Multicontrast MRI of remyelination in the central nervous system

Although magnetic resonance imaging (MRI) represents the most sensitive tool for the detection of white matter abnormalities in patients with multiple sclerosis (MS), the heterogeneity of MS placques severely hampers the elucidation of specific pathophysiological processes. In order to identify putative MRI markers for de- and remyelination, we employed the cuprizone mouse model which leads to a selective and reversible demyelination of the corpus callosum with little or no axonal damage. Apart from histopathology, animals were studied with high-resolution three-dimensional MRI in vivo using multiple contrasts. While individual MRI findings significantly correlated with electron microscopy, the differentiation of regions with normal, demyelinated or remyelinated white matter by one contrast alone was less specific than by histology or electron microscopy. However, an accurate MRI prediction of the in vivo myelin status was achieved by a discriminant function analysis using a combination of T1, T2 and magnetization transfer contrast. With a correct assignment of 95% of all animals examined, the procedure will allow for the survey of new therapeutic approaches aiming at improved remyelination.     

Frequent carriage of Panton-Valentine leucocidin genes by Staphylococcus aureus isolates from surgically drained abscesses

Between 1 February and 15 April 2002, 95 patients were admitted to Gaston Bourret Territorial Hospital (New Caledonia, France) for drainage of community-acquired soft tissue abscesses. Staphylococcus aureus was detected in 68 cases (72%). Two-thirds of the patients with S. aureus infection had furuncles, which were located on the limbs in 82% of cases. The median interval between symptom onset and hospital admission was 5.7 days. Three-quarters of the patients were Melanesians living in tribes. Fifty-four S. aureus isolates were screened for toxin genes. Panton-Valentine leucocidin (PVL) genes were detected in 48 isolates (89%), the exfoliative toxin A gene was detected in 1 isolate, and no toxin genes were detected in 4 isolates. S. aureus nasal carriage was detected in 39.7% of patients with S. aureus infections. Two infecting S. aureus strains and two nasal carriage strains were resistant to methicillin. Comparative pulsed-field gel electrophoresis, performed in 16 cases, showed that five of six patients with PVL-positive nasal carriage strains were infected by the same strains. In contrast, 8 of 10 patients with PVL-negative nasal carriage strains were infected by PVL-positive strains. PVL genes thus appear to be a major virulence factor in both primary and secondary S. aureus skin infections.     

Increasing Preload Volume with Water Reduces Rated Appetite But Not Food Intake in Healthy Men Even with Minimum Delay Between Preload and Test Meal

Abstract

The role of gastric volume in the short-term control of eating in humans remains unclear, with some studies reporting that food volume alone can reduce appetite but others finding no such effect. A recent study in our laboratory, found effects of preload volume on subjective appetite (hunger, fullness) but not intake, and found effects of preload energy on intake but not appetite. That study used an interval of 30 min between serving preloads and the test meal, and the present study attempted to maximise the effects of the volume manipulation by removing the delay between the preload and test meal. We administered four soup-based preloads varying in volume (150 and 450 ml) using water, and energy density (1.4 and 4.2 kJ/ml) using maltodextrin, producing three energy levels (209, 629, 629 and 1886 kJ; repeated measures). These were followed immediately by an unlimited hot pasta lunch, during which food weight was monitored continuously by computer. Increasing soup volume at constant energy (629 kJ) reduced appetite ratings, but not intake. In contrast, increasing soup energy at constant volume (450 ml) reduced intake, without affecting appetite. The discrepancies between our results and other reported studies suggest that volume is more influential when intakes are large, or that there may be a threshold concentration for nutrients in the GI tract before volume alone is tangibly expressed in subsequent eating.     

Tackling the Urban Health Divide Though Enabling Intersectoral Action on Malnutrition in Chile and Kenya

As momentum grows for a sustainable urbanisation goal in the post-2015 development agenda, this paper reports on an action research study that sought to tackle the urban health divide by enabling intersectoral action on social determinants at the local level. The study was located in the cities of Mombasa in Kenya and Valparaíso in Chile, and the impact of the intervention on child nutrition was evaluated using a controlled design. The findings showed that an action research process using the social educational process known as PLA could effectively build the capacity of multisectoral teams to take coordinated action which in turn built the capacity of communities to sustain them. The impact on child nutrition was inconclusive and needed to be interpreted within the context of economic collapse in the intervention area. Four factors were found to have been crucial for creating the enabling environment for effective intersectoral action (i) supportive government policy (ii) broad participation and capacity building (iii) involving policy makers as advisors and establishing the credibility of the research and (iii) strengthening community action. If lessons learned from this study can be adapted and applied in other contexts then they could have a significant economic and societal impact on health and nutrition equity in informal urban settlements.     

The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia

Venetoclax is a promising agent in the treatment of acute myeloid leukemia (AML), though its antileukemic activity is limited to combination therapies. Mcl-1 downregulation, Bim upregulation, and DNA damage have been identified as potential ways to enhance venetoclax activity. In this study, we combine venetoclax with the dual PI3K and histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, and induce DNA damage, as well as downregulate c-Myc. We establish that CUDC-907 and venetoclax synergistically induce apoptosis in AML cell lines and primary AML patient samples ex vivo. CUDC-907 downregulates CHK1, Wee1, RRM1, and c-Myc, which were found to play a role in venetoclax-induced apoptosis. Interestingly, we find that venetoclax treatment enhances CUDC-907-induced DNA damage potentially through inhibition of DNA repair. In vivo results show that CUDC-907 enhances venetoclax efficacy in an AML cell line derived xenograft mouse model, supporting the development of CUDC-907 in combination with venetoclax for the treatment of AML.     

New microbiologic diagnostic techniques in infective endocarditis

The new techniques used for identifying causal germs in infective endocarditis are reviewed. Techniques such as polymerase chain reaction are now used to identify previously unrecognised germs. Choosing the appropriate microbiologic technique requires close collaboration between clinicians and microbiologists.     

Infection with hepatitis E virus in kidney transplant recipients in southeastern France

Hepatitis E virus (HEV) is an emerging cause of acute hepatitis in Europe, particularly in southern France, and HEV is a new causative agent of chronic hepatitis and cirrhosis in immunocompromised patients. However, the data regarding HEV infection after kidney transplantation are still scarce with respect to the clinical issues that have been raised, and no study has specifically focused on kidney transplant recipients. This study described the clinical features and outcomes of HEV infections in a cohort of kidney transplant recipients living in southeastern France. The epidemiological, clinical, and virological characteristics of HEV infections diagnosed by PCR over a 53‐month period were retrospectively analyzed in a cohort of 1,350 kidney transplant recipients monitored at the Marseille University Hospital. Sixteen HEV infections were diagnosed, all of which were autochthonous and involved genotype 3 viruses (HEV‐3). Chronic infections occurred in 80% of these patients and resolved in half of the cases after a median time of 39 months. The rate of HEV clearance was 54% after a decrease in the dose of immunosuppressants. One patient developed liver cirrhosis 14 months after infection and experienced acute rejection after a decrease in the dose of immunosuppressants. Autochthonous HEV‐3 infections in kidney transplant recipients progress to chronicity in most cases and might be complicated by early liver cirrhosis. Chronic HEV infection can resolve following the reduction of immunosuppressive therapy, but ribavirin may be required if reduction of the immunosuppressant dose is not associated with HEV clearance or is inappropriate for the patient management. J. Med. Virol. 85:462–471, 2013. © 2012 Wiley Periodicals, Inc.