Livelihood Experiences and Adherence to HIV Antiretroviral Therapy among Participants in a Food Assistance Pilot in Bolivia: A Qualitative Study

Introduction

Health and development organizations increasingly promote livelihood interventions to improve health and economic outcomes for people living with HIV (PLHIV) receiving treatment with antiretroviral therapy (ART). In-depth understanding about how PLHIV make labor decisions in the context of treatment for HIV – and treatment decisions in the context of their livelihoods – is essential to guiding intervention design and developing hypotheses for future research on livelihoods and ART. However, few studies have explored the perspectives of PLHIV regarding integration of livelihoods and ART in urban, resource-limited settings.

Methods

Qualitative interviews explored the livelihood experiences of food insecure ART patients in four Bolivian cities (n = 211). Topics included work-related barriers to ART adherence, HIV-related barriers to work, and economic coping mechanisms. Themes were identified using content coding procedures, with two coders to maximize reliability.

Results

Participants reported complex economic lives often characterized by multiple economic activities, including both formal and informal labor. They struggled to manage ART treatment and livelihoods simultaneously, and faced a range of interpersonal and structural barriers. In particular, lack of HIV status disclosure, stigma, and discrimination were highly salient issues for study participants and likely to be unique to people with HIV, leading to conflict around requesting time off for clinic visits, resentment from co-workers about time off, and difficulties adhering to medication schedules. In addition, health system issues such as limited clinic hours or drug shortages exacerbated the struggle to balance economic activities with HIV treatment adherence.

Conclusions

Improved policy-level efforts to enforce existing anti-discrimination laws, reduce HIV-related stigma, and expand health services accessibility could mitigate many of the barriers discussed by our participants, improve adherence, and reduce the need for livelihoods interventions.     

A Vaccine against CCR5 Protects a Subset of Macaques upon Intravaginal Challenge with Simian Immunodeficiency Virus SIVmac251

As an alternative to targeting human immunodeficiency virus (HIV), we have developed vaccines targeting CCR5, a self-protein critically involved in HIV replication and pathogenesis. By displaying peptides derived from CCR5 at high density on the surface of virus-like particles, we can efficiently induce high-titer IgG antibodies against this self-molecule. Here, we investigated whether prophylactic immunization of rhesus macaques with a particle-based vaccine targeting two regions of macaque CCR5 could prevent or suppress vaginal infection with highly virulent SIVmac251. Twelve macaques were vaccinated with a bacteriophage Qß-based vaccine targeting macaque CCR5 (Qß.CCR5). Six control animals were immunized with the Qß platform alone. All animals immunized with Qß.CCR5 developed high-titer anti-CCR5 antibody responses. Macaques were vaginally challenged with a high dose of SIVmac251. The mean peak viral RNA levels in the vaccinated groups were 30-fold lower than in the control group (10^6.8 versus 10^8.3 copies/ml plasma). Three of the 12 vaccinated macaques dramatically suppressed simian immunodeficiency virus (SIV) replication: peak viral loads were low (10³ to 10⁴ RNA copies/ml), and SIV RNA became undetectable from 6 weeks onward. No viral RNA or DNA could be detected in colon and lymph node biopsy specimens collected 13 months after challenge. In vivo depletion of CD8⁺ cells failed to induce a viral rebound. However, once anti-CCR5 antibody responses had waned, the 3 animals became infected after intravaginal and/or intravenous rechallenge. In conclusion, vaccination against CCR5 was associated with dramatic suppression of virus replication in a subset (25%) of macaques. These data support further research of vaccination against CCR5 to combat HIV infection.     

Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development—Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus

Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS) was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA) 26 (p = 2.8 x 10⁻⁸). Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility.     

Magnetic characterizations of nickel hyperaccumulating plants (Planchonella oxyhedra and Rinorea bengalensis) from Halmahera,Indonesia

Magnetic minerals, such as magnetite and hematite, have been reported to be present, in particular, leaves as biogenic particles. The magnetic minerals and properties of Ni hyperaccumulators have not previously been reported in the literature. This study aimed to characterize the magnetic properties of two Ni hyperaccumulating plant species, R. bengalensis and P. oxyhedra, which grow in an ultramafic region on Halmahera Island, Indonesia. For comparison, similar characterization was carried out on two non-hyperaccumulating plant species which grow in the same region. Concentrations of Ni, Fe, and Mn in the leaves of the hyperaccumulating plants were measured using atomic absorption spectroscopy (AAS) and their magnetic properties were characterized using measurements of magnetic susceptibility, low temperature magnetic susceptibility, and hysteresis curves. The results show that, compared to the non-hyperaccumulating plants, the Ni hyperaccumulating plants have higher concentrations of Ni and similar concentration of Fe. The magnetic susceptibilities of hyperaccumulating plants are positive, and those of non-hyperaccumulating plants are negative. This suggests that the abundance of Ni, rather than Fe, may control the magnetic properties of Ni hyperaccumulating plants. This probable connection between Ni concentration and plant magnetic properties could be advantageous for identifying hyperaccumulators, and should, therefore, be explored further.     

Metabarcoding of PalEnDNA as An Efficient Tool to Recover Ancient Bacterial Diversity

Past bacterial diversity of a paleosol was reconstructed using metabarcoding of paleo environmental DNA (PalEnDNA). The paleosol was subsampled from a sediment core which was excavated from a palaeo beach-ridge located 2.6?km away from present sea shore and identified that it was deposited under marine influence ～6000?years ago, using geological proxies. The bacterial community contained 37 bacterial phyla and dominated by Proteobacteria, followed by Bacteroidetes, Firmicutes, Actinobacteria, Verrucomicrobia, and Chloroflexi. The bacterial community was a mix-up of marine and terrestrial population, and thereby diversity was higher than marine populations. The result shows metabarcoding of PalEnDNA can effectively reconstruct past bacterial community structure.     

Ovitrap surveillance of dengue vector mosquitoes in Bandung City,West Java Province,Indonesia

Larval surveillance is the central approach for monitoring dengue vector populations in Indonesia. However, traditional larval indices are ineffective for measuring mosquito population dynamics and predicting the dengue transmission risk. We conducted a 14-month ovitrap surveillance. Eggs and immature mosquitoes were collected on a weekly basis from an urban village of Bandung, namely Sekejati. Ovitrap-related indices, namely positive house index (PHI), ovitrap index (OI), and ovitrap density index (ODI), were generated and correlated with environmental variables, housing type (terraced or high-density housing), ovitrap placement location (indoor or outdoor; household or public place), and local dengue cases. Our results demonstrated that Aedes aegypti was significantly predominant compared with Aedes albopictus at each housing type and ovitrap placement location. Ovitrap placement locations and rainfall were the major factors contributing to variations in PHI, OI, and ODI, whereas the influences of housing type and temperature were subtle. Indoor site values were significantly positively correlated to outdoor sites’ values for both OI and ODI. OI and ODI values from households were best predicted with those from public places at 1- and 0-week lags, respectively. Weekly rainfall values at 4- and 3-week lags were the best predictors of OI and ODI for households and public places, respectively. Monthly mean PHI, OI, and ODI were significantly associated with local dengue cases. In conclusion, ovitrap may be an effective tool for monitoring the population dynamics of Aedes mosquitoes, predicting dengue outbreaks, and serving as an early indicator to initiate environmental clean-up. Ovitrap surveillance is easy for surveyors if they are tasked with a certain number of ovitraps at a designated area, unlike the existing larval surveillance methodology, which entails identifying potential breeding sites largely at the surveyors’ discretion. Ovitrap surveillance may reduce the influence of individual effort in larval surveillance that likely causes inconsistency in results.     

Correlation of C4ST-1 and ChGn-2 expression with chondroitin sulfate chain elongation in atherosclerosis

Mxi1, a member of the Myc–Max–Mad network, is an antagonist of the c-Myc oncogene and is associated with excessive cell proliferation. Abnormal cell proliferation and tumorigenesis are observed in organs of Mxi1−/− mice. However, the Mxi1-reltaed mechanism of proliferation is unclear. The present study utilized microarray analysis using Mxi1 mouse embryonic fibroblasts (MEFs) to identify genes associated with cell proliferation. Among these genes, insulin-like growth factor binding protein-3 (IGFBP-3) was selected as a candidate gene for real-time PCR to ascertain whether IGFBP-3 expression is regulated by Mxi1. Expression of IGFBP-3 was decreased in Mxi1−/− MEFs and Mxi1−/− mice, and the gene was regulated by Mxi1 in Mxi1 MEFs. Furthermore, proliferation pathways related to IGFBP-3 were regulated in Mxi1−/− mice compared to Mxi1+/+ mice. To determine the effect of Mxi1 inactivation on the induction of cell proliferation, a proliferation assay is performed in both Mxi1 MEFs and Mxi1 mice. Cell viability was regulated by Mxi1 in Mxi1 MEFs and number of PCNA-positive cells was increased in Mxi1−/− mice compared to Mxi1+/+ mice. Moreover, the IGFBP-3 level was decreased in proliferation defect regions in Mxi1−/− mice. The results support the suggestion that inactivation of Mxi1 has a positive effect on cell proliferation by down-regulating IGFBP-3.     

The Relevance of Circular Economy Practices to the Sustainable Development Goals

This paper identifies the extent to which circular economy (CE) practices are relevant for the implementation of the Sustainable Development Goals (SDGs). The results of a literature review and a matching exercise to determine the relationship between CE practices and SDG targets show that CE practices, potentially, can contribute directly to achieving a significant number of SDG targets. The strongest relationships exist between CE practices and the targets of SDG 6 (Clean Water and Sanitation), SDG 7 (Affordable and Clean Energy), SDG 8 (Decent Work and Economic Growth), SDG 12 (Responsible Consumption and Production), and SDG 15 (Life on Land). The paper also explores synergies that can be created through CE practices among several of the SDG targets. Furthermore, it identifies several potential trade‐offs between targets for decent work, safe working environments, human health and current CE practices relating to recycling of municipal waste, e‐waste and wastewater, and provides suggestions how these can be overcome. The paper concludes that CE practices can be applied as a “toolbox” and specific implementation approaches for achieving a sizeable number of SDG targets. Further empirical research is necessary to determine which specific types of partnerships and means of implementation are required to apply CE practices in the SDG context.     

Protective roles of cytoplasmic p21Cip1 /Waf1 in senolysis and ferroptosis of lung cancer cells

ObjectiveTherapy‐induced senescent cancer cells increase the expression of the cyclin‐dependent kinase inhibitors p16^Ink4a and p21^Cip1/Waf1. Given that p21 regulates not only the cell cycle but also cell death, we investigated the roles of p21 in cell death using a p16‐negative A549 human lung adenocarcinoma cell line.MethodsSenescence was induced by doxorubicin (DXR) or pemetrexed (PEM). The protein expression of p21 was examined by immunoblot. Cell death, reactive oxygen species (ROS) and lipid peroxidation were determined by flow cytometry. ABT‐263 and ABT‐737 were used as senolytic drugs. In vivo growth of A549 cells with different levels of p21 and their sensitivity to PEM were examined in xenograft models.ResultsDXR‐induced senescent A549 cells increased the expression of cytoplasmic p21, and the sensitivity to ABT‐263 was augmented in p21‐knockout A549 (A549‐KOp21) cells. A similar senolytic effect was observed when PEM was combined with ABT‐737. PEM alone induced a higher level of non‐apoptotic cell death, ferroptosis, in A549‐KOp21 cells than in A549 cells. Although there was no difference in the level of lipid peroxidation, ROS levels were higher in PEM‐treated A549‐KOp21 cells than in PEM‐treated A549 cells. A loss of p21 increased the sensitivity of A549 cells to PEM both in vitro and in vivo. A clinical database analysis showed that CDKN1A ^high lung adenocarcinoma patients had a poorer prognosis compared to CDKN1A ^low patients.ConclusionCytoplasmic p21, which was increased in therapy‐induced senescent lung cancer cells, plays protective roles in senolysis and ferroptosis.

Doxorubicin or pemetrexed could induce senescence in p21‐expressing parental A549 cells and increase the expression of cytoplasmic p21. However, such drug‐induced senescent A549 cells were relatively resistant to apoptosis by senolytic drugs. By contrast, p21‐knockout A549 (A549‐KOp21) cells increased their sensitivity to senolytic drugs. On the other hand, pemetrexed induced a higher level of non‐apoptotic cell death, ferroptosis, in A549‐KOp21 cells than in A549 cells. These findings highlight the protective roles of cytoplasmic p21 against senolysis and ferroptosis in therapy‐induced senescent lung cancer cells.