Vibrational properties of anhydrous and partially hydrated uranyl fluoride.

Uranyl fluoride (UO2F2) is a hygroscopic powder with two main structural phases: an anhydrous crystal and a partially hydrated crystal of the same R3¯m symmetry. The formally closed-shell electron structure of anhydrous UO2F2 is amenable to density functional theory calculations. We use density functional perturbation theory (DFPT) to calculate the vibrational frequencies of the anhydrous crystal structure and employ complementary inelastic neutron scattering and temperature-dependent Raman scattering to validate those frequencies. As a model closed-shell actinide, we investigated the effect of LDA, GGA, and non-local vdW functionals as well as the spherically averaged Hubbard +U correction on vibrational frequencies, electronic structure, and geometry of anhydrous UO2F2. A particular choice of Ueff=5.5 eV yields the correct U-Oyl bond distance and vibrational frequencies for the characteristic Eg and A1g modes that are within the resolution of experiment. Inelastic neutron scattering and Raman scattering suggest a degree of water coupling to the lattice vibrations in the more experimentally accessible partially hydrated UO2F2 system, with the symmetric stretching vibration shifted approximately 47 cm-1 lower in energy compared to the anhydrous structure. Evidence of water interaction with the uranyl ion is present from a two-peak decomposition of the uranyl stretching vibration in the Raman spectra and anion-hydrogen stretching vibrations in the inelastic neutron scattering spectra. A first-order dehydration phase transition temperature is definitively identified to be 125 °C using temperature-dependent Raman scattering.

Mechanisms of blast induced brain injuries, experimental studies in rats.

Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects.

Multiple cytokine and acute-phase protein gene transcription in West Greenland sledge dogs (Canis familiaris) dietary exposed to organic environmental pollutants.

Exposure levels of persistent organic pollutants, such as polychlorinated biphenyls and DDTs, are high in Arctic apex predators and Inuit peoples and are suspected to have negative impacts on their immune systems. We conducted a controlled generational study on liver tissue and ethylenediaminetetraacetic acid blood cytokine and acute-phase protein (APP) mRNA expressions using reverse transcriptionase-polymerase chain reaction in West Greenland sledge dogs (Canis familiaris); contaminated minke whale (Balaenoptera acutorostrata) blubber serves as dietary pollutant source. Two of seven blood cytokine expressions (IL-6 and IL-12) and three of five APP expressions (haptoglobin [HP], heat shock protein, and fatty acid-binding protein [FABP]) were lowest in the exposed group, whereas the remaining five blood cytokine expressions (IL-2, IL-10, IFN-gamma, TNF-alpha, and TGF-beta) and two APP expressions (MT1 and MT2) were highest in the exposed group. In liver tissue, three cytokine expressions (IL-10, IFN-gamma, and TNF-alpha) and two APP expressions (MT1 and MT2) were highest in the exposed group, and the remaining cytokine and APP expressions were lowest in the exposed group. Of these, the liver tissue expression of HP and FABP was significantly lowest in the exposed group (both p < 0.05). As a consequence of our findings, we suggest that a daily intake of 50 to 200 g polluted whale blubber is associated with a genotoxic decrease in HP and FABP gene expression in the liver of sledge dog and possibly of other top mammalian marine predators and consumers in the Arctic, indicating a restricted acute-phase reaction and insufficient immune response. Finally, HP and FABP liver expression appear to be new and sensitive biomarkers of organohalogen compound exposure.

Differential gene expression in the rat cochlea after exposure to impulse noise.

Understanding the molecular biology of noise trauma is vital to developing effective and timely interventions. In a model of explosion-mediated impulse noise injury, differential gene expression was studied in whole rat cochlea preparations at 3 and 24 h following the exposure. We developed a technique using mRNA from a single cochlea on each oligonucleotide microarray to avoid pooling of mRNA samples. Application of a conservative statistical analysis approach resulted in the identification of 61 differentially expressed genes. Within 3 h after the exposure, there was an up-regulation of immediate early genes, mainly transcription factors and genes involved in the tissue's response to oxidative stress. No genes were found to be significantly down-regulated. At 24 h following the exposure, up-regulated genes included members of inflammatory and antioxidant pathways and one gene involved in glutathione metabolism was down-regulated. A subset of genes was confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The present study demonstrates the power of the microarray technique in providing a global view of the gene regulation following noise exposure, and in identifying genes that may be mechanistically important in hearing loss, and thereby serve as a basis for the development of therapeutic interventions.

Trends in mercury in hair of Greenlandic polar bears (Ursus maritimus) during 1892-2001.

Mercury concentrations in hair from 397 Greenland polar bears (Ursusmaritimus) sampled between 1892 and 2001 were analyzed for temporal trends. In East Greenland the concentrations showed a significant (p < 0.0001, n = 27) increase of 3.1%/year in the period 1892-1973. In Northwest Greenland, a similar (p < 0.0001, n = 69) increase of 2.1%/year was found, which continued until 1991, when the most recent samples were obtained. In East Greenland, a significant (p = 0.009, n = 322) decrease of 0.8%/year was observed after 1973. Two Northwest Greenland samples from 1300 A.D. had a mean value of 0.52 mg/kg of dry weight, which can be considered as a baseline level. The Hg concentration during 1985-1991 from Northwest Greenland (mean value of 7.45 mg/kg of dry weight) was more than 14-fold higher than the assumed baseline level from 1300 A.D. from the same region (i.e., about 93% anthropogenic). Although a decrease was found in East Greenland after 1973, the concentration is still ca. 11-fold higher than the baseline level (i.e., about 90% anthropogenic).

Trends in fluctuating asymmetry in East Greenland polar bears (Ursus maritimus) from 1892 to 2002 in relation to organohalogen pollution.

Fluctuating asymmetry (FA) was studied in skulls of 283 polar bears (Ursus maritimus) sampled in East Greenland from 1892 to 2002. Fourteen metric bilateral traits in skull and lower jaw were measured and compared between polar bears born until 1960 (n = 94) and from 1961 (n = 189). The period 1892-1960 was chosen to represent a period prior to appearance of organohalogens (polychlorinatedbiphenyls [PCBs], dichlorodiphenyltrichloroethanes [DDTs], hexacyclohexanes [HCHs], chlordanes [CHLs], hexachlorobenzene [HCB], polybrominateddiphenylethers [PBDEs] and dieldrin) originating from long-range transport to East Greenland from southern latitudes. The period 1961-2002 represents the period when polar bears have been exposed to organohalogens. During this latter period, the level of organochlorines is believed to have increased from 1960 to the late 1980s followed by a likely decrease from 1990 to 2002. Within this later period, other compounds such as, e.g., polybrominated flame retardants are believed to have increased throughout the period. Two different analysis showed, that the degree of fluctuating asymmetry did not differ statistically between the two periods in ten of thirteen traits (one trait excluded due to high measurement error). In fact, when significant differences were found in four of the traits, the fluctuating asymmetry was lower in skulls sampled after 1960. The degree of fluctuating asymmetry was higher in adults than in subadults for 6 of the 14 traits, whereas a higher degree of fluctuating asymmetry was found for only one trait in one of the analyses for subadults relative to adults. Females had a higher degree of fluctuating asymmetry than males in one trait. A time trend analysis did find fluctuations over time for five traits but the relationship was weak as the trend appeared to occur by chance due to the high number of regressions analysed (n = 42). A correlation analysis of FA versus the sum concentrations of various classes of organohalogens in adipose tissue from a subsample of 94 recently collected polar bears (1999-2002) did not show a trend either. Hence, the present study could not document a relationship between skull asymmetry in polar bears and periods with different exposure to organohalogens. These findings are possibly influenced by nutritional status, genetic factors, a subeffect exposure of organohalogens or confounded by other environmental factors (e.g. temperature) within the two investigated periods.

Histology of selected immunological organs in polar bear (Ursus maritimus) from East Greenland in relation to concentrations of organohalogen contaminants.

Samples of lymph nodes (axillary, n = 54 and inguinal, n = 45), spleen (n = 60), thymus (n = 11) and thyroid tissue (n = 5) from a total of 82 polar bears (Ursus maritimus) collected in East Greenland 1999-2002 were examined histologically. The purpose was to relate histology to concentrations of organohalogen contaminants (OHCs) [i.e., sum (Sigma)PCBs, SigmaDDTs, SigmaHCHs, SigmaCHLs, HCB, Dieldrin and SigmaPBDEs] determined in adipose tissue, as studies on polar bears have indicated that some OHCs act as immunosuppressive agents. Secondary follicle counts were evaluated in spleen and lymph nodes, and semiquantitively divided into four groups (0: few/absent to 3: high). In the spleen, a high secondary follicle count was found in 21% of the cases (12/60), and this was significantly higher in subadults (p < 0.01) compared to adults of both sexes. Also in the lymph nodes a high secondary follicle count was found in 20% of the cases (20/99), and in the axillary lymph nodes changes were significantly higher in subadults (p < 0.05) compared to adults of both sexes. Significantly weak correlations between concentrations of OHCs and the amount of secondary follicles in lymph nodes was found, but probably occurred as a consequence of other multiple stress factor(s) (all: p < 0.05) and also one significant, but modest positive correlation was found between SigmaPBDE concentrations and secondary follicle counts (p < 0.01; r = 0.41). In spleen, a significant relation between low concentrations of OHCs in adipose tissue and few/absent secondary follicles was found with respect to SigmaCHLs, SigmaHCHs, HCB and Dieldrin. No histopathological observations (e.g., neoplasia) were found in spleen or lymph nodes, nor in thymus or thyroid. In conclusion, the present data suggest that the exposure concentrations of OHCs to polar bears are unlikely to have resulted in adverse effects on the tissues in question, although SigmaCHLs, SigmaHCHs, HCB and Dieldrin were related to increased secondary follicle counts in the spleen.

Enlarged clitoris in wild polar bears (Ursus maritimus) can be misdiagnosed as pseudohermaphroditism.

A 23-year-old female polar bear (Ursus maritimus) killed in an Inuit hunt in East Greenland on July 9, 1999 had a significantly enlarged clitoris resembling, in size, form and colour, those of previously reported 'pseudohermaphroditic' polar bears from Svalbard. It has been suggested that an enzyme defect (21-hydroxylase deficiency), androgen producing tumour or high exposure to organochlorines during the foetal stage or early development could be the reason for the supposed pseudohermaphroditism observed for Svalbard bears. Except for the enlarged clitoris, all dimensions of the external and internal reproductive organs of the present were similar to a reference group of 23 normal adult female polar bears from East Greenland collected in 1999-2002. The aberrant bear was a female genotype, and macroscopic examination of her internal reproductive organs indicated that she was reproductively functional. A histological examination of the clitoral enlargement in the present East Greenland specimen allows a first-time histological evaluation of the earlier macroscopic field diagnosis from Svalbard. This examination revealed intense chronic ulcerative and perivascular clitoriditis similar to "acral lick dermatitis" frequently seen in domestic dogs (i.e., we did not find any signs of pseudohermaphroditic hyperplasia of clitoral tissue due to androgenic or antiestrogenic endocrine disruption). The levels of organohalogens and TEQ values were lower than concentration thresholds of toxicological risk. It is hence possible that the previously reported adult female polar bear pseudohermaphrodites from Svalbard are in fact misdiagnoses. Therefore, future studies examining pseudohermaphroditism in wildlife should consider that certain occurrences are natural events, e.g., enlarged clitoris in the present East Greenland polar bear. Furthermore, caution should be exercised in suggesting linkages of such inflammatory abnormalities with correlations to anthropogenic pollutant exposures.

The inner ear macular sensory epithelia of the Daubenton's bat.

The inner ear macular sensory epithelia of the Daubenton's bat were examined quantitatively to estimate the area and total number of hair cells. Ultrastructural examination of the sensory epithelium reveals two main types of hair cells: the chalice-innervated hair cell and the bouton-innervated hair cell. The existence of an intermediate type, with a nerve ending covering the lateral side of the hair cell, indicates that the chalice-innervated hair cells are derived from bouton-innervated hair cells. Thus, at least a part of the bouton-innervated hair cells forms a transitional stage. A number of immature as well as apoptotic hair cells were observed. It is suggested that a continuous production of new hair cells takes place in mature individuals, probably based on transdifferentiation of supporting cells.

Continuous hair cell turnover in the inner ear vestibular organs of a mammal, the Daubenton's bat (Myotis daubentonii).

In both humans and mice the number of hair cells in the inner ear sensory epithelia declines with age, indicating cell death (Park et al. 1987; Rosenhall 1973). However, recent reports demonstrate the ability of the vestibular sensory epithelia to regenerate after injury (Forge et al. 1993, 1998; Kuntz and Oesterle 1998; Li and Forge 1997; Rubel et al. 1995; Tanyeri et al. 1995). Still, a continuous hair cell turnover in the vestibular epithelia has not previously been demonstrated in mature mammals. Bats are the only flying mammals, and they are known to live to a higher age than animals of equal size. The maximum age of many species is 20 years, with average lifespans of 4-6 years (Schober and Grimmberger 1989). Further, the young are fully developed and able to fly at the age of 2 months, and thus the vestibular organs are thought to be differentiated at that age. Consequently, long-lived mammals such as bats might compensate for the loss of hair cells by producing new hair cells in their postembryonic life. Here we show that the utricular macula of adult Daubenton's bats (more than 6 months old) contains innervated immature hair cells as well as apoptotic hair cells, which strongly indicates a continuous turnover of hair cells, as previously demonstrated in birds.

The physician's role in health care reform.

Health care in the United States is in crisis. The desire to provide care continually conflicts with the need to contain costs. Historically, physicians have opposed the demand for health care reform, and although many physicians have responded to the current crisis with ambivalence, apathy, or frustration, they have the knowledge, capability, and opportunity to advocate for and to effect reform within the health care delivery system. Many believe that the acknowledgment of costs as a factor in treatment decisions compromises their role as patient advocates, but in the face of increasing government controls and the corporatism of medicine, the human link between physician and patient is even more valuable. The current crisis in health care necessitates cost control. If physicians conscientiously undertake their political, professional, and personal roles, they can reform the health care delivery system in the United States while compassionately advocating for their patients.

Rapid slide coagglutination test for identifying and typing group B streptococci.

A Cowan I strain of Staphylococcus aureus was labeled with either group B streptococcal grouping or typing antiserum. These antibody-labeled reagent cells (ARC) were used in a slide coagglutination test to identify and type group B streptococci from blood agar plates. All streptococci were also identified by the standard Lancefield capillary precipitin test. In a blind study, all 141 group B streptococci were correctly identified by the coagglutination grouping test. None of the 148 non-group B streptococci caused agglutination of ARC. The coagglutination grouping test required an acid extract prepared from only four colonies and could be completed less than 30 min after colonies were removed from plates. The coagglutination typing test correctly identified 98.6% of the types of the 141 group B streptococcal strains tested. At least 88.6% of these streptococci could be typed directly from blood agar plates within 5 min by the coagglutination typing test. The remaining 11.4% of the group B streptococci were acid extracted (less than a 30-min procedure), and the extract was used for coagglutination typing. Coagglutination typing can be performed with only four colonies. The coagglutination grouping and typing tests are inexpensive, rapid, reliable, and easy to perform.