A miRNA signature for defining aggressive phenotype and prognosis in gliomas

Gliomas represent a disparate group of tumours for which there are to date no cure. Thus, there is a recognized need for new diagnostic and therapeutic approaches based on increased understanding of their molecular nature. We performed the comparison of the microRNA （miRNA） profile of 8 WHO grade II gliomas and 24 higher grade tumours （2 WHO grade III and 22 glioblastomas） by using the Affymetrix GeneChip miRNA Array v. 1.0. A relative quantification method （RT-qPCR） with standard curve was used to confirm the 22 miRNA signature resulted by array analysis. The prognostic performances of the confirmed miRNAs were estimated on the Tumor Cancer Genome Atlas （TCGA） datasets. We identified 22 miRNAs distinguishing grade II gliomas from higher grade tumours. RT-qPCR confirmed the differential expression in the two patients＇groups for 13 out of the 22 miRNAs. The analysis of the Glioblastoma Multiforme （GBM） and Lower Grade Glioma （LGG） datasets from TCGA demonstrated the association with prognosis for 6 of those miRNAs. Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses （ HR 1.19, P = O. 04, and HR 1.18, P = 0. 029 respectively）. Our results support a direct contribution of miRNAs to glioma cancerogenesis and suggest that miR-21 and miR-210 may play a role in the aggressive clinical behaviour of glioblastomas.     

Identification of Candida species in the clinical laboratory: a review of conventional,commercial, and molecular techniques

In healthy individuals, Candida species are considered commensal yeasts of the oral cavity. However, these microorganisms can also act as opportunist pathogens, particularly the so‐called non‐albicans Candida species that are increasingly recognized as important agents of human infection. Several surveys have documented increased rates of C. glabrata, C. tropicalis, C. guilliermondii, C. dubliniensis, C. parapsilosis, and C. krusei in local and systemic fungal infections. Some of these species are resistant to antifungal agents. Consequently, rapid and correct identification of species can play an important role in the management of candidiasis. Conventional methods for identification of Candida species are based on morphological and physiological attributes. However, accurate identification of all isolates from clinical samples is often complex and time‐consuming. Hence, several manual and automated rapid commercial systems for identifying these organisms have been developed, some of which may have significant sensitivity issues. To overcome these limitations, newer molecular typing techniques have been developed that allow accurate and rapid identification of Candida species. This study reviewed the current state of identification methods for yeasts, particularly Candida species.     

Changing mortality patterns in East and West Germany and Poland. II: short-term trends during transition and in the 1990s

OBJECTIVES: To examine trends in life expectancy at birth and age and cause specific patterns of mortality in the former German Democratic Republic (GDR) and Poland during political transition and throughout the 1990s in both parts of Germany and in Poland. METHODS: Decomposition of life expectancy by age and cause of death. Changes in life expectancy during transition by cause of death were examined using data for 1988/89 and 1990/91 for the former GDR and Poland; examination of life expectancy changes after transition were based on 1992-97 data for Germany and 1991-96 data for Poland. RESULTS: In both the former GDR and Poland male life expectancy at birth declined by almost one year during transition, mainly attributable to rising death rates from external causes and circulatory diseases. Female life expectancy in Poland deteriorated by 0.3 years, largely attributable to increasing circulatory mortality among the old, while in East German female rising death rates in children and young adults were nearly outbalanced by declining circulatory mortality among those over 70. Between 1991/92 and 1996/97, male life expectancy at birth increased by 2.4 years in the former GDR, 1.2 years in old Federal Republic, and 2.0 years in Poland (women: 2.3, 0.9, and 1.2 years). In East Germany and Poland, the overall improvement was largely attributable to falling mortality among men aged 40-64, while those over 65 contributed the largest proportion to life expectancy gains in women. The change in deaths among men aged 15-39 accounted for 0.4 of a year to life expectancy at birth in East Germany and Poland, attributable largely to greater decreases from external causes. Among those over 40, absolute contributions to changing life expectancy were greater in the former GDR than in the other two entities in both sexes, largely attributable to circulatory diseases. A persisting East-west life expectancy gap in Germany of 2.1 years in men in 1997 was largely attributable to external causes, diseases of the digestive system and circulatory diseases. Higher death rates from circulatory diseases among the elderly largely explain the female life expectancy gap of approximately one year. CONCLUSIONS: This study provides further insights into the health effects of political transition. Post-transition improvements in life expectancy and mortality have been much steeper in East Germany compared with Poland. Changes in dietary pattern and, in Germany, medical care may have been important factors in shaping post-transition mortality trends.     

The changing nature of murder in Russia

The death rate from homicide in Russia increased rapidly during the 1990 s. It is now about 20 times higher than in western Europe and is among the highest recorded anywhere in the world. However, this issue has received little attention so far from public health researchers or policymakers.This paper describes the changing nature of homicide during the 1990 s in Russia as a whole and, in more detail, in the Udmurt Republic. The study uses data from three sources: routine mortality data for Russia from 1970 to 1999; statistics on criminal investigations and convictions in Russia between 1990 and 1997; and an in-depth study of homicide trial records in the Udmurt Republic in 1989-1991 and 1998.Deaths from homicide increased between 1970 and 1985, falling slightly during the 1985 anti-alcohol campaign and then resuming their increase until 1994. Another fall in the late 1990 s was arrested in 1998, with an increase in 1999. By 1999 the age standardised homicide death rate in Russia was 81% higher than in 1990, an increase almost twice that of all causes of death combined. Throughout the 1990 s about 10% of those convicted of homicide were female. Of those homicides leading to convictions in the Udmurt Republic, 71% of those killed by males were male, as were 76% of those killed by females. Killings of women by men often involved sexual assaults. In Russia as a whole, about 80% of those convicted of homicide were reported to be under the influence of alcohol at the time. In the Udmurt Republic, where data on both offender and victim were available, victims were also commonly intoxicated.The nature of homicide in Russia has changed considerably in less than a decade, with many more now involving aggravating circumstances, such as murder to conceal another crime, in association with robbery or rape, or by a group of people. Although still a small proportion of the total convicted, the number of murders by hired killers is also on the rise.The characteristics of those convicted of homicide have also changed during the 1990 s. They are now younger, less likely to have previous convictions, and to have a more diverse range of educational levels. The previous urban-rural gap, with higher levels in rural areas, has also narrowed.     

Resistance of Copenhagen rats to chemical induction of glutathione S- transferase 7-7-positive liver foci

Copenhagen (Cop) rats are completely resistant to the chemical induction of mammary adenocarcinomas, but their susceptibility to hepatocarcinogenesis is virtually unknown. Rat liver is a well- characterized and easily manipulated tissue in which to study carcinogenesis. Therefore, if Cop rats are resistant to hepatocarcinogenesis, studies into resistance mechanisms may be feasible. Male Cop and F344 rats, 7-8 weeks old, were initiated using either N-nitrosodiethylamine (DEN) (200 mg/kg, i.p.) or a two-thirds partial hepatectomy (PH) followed by N-methyl-N-nitrosourea (MNU) (60 mg/kg, i.p.). The rats were then promoted using a modified resistant hepatocyte (RH) protocol (a combination of four doses of 2- acetylaminofluorene (2-AAF) and a single dose of CCl4 that provides a selective mitotic stimulus for initiated cells). Six weeks after initiation the rats were killed and liver sections were stained for glutathione S-transferase 7-7 (GST 7-7), a marker for putative preneoplastic hepatocytes. Cop rats were found to be highly resistant, having a approximately 9- and approximately 27-fold smaller percentage of liver area occupied by GST 7-7-positive foci than susceptible F344 rats following initiation by DEN and MNU respectively. Furthermore, gross liver nodules did not form in any of the Cop rats, whereas all F344 rat livers contained nodules. Hepatic necrosis caused by DEN during initiation, and CCl4 during promotion is necessary to stimulate compensatory hepatocyte division. We demonstrated that these agents do indeed increase serum transaminase levels and produce histologic evidence of necrosis in Cop rats. In order for liver foci to grow rapidly in the RH protocol, the surrounding normal hepatocytes must be mito-inhibited by 2-AAF. We found that the degree of mito-inhibition of normal hepatocytes by 2-AAF is the same in Cop and F344 rats. These results show that the Cop rat is highly resistant to the chemical induction of putative preneoplastic liver foci and nodules.      

Desmoplastic fibroma of the proximal ulna

A young man presented with desmoplastic fibroma in the proximal ulna. This rare tumour was treated by curettage and bone grafting.     

World mortality 1950-2000: divergence replaces convergence from the late 1980s

OBJECTIVE: We sought to investigate to what extent worldwide improvements in mortality over the past 50 years have been accompanied by convergence in the mortality experience of the world's population. METHODS: We have adopted a novel approach to the objective measurement of global mortality convergence. The global mortality distribution at a point in time is quantified using a dispersion measure of mortality (DMM). Trends in the DMM indicate global mortality convergence and divergence. The analysis uses United Nations data for 1950-2000 for all 152 countries with populations of at least 1 million in 2000 (99.7% of the world's population in 2000). FINDINGS: The DMM for life expectancy at birth declined until the late 1980s but has since increased, signalling a shift from global convergence to divergence in life expectancy at birth. In contrast, the DMM for infant mortality indicates continued convergence since 1950. CONCLUSION: The switch in the late 1980s from the global convergence of life expectancy at birth to divergence indicates that progress in reducing mortality differences between many populations is now more than offset by the scale of reversals in adult mortality in others. Global progress needs to be judged on whether mortality convergence can be re-established and indeed accelerated.