Carcinogenic potential of ovulatory genotoxicity

Ovulation is a rate-limiting event for the perpetuation of a species; unfortunately, it imparts a cancer risk. Reactive oxidants generated during the mechanics of ovulatory follicular rupture damage the DNA of ovarian surface epithelial cells that are located within a limited diffusion radius. Those cells that survive the trauma of ovulation, along the margins of a ruptured follicle, proliferate and migrate to reconcile the discontinuity within the ovarian epithelium created at the site of oocyte release. It is conceivable that clonal expansion of an ovarian surface epithelial cell with unrepaired DNA, but not committed to death, could be an initiating factor in the etiology of common ovarian cancer. In fact, the majority of cancers of the ovary are derived from the surface epithelium; and circumstances that avert ovulation (oral contraceptive use, pregnancy/lactation) protect against ovarian adenocarcinoma. Not surprisingly, the genotoxic potential of ovulation is exacerbated by malfunctions in tumor suppressor/cell-cycle arrest and base-excision repair mechanisms. Recent experimental evidence indicates that vitamin E and progesterone protect against ovarian metaplasia by negating the oxidative stress of ovulation and by enhancing the repair capacity (genomic integrity) of the surface epithelium, respectively. Ovarian cancer of surface epithelial origin is a deadly insidious disease because it characteristically remains asymptomatic until it has metastasized throughout the abdominal cavity; therefore, prevention is a high priority.     

Retinal axon misrouting at the optic chiasm in mice with neural tube closure defects

In a new mouse mutant, circletail (Crc), failure of neural tube closure (embryonic day [E] 8-9) is associated with errors in retinal axon projection at the optic chiasm (E12-18), such that many axons normally projecting contralaterally instead grow to ipsilateral targets. Although the architecture of the chiasmatic region is altered, neurons and glia containing putative cues for axon guidance are present. The aberrant ipsilateral-projecting cells originate from a nonrandom expansion of the wild-type uncrossed retinal region. These axon pathway defects are found in two other mutants with cephalic neural tube defects (NTD), loop-tail (Lp) and Pax3 (splotch; Sp(2H)). Crc is phenotypically similar to Lp, exhibiting an open neural tube from midbrain to tail (craniorachischisis), while splotch has spina bifida with or without a cranial NTD. The retinal axon abnormalities occur only in the presence of NTD and not in homozygous mutants lacking cranial NTD. Thus, failure of neural tube closure is associated with failure of many retinal axons to cross the ventral midline. This study therefore reveals an unexpected connection between closure of the neural tube at the dorsal midline and development of ventral axon tracts. genesis 27:32-47, 2000.     

DNA damages in ovarian surface epithelial cells of ovulatory hens

A cause-effect relationship between ovulation and common (surface) epithelial ovarian cancer has been suspected for many years. The ovarian surface epithelium apparently becomes exposed to genotoxins that are generated during the ovulatory process. Intensive egg-laying hens readily develop ovarian carcinomatosis. Indeed, elevated levels of potentially mutagenic 8-oxo-guanine adducts were detected in avian ovarian epithelial cells isolated from the apical surfaces and perimeters of pre-and postovulatory follicles, respectively. Internucleosomal DNA fragmentation indicative of apoptosis was evident in ovarian surface epithelial cells associated with the formative site of ovulation (stigma line) and regressive ruptured follicles. It is conceivable that a genetically altered progenitor cell with unrepaired DNA but not committed to death (i.e., a unifocal "escape") could give rise to a transformed phenotype. Hence, the high rate of ovarian cancer in egg-laying hens could be the consequence of genomic damages to the ovarian surface epithelium associated with incessant ovulations, thereby increasing the likelihood of mutation and clonal expansion.     

Ecological risk assessment of multiple hatchery programs in the upper Columbia watershed using Delphi and modeling approaches

Ecological risks of Pacific salmon (spring, summer, and fall run Chinook, coho, and sockeye salmon) and steelhead trout hatchery programs operated between 2013 and 2023 in the Upper Columbia Watershed will be assessed using Delphi and modeling approaches. Committees composed of resource managers and public utility districts identified non-target taxa of concern (i.e., taxa that are not the target of supplementation), and acceptable hatchery impacts (i.e., change in population status) to those taxa. Biologists assembled information about hatchery programs, non-target taxa, and ecological interactions and this information will be provided to expert panelists in the Delphi process to facilitate assessment of risks and also used to populate the Predation, Competition, and Disease (PCD) Risk 1 model. Delphi panelists will independently estimate the proportion of a non-target taxa population that will be affected by each individual hatchery program. Estimates from each of the two approaches will be independently averaged, a measure of dispersion calculated (e.g., standard deviation), and subsequently compared to the acceptable hatchery impact levels that were determined previously by committees of resource managers and public utility districts. Measures of dispersion will be used to estimate the scientific uncertainty associated with risk estimates. Delphi and model results will be compared to evaluate the qualities of the two approaches. Furthermore, estimates of impacts from each hatchery program will be combined together to generate an estimate of cumulative impact to each non-target taxon.     

How safe are gloves and masks used for protection against Legionella longbeachae infection when gardening?

Legionella longbeachae has been frequently identified in composted plant material and can cause Legionnaires’ disease (LD). We wanted to determine how frequently L. longbeachae DNA was present on gardeners’ gloves, and how long L. longbeachae could persist on inoculated gloves and masks. Volunteers completed a survey of gardening practices and their gardening gloves were tested for L. longbeachae DNA by qPCR. The persistence of viable L. longbeachae was assessed by timed subcultures after inoculation of gardening gloves and masks. Gloves but not masks were used regularly. L. longbeachae was detected on 11 (14%; 95% CI 8–24%) gloves. Viable organisms were recovered from 25–50% of inoculated cotton, leather and PU coated gloves but not rubber gloves after 8 h incubation. There was a difference in dose-response curve slopes by glove material (P = 0·001) and time to 50% sterility (P = 0·036). There were differences in persistence of L. longbeachae between mask types from analysis of the slopes and 50% sterility on the decay curves (P = 0·042, P < 0·001 respectively). Gardening gloves and masks may act as a vector for transmission of L. longbeachae during gardening. Washing gardening gloves and prompt disposal of masks could reduce risk of LD.     

Etiology of Severe Febrile Illness in Low- and Middle-Income Countries: A Systematic Review

Background

With apparent declines in malaria worldwide during the last decade and more widespread use of malaria rapid diagnostic tests, healthcare workers in low-resource areas face a growing proportion of febrile patients without malaria. We sought to describe current knowledge and identify information gaps of the etiology severe febrile illness in low-and middle-income countries.

Methods and Findings

We conducted a systematic review of studies conducted in low-and-middle income countries 1980–2013 that prospectively assessed consecutive febrile patients admitted to hospital using rigorous laboratory-based case definitions. We found 45 eligible studies describing 54,578 patients; 9,771 (17.9%) had a positive result for ≥1 pathogen meeting diagnostic criteria. There were no eligible studies identified from Southern and Middle Africa, Eastern Asia, Oceania, Latin American and Caribbean regions, and the European region. The median (range) number of diagnostic tests meeting our confirmed laboratory case definitions was 2 (1 to 11) per study. Of diagnostic tests, 5,052 (10.3%) of 49,143 had confirmed bacterial or fungal bloodstream infection; 709 (3.8%) of 18,142 had bacterial zoonosis; 3,488 (28.5%) of 12,245 had malaria; and 1,804 (17.4%) of 10,389 had a viral infection.

Conclusions

We demonstrate a wide range of pathogens associated with severe febrile illness and highlight the substantial information gaps regarding the geographic distribution and role of common pathogens. High quality severe febrile illness etiology research that is comprehensive with respect to pathogens and geographically representative is needed.