The economic costs associated with physical inactivity and obesity in Canada: an update.

The purpose of this analytical review was to estimate the direct and indirect economic costs of physical inactivity and obesity in Canada in 2001. The relative risks of diseases associated with physical inactivity and obesity were determined from a meta-analysis of existing prospective studies and applied to the health care costs of these diseases in Canada. Estimates were derived for both the direct health care expenditures and the indirect costs, which included the value of economic output lost because of illness, injury-related work disability, or premature death. The economic burden of physical inactivity was $5.3 billion ($1.6 billion in direct costs and $3.7 billion in indirect costs) while the cost associated with obesity was $4.3 billion ($1.6 billion of direct costs and $2.7 billion of indirect costs). The total economic costs of physical inactivity and obesity represented 2.6% and 2.2%, respectively, of the total health care costs in Canada. The results underscore the importance of public health efforts aimed at combating the current epidemics of physical inactivity and obesity in Canada.     

Role of nitric oxide in the biology, physiology and pathophysiology of reproduction

Following its benchmark discovery, nitric oxide (NO) is nowknown to play important functional roles in a variety of physiologicalsystems. Within the vasculature, NO induces vasodilation, inhibitsplatelet aggregation, prevents neutrophil/platelet adhesionto endothelial cells, inhibits smooth muscle cell proliferationand migration, regulates programmed cell death (apoptosis) andmaintains endothelial cell barrier function. NO generated byneurons acts as a neurotransmitter, whereas NO generated bymacrophages in response to invading microbes acts as an antimicrobialagent. Because neurons, blood vessels and cells of the immunesystem are integral parts of the reproductive organs, and inview of the important functional role that NO plays in thosesystems, it is likely that NO is an important regulator of thebiology and physiology of the reproductive system. Indeed, inthe past 10 years, NO has established itself as a polyvalentmolecule which plays a decisive role in regulating multiplefunctions within the female as well as the male reproductivesystem. This review provides an overview of the role of NO invarious reproductive organs under physiological and pathologicalconditions.     

The pulmonary biology of isoprostanes

Isoprostanes were first recognized as convenient markers of oxidative stress, but their powerful effects on a variety of cell functions are now also being increasingly appreciated. This is particularly true of the lung, which is comprised of a wide variety of different cell types (smooth muscle, innervation, epithelium, lymphatics, etc.), all of which have been shown to respond to exogenously applied isoprostanes. In this review, we summarize these biological responses in the lung, and also consider the roles that isoprostanes might play in a range of pulmonary clinical disorders.     

First confirmed case with paternal uniparental disomy of chromosome 16

The existence of paternal uniparental disomy of chromosome 16 [upd(16)pat] has previously been suspected but has not been proven. We report prenatal detection and follow-up of isodisomic upd(16)pat in a child with minimal defects but otherwise normal development. Our results indicate that isodisomic upd(16)pat is associated with a normal outcome if no recessive mutation is reduced to homozygosity.     

Molecular characterization and determination of the coding capacity of the genome of equine herpesvirus type 2 between the genome coordinates 0.235 and 0.258 (theEcoRI DNA fragment N; 4.2 kbp)

The complete DNA nucleotide sequence of theEcoRI DNA fragment N (0.235 to 0.258 viral map units) of equine herpes virus type 2 (EHV-2) strain T400/3 was determined. This DNA fragment comprises 4237 bp with a base composition of 55.23% G+C and 44.77% A+T. Nineteen open reading frames (ORFs) of 50-287 amino acid (aa) residues were detected. ORF number 10 is located between the nucleotide position 2220 and 2756 coding for a protein of 179 amino acid residues. This protein shows significant homology to the cytokine synthesis inhibitory factor (CSIF; interleukin 10) of human (76.4%) and mouse (68.5%), and to the Epstein-Barr virus (EBV) protein BCRF1 (70.6%). The existence of an interleukin 10 (IL-10) analogous gene within the genome of the EHV-2 was confirmed by screening the genome of nine EHV-2 strains using specific oligonucleotide primers corresponding to the 5 and 3 region of this particular gene by polymerase chain reaction. In all experiments an 870 bp DNA product was amplified. The specifity of the amplified DNA fragments obtained from individual EHV-2 strains was confirmed by DNA-DNA hybridization experiments. The DNA sequence analysis of the amplified DNA products of the EHV-2 strain LK was carried out. This analysis revealed the identity of the corresponding IL-10 gene (540 bp) of this strain to the IL-10 gene of EHV-2 strain T400/3. The presented data indicate that the EHV-2 genome harbors a viral interleukin 10-like gene. This is further evidence that the IL-10 gene can be present in the genomes of members of the Herpesviridae family.     

Molecular epidemiology of apparent outbreak of invasive aspergillosis in a hematology ward.

During a 2-month period, five patients suffering from invasive infections caused by Aspergillus flavus or Aspergillus fumigatus were identified in the Hematology Department of the University Hospital Dijkzigt (Rotterdam, The Netherlands). To study the epidemiological aspects of invasive aspergillosis, strains from these patients and from the hospital environment, isolated during extensive microbiological screening, were subjected to genotyping. A novel DNA extraction technique, involving freezing, grinding, and direct lysis in guanidium isothiocyanate-containing buffers of mycelial material, was applied. DNA isolation was followed by typing by random amplification of polymorphic DNA (RAPD) analysis. This showed that strains isolated from all patients infected with the same fungal species were genotypically distinct, thus providing evidence against the possibility of an ongoing, single-source nosocomial outbreak. Strains could also be differentiated from strains of geographically diverse origins. However, an A. flavus strain from one of the patients was also frequently encountered in the hospital environment. As all environmental strains were collected after this patient had been diagnosed with invasive disease, the epidemiological value of this observation could not be ascertained. Intensive investigations showed no single source of A. flavus or other aspergilli. RAPD genotyping proved that the outbreak of invasive aspergillosis in the hematology ward consisted of a series of unrelated events and was not due to a common source within the hospital. RAPD fingerprinting of aspergilli may greatly facilitate future investigations of the epidemiology of invasive disease caused by these pathogens.     

ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome

It was shown recently that mutations of the ATRX gene give rise to a severe, X-linked form of syndromal mental retardation associated with alpha thalassaemia (ATR-X syndrome). In this study, we have characterised the full-length cDNA and predicted structure of the ATRX protein. Comparative analysis shows that it is an entirely new member of the SNF2 subgroup of a superfamily of proteins with similar ATPase and helicase domains. ATRX probably acts as a regulator of gene expression. Definition of its genomic structure enabled us to identify four novel splicing defects by screening 52 affected individuals. Correlation between these and previously identified mutations with variations in the ATR-X phenotype provides insights into the pathophysiology of this disease and the normal role of the ATRX protein in vivo.      

Regulation of the density of spermatogonia in the seminiferous epithelium of the Chinese hamster: I. Undifferentiated spermatogonia

The topographical arrangement of the clones of A single, A paired, and A aligned (As, Apr, and Aal) spermatogonia on the basement membrane of seminiferous tubules of the Chinese hamster was studied. It was found that at least some of these clones are not distributed at random as clones of similar cell number were often seen in clusters. Areas were found with few or many As spermatogonia. Also, clusters of Apr spermatogonia were found, indicating that in such an area many As spermatogonia more or less synchronously formed Apr spermatogonia. Since clusters of clones of 16 Aal spermatogonia were observed, it can be concluded that these clusters of Apr spermatogonia may proliferate in at least a roughly synchronous way. It was found that over large areas the densities of undifferentiated spermatogonia may be very low or high in comparison to the mean density in the animal. Whether the ratio of self-renewal and differentiation of the stem cells changed locally in response to the high or low density of undifferentiated spermatogonia in particular areas was investigated. No indications for a regulatory mechanism to keep the density of stem cells and/or the density of undifferentiated spermatogonial clones at a certain level could be detected in the normal Chinese hamster. This lack of regulation was at least partly responsible for the widely different numbers of A1 spermatogonia that were formed in the various areas studied in stage IX.