23 research outputs found
Interstitial telomeric repeats are not preferentially involved in radiation-induced chromosome aberrations in human cells
Interstitial telomeric repeats are not preferentially involved in radiation-induced chromosome aberrations in human cells
Telomeric repeat sequences, located at the end of eukaryotic chromosomes, have been detected at intrachromosomal locations in many species. Large blocks of telomeric sequences are located near the centromeres in hamster cells, and have been reported to break spontaneously or after exposure to ionizing radiation, leading to chromosome aberrations. In human cells, interstitial telomeric sequences (ITS) can be composed of short tracts of telomeric repeats (less than twenty), or of longer stretches of exact and degenerated hexanucleotides, mainly localized at subtelomeres. In this paper, we analyzed the radiation sensitivity of a naturally occurring short ITS localized in 2q31 and we found that this region is not a hot spot of radiation-induced chromosome breaks. We then selected a human cell line in which approximately 800 bp of telomeric DNA had been introduced by transfection into an internal euchromatic chromosomal region in chromosome 4q. In parallel, a cell line containing the plasmid without telomeric sequences was also analyzed. Both regions containing the transfected plasmids showed a higher frequency of radiation-induced breaks than expected, indicating that the instability of the regions containing the transfected sequences is not due to the presence of telomeric sequences. Taken together, our data show that ITS themselves do not enhance the formation of radiation-induced chromosome rearrangements in these human cell lines
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Initiation of antiretroviral therapy and viral suppression after home HIV testing and counselling in KwaZulu-Natal, South Africa, and Mabarara district, Uganda: a prospective, observational intervention study
Antiretroviral therapy significantly decreases HIV-associated morbidity, mortality, and HIV transmission through HIV viral load suppression. In settings of high prevalence, outreach strategies are needed to find asymptomatic HIV-positive people, to link them to HIV care, to initiate antiretroviral therapy, and to achieve viral suppression. We aimed to assess the effect of a community-based strategy of HIV testing and counselling (HTC) and linkage to care in households. We did an uncontrolled prospective intervention study in 1600 households in two rural communities in KwaZulu-Natal, South Africa, and Mbabara district, Uganda, between Sept 27, 2011, and May 6, 2013. The intervention consisted of home HTC and, for HIV-positive people, point-of-care CD4 count testing, referral to care, and follow-up visits by lay counsellors, including the off er of couples HTC. We identifi ed 3545 adults in 1549 households in the two communities. 3393 adults (96%) were enrolled and tested for HIV, of whom 635 (19%) were HIV positive. At baseline, 229 (36%) HIV-positive people were newly identifi ed, 406 (64%) were previously known to be HIV positive, and 254 (40%) were taking antiretroviral therapy. By month 12, 619 (97%) HIV-positive people had visited an HIV clinic, and of 123 participants eligible for antiretroviral therapy, 94 (76%) had initiated antiretroviral therapy by 12 months. Of the 77 participants on antiretroviral therapy by month 9, 59 (77%) achieved viral suppression by month 12. Among all HIV-positive people, the number with viral suppression (<1000 copies per mL) increased from 287 (50%) to 370 (65%; p<0.0001) at 12 months. There were no reported cases of study-related social harm during the study. Community-based HTC in rural South Africa and Uganda achieved high coverage of testing and linkage to care. Among people eligible for antiretroviral therapy, a high proportion initiated antiretroviral therapy and
achieved viral suppression, suggesting high adherence. Our results could be generalisable to other southern African countries with a high burden of HIV, but pilot studies would be useful in other settings before initiation of clinical trials to estimate the effectiveness and cost-effectiveness of the intervention.