Development of the Longitudinal Study of Health and Ageing in Kenya (LOSHAK).

In Kenya, the number of adults aged ≥60 is expected to nearly quadruple by 2050, making it one of the most rapidly aging countries in Sub-Saharan Africa (SSA). Accordingly, we designed the Longitudinal Study of Health and Ageing in Kenya (LOSHAK) to generate novel data to address the health and economic consequences of this demographic transition. Specifically, LOSHAK will investigate the social, economic, environmental, biological, and policy processes that shape late-life health and economic well-being in Kenya. Modeled on the U.S. Health and Retirement Study (HRS), LOSHAK joins a network of harmonized studies on aging in >45 countries worldwide; however, LOSHAK will be only the 2nd such study in SSA. The current feasibility and pilot phase of LOSHAK will validate measures and data collection procedures in a purposive sample of Kenyan adults aged ≥45 years. We have linguistically and culturally translated instruments while aiming to maintain harmonization with both existing HRS network studies and the ongoing Kenya Life Panel Survey. The current phase of LOSHAK is nested within the Kaloleni/Rabai Community Health and Demographic Surveillance System on the coast of Kenya. LOSHAK will advance population aging research in low- and middle-income countries through the study of (a) biomarkers and physiological measures; (b) the impacts of air pollution and climate vulnerability; (c) Alzheimer's disease and related dementias, mental health, disability, caregiving, and psychosocial wellbeing; and (d) economic security, including the impact of social welfare. LOSHAK will inform future public health and economic policy to address challenges related to rapid aging in Kenya and throughout SSA. Accordingly, this paper aims to introduce and provide a description of LOSHAK and its aims and objectives, as well as to inform the scientific community of current study activities being used to build toward the full population-representative study.

MicroRNAs sequencing unveils distinct molecular subgroups of plasmablastic lymphoma.

Plasmablastic lymphoma (PBL) is an aggressive lymphoma, often arising in the context of immunodeficiency and associated with Epstein-Barr virus (EBV) infection. The most frequently detected genetic alteration is the deregulation of MYC gene through the translocation - t(8;14)(q24;q32). The diagnosis of PBL is often challenging because it has an overlap in morphology, immunophenotype, cytogenetics and virus association with other lymphomas and plasma cell neoplasms; further, its molecular basis remains elusive. In the present study we aimed to better define the possible contribution of EBV infection as well as miRNA deregulation in PBL pathogenesis. We studied 23 cases of PBL, 19 Burkitt lymphomas (BL), and 17 extra-medullary plasmacytoma (EMPC). We used qPCR and immunohistochemistry to assess EBV latency patterns, while micro-RNA (miRNA) profiling was performed by next generation sequencing (Illumina) and validated by qPCR. Our analysis revealed a non-canonical EBV latency program with the partial expression of some proteins characterizing latency II and the activation of an abortive lytic cycle. Moreover, we identified miRNA signatures discriminating PBL from BL and EMPC. Interestingly, based on the miRNA profile, PBL appeared constituted by two discrete subgroups more similar to either BL or EMPC, respectively. This pattern was confirmed in an independent set of cases studied by qPCR and corresponded to different clinico-pathological features in the two groups, including HIV infection, MYC rearrangement and disease localization. In conclusion, we uncovered for the first time 1) an atypical EBV latency program in PBL; 2) a miRNA signature distinguishing PBL from the closest malignant counterparts; 3) the molecular basis of PBL heterogeneity.

Alteration of microRNAs regulated by c-Myc in Burkitt lymphoma.

BACKGROUND: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, with a characteristic clinical presentation, morphology and immunophenotype. Over the past years, the typical translocation t(8;14) and its variants have been considered the molecular hallmark of this tumor. However, BL cases with no detectable MYC rearrangement have been identified. Intriguingly, these cases express MYC at levels comparable with cases carrying the translocation. In normal cells c-Myc expression is tightly regulated through a complex feedback loop mechanism. In cancer, MYC is often dysregulated, commonly due to genomic abnormalities. It has recently emerged that this phenomenon may rely on an alteration of post-transcriptional regulation mediated by microRNAs (miRNAs), whose functional alterations are associated with neoplastic transformation. It is also emerging that c-Myc modulates miRNA expression, revealing an intriguing crosstalk between c-Myc and miRNAs. PRINCIPAL FINDINGS: Here, we investigated the expression of miRNAs possibly regulated by c-Myc in BL cases positive or negative for the translocation. A common trend of miRNA expression, with the exception of hsa-miR-9*, was observed in all of the cases. Intriguingly, down-regulation of this miRNA seems to specifically identify a particular subset of BL cases, lacking MYC translocation. Here, we provided evidence that hsa-miR-9-1 gene is heavily methylated in those cases. Finally, we showed that hsa-miR-9* is able to modulate E2F1 and c-Myc expression. CONCLUSIONS: Particularly, this study identifies hsa-miR-9* as potentially relevant for malignant transformation in BL cases with no detectable MYC translocation. Deregulation of hsa-miR-9* may therefore be useful as a diagnostic tool, suggesting it as a promising novel candidate for tumor cell marker.

Geographic variation and environmental conditions as cofactors in Chlamydia psittaci association with ocular adnexal lymphomas: a comparison between Italian and African samples.

A particular extra-nodal lymphoma type arises from B cells of the marginal zone (MZ) of mucosa-associated lymphoid tissue (MALT). The aetiology of MZ lymphomas suggests that they are associated with chronic antigenic stimulation by microbial pathogens, among which Helicobacter pylori-associated gastric MALT lymphoma is the best studied. Recently, MALT lymphomas have been described in the context of chronic conjunctivitis, which can be associated with Chlamydia spp. infection. Studies from Italy showed the presence of Chlamydia psittaci in 87% of ocular adnexal lymphomas (OAL), and C. psittaci has been described in a large part of samples from Austria and Korea as well. However, this finding was not always confirmed by other studies, suggesting that the association with C. psittaci may depend on geographic heterogeneity. Interestingly, none of the studies up to now has been carried out in the African population, where a strong association between infectious agents and the occurrence of human neoplasms has been reported. This study was designed to investigate the possible association of Chlamydia psittaci in cases retrieved from Kenya, compared to cases from Italy. Our results showed that there was a marked variation between the two geographical areas in terms of association with C. psittaci, as 17% (5/30) of the samples from Italy were positive for C. psittaci, whereas no association with this pathogen was observed in any of the African samples (0/9), suggesting that other cofactors may determine the OAL occurrence in those areas. OAL cases are often characterized by down-regulation of p16/INK4a expression and promoter hypermethylation of the p16/INK4a gene. Our results showed a partial methylation of p16/INK4a promoter in C. psittaci-negative cases, whereas no hypermethylation of this gene was found in C. psittaci-positive cases, suggesting that mechanisms other than promoter hypermethylation lead to p16/INK4a silencing in C. psittaci-positive cases. We may conclude that the role of epidemiologic, environmental and genetic factors, must be considered in the aetiology of this disease.