Biochemical characterization of a cefotaximehydrolysing &#946-lactamase encoded by a conjugative plasmid

During the nosocomials infections occurring in the intensive care unit of the military hospital of Tunis in 2005, the Enterobacter cloacae BW 1150 strain was isolated from a stool culture. This strain was found to have a high level resistance to broad-spectrum -lactams. Resistance profile against thevarious families of antibiotics was determined using the disc diffusion test. The minimal inhibitory concentrations values showed that this strain was resistant to the -lactams such as ampicillin and the extended spectrum cephalosporins (cefotaxime, ceftriaxon and cefpirome). Analysis of this strain by the disk diffusion test revealed synergies between amoxicillin-clavulanate (AMX-CA) and ceftriaxon, ceftazidime and cefotaxime. Cell sonicate of this isolate is very active against cefotaxime and showed aspecific activity (AS) of 7.54 U/mg for the same antibiotic. This activity was inhibited by the sulbactam and the clavulanic acid. Isoelectrofocusing methods revealed that the crude extract of the E. cloacae BW 1150 strain showed 1 - lactamase activity with an isoelectric piont (pI) of about 8. This activity was transferred by conjugation and was highly expressed in the transconjugant

Menopause and metabolic syndrome in Tunisian women

Objectives. This study aimed to evaluate the effect of menopausal status on the risk of metabolic syndrome (MetS) in Tunisian women. Methods. We analyzed a total of 2680 women aged between 35 and 70 years. Blood pressure, anthropometric indices, fasting glucose, and lipid profile were measured. The MetS was assessed by the modified NCEP-ATPIII definition. Results. The mean values of waist circumference, blood pressure, plasma lipids, and fasting glucose were significantly higher in postmenopausal than in premenopausal women, a difference that was no longer present when adjusting for age. Except for hypertriglyceridaemia, the frequency of central obesity, hyperglycemia, high blood pressure, and high total cholesterol was significantly higher in postmenopausal than in premenopausal women. After adjusting for age, the significance persisted only for hyperglycemia. The overall prevalence of MetS was 35.9%, higher in postmenopausal (45.7% versus 25.6%) than in premenopausal women. A binary logistic regression analysis showed that menopause was independently associated with MetS (OR = 1.41, 95% CI 1.10-1.82) after adjusting for age, residence area, marital status, family history of cardiovascular disease, education level, and occupation. Conclusions. The present study provides evidence that the MetS is highly prevalent in this group of women. Menopause can be a predictor of MetS independent of age in Tunisian women

Genetic Association of rs1021188 and DNA Methylation Signatures of TNFSF11 in the Risk of Conductive Hearing Loss

Otosclerosis (OTSC) is a complex bone disorder of the otic capsule, which causes conductive hearing impairment in human adults. The dysregulation of the signaling axis mediated by the receptor activator of nuclear factor-kappa-B (RANK), RANK ligand (RANKL), and osteoprotegerin has been widely attributed to the context of metabolic bone disorders. While genetic associations and epigenetic alterations in the TNFSF11 gene (RANKL) have been well-linked to metabolic bone diseases of the skeleton, particularly osteoporosis, they have never been addressed in OTSC. This study aimed to assess whether the genetic association of rs1021188 polymorphism in the upstream of TNFSF11 and the DNA methylation changes in its promoter CpG-region reveal the susceptibility of OTSC. Peripheral blood DNA samples were collected from unrelated Tunisian-North African subjects for genotyping (109 cases and 120 controls) and for DNA methylation analysis (40 cases and 40 controls). The gender-stratified analysis showed that the TNFSF11 rs1021188 C/T was associated with OTSC in men (p = 0.023), but not in women (p = 0.458). Individuals with CC genotype were more susceptible to OTSC, suggesting an increased risk to disease development. Using publicly available data, the rs1021188 was within a cluster grouping the subpopulations with African ethnicity. Moreover, 26 loci in the TNFSF11 gene were in linkage disequilibrium with rs1021188, revealing relative similarities between different populations. Significant differences in both DNA methylation and unmethylation status were detected with 4.53- and 4.83-fold decreases in the global DNA methylation levels in female and male OTSC groups, respectively. These changes could contribute to an increased risk of OTSC development. Bioinformatic analyses indicated that each of the rs1021188 variations and the DNA methylation changes in the promoter CpG-sites within TNFSF11 may play an important role in its transcription regulation. To our knowledge, this is the first study that investigates an independent effect of the rs1021188 polymorphism and DNA hypomethylation of TNFSF11 promoter in OTSC. Genetic and epigenetic changes in the regulatory regions of TNFSF11 could offer new molecular insights into the understanding of the complexity of OTSC

A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries.

BACKGROUND: Coronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey. METHODS AND FINDINGS: Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia;$39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and$1,3000,000,000 and 378439 LYG in Turkey. CONCLUSION: Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives

First Molecular Epidemiological Study of Cutaneous Leishmaniasis in Libya

Cutaneous leishmaniasis (CL) is caused by protozoan parasites of the genus Leishmania. The disease is characterized by the formation of chronic skin lesions followed by permanent scars and deformation of the infected area. It is distributed in many tropical and subtropical countries with more than 2 million cases every year. During the past few years CL has emerged as a major public health problem in Libya. So far, diagnosis was based on clinical symptoms and microscopic observation of parasites. Disease outbreaks were not investigated and the causative leishmanial species of CL were not identified so far. Our study indicates the presence of two coexisting species: Leishmania major and Leishmania tropica. These results are crucial in order to provide accurate treatment, precise prognosis and appropriate public health control measures. The recent armed conflict in Libya that ended with the Gadhafi regime collapse on October 2011 has affected all aspects of the life in the country. In this study we discussed multiple risk factors that could be associated with this conflict and present major challenges that should be considered by local and national health authorities for evaluating the CL burden and highlighting priority actions for disease control

A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses

Many contemporary studies have shown that astrocytes play a significant role in modulating both short and long form of synaptic plasticity. There are very few experimental models which elucidate the role of astrocyte over Long-term Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of astrocytes in induction of LTP at single hippocampal synapses. They suggested a purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic induction were not investigated. Here, in this article, we propose a mathematical model for astrocyte modulated LTP which successfully emulates the experimental findings of Perea & Araque (2007). Our study suggests the role of retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to appear

Squeezed tensor non-Gaussianity in non-attractor inflation

We investigate primordial tensor non-Gaussianity in single field inflation, during a phase of non-attractor evolution when the spectrum of primordial tensor modes can be enhanced to a level detectable at interferometer scales. Making use of a tensor duality we introduced in arXiv:1808.10475, we analytically compute the full bispectrum of primordial tensor fluctuations during the non-attractor era. During this epoch the shape of the tensor bispectrum is enhanced in the squeezed limit, its amplitude can be amplified with respect to slow-roll models, and tensor non-Gaussianity can exhibit a scale dependence distinctive of our set-up. We prove that our results do not depend on the frame used for the calculations. Squeezed tensor non-Gaussianity induces a characteristic quadrupolar anisotropy on the power spectrum of the stochastic background of primordial tensor perturbations. As a step to make contact with gravitational wave experiments, we discuss the response function of a ground based Michelson interferometer to a gravitational wave background with such a feature.Comment: 34 pages, 4 figure

Evaluation of Leishmania donovani Protein Disulfide Isomerase as a Potential Immunogenic Protein/Vaccine Candidate against Visceral Leishmaniasis

In Leishmania species, Protein disulfide isomerase (PDI) - a redox chaperone, is reported to be involved in its virulence and survival. This protein has also been identified, through proteomics, as a Th1 stimulatory protein in the soluble lysate of a clinical isolate of Leishmania donovani (LdPDI). In the present study, the molecular characterization of LdPDI was carried out and the immunogenicity of recombinant LdPDI (rLdPDI) was assessed by lymphocyte proliferation assay (LTT), nitric oxide (NO) production, estimation of Th1 cytokines (IFN-γ and IL-12) as well as IL-10 in PBMCs of cured/endemic/infected Leishmania patients and cured L. donovani infected hamsters. A significantly higher proliferative response against rLdPDI as well as elevated levels of IFN-γ and IL-12 were observed. The level of IL-10 was found to be highly down regulated in response to rLdPDI. A significant increase in the level of NO production in stimulated hamster macrophages as well as IgG2 antibody and a low level of IgG1 in cured patient's serum was observed. Higher level of IgG2 antibody indicated its Th1 stimulatory potential. The efficacy of pcDNA-LdPDI construct was further evaluated for its prophylactic potential. Vaccination with this construct conferred remarkably good prophylactic efficacy (∼90%) and generated a robust cellular immune response with significant increases in the levels of iNOS transcript as well as TNF-α, IFN-γ and IL-12 cytokines. This was further supported by the high level of IgG2 antibody in vaccinated animals. The in vitro as well as in vivo results thus indicate that LdPDI may be exploited as a potential vaccine candidate against visceral Leishmaniasis (VL)

Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation

BackgroundChemokines have been implicated in tumor progression and metastasis. In melanoma, chemokine receptors have been implicated in organ selective metastasis by regulating processes such as chemoattraction, adhesion and survival.MethodsIn this study we have analyzed, using flow cytometry, the systems formed by the chemokine receptors CXCR3, CXCR4, CXCR7, CCR7 and CCR10 and their ligands in thirteen human melanoma cell lines (five established from primary tumors and eight established from metastasis from different tissues). WM-115 and WM-266.4 melanoma cell lines (obtained from a primary and a metastatic melanoma respectively) were xenografted in nude mice and the tumors and cell lines derived from them were also analyzed.ResultsOur results show that the melanoma cell lines do not express or express in a low degree the chemokine receptors on their cell surface. However, melanoma cell lines show intracellular expression of all the aforementioned receptors and most of their respective ligands. When analyzing the xenografts and the cell lines obtained from them we found variations in the intracellular expression of chemokines and chemokine receptors that differed between the primary and metastatic cell lines. However, as well as in the original cell lines, minute or no expression of the chemokine receptors was observed at the cell surface.ConclusionsCoexpression of chemokine receptors and their ligands was found in human melanoma cell lines. However, this expression is intracellular and receptors are not found at the cell membrane nor chemokines are secreted to the cell medium. The levels of expressed chemokine receptors and their ligands show dynamic variations after xenotransplantation that differ depending on the origin of the cell line (from primary tumor or from metastasis)

Astrocytes: orchestrating synaptic plasticity?

Synaptic plasticity is the capacity of a preexisting connection between two neurons to change in strength as a function of neural activity. Because synaptic plasticity is the major candidate mechanism for learning and memory, the elucidation of its constituting mechanisms is of crucial importance in many aspects of normal and pathological brain function. In particular, a prominent aspect that remains debated is how the plasticity mechanisms, that encompass a broad spectrum of temporal and spatial scales, come to play together in a concerted fashion. Here we review and discuss evidence that pinpoints to a possible non-neuronal, glial candidate for such orchestration: the regulation of synaptic plasticity by astrocytes.Comment: 63 pages, 4 figure