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Purpose To test for associations between genetic polymorphisms of adrenergic receptors (AR) and other candidate genes and healthcare utilization in heart failure patients, taking into account other important factors, such as medication adherence. Methods One year-hospital utilization data were collected from 140 participants with heart failure, aged 50 years or older. Medication adherence was measured. Hospitalization and emergency department (ED) visits due to heart failure were used as healthcare outcomes. The genotypes of polymorphisms in six genes were determined: α 2C -AR ( ADRA2C ), β 1 -AR ( ADRB1 ), β 2 -AR ( ADRB2 ), endothelial nitric oxide synthase ( eNOS ), angiotensin converting enzyme ( ACE ), and CYP4A11. Haplotypes for ADRB1 and ADRB2 were estimated. The genotype effects on healthcare outcomes were examined using log-linear regression models. Results Compared to ADRB1 Arg389 carriers, homozygous Gly389Gly carriers experienced fewer ED visits [incidence rate ratio (IRR) 0.07, 95 % confidence interval (CI) 0.01–0.54, P  = 0.022]. Compared to ADRB2 homozygous Gly16Gly carriers, Arg16Gly carriers had fewer ED visits (IRR 0.23, 95 % CI 0.09–0.59, P  = 0.006). Polymorphisms in ADRB1 as well as those in ADRB2 were in linkage disequilibrium, with three defining haplotypes, respectively. For ADRB2 , the risk of hospitalizations and ED visits were relatively lower in Arg16/Gln27 carriers but relatively higher in homozygous Gly16/Gln27 carriers ( P  < 0.05). Compared to eNOS 894TT homozygous variants, 894GG and 894GT carriers had notably fewer ED visits (IRR 0.05, 95 % CI 0.01–0.25, P  = 0.0013 and IRR 0.10, 95 % CI 0.02–0.42, P  = 0.006, respectively). The other polymorphisms showed no association with healthcare outcomes. Conclusions After controlling for demographics, functional status, and treatment adherence, polymorphisms in ADRB1 , ADRB2 and eNOS are associated with healthcare outcomes in heart failure patients.

Rifampin is a pleiotropic inducer of multiple drug metabolizing enzymes and transporters. This work utilized a global approach to evaluate rifampin effects on conjugating enzyme gene expression with relevance to human xeno‐ and endo‐biotic metabolism. Primary human hepatocytes from 7 subjects were treated with rifampin (10 μmol/L, 24 hours). Standard methods for RNA‐seq library construction, EZBead preparation, and NextGen sequencing were used to measure UDP‐glucuronosyl transferase UGT, sulfonyltransferase SULT, N acetyltransferase NAT, and glutathione‐S‐transferase GST mRNA expression compared to vehicle control (0.01% MeOH). Rifampin‐induced (>1.25‐fold) mRNA expression of 13 clinically important phase II drug metabolizing genes and repressed (>1.25‐fold) the expression of 3 genes (P < .05). Rifampin‐induced miRNA expression changes correlated with mRNA changes and miRNAs were identified that may modulate conjugating enzyme expression. NAT2 gene expression was most strongly repressed (1.3‐fold) by rifampin while UGT1A4 and UGT1A1 genes were most strongly induced (7.9‐ and 4.8‐fold, respectively). Physiologically based pharmacokinetic modeling (PBPK) was used to simulate the clinical consequences of rifampin induction of CYP3A4‐ and UGT1A4‐mediated midazolam metabolism. Simulations evaluating isolated UGT1A4 induction predicted increased midazolam N‐glucuronide exposure (~4‐fold) with minimal reductions in parent midazolam exposure (~10%). Simulations accounting for simultaneous induction of both CYP3A4 and UGT1A4 predicted a ~10‐fold decrease in parent midazolam exposure with only a ~2‐fold decrease in midazolam N‐glucuronide metabolite exposure. These data reveal differential effects of rifampin on the human conjugating enzyme transcriptome and potential associations with miRNAs that form the basis for future mechanistic studies to elucidate the interplay of conjugating enzyme regulatory elements.

Isolated foot anomalies, including congenital vertical talus, were shown recently to occur in heterozygous carriers of CDMP-1 (cartilage-derived morphogenetic protein-1) gene mutations. Six families with isolated congenital vertical talus with apparent autosomal dominant inheritance were ascertained. DNA was isolated from 17 affected individuals and 24 unaffected individuals from these families and subjected to mutational analysis of the CDMP-1 gene. A missense mutation was identified (1312C>T) that results in an R438C substitution in the CDMP-1 active domain. This segregated with disease in one Northeren American family. Phenotypic variability in this family includes brachydactyly type C, clinodactyly, calcaneo valgus deformity, and congenital vertical talus. Metacarpophalangeal profiles (MCPPs) confirm incomplete penetrance in one family member. Hence, CDMP-1 mutations may be found in individuals with apparently isolated CVT, although careful examination of family members may reveal additional, subtle hand and foot abnormalities. However, mutations in CDMP-1 do not appear to be a frequent cause of isolated congenital vertical talus.

Identity defines who and what a people consider themselves to be at a specific time. In most cases, identity is “invented” since the delineating boundaries that define a people or community are formed and reshaped from historical “identifiers” selected from the past. How far back in history a community or people will choose to go to begin to define themselves is what makes identity an evolving characteristic in any society. This study argues that in the Dominican Republic the defined boundaries for that nation's identity have been rigidly based on the racial myths and symbols introduced by the Spanish during the colonial period. Historically, Dominicans have formed and reshaped their identity to reinforce Hispanic cultural and racial values that have consistently rejected contributions from their African ancestry. After 1844, when the Republic declared its independence after a bloody struggle with Haiti, the relationship between Haiti and the Dominican Republic remained contentious. Nevertheless, despite the bitterness that evolved between the two nations, Dominican identity is not the result of the historical tensions between the two nations, but an expression of the professed racial superiority of Dominicans over Haitians based on historical Spanish racial paradigms. Haiti, with its African heritage has evolved into a visual representation for Dominicans on whom Dominicans can displace their anti-African, anti-Black, racial sentiment thereby reinforcing traditional colonial racial and social constructs. Historically, Dominicans have reminded themselves and been told by outsiders of their African heritage. This has not only reinforced Dominicans concerns of being “uncivilized” but also promoted policies that encouraged white immigration. Annexation of the island by Spain, and later statehood efforts by the United States, reveal Dominican efforts to preserve not just a Hispanic identity, but also the desire to whiten the Republic's growing Black population. Perceptions of being an “uncivilized” nation because of their race also motivated Dominicans to erase their Blackness. They replaced it with images and symbols, still used today, based on the extinct Indigenous population of the island that helps preserve the racial categorization introduced by the Spanish.