice rather than treatment of neural tube defects.

[Application of a hospital audit to the use of nebulizers: the Case of the Hôtel-Dieu de France-Lebanon]. / Application d'un audit hospitalier à l'utilisation de la nébulisation : l'exemple de l'Hôtel-Dieu de France-Liban.

PROBLEM: The aim of the study was to reduce the unjustified prescriptions of nebulised therapy, in order to comply with the international guidelines and to reduce healthcare costs. DESIGN: We performed a controlled, prospective study to evaluate the impact of local guidelines aimed at improving doctors' behaviour on appropriateness and costs of implementation. BACKGROUND AND SETTING: All the departments of a university hospital: medical and surgical wards, intensive care units, emergency rooms and one-day admission units. KEY MEASURE FOR CHANGE: Reduction in the number of inappropriate prescriptions of nebulised therapy. STRATEGIES FOR CHANGE: Implementation included two educational presentations, posters displayed in all departments, emails sent to all doctors and residents, and reassessment of the prescription one week after. RESULTS: Prior to the intervention, the rate of inappropriate prescriptions was 11.9% (42/358 of patients treated with nebulizers did not have an indication for this treatment and 3/19 of patients had an indication for nebulisation but were not treated); in the postintervention, the rate of inappropriate prescriptions was 14.6% (15.7% of patients without indication for treatment, but no patient with an indication for treatment untreated), reflecting a lack of significant impact of the intervention. CONCLUSIONS: Simple presentation of clinical guidelines did not lead to a change in medical practices. Another approach is needed to improve this outcome effectively.

Feasibility and cost-benefit of implementing pooled screening for HCVAg in small blood bank settings.

To examine the accuracy, feasibility and benefits of screening for hepatitis C virus core antigen (HCVAg) using enzyme-linked immunosorbent assay (ELISA) test in pools. Many countries cannot afford to test blood donations for hepatitis C using molecular methods. Screening individual units using the ELISA HCVAg test is an acceptable, yet still expensive, alternative, especially for small blood bank settings. This study evaluated the option of screening for HCVAg in pools. The sensitivity (Se) and specificity (Sp) of HCVAg in pools of three and six antibody-negative samples were estimated and compared with polymerase chain reaction (PCR). The feasibility and cost-benefit of the assay was assessed on 960 routine samples collected at a hospital blood bank in Gaza. Based on results for 50 PCR-positive pools and 50 and 110 PCR-negative pools of three and six, the Se of testing in pools of three and six samples is 80-82% [95% confidence interval (CI): 66.3-91.4] and Sp >or=98% (95% CI: 89.4-100.0) compared with PCR. The incidence of antigen in donors in Gaza was 0.1% (95% CI: 0-0.56). Cost analyses suggested significant benefits from implementing screening blood donations for HCVAg when the incidence rate is >4.2/10,000, leading to reduction in the expenditures needed to treat patients infected with HCV. The risk of transfusion-transmitted hepatitis C in resource-deprived developing countries can be efficiently reduced by additional screening of antibody-negative blood donations for HCVAg in pools of six.

Anti-malarial drug targets: screening for inhibitors of 2C-methyl-D-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants.

The recently discovered non-mevalonate pathway of isoprenoid biosynthesis serves as the unique source of terpenoids in numerous pathogenic eubacteria and in apicoplast-type protozoa, most notably Plasmodium, but is absent in mammalian cells. It is therefore an attractive target for anti-infective chemotherapy. The first committed step of the non-mevalonate pathway is catalyzed by 2C-methyl-D-erythritol 4-phosphate synthase (IspC). Using photometric and NMR spectroscopic assays, we screened extracts of Mediterranean plants for inhibitors of the enzyme. Strongest inhibitory activity was found in leaf extracts of Cercis siliquastrum.

Hematological biomarkers in farm workers exposed to organophosphorus pesticides in the Gaza Strip.

To assess serum cholinesterase levels and symptoms among farm workers who used mainly organophosphorus pesticides in the Gaza Strip, the authors took blood samples from and administered symptom questionnaires to an occupational cohort of 48 field workers. The authors tested the workers for serum acetylcholinesterase and serum butyrylcholinesterase (SBuChE) levels at the beginning and end of each work day. The authors took 20 employees as referents. The mean activity of SBuChE of the farm workers at the end of the spraying day (X = 3.28+/-0.12 kU/l) was lower by 13.2% than that of the referents at the end of the follow-up day (3.78+/-0.20 kU/l). Many symptoms were self-reported by farm workers. Certain symptoms, such as itching, skin irritation, and a burning sensation in eyes or face, were significantly associated with cholinesterase inhibition. A greater end-of-day reduction in SBuChE activity occurred in younger workers, those workers mixing pesticides, and with day of direct re-entry to the workplace. The authors detected alterations in some blood indexes. The study confirmed the finding that illness in pesticide workers exposed to organophosphorus pesticides can occur with trivial reductions in cholinesterase.

Pesticide use, exposure, and risk: A joint Israeli-Palestinian perspective.

The major predictors of health risk from pesticide exposure are quantity and toxicity of pesticides reaching end-users, field workers, and persons (including children) with casual and indirect exposures to field and food residues, drift, and contaminated groundwater. Past work in Israel and the Palestinian National Authority has documented risks for acute poisoning, daily illness, transient neurotoxic effects, and potential cancer hazards in workers, populations exposed to pesticide drift, and the general population. Risk assessment predicts that reduction in use of agents with high toxicity and pesticide substitution are desired strategies for achieving the largest reductions in risk, but successful implementation and program sustainability depend on maintaining crop yield and increasing farmer earnings. A joint pilot Israeli-Palestinian-NGO program aims to determine whether crop yields and profits can be sustained while reducing pesticide use, promoting integrated pest management, and restricting ecosystem damage. The project involves six components: (1) assessments of health risk and crop yield in relation to pesticide use and exposure; (2) training health-agricultural teams to introduce and evaluate crop growth and managements with reduced pesticide use; (3) tracing and stopping import and trade in banned or restricted pesticides; (4) restricting child labor; (5) promoting information delivery and worker and community right-to-know and right-to-act; and (6) establishing a uniform regional standard for protection of workers and the general public. Preliminary evidence (organochlorines and breast cancer, organophosphates and illness in field workers) indicates that (1) a reduction of use is the foremost determinant of a reduction in health risk; (2) cotton yield can be increased despite a reduction in pesticide use (organophosphates); and (3) a reduction in pesticide use (organophosphates and organochlorines) has to be part of a crop rotation program for food crops timed to seasonal fluctuations in supply, demand, and crop price.

Cryptogenic mycotic aneurysm of the right coronary artery.

A 61-year-old man with chest pain and fever was referred to our hospital. The physical examination and electrocardiogram were unrevealing. Laboratory tests showed leukocytosis, and echocardiography showed mild pericardial effusion. The patient died soon after hospital admission. Necropsy revealed ruptured mycotic aneurysm of the right coronary artery in the absence of infective endocarditis. Thus, mycotic aneurysm of the coronary artery may occur without infective endocarditis and may be clinically manifested as pericarditis and leukocytosis.

Knowledge, attitude, practice, and toxicity symptoms associated with pesticide use among farm workers in the Gaza Strip.

AIMS: To assess knowledge, attitude, practice, and toxicity symptoms associated with pesticide use and exposure among 189 farm workers in the Gaza Strip. METHODS: A cross section of agricultural farm workers in the Gaza Strip were asked to fill in a questionnaire on knowledge, attitudes, practice towards pesticide use, and associated toxicity symptoms. RESULTS: Farm workers reported high levels of knowledge on the health impact of pesticides (97.9%). Moderate to high levels of knowledge were recorded on toxicity symptoms related to pesticides. Most farm workers were aware of the protective measures to be used during applying pesticides. However, no one took precautions unless they knew about the measures. Burning sensation in eyes/face was the commonest symptom (64.3%). The prevalence of self reported toxicity symptoms was dependent on mixing and use of high concentrations of pesticides. The highest percentage of self reported toxicity symptoms was found among the farm workers who returned to sprayed fields within one hour of applying pesticides. CONCLUSIONS: Farm workers in the Gaza Strip used pesticides extensively. Despite their knowledge about the adverse health impact of the pesticides, the use of protective measures was poor. Most had self reported toxicity symptoms, particularly the younger workers. It would be useful to minimise the use of pesticides and encourage alternative measures. Prevention and intervention programmes regarding the use of protective measures and monitoring the health status of farm workers should be implemented.