Molecular epidemiology of Panton-Valentine leukocidin-positive Staphylococcus aureus in Spain: emergence of the USA300 clone in an autochthonous population

We characterized all of the Panton-Valentine leukocidin (PVL)-positive Staphylococcus aureus isolates collected between 2005 and 2008 in the Bilbao, Spain, area. For the first time, the USA300 clone is reported as predominant among PVL-positive clones in a European autochthonous population, requiring active monitoring of the incidence of USA300 in Spain and throughout Europe.     

Evaluation of Preoperative Computed Tomography in Estimating Peritoneal Cancer Index in Colorectal Peritoneal Carcinomatosis

Peritoneal Cancer Index (PCI) has been recognized as an independent prognostic indicator for long-term outcomes. It also influences the likelihood of complete cytoreduction, another principal determinant of long-term survival. The objective of this study was to evaluate the utility of preoperative CT in estimating PCI during the patient selection process. The efficacy of CT in demonstrating peritoneal disease was evaluated by comparing the radiological and intraoperative lesion size and PCI scores using the Wilcoxon signed-rank test. Tumor distribution was assessed in each abdominopelvic region as tumor present versus absent. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated in each abdominopelvic region. Overall, where CT identifies the presence of disease, it portrayed lesion size accurately in 60%, underestimated in 33%, and overestimated in 7% of cases. Analysis of individual abdominopelvic regions demonstrated a statistically significant difference between radiologically and intraoperatively visualized lesion sizes (P < 0.05) except in the epigastrium, left upper, and left flank regions. The sensitivity of CT in detecting peritoneal implants was influenced by lesion size. Small nodules (<0.5 cm) were visualized on CT with only a sensitivity of 11%, which is in contrast to 94% with nodules exceeding 5 cm. Radiological PCI scores significantly underestimated intraoperative PCI (P < 0.001). This study demonstrated that the sensitivity of CT in detecting peritoneal implants was influenced by lesion size and CT PCI significantly underestimated clinical PCI. The role of CT in refining patient selection and improving prognosis remains to be closely evaluated.     

Perinatal gene transfer to the liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer.     

Interannual Variability of Human Plague Occurrence in the Western United States Explained by Tropical and North Pacific Ocean Climate Variability

Plague is a vector-borne, highly virulent zoonotic disease caused by the bacterium Yersinia pestis. It persists in nature through transmission between its hosts (wild rodents) and vectors (fleas). During epizootics, the disease expands and spills over to other host species such as humans living in or close to affected areas. Here, we investigate the effect of large-scale climate variability on the dynamics of human plague in the western United States using a 56-year time series of plague reports (1950–2005). We found that El Niño Southern Oscillation and Pacific Decadal Oscillation in combination affect the dynamics of human plague over the western United States. The underlying mechanism could involve changes in precipitation and temperatures that impact both hosts and vectors. It is suggested that snow also may play a key role, possibly through its effects on summer soil moisture, which is known to be instrumental for flea survival and development and sustained growth of vegetation for rodents.     

short report: Bleeding disorders in Lowe syndrome patients: evidence for a link between OCRL mutations and primary haemostasis disorders

Lowe syndrome (LS) is a rare X‐linked disorder caused by mutations in the oculocerebrorenal gene (OCRL), encoding OCRL, a phosphatidylinositol 5–phosphatase with a RhoGAP domain. An abnormal rate of haemorrhagic events was found in a retrospective clinical survey. Herein, we report the results of exploration of haemostasis in six LS patients. All patients had normal coagulation tests but prolonged closure times (CTs) in the PFA–100 system. Healthy donors’ blood samples incubated with a RhoA kinase inhibitor had prolonged CTs. This suggests that an aberrant RhoA pathway in platelets contributes to CT prolongation and primary haemostasis disorders in LS.     

Radiometric dating of the type-site for Homo heidelbergensis at Mauer, Germany

The Mauer mandible, holotype of Homo heidelbergensis, was found in 1907 in fluvial sands deposited by the Neckar River 10 km southeast of Heidelberg, Germany. The fossil is an important key to understanding early human occupation of Europe north of the Alps. Given the associated mammal fauna and the geological context, the find layer has been placed in the early Middle Pleistocene, but confirmatory chronometric evidence has hitherto been missing. Here we show that two independent techniques, the combined electron spin resonance/U-series method used with mammal teeth and infrared radiofluorescence applied to sand grains, date the type-site of Homo heidelbergensis at Mauer to 609 ± 40 ka. This result demonstrates that the mandible is the oldest hominin fossil reported to date from central and northern Europe and raises questions concerning the phyletic relationship of Homo heidelbergensis to more ancient populations documented from southern Europe and in Africa. We address the paleoanthropological significance of the Mauer jaw in light of this dating evidence.