Effectiveness of Fluorescence-based Methods in Monitoring Progression of Noncavitated Caries-like Lesions on Smooth Surfaces

Although there has been a significant decrease in caries prevalence in developed countries, the slower progression of dental caries requires methods capable of detecting and quantifying lesions at an early stage. The aim of this study was to evaluate the effectiveness of fluorescence-based methods (DIAGNOdent 2095 laser fluorescence device [LF], DIAGNOdent 2190 pen [LFpen], and VistaProof fluorescence camera [FC]) in monitoring the progression of noncavitated caries-like lesions on smooth surfaces. Caries-like lesions were developed in 60 blocks of bovine enamel using a bacterial model of Streptococcus mutans and Lactobacillus acidophilus . Enamel blocks were evaluated by two independent examiners at baseline (phase I), after the first cariogenic challenge (eight days) (phase II), and after the second cariogenic challenge (a further eight days) (phase III) by two independent examiners using the LF, LFpen, and FC. Blocks were submitted to surface microhardness (SMH) and cross-sectional microhardness analyses. The intraclass correlation coefficient for intra- and interexaminer reproducibility ranged from 0.49 (FC) to 0.94 (LF/LFpen). SMH values decreased and fluorescence values increased significantly among the three phases. Higher values for sensitivity, specificity, and area under the receiver operating characteristic curve were observed for FC (phase II) and LFpen (phase III). A significant correlation was found between fluorescence values and SMH in all phases and integrated loss of surface hardness (ΔKHN) in phase III. In conclusion, fluorescence-based methods were effective in monitoring noncavitated caries-like lesions on smooth surfaces, with moderate correlation with SMH, allowing differentiation between sound and demineralized enamel.

Transfer and effects of 1,2,3,5,7-pentachloronaphthalene in an experimental food chain.

Polychlorinated naphthalenes are environmentally relevant compounds that are measured in biota at concentrations in the μg/kg lipid range. Despite their widespread occurrence, literature data on the accumulation and effects of these compounds in aquatic ecosystems are sparsely available. The goal of this study was to gain insights into the biomagnification and effects of 1,2,3,5,7-pentachloronaphthalene (PeCN52) in an experimental food chain consisting of benthic worms and juvenile rainbow trout. Worms were contaminated with PeCN52 by passive dosing from polydimethylsiloxane silicone. The contaminated worms were then used to feed the juvenile rainbow trout at 0.12, 0.25 or 0.50 μg/g fish wet weight/day, and the resulting internal whole-body concentrations of the individual fish were linked to biological responses. A possible involvement of the cellular detoxification system was explored by measuring PeCN52-induced expression of the phase I biotransformation enzyme gene cyp1a1 and the ABC transporter gene abcb1a. At the end of the 28-day study, biomagnification factors were similar for all dietary intake levels with values between 0.5 and 0.7 kg lipid(fish)/kg lipid(worm). The average uptake efficiency of 60% indicated that a high amount of PeCN52 was transferred from the worms to the fish. Internal concentrations of up to 175 mg/kg fish lipid in the highest treatment level did not result in effects on survival, behavior, or growth of the juvenile trout, but were associated with the induction of phase I metabolism which was evident from the significant up-regulation of cyp1a1 expression in the liver. In contrast, no changes were seen in abcb1a transcript levels.

Perspective transformation: Women in long-term recovery from alcohol abuse

Objective. The purpose of this study was to determine the meaning of personal transformation for twenty women in long term, stable recovery from alcohol abuse; to identify themes or patterns of this recovery, and; to determine the extent to which they experienced the phenomenon of perspective transformation. ^ Method. Volunteers were recruited by advertisement, word of mouth, and through a closed circuit web based broadcast. A descriptive, exploratory study, which analyzed perspective transformation from the standpoint of five action phases, was conducted. Data was collected using in-depth personal interviews and questionnaires. Subjects' responses were analyzed by qualitative methods. Triangulation was performed on the grouped data comparing the interviews to the data produced by the questionnaires. Quantitative analysis of questionnaire items explored behavioral changes experienced before and after alcoholism recovery. ^ Results. Five phases of recovery were identified. Phase I which involved recognition that alcohol was a problem and change might be possible took several years during which 3 major transitions occurred: (1) from often being alienated to having relationships with family and friends; (2) from daily upheavals to eventually a more peaceful existence, and; (3) from denial that alcohol was a problem to acceptance and willingness to change. Recovery was often seen in a spiritual context, which also required ongoing support. During Phase II there was an assessment of self, others, and the environment which revealed a pattern of intense unhappiness and negative feelings toward self and others with a disregard for cultural norms. Phase III revealed a period of desperation as life became unmanageable, but gradual willingness to accept support and guidance and a desire to improve self and help others. This led to improvement of existing role performance and the willingness to try out new roles. In Phase IV there was a pattern of personal growth which included: the establishment of boundaries, setting priorities, a willingness to place others' needs above their own, acceptance of responsibility, and learning to cope without alcohol, often with the use of tools learned in AA. During Phase V, many experienced knowledge of frailties but growing respect for self and others, with an improved ability to function in giving relationships. Implications for Prevention and Recovery: Early education concerning addiction and recovery may play a crucial role in prevention and early recovery, as it did for children of women in this study. Recovery requires persistent effort and organized support. ^

Arabinosylguanine: Metabolism, action, and lineage-specific cytotoxicity in human leukemia cells

9-β-D-arabinosylguanine (ara-G), an analogue of deoxyguanosine, has demonstrated T-lymphoblast selective anti-leukemia activity both in vitro and in vivo in cell lines and primary cells and in phase I investigations. The present work was initiated to identify factors that result in this selectivity. ^ The cytotoxicity of ara-G is manifest only after its phosphorylation. Experiments using cell lines transfected to overexpress specific nucleoside kinases demonstrated that the phosphorylation of ara-G to its monophosphate is by both cytoplasmic deoxycytidine kinase and mitochondria) deoxyguanosine kinase. Ara-G monophosphate is converted to its 5′-triphosphate (ara-GTP) in cells by these kinases and then incorporated into DNA. Mechanistic studies demonstrated that incorporation of ara-GTP into DNA was a necessary event for the induction of cell death. ^ Pharmacokinetic and pharmacodynamic studies utilizing three human acute leukemia cell lines, CEM (T-lymphoblastic), Raji (B-lymphoblastic), and ML-1 (myeloid) were performed. CEM cells were most sensitive to ara-G-induced inhibition of colony formation, accumulated ara-GTP at a faster rate and to a greater degree than either Raji or ML-1, but incorporated the lowest number of ara-G molecules into DNA. The position of incorporation was internal and similar in all cell lines. The terminal elimination phase of ara-GTP was >24 h and similar in these cells. Comparisons between inhibition of colony formation and ara-GTP incorporation into DNA demonstrated that while within a cell line there was correlation among these parameters, between cell lines there was no relationship between number of incorporated ara-G molecules and ara-G(TP)-mediated toxicity suggesting that there were additional factors. ^ The expression of membrane bound Fas and Fast was unchanged in all cell lines. In contrast, there was a 2-fold increase in soluble Fast, which was found exclusively in CEM cells. Ara-G-mediated apoptosis in CEM occurred from all phases of the cell cycle and was abrogated partially by Fas antagonist antibodies. These data suggest that Fas-mediated cell death due to the liberation of sFasL may be responsible for the hypersensitivity to ara-G manifested by immature T-cells such as CEM. The role of Fas in ara-G induced death of acute T-lymphoblastic leukemia cells during therapy needs to be tested. ^

Female-specific regulation of cytochrome P450 3As and their response to xenobiotic stress

Cytochrome P450 3As (CYP3As) are phase I enzymes responsible for metabolizing more than 50% of clinical drugs. Recent studies have revealed that expression of CYP3As is two-fold higher in women than in men leading to a faster metabolic clearance of therapeutic drugs in women. In this study, we analyzed the female specific rat CYP3A isoform, CYP3A9. We evaluated the effects of progesterone and estrogen on CYP3A9 regulation and showed a distinct role for estrogen in mediating female dominance of CYP3A9. We also observed changes in CYP3A9 expression at various stages of pregnancy which correlates well with varying physiological estradiol concentrations. In addition, by the in vitro data shows that estradiol mediated induction can be abrogated with estrogen receptor antagonist ICI182,780. We also identified three novel murine CYP3A isoforms CYP3A13, CYP3A41 and CYP3A44 and characterized their genomic structures and expression profiles. CYP3A41 and CYP3A44 show female specific expression but surprisingly this female dominance is not mediated via estrogen. Control male mice did not exhibit any CYP3A41 mRNA levels but showed minimal levels of CYP3A44. In order to gain insights into the governance ofαthe female specific genes, the hepatic regulation of CYP3A41 and CYP3A44 by the xeno-sensors PXR and CAR was examined. In female mice, pregnenolone-16α-carboxynitrile, suppressed CYP3A41 and CYP3A44 mRNA levels in PXR−/− background whereas dexamethasone-dependent suppression of CYP3A41 was mediated by PXR. In addition, phenobarbital challenge in PXR−/− revealed up-regulation of both CYP3A44, CYP3A41 levels only in males. No role for CAR was seen in the regulation of either CYP3A41 or CYP3A44 gene expression in female mice. Interestingly, PXR and CAR ligands induced male CYP3A44 levels in a receptor dependent fashion. This increase of CYP3A44 transcript in male mice is in contrast to the response seen in female mice, which clearly indicates an additional layer of regulation. Our findings suggest that gender plays a strategic role in directing the CAR/PXR mediated effects of CYP3A44/CYP3A41. This implies that differential regulation of female specific CYP3A isoforms may be the key to explain some of the gender differences observed in clearance of certain therapeutics like antidepressants and analgesics. ^

RNA polymerase II large subunit degradation induced by ecteinascidin 743: Molecular characterization and subsequent rational investigation of antitumor mechanisms in cancers with clinical response

Ecteinascidin 743 (Et-743), which is a novel DNA minor groove alkylator with a unique spectrum of antitumor activity, is currently being evaluated in phase II/III clinical trials. Although the precise molecular mechanisms responsible for the observed antitumor activity are poorly understood, recent data suggests that post-translational modifications of RNA polymerase II Large Subunit (RNAPII LS) may play a central role in the cellular response to this promising anticancer agent. The stalling of an actively transcribing RNAPII LS at Et-743-DNA adducts is the initial cellular signal for transcription-coupled nucleotide excision repair (TC-NER). In this manner, Et-743 poisons TC-NER and produces DNA single strand breaks. Et-743 also inhibits the transcription and RNAPII LS-mediated expression of selected genes. Because the poisoning of TC-NER and transcription inhibition are critical components of the molecular response to Et-743 treatment, we have investigated if changes in RNAPII LS contribute to the disruption of these two cellular pathways. In addition, we have studied changes in RNAPII LS in two tumors for which clinical responses were reported in phase I/II clinical trials: renal cell carcinoma and Ewing's sarcoma. Our results demonstrate that Et-743 induces degradation of the RNAPII LS that is dependent on active transcription, a functional 26S proteasome, and requires functional TC-NER, but not global genome repair. Additionally, we have provided the first experimental data indicating that degradation of RNAPII LS might lead to the inhibition of activated gene transcription. A set of studies performed in isogenic renal carcinoma cells deficient in von Hippel-Lindau protein, which is a ubiquitin-E3-ligase for RNAPII LS, confirmed the central role of RNAPII LS degradation in the sensitivity to Et-743. Finally, we have shown that RNAPII LS is also degraded in Ewing's sarcoma tumors following Et-743 treatment and provide data to suggest that this event plays a role in decreased expression of the Ewing's sarcoma oncoprotein, EWS-Fli1. Altogether, these data implicate degradation of RNAPII LS as a critical event following Et-743 exposure and suggest that the clinical activity observed in renal carcinoma and Ewing's sarcoma may be mediated by disruption of molecular pathways requiring a fully functional RNAPII LS. ^

Is maternal separation anxiety associated with school readiness?

Background. Increasing rates of maternal employment highlight the need for non-maternal child care for infants at an earlier age. Several studies have shown that employment induced maternal depression or psychological distress is associated with the child's socio-emotional and cognitive development. However, separation anxiety, a common phenomenon observed among employed mothers during early years, has seldom been studied. Therefore, the purpose of this study was to evaluate the role of maternal separation anxiety in the child's cognitive development.^ Methods. Data were obtained from Phase I (birth to 36 months) of the National Institute of Child Health and Human Development, Study of Early Child Care and Youth Development (NICHD SECCYD). Bivariate and multivariate analyses were performed to determine the association between separation anxiety groups and child outcomes. Multivariate analysis was also used to examine the mediating and/or moderating effect of sensitivity and moderating effect of difficult temperament.^ Results. Separation anxiety showed a negative association with the Bracken, attachment security, maternal sensitivity and psychological state. Children whose mothers never reported high levels of separation anxiety showed higher levels of school readiness and attachment security compared to those whose mothers experienced high levels of separation anxiety at least once. There was a significant interaction between separation anxiety and maternal sensitivity for the Bracken and attachment security indicating the moderating effect of sensitivity. Maternal sensitivity was also found to partially mediate the association between high levels of separation anxiety and school readiness or attachment security. However, the interaction between difficult temperament and separation anxiety was not significant for any of the child outcomes. ^ Conclusions. High levels of separation anxiety have a negative impact on school readiness, attachment security, maternal sensitivity and psychological state. In addition, mothers who experience high levels of separation anxiety but are sensitive during the mother-child interaction have children with high school readiness and attachment security compared to those who are less sensitive.^ Keywords. Maternal separation anxiety, School readiness. ^

TECHNOLOGY ASSESSMENT: SMALL-VOLUME INFUSION PUMPS

"Technology assessment is a comprehensive form of policy research that examines the short- and long-term social consequences of the application or use of technology" (US Congress 1967).^ This study explored a research methodology appropriate for technology assessment (TA) within the health industry. The case studied was utilization of external Small-Volume Infusion Pumps (SVIP) at a cancer treatment and research center. Primary and secondary data were collected in three project phases. In Phase I, hospital prescription records (N = 14,979) represented SVIP adoption and utilization for the years 1982-1984. The Candidate Adoption-Use (CA-U) diffusion paradigm developed for this study was germane. Compared to classic and unorthodox curves, CA-U more accurately simulated empiric experience. The hospital SVIP 1983-1984 trends denoted assurance in prescribing chemotherapy and concomitant balloon SVIP efficacy and efficiency. Abandonment of battery pumps was predicted while exponential demand for balloon SVIP was forecast for 1985-1987. In Phase II, patients using SVIP (N = 117) were prospectively surveyed from July to October 1984; the data represented a single episode of therapy. The questionnaire and indices, specifically designed to measure the impact of SVIP, evinced face validity. Compeer group data were from pre-SVIP case reviews rather than from an inpatient sample. Statistically significant results indicated that outpatients using SVIP interacted socially more than inpatients using the alternative technology. Additionally, the hospital's education program effectively taught clients to discriminate between self care and professional SVIP services. In these contexts, there was sufficient evidence that the alternative technology restricted patients activity whereas SVIP permitted patients to function more independently and in a social lifestyle, thus adding quality to life. In Phase III, diffusion forecast and patient survey findings were combined with direct observation of clinic services to profile some economic dimensions of SVIP. These three project phases provide a foundation for executing: (1) cost effectiveness analysis of external versus internal infusors, (2) institutional resource allocation, and (3) technology deployment to epidemiology-significant communities. The models and methods tested in this research of clinical technology assessment are innovative and do assess biotechnology. ^

Sacred vocation program follow up evaluation at the Baylor healthcare system

Background: The Sacred Vocation Program (SVP) (Amick B, Karff S., 2003) helps workers find meaning, spirituality, and see their job as a sacred vocation. The SVP is based on Participatory Action Research (PAR) (Minkler & Wallerstein, 1997; Parker & Wall, 1998). This study aims to evaluate the SVP implemented at the Baylor Healthcare System, Dallas-Fort Worth. ^ Methods: The study design is a qualitative design. We used data from study participants who have participated in focus groups. During these focus groups specific questions and probes regarding the effectiveness of the SVP have been asked. We analyzed the focus groups and derived themes. ^ Results: Results of this study demonstrate SVP helps graduates feel valued and important. The SVP has improved meaningful work for employees and improved a sense of belonging for participants. The program has also increased participant spirituality. The coping techniques developed during a SVP class helps participants deal with stressful situations. The SVP faces challenges of implementation fidelity, poor communication, program viability in tough economic times and implementation of phase II. Another sustainability challenge for SVP is the perception of the program being a religious one versus a spiritual program. ^ Conclusion: Several aspects of the SVP work. The phase I of SVP is successful in improving meaningful work and a sense of belonging for participants. The coping techniques help participants deal with difficult work situations. The SVP can increase effectiveness through improvements in implementation fidelity, communication and leadership commitment. ^

TIC en el aprendizaje de la historia : Utilización e historización de estas herramientas en el capitalismo cognitivo

En el presente trabajo se intentará desarrollar un análisis en torno a la potencialidad de incluir en la formación de futuros docentes e investigadores de historia lo que podemos denominar educación con medios y educación en medios. Esto, por un lado, consistiría en la introducción didáctica de tecnologías de información-comunicación -entendiendo por ello la importancia vital para nuestro oficio de apropiarse de herramientas que posibiliten el trabajo con fuentes de diversa índole y en diferentes soportes- y, por otro lado, la realización en el espacio del aula de una historización que problematice y contextualice los espacios de producción y circulación de dichas tecnologías en el sistema capitalista posterior a la crisis económica mundial de la década del 70. En una primera instancia, se hará una revisión de la génesis de esta fase para luego reflexionar respecto de casos concretos dentro del ámbito universitario local que proponen construcciones colaborativas de contenidos, con empleo de edición de imagen y sonido digital, vinculación dentro de redes sociales, socialización de conocimiento. Se postula la posibilidad de que estas prácticas supongan elementos que obturen los fundamentos restrictivos del capitalismo cognitivo

TIC en el aprendizaje de la historia : Utilización e historización de estas herramientas en el capitalismo cognitivo

En el presente trabajo se intentará desarrollar un análisis en torno a la potencialidad de incluir en la formación de futuros docentes e investigadores de historia lo que podemos denominar educación con medios y educación en medios. Esto, por un lado, consistiría en la introducción didáctica de tecnologías de información-comunicación -entendiendo por ello la importancia vital para nuestro oficio de apropiarse de herramientas que posibiliten el trabajo con fuentes de diversa índole y en diferentes soportes- y, por otro lado, la realización en el espacio del aula de una historización que problematice y contextualice los espacios de producción y circulación de dichas tecnologías en el sistema capitalista posterior a la crisis económica mundial de la década del 70. En una primera instancia, se hará una revisión de la génesis de esta fase para luego reflexionar respecto de casos concretos dentro del ámbito universitario local que proponen construcciones colaborativas de contenidos, con empleo de edición de imagen y sonido digital, vinculación dentro de redes sociales, socialización de conocimiento. Se postula la posibilidad de que estas prácticas supongan elementos que obturen los fundamentos restrictivos del capitalismo cognitivo

TIC en el aprendizaje de la historia : Utilización e historización de estas herramientas en el capitalismo cognitivo

En el presente trabajo se intentará desarrollar un análisis en torno a la potencialidad de incluir en la formación de futuros docentes e investigadores de historia lo que podemos denominar educación con medios y educación en medios. Esto, por un lado, consistiría en la introducción didáctica de tecnologías de información-comunicación -entendiendo por ello la importancia vital para nuestro oficio de apropiarse de herramientas que posibiliten el trabajo con fuentes de diversa índole y en diferentes soportes- y, por otro lado, la realización en el espacio del aula de una historización que problematice y contextualice los espacios de producción y circulación de dichas tecnologías en el sistema capitalista posterior a la crisis económica mundial de la década del 70. En una primera instancia, se hará una revisión de la génesis de esta fase para luego reflexionar respecto de casos concretos dentro del ámbito universitario local que proponen construcciones colaborativas de contenidos, con empleo de edición de imagen y sonido digital, vinculación dentro de redes sociales, socialización de conocimiento. Se postula la posibilidad de que estas prácticas supongan elementos que obturen los fundamentos restrictivos del capitalismo cognitivo

Enzyme activity and liver tissue PCB concentrations of chicks of northern fulmars (F. glacialis) and black-legged kittiwakes (R. tridactyla) from Kongsfjorden

Arctic seabirds are exposed to a wide range of halogenated organic contaminants (HOCs). Exposure occurs mainly through food intake, and many pollutants accumulate in lipid-rich tissues. Little is known about how HOCs are biotransformed in arctic seabirds. In this study, we characterized biotransformation enzymes in chicks of northern fulmars (Fulmarus glacialis) and black-legged kittiwakes (Rissa tridactyla) from Kongsfjorden (Svalbard, Norway). Phase I and II enzymes were analyzed at the transcriptional, translational and activity levels. For gene expression patterns, quantitative polymerase chain reactions (qPCR), using gene-sequence primers, were performed. Protein levels were analyzed using immunochemical assays of western blot with commercially available antibodies. Liver samples were analyzed for phase I and II enzyme activities using a variety of substrates including ethoxyresorufin (cytochrome (CYP)1A1/1A2), pentoxyresorufin (CYP2B), methoxyresorufin (CYP1A), benzyloxyresorufin (CYP3A), testosterone (CYP3A/CYP2B), 1-chloro-2,4-nitrobenzene (CDNB) (glutathione S-transferase (GST)) and 4-nitrophenol (uridine diphosphate glucuronyltransferase (UDPGT)). In addition, the hydroxylated (OH-) polychlorinated biphenyls (PCBs) were analyzed in the blood, liver and brain tissue, whereas the methylsulfone (MeSO2-) PCBs were analyzed in liver tissue. Results indicated the presence of phase I (CYP1A4/CYP1A5, CYP2B, and CYP3A) and phase II (GST and UDPGT) enzymes at the activity, protein and/or mRNA level in both species. Northern fulmar chicks had higher enzyme activity than black-legged kittiwake chicks. This in combination with the higher XOH-PCB to parent PCB ratios suggests that northern fulmar chicks have a different biotransformation capacity than black-legged kittiwake chicks.

Geochemistry on ferromanganese crusts and nodules from Green Bay, Lake Michigan

The differential solubility of ferromanganese oxides can lead to stratigraphic separation of iron and manganese. Results of chemical analysis of a sequence of ferromanganese nodules overlying iron-rich crusts in northern Green Bay show that selec¬tive ion transport is important in concentrating manganese and associated trace elements near the oxygenated water-sediment interface. Manganese carbonate, which cements ferromanganese nodules, occurs in dark-gray silty sands that are located adjacent to the organic-rich muds of southern Green Bay. These muds contain an average of approximately 3.5 ppm (6x10-5M) interstitial Mn with 2.8 meq/l carbonate alkalinity. Thermodynamic calculation shows that interstitial water approaches equilibrium with MnCO3 in the upper 10 cm of sediment. This carbonate has a composition (Mn73Ca22Fe5)CO3 and has been identified as rhodochrosite.