RESUMEN
OBJECTIVE: Our study describes the 2014 Chikungunya outbreak in Western Jamaica in terms of geographic distribution and trend of the outbreak over time, and evaluates clinical symptoms of the disease based on pre-existing conditions. METHODS: We conducted a retrospective, cross-sectional study of 609 clinically defined Chikungunya virus (CHIKV) fever cases that occurred in the four parishes of the Western Regional Health Authority of Jamaica from July 2014 to December 2014. Cases were not confirmed by laboratory tests but met clinical and epidemiological criteria of CHIKV fever. RESULTS: Our results show a propagated spread of CHIKV fever during the outbreak period with the peak at the end of October. Main urban cities, such as Montego Bay and Lucea, were identified as places that had high numbers of cases. Fever and arthralgia were the two most common clinical symptoms in CHIKV patients. Although a majority (80%) of infants aged <2 years had up to four symptoms (80%), the percentage of infants with higher numbers of symptoms (9-10) was higher than in older age groups. However, back pain was found to occur significantly more in older patients. Those with arthritis as a pre-existing condition were more likely to experience headache, asthenia, back pain, and periarticular edema. CONCLUSION: These findings can help public health officials develop more effective programs to prevent the spread of CHIKV outbreaks by focusing on crowded urban cities. The findings indicate that those who are likely to develop a higher number of symptoms, such as young infants and people with pre-existing conditions, such as arthritis, should be more closely monitored to better manage the disease outcome.
RESUMEN
The recognition of ß cell dedifferentiation in type 2 diabetes raises the translational relevance of mechanisms that direct and maintain ß cell identity. LIM domain-binding protein 1 (LDB1) nucleates multimeric transcriptional complexes and establishes promoter-enhancer looping, thereby directing fate assignment and maturation of progenitor populations. Many terminally differentiated endocrine cell types, however, remain enriched for LDB1, but its role is unknown. Here, we have demonstrated a requirement for LDB1 in maintaining the terminally differentiated status of pancreatic ß cells. Inducible ablation of LDB1 in mature ß cells impaired insulin secretion and glucose homeostasis. Transcriptomic analysis of LDB1-depleted ß cells revealed the collapse of the terminally differentiated gene program, indicated by a loss of ß cell identity genes and induction of the endocrine progenitor factor neurogenin 3 (NEUROG3). Lineage tracing confirmed that LDB1-depleted, insulin-negative ß cells express NEUROG3 but do not adopt alternate endocrine cell fates. In primary mouse islets, LDB1 and its LIM homeodomain-binding partner islet 1 (ISL1) were coenriched at chromatin sites occupied by pancreatic and duodenal homeobox 1 (PDX1), NK6 homeobox 1 (NKX6.1), forkhead box A2 (FOXA2), and NK2 homeobox 2 (NKX2.2) - factors that co-occupy active enhancers in 3D chromatin domains in human islets. Indeed, LDB1 was enriched at active enhancers in human islets. Thus, LDB1 maintains the terminally differentiated state of ß cells and is a component of active enhancers in both murine and human islets.