Acute hydrogen sulfide-induced neuropathology and neurological sequelae: challenges for translational neuroprotective research.

Hydrogen sulfide (H2 S), the gas with the odor of rotten eggs, was formally discovered in 1777, over 239 years ago. For many years, it was considered an environmental pollutant and a health concern only in occupational settings. Recently, however, it was discovered that H2 S is produced endogenously and plays critical physiological roles as a gasotransmitter. Although at low physiological concentrations it is physiologically beneficial, exposure to high concentrations of H2 S is known to cause brain damage, leading to neurodegeneration and long-term neurological sequelae or death. Neurological sequelae include motor, behavioral, and cognitive deficits, which are incapacitating. Currently, there are concerns about accidental or malicious acute mass civilian exposure to H2 S. There is a major unmet need for an ideal neuroprotective treatment, for use in the field, in the event of mass civilian exposure to high H2 S concentrations. This review focuses on the neuropathology of high acute H2 S exposure, knowledge gaps, and the challenges associated with development of effective neuroprotective therapy to counteract H2 S-induced neurodegeneration

The microflora of Blue Stilton cheese

Blue Stilton is a blue-veined cheese manufactured in a restricted area of the UK, using lactic starter cultures plus a secondary culture of Penicillium roquefotti. The aim of this study was to determine the change in microflora during ripening of the cheese and to investigate potential microbial interactions. Additionally, the volatile compounds present in mature samples of cheeses exhibiting few blue veins were compared with those in good quality cheeses, showing ample blue veining. Experiments on cheeses from a single dairy, monitored during the ripening process, showed that the total Lactobacillus count increased from levels of around 103 cfu g-1 on day one to around 107 cfu g-1 after 8 weeks of ripening. This is comparable to values found in other cheeses including both mould-ripened and non mould-ripened varieties. Yeast counts were generally higher than those found in other cheeses and also increased to levels in the region of 107 g-1. The total viable count (TVC) decreased from around 109 g-1 initially, reflecting the presence of the starter bacteria, to 107 g.1, suggesting a decline in the starter bacteria similar to that found in other cheeses. Mature cheeses always exhibited similar numbers of microorganisms although the species varied between cheeses. High quality, mature, cheeses were compared with sub-standard cheeses from the same production site. The predominant species of lactobacilli in good quality cheeses were Lb. plantarum and Lb. curvatus, whereas in poor quality cheeses Lb. brevis predominated. This corresponded to the results of gas chromatography-olfactometry, which indicated the presence of fruity off flavours in poor quality cheeses. Several strains of these species were isolated, as indicated by differing capabilities in utilisation of a range of carbon sources. Yeast species also varied between good and poor quality cheeses with Candida sphaerlca and C. catenulata predominating in good cheeses and C. famata, C. lipolytica and C. catenulata also occurring in both good and poor quality samples. Strain differences were observed by the biochemical profiles and two strains of C. famata demonstrated inhibitory effects against P. roqueforti when incubated under anaerobiosis. It was concluded that these strains may affect the development of blue veins in Stilton cheese when maturation conditions encourage their proliferation. Comparisons were made between samples of cheeses from several Stilton producers and the results suggested that although the levels of the groups of microorganisms tested were similar, the species of lactobacilli and yeasts present were different. This suggests that the indigenous microflora may have a significant impact on the flavour of cheeses from individual production sites. It was concluded that the microflora of Blue Stilton cheese may have a significant impact on the quality of the product both in terms of flavour and the development of the blue veins

The microflora of Blue Stilton cheese

Blue Stilton is a blue-veined cheese manufactured in a restricted area of the UK, using lactic starter cultures plus a secondary culture of Penicillium roquefotti. The aim of this study was to determine the change in microflora during ripening of the cheese and to investigate potential microbial interactions. Additionally, the volatile compounds present in mature samples of cheeses exhibiting few blue veins were compared with those in good quality cheeses, showing ample blue veining. Experiments on cheeses from a single dairy, monitored during the ripening process, showed that the total Lactobacillus count increased from levels of around 103 cfu g-1 on day one to around 107 cfu g-1 after 8 weeks of ripening. This is comparable to values found in other cheeses including both mould-ripened and non mould-ripened varieties. Yeast counts were generally higher than those found in other cheeses and also increased to levels in the region of 107 g-1. The total viable count (TVC) decreased from around 109 g-1 initially, reflecting the presence of the starter bacteria, to 107 g.1, suggesting a decline in the starter bacteria similar to that found in other cheeses. Mature cheeses always exhibited similar numbers of microorganisms although the species varied between cheeses. High quality, mature, cheeses were compared with sub-standard cheeses from the same production site. The predominant species of lactobacilli in good quality cheeses were Lb. plantarum and Lb. curvatus, whereas in poor quality cheeses Lb. brevis predominated. This corresponded to the results of gas chromatography-olfactometry, which indicated the presence of fruity off flavours in poor quality cheeses. Several strains of these species were isolated, as indicated by differing capabilities in utilisation of a range of carbon sources. Yeast species also varied between good and poor quality cheeses with Candida sphaerlca and C. catenulata predominating in good cheeses and C. famata, C. lipolytica and C. catenulata also occurring in both good and poor quality samples. Strain differences were observed by the biochemical profiles and two strains of C. famata demonstrated inhibitory effects against P. roqueforti when incubated under anaerobiosis. It was concluded that these strains may affect the development of blue veins in Stilton cheese when maturation conditions encourage their proliferation. Comparisons were made between samples of cheeses from several Stilton producers and the results suggested that although the levels of the groups of microorganisms tested were similar, the species of lactobacilli and yeasts present were different. This suggests that the indigenous microflora may have a significant impact on the flavour of cheeses from individual production sites. It was concluded that the microflora of Blue Stilton cheese may have a significant impact on the quality of the product both in terms of flavour and the development of the blue veins

Study of Selected Office Occupations in Muskogee, Oklahoma

Business Educatio

Midazolam Efficacy Against Acute Hydrogen Sulfide-Induced Mortality and Neurotoxicity.

Hydrogen sulfide (H2S) is a colorless, highly neurotoxic gas. It is not only an occupational and environmental hazard but also of concern to the Department of Homeland Security for potential nefarious use. Acute high-dose H2S exposure causes death, while survivors may develop neurological sequelae. Currently, there is no suitable antidote for treatment of acute H2S-induced neurotoxicity. Midazolam (MDZ), an anti-convulsant drug recommended for treatment of nerve agent intoxications, could also be of value in treating acute H2S intoxication. In this study, we tested the hypothesis that MDZ is effective in preventing/treating acute H2S-induced neurotoxicity. This proof-of-concept study had two objectives: to determine whether MDZ prevents/reduces H2S-induced mortality and to test whether MDZ prevents H2S-induced neurological sequelae. MDZ (4 mg/kg) was administered IM in mice, 5 min pre-exposure to a high concentration of H2S at 1000 ppm or 12 min post-exposure to 1000 ppm H2S followed by 30 min of continuous exposure. A separate experiment tested whether MDZ pre-treatment prevented neurological sequelae. Endpoints monitored included assessment of clinical signs, mortality, behavioral changes, and brain histopathological changes. MDZ significantly reduced H2S-induced lethality, seizures, knockdown, and behavioral deficits (p < 0.01). MDZ also significantly prevented H2S-induced neurological sequelae, including weight loss, behavior deficits, neuroinflammation, and histopathologic lesions (p < 0.01). Overall, our findings show that MDZ is a promising drug for reducing H2S-induced acute mortality, neurotoxicity, and neurological sequelae

Status and Trends of the Secretarial Skills Courses in the Four-year Colleges and Universities of California

The teaching of the basic secretarial skills in the four-year colleges and universities is often questioned. This study was made to determine to what extent the skills were being taught in the four-year educational institutions of California.Business Educatio

Legislators\u27 Perceptions about Poverty: Views from the Georgia General Assembly

This study sought to explore legislators perspectives about causes of poverty. Members of the Georgia General Assembly rated the importance of 10 behavioral and structural explanations of poverty, and indicated whether they thought poor women and children would be better served under AFDC or TANF. Whereas all groups of legislators found behavioral explanations moderately important, there was significant variation by race, gender, and political party about the importance of structural explanations of poverty. Support for several structural explanations of poverty correlated with a preference for AFDC, but no correlations were found with behavioral explanations. This study holds implications for affecting future debates about TANF

Broad spectrum proteomics analysis of the inferior colliculus following acute hydrogen sulfide exposure.

Acute exposure to high concentrations of H2S causes severe brain injury and long-term neurological disorders, but the mechanisms involved are not known. To better understand the cellular and molecular mechanisms involved in acute H2S-induced neurodegeneration we used a broad-spectrum proteomic analysis approach to identify key molecules and molecular pathways involved in the pathogenesis of acute H2S-induced neurotoxicity and neurodegeneration. Mice were subjected to acute inhalation exposure of up to750 ppm of H2S. H2S induced behavioral deficits and severe lesions including hemorrhage in the inferior colliculus (IC). The IC was microdissected for proteomic analysis. Tandem mass tags (TMT) liquid chromatography mass spectrometry (LC-MS/MS)-based quantitative proteomics was applied for protein identification and quantitation. LC-MS/MS identified 598, 562, and 546 altered proteomic changes at 2 h, and on days 2 and 4 post-H2S exposure, respectively. Of these, 77 proteomic changes were statistically significant at any of the 3 time points. Mass spectrometry data were subjected to Perseus 1.5.5.3 statistical analysis, and gene ontology heat map clustering. Expressions of several key molecules were verified to confirm H2S-dependent proteomics changes. Webgestalt pathway overrepresentation enrichment analysis with Panther engine revealed H2S exposure disrupted several biological processes including metabotropic glutamate receptor group 1 and inflammation mediated by chemokine and cytokine signaling pathways among others. Further analysis showed that energy metabolism, integrity of blood-brain barrier, hypoxic, and oxidative stress signaling pathways were also implicated. Collectively, this broad-spectrum proteomics data has provided important clues to follow up in future studies to further elucidate mechanisms of H2S-induced neurotoxicity

Titanium dioxide nanoparticles enhance mortality of fish exposed to bacterial pathogens

Nano-TiO2 is immunotoxic to fish and reduces the bactericidal function of fish neutrophils. Here, fathead minnows (Pimephales promelas) were exposed to low and high environmentally relevant concentration of nano-TiO2 (2 ng g−1 and 10 μg g−1 body weight, respectively), and were challenged with common fish bacterial pathogens, Aeromonas hydrophila or Edwardsiella ictaluri. Pre-exposure to nano-TiO2 significantly increased fish mortality during bacterial challenge. Nano-TiO2 concentrated in the kidney and spleen. Phagocytosis assay demonstrated that nano-TiO2 has the ability to diminish neutrophil phagocytosis of A. hydrophila. Fish injected with TiO2 nanoparticles displayed significant histopathology when compared to control fish. The interplay between nanoparticle exposure, immune system, histopathology, and infectious disease pathogenesis in any animal model has not been described before. By modulating fish immune responses and interfering with resistance to bacterial pathogens, manufactured nano-TiO2 has the potential to affect fish survival in a disease outbreak