A Positive Association Between Cryptosporidiosis Notifications and Ambient Temperature, Victoria, Australia, 2001-2009

Increased temperatures provide optimal conditions for pathogen survival, virulence and replication as well as increased opportunities for human-pathogen interaction. This paper examined the relationship between notifications of cryptosporidiosis and temperature in metropolitan and rural areas of Victoria, Australia between 2001-2009. A negative binomial regression model was used to analyse monthly average maximum and minimum temperatures, rainfall and the monthly count of cryptosporidiosis notifications. In the metropolitan area, a 1°C increase in monthly average minimum temperature of the current month was associated with a 22% increase in cryptosporidiosis notifications (IRR 1.22; 95% CI 1.13 – 1.31). In the rural area, a 1°C increase in monthly average minimum temperature, lagged by 3 months, was associated with a 9% decrease in cryptosporidiosis notifications (IRR 0.91; 95% CI 0.86 – 0.97). Rainfall was not associated with notifications in either area. These relationships should be considered when planning public health response to ecological risks as well as when developing policies involving climate change. Rising ambient temperature may be an early warning signal for intensifying prevention efforts, including appropriate education for pool users about cryptosporidiosis infection and management, which might become more important as temperatures are projected to increase as a result of climate change

The Epidemiology of Cryptosporidiosis in Victoria, 2001-2009

Cryptosporidiosis is a protozoan parasitic infection that most commonly presents as gastroenteritis and less commonly infects the respiratory and biliary tracts. Enteric symptoms usually include diarrhoea, bloating, cramping, abdominal pain, vomiting and fever. The disease is usually mild and self-limiting but in immunocompromised individuals is prolonged and can lead to death. The infective dose in humans is low and the incubation period ranges from one to 12 days, with an average of seven days. The infectious period lasts from the onset of symptoms, as the oocysts are excreted in the stool, until several weeks after symptoms resolve. The oocysts are widespread and may remain infective outside the body for two to six months, particularly if the environment is moist. They are highly resistant to standard levels of chemical disinfection of water such as chlorine. Outbreaks have been reported in day care centres, and been associated with drinking water, recreational water (waterslides, swimming pools and lakes) and consumption of contaminated beverages. In Australia, increases in notifications tend to occur in the warmer months and over irregular cycles, with more than 3000 cases notified in Australia in 2002, 2005 and 2006. Cryptosporidiosis became notifiable in both Australia and Victoria in 2001, with more than 15,000 cases notified between 2002 and 2009. The aim of this study was to describe the epidemiology of notified cases of cryptosporidiosis in Victoria for the period 2001 to 2009 in terms of age, sex, location and season

Foodborne disease outbreaks in Australia 2001-2009

BACKGROUND: Analysis of surveillance data from foodborne disease outbreaks can help identify high-risk aetiological agents, food vehicles and settings. This information may help prevent future illness by informing the development of public health policy

Identification of genes expressed by immune cells of the colon that are regulated by colorectal cancer-associated variants.

A locus on human chromosome 11q23 tagged by marker rs3802842 was associated with colorectal cancer (CRC) in a genome-wide association study; this finding has been replicated in case-control studies worldwide. In order to identify biologic factors at this locus that are related to the etiopathology of CRC, we used microarray-based target selection methods, coupled to next-generation sequencing, to study 103 kb at the 11q23 locus. We genotyped 369 putative variants from 1,030 patients with CRC (cases) and 1,061 individuals without CRC (controls) from the Ontario Familial Colorectal Cancer Registry. Two previously uncharacterized genes, COLCA1 and COLCA2, were found to be co-regulated genes that are transcribed from opposite strands. Expression levels of COLCA1 and COLCA2 transcripts correlate with rs3802842 genotypes. In colon tissues, COLCA1 co-localizes with crystalloid granules of eosinophils and granular organelles of mast cells, neutrophils, macrophages, dendritic cells and differentiated myeloid-derived cell lines. COLCA2 is present in the cytoplasm of normal epithelial, immune and other cell lineages, as well as tumor cells. Tissue microarray analysis demonstrates the association of rs3802842 with lymphocyte density in the lamina propria (p = 0.014) and levels of COLCA1 in the lamina propria (p = 0.00016) and COLCA2 (tumor cells, p = 0.0041 and lamina propria, p = 6 × 10(-5)). In conclusion, genetic, expression and immunohistochemical data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. Histologic analyses indicate the involvement of immune pathways

Paternal under-nutrition programs metabolic syndrome in offspring which can be reversed by antioxidant/vitamin food fortification in fathers

There is an ever increasing body of evidence that demonstrates that paternal over-nutrition prior to conception programs impaired metabolic health in offspring. Here we examined whether paternal under-nutrition can also program impaired health in offspring and if any detrimental health outcomes in offspring could be prevented by micronutrient supplementation (vitamins and antioxidants). We discovered that restricting the food intake of male rodents reduced their body weight, fertility, increased sperm oxidative DNA lesions and reduced global sperm methylation. Under-nourished males then sired offspring with reduced postnatal weight and growth but somewhat paradoxically increased adiposity and dyslipidaemia, despite being fed standard chow. Paternal vitamin/antioxidant food fortification during under-nutrition not only normalised founder oxidative sperm DNA lesions but also prevented early growth restriction, fat accumulation and dyslipidaemia in offspring. This demonstrates that paternal under-nutrition reduces postnatal growth but increases the risk of obesity and metabolic disease in the next generation and that micronutrient supplementation during this period of under-nutrition is capable of restoring offspring metabolic health

Obese father's metabolic state, adiposity, and reproductive capacity indicate son's reproductive health

ObjectiveTo determine whether dietary and exercise regimes in obese males can provide a novel intervention window for improving the reproductive health of the next generation.DesignExperimental animal study.SettingUniversity research facilities.Animal(s)C57BL6 male and female mice.Intervention(s)Mice were fed a control diet (6% fat) or high-fat diet (21% fat) for 9 weeks. After the initial feeding, high-fat-diet males were allocated to diet and/or exercise interventions for a further 9 weeks. After intervention males were mated with females fed standard chow (4% fat) before and during pregnancy.Main outcome measure(s)F1 sperm motility, count, morphology, capacitation, mitochondrial function, and sperm binding and weight of reproductive organs.Result(s)Our primary finding was that diet intervention alone in founders improved offspring sperm motility and mitochondrial markers of sperm health (decreased reactive oxygen species and mitochondrial membrane potential), ultimately improving sperm binding. Sperm binding and capacitation was also improved in F1 males born to a combined diet and exercise intervention in founders. Founder sperm parameters and metabolic measures as a response to diet and/or exercise (i.e., lipid/glucose homeostasis, sperm count and morphology) correlated with offspring's sperm function, independent of founder treatment. This implicates paternal metabolic and reproductive status in predicting male offspring's reproductive function.Conclusion(s)This is the first study to show that improvements to both metabolic (lipids, glucose and insulin sensitivity) and reproductive function (sperm motility and morphology) in obese fathers via diet and exercise interventions can improve subsequent reproductive health in offspring.Nicole O. McPherson, Tod Fullston, Hassan W. Bakos, Brian P. Setchell and Michelle Lan

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN