Adherence to antiretroviral therapy in HIV-infected adults in Soweto, South Africa.

Little is known about achievable levels of antiretroviral treatment (ART) adherence in resource-limited settings. We conducted a cross-sectional study of adherence among patients at Chris Hani Baragwanath Hospital's Adult HIV Clinic in Soweto, South Africa. Adherence was assessed using a 1-month, self-report questionnaire and was calculated as a ratio of doses taken to doses prescribed. The 66 patients studied had a mean age of 36.1 years, a median duration of ART use of 18 months, and an overall baseline median CD4(+) cell count of 200/mm(3) (IQR: 114-364). The adherence reported by these patients for the previous month was >95% for 58 patients (88%), 90-95% for 6 (9%) and, < 90% for 2 (3%). The main reasons given for missing doses were being away from home (30%), difficulty with the dosing schedules (23%), and running out of pills (12%). Adherence decreased considerably with fear of being stigmatized by the sexual partner (OR = 0.13 95%, CI 0.02-0.70). Plasma HIV RNA levels were <400 copies/ml in the majority of patients (73% of those with adherence >95% and 88% of patients with < or =95% adherence) and the overall median CD4(+) cell count rose to 324/mm(3) (IQR: 193-510). High adherence and viral suppression are achievable for a significant proportion of HIV-infected patients taking ART in a resource-limited area such as Soweto, South Africa. Strategies to maximize adherence in this setting should emphasize ready access to affordable and simple ART regimens, as well as HIV education programs to help increase awareness and decrease disease stigmatization.

The effects of a balance and strength training program on equilibrium in Parkinsonism: A preliminary study.

The purpose of this study was to determine if a balance and strength training program could improve equilibrium and strength in persons with stage I-III Parkinsonism. Subjects were pre-tested on strength and balance (EquiTest) and randomized into either a treatment or a control group. The treatment subjects participated in 10 weeks of lower limb strength training and balance exercises designed to challenge a stable posture and increase limits of stability. Both groups were then posttested on balance, knee flexion, knee extension, and ankle inversion strength. Subjects who received strength and balance training demonstrated significantly improved equilibrium and modest gains in knee flexion and extension strength, while the control group showed no improvement in conditions of destabilizing balance environments and significant declines in strength. Results indicate that 10 weeks of balance and strength training lead to improved equilibrium by producing positive changes in two different control mechanisms. One, training altered the ability to control the motor system when vestibular cues had to be the primary source of reliable feedback; and two, training helped subjects to override faulty proprioceptive feedback and utilize reliable visual or vestibular cues.

Cis-regulatory elements of the mitotic regulator, string/Cdc25.

Mitosis in most Drosophila cells is triggered by brief bursts of transcription of string (stg), a Cdc25-type phosphatase that activates the mitotic kinase, Cdk1 (Cdc2). To understand how string transcription is regulated, we analyzed the expression of string-lacZ reporter genes covering approximately 40 kb of the string locus. We also tested protein coding fragments of the string locus of 6 kb to 31.6 kb for their ability to complement loss of string function in embryos and imaginal discs. A plethora of cis-acting elements spread over >30 kb control string transcription in different cells and tissue types. Regulatory elements specific to subsets of epidermal cells, mesoderm, trachea and nurse cells were identified, but the majority of the string locus appears to be devoted to controlling cell proliferation during neurogenesis. Consistent with this, compact promotor-proximal sequences are sufficient for string function during imaginal disc growth, but additional distal elements are required for the development of neural structures in the eye, wing, leg and notum. We suggest that, during evolution, cell-type-specific control elements were acquired by a simple growth-regulated promoter as a means of coordinating cell division with developmental processes, particularly neurogenesis.

Opposite modulation of cocaine-seeking behavior by D1- and D2-like dopamine receptor agonists.

Activation of the mesolimbic dopamine system is known to trigger relapse in animal models of cocaine-seeking behavior. We found that this "priming" effect was selectively induced by D2-like, and not by D1-like, dopamine receptor agonists in rats. Moreover, D1-like receptor agonists prevented cocaine-seeking behavior induced by cocaine itself, whereas D2-like receptor agonists enhanced this behavior. These results demonstrate an important dissociation between D1- and D2-like receptor processes in cocaine-seeking behavior and support further evaluation of D1-like receptor agonists as a possible pharmacotherapy for cocaine addiction.

The multicomponent nature of equilibrium in persons with parkinsonism: a regression approach.

Lower extremity strength and joint range of motion, body sway, and electromyography responses have all been determined to be factors in balance control of healthy older individuals. The purpose of this study was to identify variables which effect balance control (equilibrium scores) of persons with Parkinsonism, and examine their relationships and predictive abilities. The composite equilibrium score from the sensory organization protocol of the Equitest was used as the dependent variable for the regression analysis. The independent variables included: 1) strategy score; 2) path sway during voluntary body displacement; 3) percent peak torque of knee flexion relative to that of knee extension (%PTKFKE); 4) peak torque of inversion of the ankle at (PTINV); 5) dorsiflexion ROM; and 6) medium loop latency (EMG). The model produced a significant overall relationship accounting for 88% of the variability in equilibrium scores. Positive and significant coefficients indicated a predicted increase in the equilibrium composite score with increases in the strategy score, PTINV and %PTKFKE. These results suggest that postural control of persons with Parkinsonism can be strongly predicted by these three variables.

Transcriptional regulation of string (cdc25): a link between developmental programming and the cell cycle.

During postblastoderm embryogenesis in Drosophila, cell cycles progress in an invariant spatiotemporal pattern. Most of these cycles are differentially timed by bursts of transcription of string (cdc25), a gene encoding a phosphatase that triggers mitosis by activating the Cdc2 kinase. An analysis of string expression in 36 pattern-formation mutants shows that known patterning genes act locally to influence string transcription. Embryonic expression of string gene fragments shows that the complete pattern of string transcription requires extensive cis-acting regulatory sequences (> 15.3 kb), but that smaller segments of this regulatory region can drive proper temporal expression in defined spatial domains. We infer that string upstream sequences integrate many local signals to direct string's transcriptional program. Finally, we show that the spatiotemporal progression of string transcription is largely unaffected in mutant embryos specifically arrested in G2 of cycles 14, 15, or 16, or G1 of cycle 17. Thus, there is a regulatory hierarchy in which developmental inputs, not cell cycle inputs, control the timing of string transcription and hence cell cycle progression.