Estimation of whole-body radiation exposure from brachytherapy for oral cancer using a Monte Carlo simulation.

Early stage oral cancer can be cured with oral brachytherapy, but whole-body radiation exposure status has not been previously studied. Recently, the International Commission on Radiological Protection Committee (ICRP) recommended the use of ICRP phantoms to estimate radiation exposure from external and internal radiation sources. In this study, we used a Monte Carlo simulation with ICRP phantoms to estimate whole-body exposure from oral brachytherapy. We used a Particle and Heavy Ion Transport code System (PHITS) to model oral brachytherapy with 192Ir hairpins and 198Au grains and to perform a Monte Carlo simulation on the ICRP adult reference computational phantoms. To confirm the simulations, we also computed local dose distributions from these small sources, and compared them with the results from Oncentra manual Low Dose Rate Treatment Planning (mLDR) software which is used in day-to-day clinical practice. We successfully obtained data on absorbed dose for each organ in males and females. Sex-averaged equivalent doses were 0.547 and 0.710 Sv with 192Ir hairpins and 198Au grains, respectively. Simulation with PHITS was reliable when compared with an alternative computational technique using mLDR software. We concluded that the absorbed dose for each organ and whole-body exposure from oral brachytherapy can be estimated with Monte Carlo simulation using PHITS on ICRP reference phantoms. Effective doses for patients with oral cancer were obtained.

Periconception HIV Risk Behavior Among Men and Women Reporting HIV-Serodiscordant Partners in KwaZulu-Natal, South Africa.

HIV-infected men and women who choose to conceive risk infecting their partners. To inform safer conception programs we surveyed HIV risk behavior prior to recent pregnancy amongst South African, HIV-infected women (N = 209) and men (N = 82) recruited from antenatal and antiretroviral clinics, respectively, and reporting an uninfected or unknown-HIV-serostatus pregnancy partner. All participants knew their HIV-positive serostatus prior to the referent pregnancy. Only 11 % of women and 5 % of men had planned the pregnancy; 40 % of women and 27 % of men reported serostatus disclosure to their partner before conception. Knowledge of safer conception strategies was low. Around two-thirds reported consistent condom use, 41 % of women and 88 % of men reported antiretroviral therapy, and a third of women reported male partner circumcision prior to the referent pregnancy. Seven women (3 %) and two men (2 %) reported limiting sex without condoms to peak fertility. None reported sperm washing or manual insemination. Safer conception behaviors including HIV-serostatus disclosure, condom use, and ART at the time of conception were not associated with desired pregnancy. In light of low pregnancy planning and HIV-serostatus disclosure, interventions to improve understandings of serodiscordance and motivate mutual HIV-serostatus disclosure and pregnancy planning are necessary first steps before couples or individuals can implement specific safer conception strategies.

Reproductive counseling by clinic healthcare workers in Durban, South Africa: perspectives from HIV-infected men and women reporting serodiscordant partners.

BACKGROUND: Understanding HIV-infected patient experiences and perceptions of reproductive counseling in the health care context is critical to inform design of effective pharmaco-behavioral interventions that minimize periconception HIV risk and support HIV-affected couples to realize their fertility goals. METHODS: We conducted semistructured, in-depth interviews with 30 HIV-infected women (with pregnancy in prior year) and 20 HIV-infected men, all reporting serodiscordant partners and accessing care in Durban, South Africa. We investigated patient-reported experiences with safer conception counseling from health care workers (HCWs). Interview transcripts were reviewed and coded using content analysis for conceptual categories and emergent themes. RESULTS: The study findings indicate that HIV-infected patients recognize HCWs as a resource for periconception-related information and are receptive to speaking to a HCW prior to becoming pregnant, but seldom seek or receive conception advice in the clinic setting. HIV nondisclosure and unplanned pregnancy are important intervening factors. When advice is shared, patients reported receiving a range of information. Male participants showed particular interest in accessing safer conception information. CONCLUSIONS: HIV-infected men and women with serodiscordant partners are receptive to the idea of safer conception counseling. HCWs need to be supported to routinely initiate accurate safer conception counseling with HIV-infected patients of reproductive age.

The relationship between HAART use and sexual activity among HIV-positive women of reproductive age in Brazil, South Africa, and Uganda.

The purpose of this study was to determine whether current HAART use is associated with recent sexual intercourse among HIV-infected women (18-49 years) from Brazil, South Africa and Uganda. We conducted an analysis of survey data from a cross-sectional study, which enrolled 179 HIV-infected women receiving regular care from the Mbarara Hospital HIV Clinic in Uganda (n=85); the Perinatal HIV Research Unit in Soweto, South Africa (n=50); and the IPEC-Fiocruz cohort in Rio de Janeiro, Brazil (n=44). The primary outcome was sexual intercourse in the previous month. Secondary outcomes were protected sex and contraceptive use. We found that overall, 46% reported recent sexual intercourse. After adjusting for covariates, recent sexual intercourse was not associated with HAART use (AOR: 0.76; 95%CI: 0.34-1.72); however, it was significantly associated with being currently married, wanting to have more children and having higher HAART optimism. Among women reporting recent sexual intercourse (n=83), HAART users were significantly more likely to practice protected sex (crude OR: 3.64; 95%CI: 1.41-9.38) and non-significantly more likely to use contraceptive methods (crude OR: 2.15; 95%CI: 0.77-5.99). In summary, self-reported recent sexual intercourse is not more likely among women on HAART. Moreover, sexually active HAART users may be more likely to practice protected sex and use contraceptives.

Unspecified falls among youth: predictors of coding specificity in the emergency department.

BACKGROUND: Deficiencies in emergency department (ED) charting is a common international problem. While unintentional falls account for the largest proportion of injury related ED visits by youth, insufficient charting details result in more than one third of these falls being coded as "unspecified". Non-specific coding compromises the utility of injury surveillance data. OBJECTIVE: To re-examine the ED charts of unspecified youth falls to determine the possibility of assigning more specific codes. METHODS: 400 ED charts for youth (aged 0-19 years) treated at four EDs in an urban Canadian health region between 1997 and 1999 and coded as "Other or unspecified fall" (ICD-9 E888) were randomly selected. A structured chart review was completed and a blinded nosologist recoded the cause of injury using the extracted data. Differences in coding specificity were compared with the original data, and logistic regression was undertaken to examine variables that predicted assignment of a specific E-code. RESULTS: A more specific code was assigned to 46% of cases initially coded as unspecified. Of these, 73% were recoded as "Slips, trips, and stumbles" (E885), which still lacks the specificity required for injury prevention planning; 2% of charts had no fall documented. Multivariate analysis revealed that dichotomized injury severity (adjusted odds ratio (OR) = 1.75 (95% confidence interval, 1.11 to 2.78)), arrival at the ED by ambulance (adjusted OR = 5.41 (1.07 to 27.0)), and the availability of nurse's notes or triage forms, or both, in the chart (adjusted OR = 3.75 (2.17 to 6.45)) were the strongest predictors of a more specific E-code assignment. CONCLUSIONS: Deficiencies in both chart documentation and coding specificity contribute to the use of non-specific E-codes. More comprehensive triage coding, improved chart documentation, and alternative methods of data collection in the acute care setting are required to improve ED injury surveillance initiatives.

A transdisciplinary perspective on the links between malaria and agroecosystems in Kenya.

An ecosystem approach was applied to study the links between malaria and agriculture in Mwea Division, Kenya. The study was organized into five phases. Phase I had two components including a stakeholder workshop conducted with community representatives and other key stakeholders, and the collation of data on common diseases from outpatient service records at the local hospital. Phase I aimed at an a priori needs-assessment in order to focus the research agenda. Workshop participants directly contributed to the selection of two villages with rice irrigation and two non-irrigated villages for detailed health studies. In Phase II, various Participatory Rural Appraisal (PRA) tools were used to gather more detailed qualitative information from the study villages. The qualitative results indicated that Mwea residents considered malaria and lack of clean drinking water to be their most important health problems, and this was corroborated by local hospital records. Phase III consisted of a comprehensive household survey developed with inputs from Phases I and II. Phase IV involved a comparative evaluation of entomological and parasitological aspects of malaria in the villages with and without rice irrigation. The malaria parasitological survey found an average Plasmodium falciparum parasite rate of 23.5% among children up to 9 years of age. Results of the entomological evaluation showed a 30-300-fold increase in the number of the local malaria vector, Anopheles arabiensis, in villages with rice irrigation compared to those without irrigation yet malaria prevalence was significantly lower in these villages (0-9% versus 17-54%). The most likely explanation of this 'paddies paradox' in Mwea appeared to be the tendency for A. arabiensis in irrigated villages to feed overwhelmingly on cattle. The results suggested that zooprophylaxis was potentially a practical option for long-term malaria control in the rice irrigated areas, in spite of the large number of A. arabiensis. Phase V consisted of end-of-project workshops for the dissemination of research results and participatory decision-making regarding follow-up actions. Owing to the utilization of a transdisciplinary and participatory approach to research, it was possible to identify opportunities for maintaining zooprophylaxis for malaria in Mwea, through the integration of agroecosystem practices aimed at sustaining livestock systems within a broader strategy for rural development.

Functional cross-talk of HIV-1 Tat with p53 through its C-terminal domain.

Human immunodeficiency virus type 1 (HIV-1) Tat repressed the p53-dependent gene expression through its C-terminal domain of Tat (amino acid residues 73-86) independent of the involvement of NF-kappaB and coactivator CBP/p300. Although Tat did not directly bind to p53, this repression required the N-terminal domain of p53. In contrast, Tat and p53 cooperated in the activation of HIV-1 gene expression. Thus, the cross-talk between Tat and p53 may be linked with cellular transformation by HIV-1 infection or activation of HIV-1 replication.

HTLV-1 tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration.

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein repressed the transcriptional activity of wild-type p53 through its N-terminal trans-activation domain. Although Tax did not directly bind to p53, this repression required the activation of CREB pathway by Tax. In contrast to a recent report by Pise-Masison et al. (1998a, b) we found that the phosphorylation of p53 on Ser 15 is not a major cause of the Tax-mediated inactivation of p53. However, Tax with a mutation in the coactivator CBP-binding site (K88A), which activates NF-kappaB but not the CREB pathway, could not repress the p53 trans-activation function. Moreover, Tax inhibited p53 binding to CBP in vitro and inhibited synergistic activation of transcription by CBP and p53. Thus, Tax is likely to compete with p53 in binding with CBP, thereby repressing its trans-activation function.

Functional impairment of p73 and p51, the p53-related proteins, by the human T-cell leukemia virus type 1 Tax oncoprotein.

We have previously demonstrated that the human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein represses the trans-activation function of p53 tumor suppressor protein. Recently, several proteins with sequence homology to p53 have been identified. In this study, we demonstrated that Tax represses the trans-activation functions of p73alpha, p73beta, and p51A, the p53-related proteins, as well as p53. Moreover, a mutant Tax of coactivator CBP-binding site (K88A), which activated NF-kappaB but not CREB pathway, could not repress the p73 nor p51 trans-activation functions, indicating that CBP-binding domain of Tax is essential for the suppression of their functions. Using proteins of Gal4-fused N-terminal region of p73 and p51, we showed that Tax-mediated inactivation of p73 or p51 requires for their N-terminal trans-activation domains. Furthermore, only the putative N-terminal trans-activation domains of them did not have enough transcriptional activities and their adjacent regions are essential for their full trans-activation, suggesting the existence of their second trans-activation subdomains. Thus, HTLV-1 Tax inactivated the p53-related proteins through their N-terminal trans-activation domains.

[On the relation between prototype abstraction and exemplar retention in the memory of melodies].

This study examined the relation between prototype abstraction and exemplar retention by using memory of melodies. Acquisition lists of melodies were constructed by applying a set of transformation rules to a fixed prototype melody (cf. Welker, 1982). Immediately after the presentation of acquisition list, recognition task was performed. The recognition rating for prototype was used as the indicator of the prototype abstraction. The discriminability of old melodies from new melodies (d') was used as the indicator of exemplar retention. In Exp. 1 with 30 undergraduates as subjects, the transformational distance of acquisition list was varied and it was demonstrated that as the transformational distance decreased, prototype abstraction was facilitated but exemplar retention was not changed. In Exp. 2 with 90 undergraduates as subjects, the number of presentation of each melody and the kinds of melodies in acquisition list were varied. Results demonstrated that as the number of presentation of each melody increased and also as the kinds of melodies decreased, the exemplar retention improved but prototype abstraction was not changed. It was argued that the systems underlying the prototype abstraction and exemplar retention were functionally independent of each other.