PCR-based detection of Helicobacter pylori and non-Helicobacter pylori species among humans and animals with potential for zoonotic infections.

Helicobacter species have been reported in animals, some of which are of zoonotic importance. This study aimed to detect Helicobacter species among human and animal samples using conventional PCR assays and to identify their zoonotic potentials. Helicobacter species was identified in human and animal samples by genus-specific PCR assays and phylogenetic analysis of partial sequencing of the 16S ribosomal RNA gene. The results revealed that Helicobacter species DNA was detected in 13 of 29 (44.83%) of the human samples. H. pylori was identified in 2 (15.38%), and H. bovis was detected in 4 (30.77%), whereas 7 (53.85%) were unidentified. H. bovis and H. heilmannii were prevalent among the animal samples. Phylogenetic analysis revealed bootstrapping of sequences with H. cinaedi in camel, H. rappini in sheep and humans, and Wollinella succinogenes in humans. In conclusion, the occurrence of non-H. pylori infections among human and animal samples suggested zoonotic potentials.

Characterization of PTEN mutations in brain cancer reveals that pten mono-ubiquitination promotes protein stability and nuclear localization.

PTEN is a PIP3 phosphatase that antagonizes oncogenic PI3-kinase signalling. Due to its critical role in suppressing the potent signalling pathway, it is one of the most mutated tumour suppressors, especially in brain tumours. It is generally thought that PTEN deficiencies predominantly result from either loss of expression or enzymatic activity. By analysing PTEN in malignant glioblastoma primary cells derived from 16 of our patients, we report mutations that block localization of PTEN at the plasma membrane and nucleus without affecting lipid phosphatase activity. Cellular and biochemical analyses as well as structural modelling revealed that two mutations disrupt intramolecular interaction of PTEN and open its conformation, enhancing polyubiquitination of PTEN and decreasing protein stability. Moreover, promoting mono-ubiquitination increases protein stability and nuclear localization of mutant PTEN. Thus, our findings provide a molecular mechanism for cancer-associated PTEN defects and may lead to a brain cancer treatment that targets PTEN mono-ubiquitination.

BMP2 sensitizes glioblastoma stem-like cells to Temozolomide by affecting HIF-1α stability and MGMT expression.

Glioblastoma multiforme (GBM) is the most common brain tumour, characterized by a central and partially necrotic (i.e., hypoxic) core enriched in cancer stem cells (CSCs). We previously showed that the most hypoxic and immature (i.e., CSCs) GBM cells were resistant to Temozolomide (TMZ) in vitro, owing to a particularly high expression of O6-methylguanine-DNA-methyltransferase (MGMT), the most important factor associated to therapy resistance in GBM. Bone morphogenetic proteins (BMPs), and in particular BMP2, are known to promote differentiation and growth inhibition in GBM cells. For this reason, we investigated whether a BMP2-based treatment would increase TMZ response in hypoxic drug-resistant GBM-derived cells. Here we show that BMP2 induced strong differentiation of GBM stem-like cells and subsequent addition of TMZ caused dramatic increase of apoptosis. Importantly, we correlated these effects to a BMP2-induced downregulation of both hypoxia-inducible factor-1α (HIF-1α) and MGMT. We report here a novel mechanism involving the HIF-1α-dependent regulation of MGMT, highlighting the existence of a HIF-1α/MGMT axis supporting GBM resistance to therapy. As confirmed from this evidence, over-stabilization of HIF-1α in TMZ-sensitive GBM cells abolished their responsiveness to it. In conclusion, we describe a HIF-1α-dependent regulation of MGMT and suggest that BMP2, by down-modulating the HIF-1α/MGMT axis, should increase GBM responsiveness to chemotherapy, thus opening the way to the development of future strategies for GBM treatment.

Quality of life in schizophrenics with and without the deficit syndrome.

We investigated the relations between deficit as part of schizophrenic symptomatology and the popular but unclear concept of quality of life (QOL). In a 47-patient sample, subjective QOL was compared in schizophrenics with and without the deficit syndrome. Self- and hetero-rated QOL is more impaired in deficit patients. Differences between deficit and non-deficit groups are more significant as the index used for measuring QOL gets less "behavioral" and more "psycho-pathological". These results are consistent with existing literature. The "behavioral" dimensions of Heinrichs' quality of life scale (QLS) are less discriminative between deficit and non-deficit schizophrenics, but they are more independent of the symptoms. They might have a special clinical meaning, which needs to be defined. The concepts of QOL (as used in QLS) and deficit symptomatology are partially redundant. QLS might be an inappropriate, or at least un-specific measure of QOL.

Characterization of IS6110 restriction fragment length polymorphism patterns and mechanisms of antimicrobial resistance for multidrug-resistant isolates of Mycobacterium tuberculosis from a major reference hospital in Assiut, Egypt.

We evaluated 25 Mycobacterium tuberculosis isolates from patients at a major Egyptian reference hospital in Assiut, Egypt, who had been treated for at least 1 year for tuberculosis. Typing patterns (IS6110) were diverse, and multidrug resistance was found among 11 (44%) of the isolates. Mutations associated with antimicrobial drug resistance were found in rpoB, katG, rpsL, and embB in the resistant isolates.

[Critical review of measures of quality of life in schizophrenia]. / Revue critique des instruments de mesure de la qualité de vie dans la schizophrénie.

UNLABELLED: In order to provide clinicians, researchers, program evaluators and administrators with current information on the assessment of humanistic outcomes of services for schizophrenic patients, a literature review is performed in which references to quality of life (QOL) assessment were made in the context of schizophrenia. Measures are summarized according to purpose, content, psychometric properties. Fifteen QOL instruments are summarized and reflect considerable variability on the relevant criteria: 11 are developed for persons with severe and persistent mental illnesses and used among populations including a major part of schizophrenic patients; 3 are specific QOL measures for schizophrenic patients; 1 is a generic QOL instrument used among psychotic patients. Given that none of these QOL measures has been widely used or accepted as a standard, the choice of a measure must rest on the investigator's particular purpose and needs. CONCLUSION: There is a clear need for a QOL instrument that is specific for schizophrenia, given its high prevalence and chronic nature. The lack of information related to responsiveness of these scales stresses the problems of their inclusion in clinical trials. Scales that have been used in studies of schizophrenia were nearly all developed in the United States and the relevance of their content must be questioned. Rather than relying on the literature or experts to determine those needs that are important to patients with schizophrenia, the content of the instrument should be derived from qualitative interviews with patients who are at different stages of their illness. Moreover, the questionnaire should be self-administered.

Psychometric qualities of the French version of the Heinrichs quality of life rating scale.

The quality of life concept has been increasingly used as a major tool for patient care and clinical investigations. The Heinrichs quality of life scale (QLS) is the quality of life assessment method widely used in schizophrenic patients. The QLS was translated into its French version by J.D. Guelfi according the back-translation method. This version of the validation study included 60 schizophrenic inpatients. The scale possesses acceptable psychometric qualities. The test-retest reliability is good for nearly all items of the scale and for the categories and overall score. The internal consistency alpha-coefficients were 0.9 for the global score and varied between 0.6 and 0.9 according to the category. Factor analysis elicited four factors. Convergent validity is good. Recommendations for future use of the QLS are proposed.

Emergency medicine in Jordan.

The kingdom of Jordan is well known in the Middle East for the high-quality health care it provides its citizens and other patients from throughout the region. The specialty of emergency medicine is developing in Jordan along unique lines, mainly as an outgrowth of family medicine.