Enrolment and programmatic trends and predictors of antiretroviral therapy initiation from president's emergency plan for AIDS Relief (PEPFAR)-supported public HIV care and treatment sites in rural Mozambique.

Many countries in sub-Saharan Africa have made antiretroviral therapy (ART) available in urban settings, but the progress of treatment expansion into rural Africa has been slower. We analysed routine data for patients enrolled in a rural HIV treatment programme in Zambézia Province, Mozambique (1 June 2006 through 30 March 2009). There were 12,218 patients who were ≥15 years old enrolled (69% women). Median age was 25 years for women and 31 years for men. Older age and higher level of education were strongly predictive of ART initiation (P < 0.001). Patients with a CD4+ count of 350 cells/µL versus 50 cells/µL were less likely to begin ART (odds ratio [OR]: 0.19, 95% confidence interval [CI]: 0.16-0.23). In rural sub-Saharan Africa, HIV testing, linkage to care, logistics for ART initiation and fears among some patients to take ART require specialized planning to maximize successes. Sustainability will require improved health manpower, infrastructure, stable funding, continuous drug supplies, patient record systems and, most importantly, community engagement.

Caveats and considerations for performing pancreas-specific gene manipulations in the mouse.

Conditional gene targeting using the Cre/loxP strategy has proven to be very useful for studies of glucose homeostasis, tissue function and dysfunction in diabetes, and pancreas development. However, use of this strategy over the past decade has revealed a variety of experimental caveats, many of which are a direct consequence of the procedures used to generate Cre-driver lines. We discuss frequently encountered experimental artefacts, the advantages of using bacterial artificial chromosome-derived transgenes or performing a Cre knockin for improving the specificity of expression, and systems for regulating Cre activity. In addition, recent studies indicate that high amounts of Cre in the pancreatic beta-cell may cause glucose intolerance and impaired insulin secretion. However, these findings, while serving as a reminder for simple experimental controls, are unlikely to diminish utilization of this very powerful and useful technology.

Functional formation of domain V of the poliovirus noncoding region: significance of unpaired bases.

Previously we have shown that polioviruses with mutations that disrupt the predicted secondary structure of the 5' noncoding region of domain V are temperature sensitive for growth. Non-temperature-sensitive revertant viruses had mutations that re-formed secondary structure by a direct back mutation of changes in the opposite strand. We mutated unpaired regions and selected revertants of viruses with single base deletions, where no obvious back mutation was available in order to gain information on secondary structure. Results indicated that conservation of length of a three base loop between two double-stranded stems was essential for a functional domain V to form. The requirement for the unpaired "hinge" base at 484 which is implicated in the attenuation of Sabin 2 was also confirmed. Results also underline the necessity for functional folding over local secondary structure stability.

Role of mutations G-480 and C-6203 in the attenuation phenotype of Sabin type 1 poliovirus.

Of the 55 point mutations which distinguish the type 1 poliovirus vaccine strain (Sabin 1) from its neurovirulent progenitor (P1/Mahoney), two have been strongly implicated by previous studies as determinants of the attenuation phenotype. A change of an A to a G at position 480, located within the 5' noncoding region, has been suggested to be the major attenuating mutation, analogous to the mutations at positions 481 and 472 in poliovirus types 2 and 3, respectively. In addition, the change of a U to a C at position 6203, resulting in an amino acid change in the polymerase protein 3D, has also been implicated as a determinant of attenuation, albeit to a lesser extent. To assess the contributions of these mutations to attenuation and temperature sensitivity, reciprocal changes were generated at these positions in infectious cDNA clones of Sabin 1 and P1/Mahoney. Assays in tissue culture and primates indicated that the two mutations make some contribution to the temperature sensitivity of the Sabin 1 strain but that neither is a strong determinant of attenuation.

Correlation of RNA secondary structure and attenuation of Sabin vaccine strains of poliovirus in tissue culture.

Part of the 5' noncoding regions of all three Sabin vaccine strains of poliovirus contains determinants of attenuation that are shown here to influence the ability of these strains to grow at elevated temperatures in BGM cells. The predicted RNA secondary structure of this region (nt 464-542 in P3/Sabin) suggests that both phenotypes are due to perturbation of base-paired stems. Ts phenotypes of site-directed mutants with defined changes in this region correlated well with predicted secondary structure stabilities. Reversal of base-pair orientation had little effect whereas stem disruption led to marked increases in temperature sensitivity. Phenotypic revertants of such viruses displayed mutations on either side of the stem. Mutations destabilizing stems led to intermediate phenotypes. These results provided evidence for the biological significance of the predicted RNA secondary structure.

The abortion issue in the 1980 elections.

The political opponents of legal abortion achieved considerable gains in the 1980 American elections. A president who was committed to a strong antiabortion position was elected, and antiabortion candidates prevailed in six out of seven Senate races that pitted supporters against opponents of legal abortion and in seven out of nine similar confrontations in the House races. However, it is not clear that abortion was an overriding or decisive factor in determining those outcomes. Democrats and Republicans, Carter voters and Reagan voters did not differ significantly in their attitudes toward abortion. The presidential voter groups were divided on several other issues, and along income and racial lines, to a far greater extent than they were on abortion. Voters were not likely to name abortion as one of the more important problems facing the nation. Carter supporters rated abortion as more important than did Reagan supporters. Although the party platforms and the presidential candidates were clearly differentiated in their abortion stands, these differences were not well communicated to the citizenry. When voters attempted to describe the position of each candidate on abortion, they displayed a great deal of uncertainty, error and confusion. In the key Senate races, those who voted for the prochoice candidates held more liberal abortion attitudes than those who voted for the right-to-life candidates. This difference, although statistically significant, was not great, and was smaller than the differences related to several other issues--such as attitudes toward the role of government, women's rights and economic policies.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: The political opponents of legal abortion achieved considerable gains in the 1980 American elections. A president who was committed to a strong antiabortion position was elected, and antiabortion candidates prevailed in 6 out of 7 Senate races that pitted supporters against opponents of legal abortion and in 7 out of 9 similar confrontations in the House races. However, it is not clear that abortion was an overriding or decisive factor in determining those outcomes. Democrats and Republicans, Carter and Reagan voters did not differ significantly in their attitudes toward abortion, nor were voters likely to name abortion as one of the more important problems facing the nation, though Carter voters did rate it as more important than did Reagan voters. Although the party platforms and the presidential candidates were clearly differentiated in their abortion stands, these differences were not well communicated to the citizenry, as voters demonstrated a great deal of confusion and uncertainty when they attempted to describe the position of each candidate. In the key Senate races, those who voted for the prochoice candidates held more liberal abortion attitudes than those who voted for the right-to-life candidates. This difference was smaller than the differences related to several other issues--such as attitudes toward the role of government, women's rights, and economic policies. In addition, the difference was reduced to nonsignificance after the voter's political affiliation and family income were controlled for. The level of public approval for legalized abortion has been stable since 1973, and the popular base for limiting access to or banning abortion seems to be lacking. The antiabortion forces appear to have made political gains in 1978 and 1980 as an incidental consequence of the electorates' shift toward political conservatism. This ascendancy began to be reversed in the 1982 congressional elections.