Gender and the use of antiretroviral treatment in resource-constrained settings: findings from a multicenter collaboration

AIMS: To compare the gender distribution of HIV-infected adults receiving highly active antiretroviral treatment (HAART) in resource-constrained settings with estimates of the gender distribution of HIV infection; to describe the clinical characteristics of women and men receiving HAART. METHODS: The Antiretroviral Therapy in Lower-Income Countries, ART-LINC Collaboration is a network of clinics providing HAART in Africa, Latin America, and Asia. We compared UNAIDS data on the gender distribution of HIV infection with the proportions of women and men receiving HAART in the ART-LINC Collaboration. RESULTS: Twenty-nine centers in 13 countries participated. Among 33,164 individuals, 19,989 (60.3%) were women. Proportions of women receiving HAART in ART-LINC centers were similar to, or higher than, UNAIDS estimates of the proportions of HIV-infected women in all but two centers. There were fewer women receiving HAART than expected from UNAIDS data in one center in Uganda and one center in India. Taking into account heterogeneity across cohorts, women were younger than men, less likely to have advanced HIV infection, and more likely to be anemic at HAART initiation. CONCLUSIONS: Women in resource-constrained settings are not necessarily disadvantaged in their access to HAART. More attention needs to be paid to ensuring that HIV-infected men are seeking care and starting HAART.

A REGIONAL ASSESSMENT OF GROUNDWATER AVAILABILITY AS CONSTRAINED BY LOCAL HYDROGEOLOGY AND ENVIRONMENTAL LIMITS TO STREAMFLOW DEPLETION

Groundwater pumping from aquifers in hydraulic connection with nearby streams is known to cause adverse impacts by decreasing flows to levels below those necessary to maintain aquatic ecosystems. The recent passage of the Great Lakes--St. Lawrence River Basin Water Resources Compact has brought attention to this issue in the Great Lakes region. In particular, the legislation requires the Great Lakes states to enact measures for limiting water withdrawals that can cause adverse ecosystem impacts. This study explores how both hydrogeologic and environmental flow limitations constrain groundwater availability in the Great Lakes Basin. A methodology for calculating maximum allowable pumping rates is presented. Groundwater availability across the basin is shown to be constrained by a combination of hydrogeologic yield and environmental flow limitations varying over both local and regional scales. The results are sensitive to factors such as pumping time and streamflow depletion limits as well as streambed conductance. Understanding how these restrictions constrain groundwater usage and which hydrogeologic characteristics and spatial variables have the most influence on potential streamflow depletions has important water resources policy and management implications.

Structural analysis of B-Box 2 from MuRF1: identification of a novel self-association pattern in a RING-like fold

The B-box motif is the defining feature of the TRIM family of proteins, characterized by a RING finger-B-box-coiled coil tripartite fold. We have elucidated the crystal structure of B-box 2 (B2) from MuRF1, a TRIM protein that supports a wide variety of protein interactions in the sarcomere and regulates the trophic state of striated muscle tissue. MuRF1 B2 coordinates two zinc ions through a cross-brace alpha/beta-topology typical of members of the RING finger superfamily. However, it self-associates into dimers with high affinity. The dimerization pattern is mediated by the helical component of this fold and is unique among RING-like folds. This B2 reveals a long shallow groove that encircles the C-terminal metal binding site ZnII and appears as the defining protein-protein interaction feature of this domain. A cluster of conserved hydrophobic residues in this groove and, in particular, a highly conserved aromatic residue (Y133 in MuRF1 B2) is likely to be central to this role. We expect these findings to aid the future exploration of the cellular function and therapeutic potential of MuRF1.

Selective pharmacological targeting of a DEAD box RNA helicase

RNA helicases represent a large family of proteins implicated in many biological processes including ribosome biogenesis, splicing, translation and mRNA degradation. However, these proteins have little substrate specificity, making inhibition of selected helicases a challenging problem. The prototypical DEAD box RNA helicase, eIF4A, works in conjunction with other translation factors to prepare mRNA templates for ribosome recruitment during translation initiation. Herein, we provide insight into the selectivity of a small molecule inhibitor of eIF4A, hippuristanol. This coral-derived natural product binds to amino acids adjacent to, and overlapping with, two conserved motifs present in the carboxy-terminal domain of eIF4A. Mutagenesis of amino acids within this region allowed us to alter the hippuristanol-sensitivity of eIF4A and undertake structure/function studies. Our results provide an understanding into how selective targeting of RNA helicases for pharmacological intervention can be achieved.

Compliance of the L5-S1 spinal unit: a comparative study between an unconstrained and a partially constrained system

A comparison between an unconstrained and a partially constrained system for in vitro biomechanical testing of the L5-S1 spinal unit was conducted. The objective was to compare the compliance and the coupling of the L5-S1 unit measured with an unconstrained and a partially constrained test for the three major physiological motions of the human spine. Very few studies have compared unconstrained and partially constrained testing systems using the same cadaveric functional spinal units (FSUs). Seven human L5-S1 units were therefore tested on both a pneumatic, unconstrained, and a servohydraulic, partially constrained system. Each FSU was tested along three motions: flexion-extension (FE), lateral bending (LB) and axial rotation (AR). The obtained kinematics on both systems is not equivalent, except for the FE case, where both motions are similar. The directions of coupled motions were similar for both tests, but their magnitudes were smaller in the partially constrained configuration. The use of a partially constrained system to characterize LB and AR of the lumbosacral FSU decreased significantly the measured stiffness of the segment. The unconstrained system is today's "gold standard" for the characterization of FSUs. The selected partially constrained method seems also to be an appropriate way to characterize FSUs for specific applications. Care should be taken using the latter method when the coupled motions are important.

The Right to Be Forgotten More Than a Pandora’s Box?

Recently, political voices have stressed the need to introduce a right to be forgotten as new human right. Individuals should have the right to make potentially damaging information disappear after a certain time has elapsed. Such new right, however, can come in conflict with the principle of free speech. Therefore, its scope needs to be evaluated in the light of appropriate data protection rules. Insofar, a more user-centered approach is to be realized. “Delete” can not be a value as such, but must be balanced within a new legal framework.