Objective. To estimate the current prevalence rates and decadal trends of gout and hyperuricemia in the US, as well as the prevalence of urate-lowering therapy (ULT) among gout patients, using 2007-2016 data from a nationally representative survey of American men and women (the National Health and Nutrition Examination Survey [NHANES]).Methods. Using data from 5,467 participants in the NHANES 2015-2016, we estimated the most recent prevalence rates of gout and hyperuricemia. When the NHANES was conducted, all participants were asked about their history of gout (as diagnosed by a health professional) and medication use. Hyperuricemia was defined as having a serum urate level of >7.0 mg/dl in men and >5.7 mg/dl in women. We examined decadal trends in these estimates using data from the NHANES 2007-2016 and investigated ULT usage trends using the NHANES 2007-14 (the most recent data available to date).Results. In 2015-2016, the prevalence of gout was 3.9% among adults in the US (9.2 million people), with 5.2% [5.9 million] in men and 2.7% [3.3 million] in women. Mean serum urate levels were 6.0 mg/dl in men and 4.8 mg/dl in women, and hyperuricemia prevalence rates were 20.2% and 20.0%, respectively. The prevalence rates of gout and hyperuricemia remained stable between 2007 and 2016 (P for trend > 0.05). The prevalence of ULT use among patients with gout was 33% in 2007-2014 and remained stable over time (P for trend > 0.05).Conclusion. In this nationally representative survey sample of adults in the US, the prevalence rates of gout and hyperuricemia remained substantial, albeit unchanged, between 2007 and 2016. Despite these rates, only one-third of gout patients were receiving ULT.

Objective To examine modifiable risk factors in relation to the presence of hyperuricemia and to estimate the proportion of hyperuricemia cases in the general population that could be prevented by risk factor modification, along with estimates of the variance explained. Methods Using data obtained from 14,624 adults representative of the US civilian noninstitutionalized population, we calculated adjusted prevalence ratios for hyperuricemia, population attributable risks (PARs), and the variance explained according to the following 4 factors: body mass index (BMI; ≥25 kg/m2), alcohol intake, nonadherence to a Dietary Approaches to Stop Hypertension (DASH) diet, and diuretic use. Results BMI, alcohol intake, adherence to a DASH‐style diet, and diuretic use were all associated with serum urate levels and the presence of hyperuricemia in a dose‐dependent manner. The corresponding PARs of hyperuricemia cases for overweight/obesity (prevalence 60%), nonadherence to a DASH‐style diet (prevalence 82%), alcohol use (prevalence 48%), and diuretic use (prevalence 8%) were 44% (95% confidence interval [95% CI] 41%, 48%), 9% (95% CI 3%, 16%), 8% (95% CI 5%, 11%), and 12% (95% CI 11%, 14%), respectively, whereas the corresponding variances explained were 8.9%, 0.1%, 0.5%, and 5.0%. Our simulation study showed the variance nearing 0% as exposure prevalence neared 100%. Conclusion In this nationally representative study, 4 modifiable risk factors (BMI, the DASH diet, alcohol use, and diuretic use) could be used to individually account for a notable proportion of hyperuricemia cases. However, the corresponding serum urate variance explained by these risk factors was very small and paradoxically masked their high prevalences, providing real‐life empirical evidence for its limitations in assessing common risk factors.

Select proteins involved in electrical and chemical neurotransmission are re-coded at the RNA level via the deamination of particular adenosines to inosine by adenosine deaminases acting on RNA (ADARs). It has been hypothesized that this process, termed RNA editing, acts to "fine-tune" neurophysiological properties in animals and potentially downstream behavioral outputs. However, the extreme phenotypes resulting from deletions of adar loci have precluded investigations into the relationship between ADAR levels, target transcripts, and complex behaviors. Here, we engineer Drosophila hypomorphic for ADAR expression using homologous recombination. A substantial reduction in ADAR activity (>80%) leads to altered circadian motor patterns and abnormal male courtship, although surprisingly, general locomotor coordination is spared. The altered phenotypic landscape in our adar hypomorph is paralleled by an unexpected dichotomous response of ADAR target transcripts, i.e. certain adenosines are minimally affected by dramatic ADAR reduction, whereas editing of others is severely curtailed. Furthermore, we use a novel reporter to map RNA editing activity across the nervous system, and we demonstrate that knockdown of editing in fruitless-expressing neurons is sufficient to modify the male courtship song. Our data demonstrate that network-wide temporal and spatial regulation of ADAR activity can tune the complex system of RNA-editing sites and modulate multiple ethologically relevant behavioral modalities.Informational recoding of RNA by the catalytic deamination of adenosine to inosine proceeds through the action of ADARs 3 (1). Long double strand RNA duplexes exhibiting perfect complementarity can be modified extensively by promiscuous ADAR activity. However, mRNAs may also serve as site-specific substrates for ADARs via base pairing interactions that generate short imperfect duplexes that generally include the exon destined for editing and a cis-acting complementary sequence, usually found in a neighboring intron (2, 3). Because inosine is recognized by the translation machinery as guanosine (4), A-to-I editing in mRNAs can lead to the incorporation of amino acids differing from those specified by the literal genome.In Drosophila, the spectrum of ADAR substrates is peculiarly specific, consisting primarily of mRNAs encoding an array of voltage-and ligand-gated ion channels, as well as numerous pre-synaptic proteins involved in exo-and endocytosis of synaptic vesicles (5-8). Similarly, several mammalian ion channels and G-protein-coupled receptors are also subject to RNA editing (2, 7, 9 -11). In light of the ontological class and high sequence conservation of ADAR target genes, RNA editing has been invoked as an essential function in controlling synaptic transmission and neurophysiology. Correspondingly, deletion of the single Drosophila adar locus (dAdar) results in severe adult-stage behavioral abnormalities, including extreme uncoordination, seizures and a complete lack of courtship in dAdar null (dAdar 5g1 ) males (1...

This racially diverse (yet mostly white) cohort study indicates that the risk of hospitalised AASCAR is rare overall, although blacks, Asians and Native Hawaiians/Pacific-Islanders have a substantially higher risk of hospitalised AASCARs, particularly among older women. These data also support the practice of initiating allopurinol at a low dose (eg, ≤100 mg/day).

Purpose of review Although gout's cardinal feature is inflammatory arthritis, it is closely associated with insulin resistance and considered a manifestation of the metabolic syndrome. As such, both gout and hyperuricemia are often associated with major cardiometabolic and renal comorbidities that drive the persistently elevated premature mortality rates among gout patients. To that end, conventional low-purine (i.e., low-protein) dietary advice given to many patients with gout warrant reconsideration. Recent findings Recent research suggests that several healthy diets, such as the Mediterranean or Dietary Approaches to Stop Hypertension (DASH) diets, in combination with weight loss for those who are overweight or obese, can drastically improve cardiometabolic risk factors and outcomes. By treating gout as a part of the metabolic syndrome and shifting our dietary recommendations to these healthy dietary patterns, the beneficial effects on gout endpoints should naturally follow for the majority of typical gout cases, mediated through changes in insulin resistance. Summary Dietary recommendations for the management of hyperuricemia and gout should be approached holistically, taking into consideration its associated cardiometabolic comorbidities. Several healthy dietary patterns, many with similar themes, can be tailored to suit comorbidity profiles and personal preferences.

Weight loss diets may reduce serum urate (SU) by lowering insulin resistance while providing cardiometabolic benefits, something urate-lowering drugs have not shown in trials. We aimed to examine the effects of weight loss diets on SU and cardiometabolic risk factors. RESEARCH DESIGN AND METHODSThis secondary study of the Dietary Intervention Randomized Controlled Trial (DIRECT) used stored samples from 235 participants with moderate obesity randomly assigned to low-fat, restricted-calorie (n 5 85); Mediterranean, restrictedcalorie (n 5 76); or low-carbohydrate, non-restricted-calorie (n 5 74) diets. We examined SU changes at 6 and 24 months overall and among those with hyperuricemia (SU ‡416 mmol/L), a relevant subgroup at risk for gout. RESULTSAmong all participants, average SU decreases were 48 mmol/L at 6 months and 18 mmol/L at 24 months, with no differences between diets (P > 0.05). Body weight, HDL cholesterol (HDL-C), total cholesterol:HDL-C ratio, triglycerides, and insulin concentrations also improved in all three groups (P < 0.05 at 6 months). Adjusting for covariates, changes in weight and fasting plasma insulin concentrations remained associated with SU changes (P < 0.05). SU reductions among those with hyperuricemia were 113, 119, and 143 mmol/L at 6 months for low-fat, Mediterranean, and low-carbohydrate diets (all P for within-group comparison < 0.001; P > 0.05 for between-group comparisons) and 65, 77, and 83 mmol/L, respectively, at 24 months (all P for within-group comparison < 0.01; P > 0.05 for between-group comparisons). CONCLUSIONSNonpurine-focused weight loss diets may simultaneously improve SU and cardiovascular risk factors likely mediated by reducing adiposity and insulin resistance. These dietary options could provide personalized pathways to suit patient comorbidity and preferences for adherence.

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Objective. To determine whether the Dietary Approaches to Stop Hypertension (DASH) diet or an alternative, simplified diet, emphasizing high-fiber fruits and vegetables (the FV diet), lowers serum urate levels.Methods. We conducted a secondary study of the DASH feeding study, a 3-arm, parallel-design, randomized trial of 459 adults with systolic blood pressure (BP) of <160 mm Hg and diastolic BP of 80-95 mm Hg, who were not receiving BP medications. Participants were randomized to receive 8 weeks of monitored feeding and ate 1 of 3 diets: 1) a typical American diet (control), 2) the FV diet, a diet rich in fruits and vegetables but otherwise similar to the control diet, or 3) the DASH diet, which was rich in fruits, vegetables, and low-fat dairy products, and reduced in fat, saturated fat, and cholesterol. Body weight was kept constant throughout the study. Serum urate levels were measured at baseline and after 8 weeks of feeding.Results. For the 327 participants with available specimens (mean ± SD age 45.4 ± 11.0 years, 47% women, 50% African American), the mean ± SD baseline serum urate level was 5.7 ± 1.5 mg/dl. Compared to the control diet, the FV diet reduced the mean serum urate level by 0.17 mg/dl (95% confidence interval [95% CI] −0.34, 0.00; P = 0.051) and the DASH diet reduced the mean serum urate level by 0.25 mg/dl (95% CI −0.43, −0.08; P = 0.004). These effects increased with increasing baseline serum urate levels (<5,