Gene expression associated with suicide attempts in US veterans.

According to a recent report from the Office of Suicide Prevention in the US Department of Veterans Affairs, veterans represent 8.5% of the US population, but account for 18% of all deaths from suicide. The aim of this study of psychiatric patients (n=39; 87% male) was to compare blood gene expression data from veterans with a history of one or more suicide attempts to veterans who had never attempted suicide. The attempter and non-attempter groups were matched for age and race/ethnicity, and both groups included veterans with a diverse psychiatric history that included posttraumatic stress disorder (PTSD) and substance-use disorders. Veterans were interviewed for lifetime psychiatric history, including a detailed assessment of prior suicide attempts and provided a blood sample. Results of Ingenuity Pathway Analysis (IPA) identified several pathways associated with suicide attempts, including the mammalian target of rapamycin (mTOR) and WNT signaling pathways. These pathways are of particular interest, given their role in explaining pharmacological treatments for suicidal behavior, including the use of ketamine and lithium. These results suggest that findings observed in civilians are also relevant for veterans and provide a context for interpreting results observed in post-mortem samples. In conclusion, an emerging body of work that shows consistency in findings across blood and brain samples suggests that it might be possible to identify molecular predictors of suicide attempts.

Whole-genome DNA methylation status associated with clinical PTSD measures of OIF/OEF veterans.

Emerging knowledge suggests that post-traumatic stress disorder (PTSD) pathophysiology is linked to the patients' epigenetic changes, but comprehensive studies examining genome-wide methylation have not been performed. In this study, we examined genome-wide DNA methylation in peripheral whole blood in combat veterans with and without PTSD to ascertain differentially methylated probes. Discovery was initially made in a training sample comprising 48 male Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) veterans with PTSD and 51 age/ethnicity/gender-matched combat-exposed PTSD-negative controls. Agilent whole-genome array detected ~5600 differentially methylated CpG islands (CpGI) annotated to ~2800 differently methylated genes (DMGs). The majority (84.5%) of these CpGIs were hypermethylated in the PTSD cases. Functional analysis was performed using the DMGs encoding the promoter-bound CpGIs to identify networks related to PTSD. The identified networks were further validated by an independent test set comprising 31 PTSD+/29 PTSD- veterans. Targeted bisulfite sequencing was also used to confirm the methylation status of 20 DMGs shown to be highly perturbed in the training set. To improve the statistical power and mitigate the assay bias and batch effects, a union set combining both training and test set was assayed using a different platform from Illumina. The pathways curated from this analysis confirmed 65% of the pool of pathways mined from training and test sets. The results highlight the importance of assay methodology and use of independent samples for discovery and validation of differentially methylated genes mined from whole blood. Nonetheless, the current study demonstrates that several important epigenetically altered networks may distinguish combat-exposed veterans with and without PTSD.

A new oral slow release form of isosorbide dinitrate. Effect on the hemodynamics and exercise capacity of patients with angina.

To assess the bioavailability of a new oral and slow release form of isosorbide dinitrate (ISDN-SR), we evaluated 12 patients with confirmed coronary artery disease, chronic stable angina pectoris and abnormal maximal exercise tests (angina-limited and associated with greater than or equal to 0.1 mV ST displacement). Each patient was known to have an increased exercise time after 0.4 mg of sublingual nitroglycerin. Patient responses to exercise on the treadmill at two, four, six, and eight hours after the double-blind administration of 40 mg of ISDN-SR were compared to an identical placebo. It is concluded that 40 mg of this slow release form of isosorbide dinitrate is bioavailable for at least eight hours as demonstrated by significantly improved exercise capacity of the majority (64 percent) of angina patients in this study, each of whom demonstrated anginal limitation to exercise and favorable responses to 0.4 mg of sublingual nitroglycerin.

The importance of measured intake in assessing exposure of breast-fed infants to organochlorines.

OBJECTIVES: To estimate infants' intake of organochlorines (OCs) from their measured intake of breast milk; to compare these with the acceptable daily intakes (ADIs) set by the World Health Organization (WHO). DESIGN: Primiparous nursing mothers were recruited from either an industrial or rural area between January and November 1992. SETTING: Mothers volunteered in response to information displayed at their Infant Welfare Centre. All sampling was undertaken in the subject's home. SUBJECTS: The sole entry criterion was primiparity. Three breast milk samples were collected at one month intervals from each mother. OC levels were measured on a milk fat basis by gas chromatograph-mass spectrometer and individual milk intakes were used to determine the infant's daily OC intake. Of the 23 mothers who entered the study, 17 finished, resulting in 57 samples for intake determination. RESULTS: Some intakes of hexachlorobenzene (HCB), chlordane, dieldrin and heptachlor epoxide (HE) exceeded the ADI. High OC levels in breast milk did not necessarily result in a high intake for the infant. CONCLUSIONS: Assessment of the exposure of infants to OC contaminants in breast milk requires an accurate estimate of OC intake. Intakes estimated using inferred rather than measured values for milk fat and milk intake are not reliable indicators of actual intakes.

A numerical test of the normal incidence uniaxial model of corneal birefringence.

The suggestion that the central cornea can be modeled as a uniaxial birefringent material with its optic axis normal to the surface is explicitly tested by numerical calculations. A theoretical framework is presented to model the corneal stroma as a series of stacked, uniaxial birefringent layers (lamellae). Calculations are then made of the transmission of normally incident, linearly polarized light through model systems having various azimuthal orientations of the layers, motivated by the suggestion of an overall "random" organization of the stromal lamellae. It is concluded that the uniaxial description, and the assumptions upon which that description is based, do not hold for the cornea. In particular, the calculations are in agreement with recent experiments in which one always observes a non-zero cross-polarized transmission (hence birefringence) at normal incidence.

Persistence of organochlorines in breast milk of women in Victoria, Australia.

Existing information on the exposure of Australian infants to environmental contaminants through maternal milk is inadequate for assessing the safety of breast feeding. This study was undertaken to determine the extent of organochlorine (OC) contamination in the milk of mothers resident in Victoria, to monitor OC elimination by the nursing mother and to estimate the infant's daily intake of OCs from breast milk. Organochlorines were extracted from the lipophilic fraction of the breast milk samples and analysed by selected ion monitoring on a gas chromatograph-mass spectrometer (GC-MS). There was widespread contamination of milk with dichlorodiphenyltrichloroethane (p,p'-DDT) and its metabolite dichlorodiphenyldichloroethene, hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), oxychlordane and hexachlorocyclohexane, with p,p'-DDT and HCB being found in nearly all samples. Dieldrin and heptachlor epoxide were detected in 43 and 30% of samples respectively. PCBs were detected in 79% of samples and chlordane in 76%. A number of infants had daily intakes above the acceptable daily intake for total chlordane, total DDT, dieldrin, heptachlor epoxide and total PCBs. These findings have implications for strategies for the reduction of environmental contamination.

Aflatoxin M1 in human breast milk samples from Victoria, Australia and Thailand.

This study examined the exposure of infants to aflatoxin M1 (AFM1) and of lactating mothers to aflatoxin B1 (AFB1), using AFM1 in breast milk as a biomarker for exposure to AFB1. An enzyme-linked immunosorbent assay was modified for the analysis of AFM1 in breast milk samples from 73 women from Victoria for comparison with breast milk samples from Thailand (n = 11). The results were compared with those obtained by HPLC. AFM1 was detected in 11 samples from Victoria and five samples from Thailand at median concentrations of 0.071 ng/ml (range 0.028 to 1.031 ng/ml) and 0.664 ng/ml (range 0.039 to 1.736 ng/ml), respectively. Levels of AFM1 in Thai milk samples were significantly higher than those in milk samples from Victoria.

The incidence of abnormal limb development in the Irish thoroughbred from birth to 18 months.

A two part survey was carried out in Irish Thoroughbred horses in 1988 and 1989 to establish the incidence and prevalence of developmental skeletal problems, particularly possible manifestations of developmental orthopaedic disease (DOD). Survey One was a retrospective study based on a questionnaire involving the foal crops of 46 stud farms for 3 successive seasons; the 1711 animals initially documented represented 10.46% of Irish foal registrations. The second survey involved repeated monitoring of the 1988 foal crop from birth to 18 months of age on 17 stud farms. The 248 foals initially examined represented 4.24% of foal registrations. Treatment for DOD was deemed necessary for 11.3% of the animals in Survey One. Angular limb deformities and physeal dysplasia ("epiphysitis") together constituted 72.9% of the cases treated. The peak incidence of DOD problems occurred between weaning and the end of December. More than half the animals treated (53.9%) recovered completely, ie achieved expected sale value as yearlings, 27.5% of those treated showed incomplete recovery and mild to moderate loss of sale value and the remaining 18.7% were killed or lost much of their sale value. In the second survey, while 67% of animals exhibited some form of DOD, the incidence and severity of problems treated were not significantly different from those of farms in Survey One. Again, physeal dysplasia and angular limb deformity were the predominant clinical conditions and their severity was greatest during the early winter. During the suckling phase colts had a significantly greater incidence of DOD. At all other stages the incidence and severity of DOD was similar in both sexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Staphylococcal scalded skin syndrome in a woman with chronic renal failure exposed to human immunodeficiency virus.

A twenty-eight-year-old woman seropositive for the human immunodeficiency virus and undergoing hemodialysis for end-stage renal disease sustained an infection of her arteriovenous graft. Multiple erythematous erosions appeared and a diagnosis of staphylococcal scalded skin syndrome was made when a frozen section of a fresh skin peel revealed an intraepidermal split through the granular layer and Staphylococcus aureus group II, phage type 71 was cultured from the wound and blood. Twenty-six cases of adult patients with staphylococcal scalded skin syndrome have been reported. Although this includes one patient with AIDS-related complex, this is the first case of an adult with staphylococcal scalded skin syndrome who showed seropositive results of testing for human immunodeficiency virus.

Depleted uranium particles in selected Kosovo samples.

Selected soil samples, collected in Kosovo locations where DU ammunition was expended during the 1999 Balkan conflict, have been investigated by secondary ion mass spectrometry (SIMS), X-ray fluorescence imaging using a micro-beam (micro-XRF) and scanning electron microscopy equipped with an energy dispersive X-ray fluorescence detector (SEM-EDXRF), with the objective to test the suitability of these techniques to identify the presence of small DU particles and measure their size distribution and the 235U/238U isotopic ratio (SIMS). Although the results do not permit any legitimate extrapolation to all the sites hit by the DU rounds used during the conflict, they indicated that there can be "spots ' where hundreds of thousands of particles may be present in a few milligrams of DU contaminated soil. The particle size distribution showed that most of the DU particles were <5 microm in diameter and more than 50% of the particles had a diameter <1.5 microm. Knowledge on DU particles is needed as a basis for the assessment of the potential environmental and health impacts of military use of DU, since it provides information on possible re-suspension and inhalation.

The future of podiatric medical education. Cautious optimism.

The leadership of the Pennsylvania College of Podiatric Medicine sets forth the following treatise on the outlook for podiatric medical education into the 21st century. Despite the seemingly impossible challenges facing the profession and its students, it is their opinion that the future is bright and with dedicated effort the profession will become stronger in the years ahead.

Searching for non-B DNA-forming motifs using nBMST (non-B DNA motif search tool).

This unit describes basic protocols on using the non-B DNA Motif Search Tool (nBMST) to search for sequence motifs predicted to form alternative DNA conformations that differ from the canonical right-handed Watson-Crick double-helix, collectively known as non-B DNA, and on using the associated PolyBrowse, a GBrowse-based genomic browser. The nBMST is a Web-based resource that allows users to submit one or more DNA sequences to search for inverted repeats (cruciform DNA), mirror repeats (triplex DNA), direct/tandem repeats (slipped/hairpin structures), G4 motifs (tetraplex, G-quadruplex DNA), alternating purine-pyrimidine tracts (left-handed Z-DNA), and A-phased repeats (static bending). The nBMST is versatile, simple to use, does not require bioinformatics skills, and can be applied to any type of DNA sequences, including viral and bacterial genomes, up to an aggregate of 20 megabasepairs (Mbp).