Gene expression responses of human cell lines exposed to a diverse set of stress agents were compared by cDNA microarray hybridization. The B-lymphoblastoid cell line TK6 (p53 wild-type) and its ...p53-null derivative, NH32, were treated in parallel to facilitate investigation of p53-dependent responses. RNA was extracted 4 h after the beginning of treatment when no notable decrease in cell viability was evident in the cultures. Gene expression signatures were defined that discriminated between four broad general mechanisms of stress agents: Non-DNA-damaging stresses (heat shock, osmotic shock, and 12-O-tetradecanoylphorbol 13-acetate), agents causing mainly oxidative stress (arsenite and hydrogen peroxide), ionizing radiations (neutron and gamma-ray exposures), and other DNA-damaging agents (ultraviolet radiation, methyl methanesulfonate, adriamycin, camptothecin, and cis-Platinum(II)diammine dichloride (cisplatin)). Within this data set, non-DNA-damaging stresses could be discriminated from all DNA-damaging stresses, and profiles for individual agents were also defined. While DNA-damaging stresses showed a strong p53-dependent element in their responses, no discernible p53-dependent responses were triggered by the non-DNA-damaging stresses. A set of 16 genes did exhibit a robust p53-dependent pattern of induction in response to all nine DNA-damaging agents, however.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Human immunodeficiency virus type 1 (HIV-1) populations are detected in cerebrospinal fluid (CSF) of some people on suppressive antiretroviral therapy (ART). Detailed analysis of these populations ...may reveal whether they are produced by central nervous system (CNS) reservoirs.
We performed a study of 101 asymptomatic participants on stable ART. HIV-1 RNA concentrations were cross-sectionally measured in CSF and plasma. In participants with CSF HIV-1 RNA concentrations sufficient for analysis, viral populations were genetically and phenotypically characterized over multiple time points.
For 6% of participants (6 of 101), the concentration of HIV-1 RNA in their CSF was ≥0.5 log copies/mL above that of plasma (ie, CSF escape). We generated viral envelope sequences from CSF of 3 participants. One had a persistent CSF escape population that was macrophage-tropic, partially drug resistant, genetically diverse, and closely related to a minor macrophage-tropic lineage present in the blood prior to viral suppression and enriched for after ART. Two participants (1 suppressed and 1 not) had transient CSF escape populations that were R5 T cell-tropic with little genetic diversity.
Extensive analysis of viral populations in 1 participant revealed that CSF escape was from a persistently replicating population, likely in macrophages/microglia, present in the CNS over 3 years of ART. CSF escape in 2 other participants was likely produced by trafficking and transient expansion of infected T cells in the CNS. Our results show that CNS reservoirs can persist during ART and that CSF escape is not exclusively produced by replicating CNS reservoirs.
Few data on the virological determinants of hepatitis B virus (HBV) infection are available from southern Africa.
We enrolled consecutive HIV-infected adult patients initiating antiretroviral therapy ...(ART) at two urban clinics in Zambia and four rural clinics in Northern Mozambique between May 2013 and August 2014. HBsAg screening was performed using the Determine® rapid test. Quantitative real-time PCR and HBV sequencing were performed in HBsAg-positive patients. Risk factors for HBV infection were evaluated using Chi-square and Mann-Whitney tests and associations between baseline characteristics and high level HBV replication explored in multivariable logistic regression.
Seventy-eight of 1,032 participants in Mozambique (7.6%, 95% confidence interval CI: 6.1-9.3) and 90 of 797 in Zambia (11.3%, 95% CI: 9.3-13.4) were HBsAg-positive. HBsAg-positive individuals were less likely to be female compared to HBsAg-negative ones (52.3% vs. 66.1%, p<0.001). Among 156 (92.9%) HBsAg-positive patients with an available measurement, median HBV viral load was 13,645 IU/mL (interquartile range: 192-8,617,488 IU/mL) and 77 (49.4%) had high values (>20,000 UI/mL). HBsAg-positive individuals had higher levels of ALT and AST compared to HBsAg-negative ones (both p<0.001). In multivariable analyses, male sex (adjusted odds ratio: 2.59, 95% CI: 1.22-5.53) and CD4 cell count below 200/μl (2.58, 1.20-5.54) were associated with high HBV DNA. HBV genotypes A1 (58.8%) and E (38.2%) were most prevalent. Four patients had probable resistance to lamivudine and/or entecavir.
One half of HBsAg-positive patients demonstrated high HBV viremia, supporting the early initiation of tenofovir-containing ART in HIV/HBV-coinfected adults.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The 60 cell lines of the National Cancer Institute Anticancer Drug Screen (NCI-60) constitute the most extensively characterized in vitro cancer cell model. They have been tested for sensitivity to ...more than 100,000 potential chemotherapy agents and have been profiled extensively at the DNA, RNA, protein, functional, and pharmacologic levels. We have used the NCI-60 cell lines and three additional lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis, and gene expression response by microarray. Although several studies have profiled relative basal gene expression in the NCI-60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. Twenty-two genes were differentially regulated in cells with low survival after 2-Gy gamma-rays; 14 genes identified lines more sensitive to 8 Gy. Unlike reported basal gene expression patterns, changes in expression in response to radiation showed little tissue-of-origin effect, except for differentiating the lymphoblastoid cell lines from other cell types. Basal expression patterns, however, discriminated well between radiosensitive and more resistant lines, possibly being more informative than radiation response signatures. The most striking patterns in the radiation data were a set of genes up-regulated preferentially in the p53 wild-type lines and a set of cell cycle regulatory genes down-regulated across the entire NCI-60 panel. The response of those genes to gamma-rays seems to be unaffected by the myriad of genetic differences across this diverse cell set; it represents the most penetrant gene expression response to ionizing radiation yet observed.
Osteoarthritis affects millions of people worldwide but current treatments using analgesics or anti-inflammatory drugs only alleviate symptoms of this disease. Here, we present an injectable, ...biodegradable piezoelectric hydrogel, made of short electrospun poly-L-lactic acid nanofibers embedded inside a collagen matrix, which can be injected into the joints and self-produce localized electrical cues under ultrasound activation to drive cartilage healing. In vitro, data shows that the piezoelectric hydrogel with ultrasound can enhance cell migration and induce stem cells to secrete TGF-β1, which promotes chondrogenesis. In vivo, the rabbits with osteochondral critical-size defects receiving the ultrasound-activated piezoelectric hydrogel show increased subchondral bone formation, improved hyaline-cartilage structure, and good mechanical properties, close to healthy native cartilage. This piezoelectric hydrogel is not only useful for cartilage healing but also potentially applicable to other tissue regeneration, offering a significant impact on the field of regenerative tissue engineering.
We sought to understand the social construction of aging in a clinic-based population, with and without HIV, to address gaps in care for older individuals living with HIV in Zambia.
Our exploratory ...qualitative study included 36 in-depth interviews with clinic clients and four focus group discussions with 36 professional and lay healthcare workers providing services to the clients. We identified themes based on social construction theory.
At the individual level, aging was multidimensional, perceived both as an achievement in the HIV era and as a period of cognitive, physical, and economic decline. In social interactions, older individuals were often stereotyped and treated as helpless, poor, and "witches." Those living with HIV faced the additional stigma of being labeled as promiscuous. Some of the participants living without HIV refused to take daily medication for non-communicable diseases to avoid being mistaken for taking antiretroviral therapy for HIV. Older individuals wanted quality healthcare and family support to address the intersectional stigma of aging, poverty, and chronic illness.
Multifaceted interventions are required to combat age-related prejudice, intersectional stigma, and discriminatory practices, particularly for people living with HIV.
•Hepatitis B virus infection is the main cause of liver cancer in sub-Saharan Africa.•Little is known about incidence of HBV infection among individuals on antiretroviral therapy.•This is among the ...first initiatives for liver cancer screening in the region.•Two percent of adults co-infected with human immunodeficiency virus/HBV had significant liver lesions.•One-quarter of patients had findings suggestive of schistosomiasis-induced liver damage.
Chronic hepatitis B virus (HBV) infection is the main cause of hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA). An HCC screening initiative was piloted in an established cohort of individuals co-infected with human immunodeficiency virus (HIV) and HBV on antiretroviral therapy (ART) at two outpatient clinics in Lusaka, Zambia.
All patients underwent abdominal ultrasound (AUS) and transient elastography.
Among 279 patients co-infected with HIV/HBV, 165 (59.1%) were men, median age was 34 years interquartile range (IQR) 28–39 years and median CD4 count was 246 cells/µL (IQR 112–355 cells/µL) at ART initiation. While 102 (55.7%) individuals had elevated transaminases, 114 (59.7%) had HBV levels >2000 IU/mL and 59 (24.6%) had significant fibrosis. At their first AUS measurement, 75 (26.9%) participants had hepatomegaly and 69 (24.7%) had periportal fibrosis. Five patients had a liver lesion >1 cm, an indication for confirmatory imaging.
In one of the first HCC screening initiatives in SSA, 2% of patients co-infected with HIV/HBV had significant liver lesions, and one-quarter had findings suggestive of schistosomiasis-induced liver damage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The emergence of the SARS‐CoV‐2 pandemic and airborne particulate matter (PM) pollution has led to remarkably high demand for face masks. However, conventional respirators are intended for single use ...and made from nondegradable materials, causing serious concern for a plastic‐waste environmental crisis. Furthermore, these facemasks are weakened in humid conditions and difficult to decontaminate. Herein, a reusable, self‐sustaining, highly effective, and humidity‐resistant air filtration membrane with excellent particle‐removal efficiency is reported, based on highly controllable and stable piezoelectric electrospun poly (l‐lactic acid) (PLLA) nanofibers. The PLLA filter possesses a high filtration efficiency (>99% for PM 2.5 and >91% for PM 1.0) while providing a favorable pressure drop (≈91 Pa at normal breathing rate) for human breathing due to the piezoelectric charge naturally activated by respiration through the mask. The filter has a long, stable filtration performance and good humidity resistance, demonstrated by a minimal declination in the filtration performance of the nanofiber membrane after moisture exposure. The PLLA filter is reusable via common sterilization tools (i.e., an ultrasonic cleaning bath, autoclave, or microwave). Moreover, a prototype of a completely biodegradable PLLA nanofiber‐based facemask is fabricated and shown to decompose within 5 weeks in an accelerated degradation environment.
The piezoelectric nanofibers of poly (l‐lactic acid) (PLLA) are employed to fabricate a reusable, moisture‐resistant, and highly effective facemask filter with long‐term biodegradability. The PLLA filter could offer an eco‐friendly solution to preventing the transmission of highly infectious viruses and resolving the environmental crisis caused by the massive use of current permanent plastic facemask filters.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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