High Risk of ART Non-Adherence and Delay of ART Initiation among HIV Positive Double Orphans in Kigali, Rwanda

Background

To reduce HIV/AIDS related mortality of children, adherence to antiretroviral treatment (ART) is critical in the treatment of HIV positive children. However, little is known about the association between ART adherence and different orphan status. The aims of this study were to assess the ART adherence and identify whether different orphan status was associated with the child’s adherence.

Methods

A total of 717 HIV positive children and the same number of caregivers participated in this cross-sectional study. Children’s adherence rate was measured using a pill count method and those who took 85% or more of the prescribed doses were defined as adherent. To collect data about adherence related factors, we also interviewed caregivers using a structured questionnaire.

Results

Of all children (N = 717), participants from each orphan category (double orphan, maternal orphan, paternal orphan, non-orphan) were 346, 89, 169, and 113, respectively. ART non-adherence rate of each orphan category was 59.3%, 44.9%, 46.7%, and 49.7%, respectively. The multivariate analysis indicated that maternal orphans (AOR 0.31, 95% CI 0.12–0.80), paternal orphans (AOR 0.35, 95% CI 0.14–0.89), and non-orphans (AOR 0.45, 95% CI 0.21–0.99) were less likely to be non-adherent compared to double orphans. Double orphans who had a sibling as a caregiver were more likely to be non-adherent. The first mean CD4 count prior to initiating treatment was 520, 601, 599, and 844 (cells/ml), respectively (p<0.001). Their mean age at sero-status detection was 5.9, 5.3, 4.8, and 3.9 (year old), respectively (p<0.001).

Conclusions

Double orphans were at highest risk of ART non-adherence and especially those who had a sibling as a caregiver had high risk. They were also in danger of initiating ART at an older age and at a later stage of HIV/AIDS compared with other orphan categories. Double orphans need more attention to the promote child’s adherence to ART.     

Induction of somatopause in adult mice compromises bone morphology and exacerbates bone loss during aging

Somatopause refers to the gradual declines in growth hormone (GH) and insulin‐like growth factor‐1 throughout aging. To define how induced somatopause affects skeletal integrity, we used an inducible GH receptor knockout (iGHRKO) mouse model. Somatopause, induced globally at 6 months of age, resulted in significantly more slender bones in both male and female iGHRKO mice. In males, induced somatopause was associated with progressive expansion of the marrow cavity leading to significant thinning of the cortices, which compromised bone strength. We report progressive declines in osteocyte lacunar number, and increases in lacunar volume, in iGHRKO males, and reductions in lacunar number accompanied by ~20% loss of overall canalicular connectivity in iGHRKO females by 30 months of age. Induced somatopause did not affect mineral/matrix ratio assessed by Raman microspectroscopy. We found significant increases in bone marrow adiposity and high levels of sclerostin, a negative regulator of bone formation in iGHRKO mice. Surprisingly, however, despite compromised bone morphology, osteocyte senescence was reduced in the iGHRKO mice. In this study, we avoided the confounded effects of constitutive deficiency in the GH/IGF‐1 axis on the skeleton during growth, and specifically dissected its effects on the aging skeleton. We show here, for the first time, that induced somatopause compromises bone morphology and the bone marrow environment.     

Molecular Characterization of Coprophilous Fungal Communities Reveals Sequences Related to Root-Associated Fungal Endophytes

This paper reports the use of molecular methods to characterize the coprophilous fungal communities (CFC) that inhabit the dung of four species of mammalian herbivores at two sites, Sevilleta National Wildlife Refuge (SNWR) in New Mexico and Wind Cave National Park (WCNP) in South Dakota. Results reveal that CFC from domesticated cattle (Bos taurus) at SNWR, and bison (Bison bison) and black-tailed prairie dogs (Cynomys ludovicianus) at WCNP were diverse but dominated primarily by members within eight taxonomic orders, including the rarely cultured and anaerobic order Neocallimastigales. In addition, 7.7% (138 of 1,788) of the sequences obtained from all dung samples were at least 97% similar to root-associated fungal (RAF) sequences previously described from blue grama (Bouteloua gracilis), a common forage grass found throughout North America and growing at both study sites. In contrast, 95.8% (295 of 308) of the sequences and four of the total seven operational taxonomic units obtained from pronghorn antelope (Antilocapra americana) dung belonged to the Pleosporalean order. We hypothesize that some herbivore vectors disperse non-systemic (non-clavicipitaceous) fungal endophytes. These dispersal events, it is argued, are most likely to occur via herbivores that occasionally forage and masticate root tissue, especially in arid regions where aboveground vegetation is sparse. The results of this study suggest that some (possibly many) members of the RAF community can expand their ecological role to include colonizing dung.     

Poor Nutrition Status and Associated Feeding Practices among HIV-Positive Children in a Food Secure Region in Tanzania: A Call for Tailored Nutrition Training

Undernutrition among HIV-positive children can be ameliorated if they are given adequate foods in the right frequency and diversity. Food insecurity is known to undermine such efforts, but even in food rich areas, people have undernutrition. As yet no study has examined feeding practices and their associations with nutrition status among as HIV-positive children in regions with high food production. We therefore examined the magnitude of undernutrition and its association with feeding practices among HIV-positive children in a high food production region in Tanzania.

Methods

We conducted this mixed-method study among 748 children aged 6 months-14 years attending 9 of a total of 32 care and treatment centers in Tanga region, Tanzania. We collected quantitative data using a standard questionnaire and qualitative data through seven focus group discussions (FGDs).

Results

HIV-positive children had high magnitudes of undernutrition. Stunting, underweight, wasting, and thinness were prevalent among 61.9%, 38.7%, 26.0%, and 21.1% of HIV-positive children, respectively. They also had poor feeding practices: 88.1% were fed at a frequency below the recommendations, and 62.3% had a low level of dietary diversity. Lower feeding frequency was associated with stunting (β = 0.11, p = 0.016); underweight (β = 0.12, p = 0.029); and thinness (β = 0.11, p = 0.026). Lower feeding frequency was associated with low wealth index (β = 0.06, p<0.001), food insecurity (β = −0.05, p<0.001), and caregiver''s education. In the FGDs, participants discussed the causal relationships among the key associations; undernutrition was mainly due to low feeding frequency and dietary diversity. Such poor feeding practices resulted from poor nutrition knowledge, food insecurity, low income, and poverty.

Conclusion

Feeding practices and nutrition status were poor among HIV-positive children even in food rich areas. Improving feeding frequency may help to ameliorate undernutrition. To improve it, tailored interventions should target children of poor households, the food insecure, and caregivers who have received only a low level of education.     

Characterization of cross-bridge elasticity and kinetics of cross-bridge cycling during force development in single smooth muscle cells

Force development in smooth muscle, as in skeletal muscle, is believed to reflect recruitment of force-generating myosin cross-bridges. However, little is known about the events underlying cross-bridge recruitment as the muscle cell approaches peak isometric force and then enters a period of tension maintenance. In the present studies on single smooth muscle cells isolated from the toad (Bufo marinus) stomach muscularis, active muscle stiffness, calculated from the force response to small sinusoidal length changes (0.5% cell length, 250 Hz), was utilized to estimate the relative number of attached cross-bridges. By comparing stiffness during initial force development to stiffness during force redevelopment immediately after a quick release imposed at peak force, we propose that the instantaneous active stiffness of the cell reflects both a linearly elastic cross-bridge element having 1.5 times the compliance of the cross-bridge in frog skeletal muscle and a series elastic component having an exponential length-force relationship. At the onset of force development, the ratio of stiffness to force was 2.5 times greater than at peak isometric force. These data suggest that, upon activation, cross-bridges attach in at least two states (i.e., low-force-producing and high-force-producing) and redistribute to a steady state distribution at peak isometric force. The possibility that the cross-bridge cycling rate was modulated with time was also investigated by analyzing the time course of tension recovery to small, rapid step length changes (0.5% cell length in 2.5 ms) imposed during initial force development, at peak force, and after 15 s of tension maintenance. The rate of tension recovery slowed continuously throughout force development following activation and slowed further as force was maintained. Our results suggest that the kinetics of force production in smooth muscle may involve a redistribution of cross-bridge populations between two attached states and that the average cycling rate of these cross-bridges becomes slower with time during contraction.     

Release of poly a(+) messenger RNA from rat liver rough microsomes upon disassembly of bound polysomes

Several procedures were used to disassemble rat liver rough microsomes (RM) into ribosomal subunits, mRNA, and ribosome-stripped membrane vesicles in order to examine the nature of the association between the mRNA of bound polysomes and the microsomal membranes. The fate of the mRNA molecules after ribosome release was determined by measuring the amount of pulse-labeled microsomal RNA in each fraction which was retained by oligo-dT cellulose or by measuring the poly A content by hybridization to radioactive poly U. It was found that ribosomal subunits and mRNA were simultaneously released from the microsomal membranes when the ribosomes were detached by: (a) treatment with puromycin in a high salt medium containing Mg++, (b) resuspension in a high salt medium lacking Mg++, and (c) chelation of Mg++ by EDTA or pyrophosphate. Poly A-containing mRNA fragments were extensively released from RM subjected to a mild treatment with pancreatic RNase in a medium of low ionic strength. This indicates that the 3' end of the mRNA is exposed on the outer microsomal surface and is not directly bound to the membranes. Poly A segments of bound mRNA were also accessible to [(3)H] poly U for in situ hybridization in glutaraldehyde-fixed RM. Rats were treated with drugs which inhibit translation after formation of the first peptide bonds or interfere with the initiation of protein synthesis. After these treatments inactive monomeric ribosomes, as well as ribosomes bearing mRNA, remained associated with their binding sites in microsomes prepared in media of low ionic strength. However, because there were no linkages provided by nascent chains, ribosomes, and mRNA, molecules were released from the microsomal membranes without the need of puromycin, by treatment with a high salt buffer containing Mg++. Thus, both in vivo and in vitro observations are consistent with a model in which mRNA does not contribute significantly to the maintenance of the interaction between bound polysomes and endoplasmic reticulum membranes in rat liver hepatocytes.