Age-specific differences in non-cardiac comorbidities among elderly patients hospitalized with heart failure: a special focus on young-old, old-old, and oldest-old

Background:Despite the growing epidemic of heart failure(HF),there is limited data available to systematically compare noncardiac comorbidities in the young-old,old-old,and oldest-old patients hospitalized for HF.The precise differences will add valuable information for better management of HF in elderly patients.Methods:A total of 1053 patients aged 65 years or older hospitalized with HF were included in this study.Patients were compared among three age groups:(1)young-old:65 to 74 years,(2)old-old:75 to 84 years,and(3)oldest-old:≥85 years.Clinical details of presentation,comorbidities,and prescribed medications were recorded.Results:The mean age was 76.7 years and 12.7%were 85 years or older.Most elderly patients with HF(97.5%)had at least one of the non-cardiac comorbidities.The patterns of common non-cardiac comorbidities were different between the young-old and oldestold group.The three most common non-cardiac comorbidities were anemia(53.6%),hyperlipidemia(45.9%),and diabetes(42.4%)in the young-old group,while anemia(73.1%),infection(58.2%),and chronic kidney disease(44.0%)in the oldest-old group.Polypharmacy was observed in 93.0%elderly patients with HF.Additionally,29.2%patients were diagnosed with infection,and 67.0%patients were prescribed antibiotics.However,60.4%patients were diagnosed with anemia with only 8.9%of them receiving iron repletion.Conclusions:Non-cardiac comorbidities are nearly universal in three groups but obviously differ by age,and inappropriate medications are very common in elderly patients with HF.Further treatment strategies should be focused on providing optimal medications for age-specific non-cardiac conditions.

Single-cell RNA Sequencing Reveals Thoracolumbar Vertebra Heterogeneity and Rib-genesis in Pigs

Development of thoracolumbar vertebra(TLV)and rib primordium(RP)is a common evolutionary feature across vertebrates,although whole-organism analysis of the expression dynamics of TLV-and RP-related genes has been lacking.Here,we investigated the single-cell transcriptome landscape of thoracic vertebra(TV),lumbar vertebra(LV),and RP cells from a pig embryo at 27 days post-fertilization(dpf)and identified six cell types with distinct gene expression signatures.In-depth dissection of the gene expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and RP development.Further analysis of cell type-specific and strand-specific expression uncovered the extremely high level of HOXA103′-UTR sequence specific to osteoblasts of LV cells,which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition.Thus,this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell type-specific resolution,which serves as a comprehensive view on the transcriptional profile of animal embryo development.

Drosophila Homolog of FMRP Maintains Genome Integrity by Interacting with Piwi

Fragile X syndrome （FraX）, the most common form of inherited mental retardation, is caused by the absence of the evolutionally conserved fragile X mental retardation protein （FMRP）. While neuronal functions of FMRP have been intensively studied for the last two decades, its role in non-neuronal cells remains poorly understood. Piwi, a key component of the Piwi-interacting RNA （piRNA） pathway, plays an essential role in germline development. In the present study, we report that similar to piwi, dfmrl, the Drosophila homolog of human FMR1, is required for transposon suppression in the germlines. Genetic analyses showed that dfmrl and piwi act synergistically in heterochromatic silencing, and in inhibiting the differentiation of primordial germline cells and transposon expression. Northern analyses showed that roo piRNA expression levels are reduced in dfmrl mutant ovaries, suggesting a role of dfmrl in piRNA biogenesis. Biochemical analysis demonstrated a physical interaction between dFMRP and Piwi via their N-termini. Taken together, we propose that dFMRP cooperates with Piwi in maintaining genome integrity by regulating heterochromatic silencing in somatic cells and suppressing transposon activity via the piRNA pathway in germlines.