Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Re-evaluating human MTL in working memory: insights from intracranial recordings.

The study of human working memory (WM) holds significant importance in neuroscience; yet, exploring the role of the medial temporal lobe (MTL) in WM has been limited by the technological constraints of noninvasive methods. Recent advancements in human intracranial neural recordings have indicated the involvement of the MTL in WM processes. These recordings show that different regions of the MTL are involved in distinct aspects of WM processing and also dynamically interact with each other and the broader brain network. These findings support incorporating the MTL into models of the neural basis of WM. This integration can better reflect the complex neural mechanisms underlying WM and enhance our understanding of WM's flexibility, adaptability, and precision.

Construction of a nomogram for early diagnosis of refractory Mycoplasma pneumoniae pneumonia in children.

Background: Refractory Mycoplasma pneumoniae pneumonia (RMPP) has a serious, rapid progression that can easily cause a variety of extra-pulmonary complications. Therefore, the early identification of RMPP is crucial. This study aimed to construct and validate a risk prediction model based on clinical manifestations, laboratory blood indicators, and radiological findings to help clinicians identify patients who are at high risk of RMPP. Methods: We retrospectively analyzed the medical records of 369 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to Xi'an Children's Hospital, China. The demographics, clinical features, laboratory data, and radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and subjected to univariate and multivariate logistic regression analyses. Results: The fever peak and duration of the children in the RMPP group (n=86) were higher and longer compared with those in the GMPP group (n=283) (P<0.05). There was a significant difference in the incidence of lobar pneumonia and pleural effusion in pulmonary imaging between the two groups (P<0.05). Laboratory tests showed that the children with RMPP had lower serum uric acid (SUA) and albumin (ALB) as compared with the GMPP group (P<0.05). White blood cells (WBCs), neutrophil count (NEP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were higher in the RMPP group (P<0.05). Binary logistic regression analysis showed that the fever duration, pleural effusion, WBC, NEP, lactate dehydrogenase (LDH), CRP, NLR, and SUA levels were independent predictors of RMPP (P<0.05). The receiver operator characteristic (ROC) curve results showed fever duration, WBC, NEP, CRP, LDH, SUA, and NLR had good predictive value. The areas under the curve (AUCs) were 0.861, 0.730, 0.758, 0.837, 0.868, 0.744, and 0.713 and the best cutoff values were 10.50, 10.13, 6.43, 29.45, 370.50, 170.50, and 3.47, respectively. Finally, fever duration of more than 10.5 days, pleural effusion, WBC >10.13×109/L, NEP >6.43×109/L, CRP >29.45 mg/L, LDH >370.50 U/L, NLR >3.47, and SUA <170.5 µmol/mL constructed a prediction model of RMPP. According to internal validation, the mean AUC of the nomogram based on the development dataset was 0.956 [95% confidence interval (CI): 0.937-0.974] with good discrimination ability for predicting RMPP patients. The calibration plot and Hosmer-Lemeshow test (P=0.70) of the prediction model showed good consistency between the predicted probability and actual probability. Decision curve analysis (DCA) showed that the nomogram is clinically useful. Conclusions: The simple and easy-to-use nomogram can help clinicians, especially primary doctors, to make early diagnoses of RMPP.

Association between oxidative balance score and serum uric acid and hyperuricemia: a population-based study from the NHANES (2011-2018).

Background: Oxidative Balance Score (OBS) is a novel indicator of the overall antioxidant/oxidant balance, providing a comprehensive reflection of the body's overall oxidative stress status, with higher OBS suggesting more substantial antioxidant exposures. We aimed to investigate the possible relationship between OBS with serum uric acid (SUA) and hyperuricemia. Methods: Data utilized in this study were sourced from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). Participants under 18 years old, those with ≤16 complete data out of 20 OBS components, incomplete serum uric acid data, and missing covariates were excluded from the analysis. OBS was computed by evaluating 16 nutrients and 4 lifestyle factors, encompassing 5 pro-oxidants and 15 antioxidants, guided by a priori knowledge of their relationship with oxidative stress. Results: A total of 1,5096 individuals were included in our analysis with 49.7% being male, and an average age of 49.05 ± 17.56 years. The mean OBS was 19.76 ± 7.17. Hyperuricemia was present in 19.28% of participants. Due to the right-skewed distribution of the OBS, a natural log transformation was applied to address this issue, and Quartiles of lnOBS 1, 2, 3, and 4 were 1.10-2.56 (N=3526), 2.64-2.94 (N=3748), 3.00-3.22 (N=4026), and 3.26-3.61 (N=3796), respectively. Multivariable logistic regression showed that higher lnOBS quantiles were correlated with lower serum uric acid levels. Compared with the lowest lnOBS quantile, participants in the highest lnOBS quantile had a significant serum uric acid decrease of 16.94 µmol/L for each unit increase in lnOBS (ß=-16.94, 95% CI: -20.44, -13.45). Similar negative associations were observed in the second-highest (ß=-8.07, 95% CI: -11.45, -4.69) and third-highest (ß=-11.69, 95% CI: -15.05, -8.34) lnOBS quantiles. The adjusted odds ratios (ORs) for hyperuricemia in Quartiles 1, 2, 3, and 4 were 1.00, 0.84 (95% CI: 0.75, 0.95), 0.78 (95% CI: 0.69, 0.88), and 0.62 (95% CI: 0.55, 0.71), respectively. Compared to Quartile 1, participants in Quartile 4 had a 38% lower prevalence of hyperuricemia. Subgroup analysis and interaction test showed that there was a significant dependence of sex between OBS and serum uric acid (p for interaction <0.05), but not hyperuricemia (p for interaction >0.05). Subgroup analysis stratified by age, BMI, hypertension, diabetes, and hyperlipidemia showed there is no significant dependence on these negative correlations (all p for interaction >0.05). Conclusions: The serum uric acid levels and prevalence of hyperuricemia in US adults exhibited a negative association with OBS. By exploring this connection, our research aims to gain a better understanding of how oxidative balance affects the prevalence of hyperuricemia. This could provide valuable insights for developing preventive strategies and interventions for hyperuricemia. Additional large-scale prospective studies are required to explore the role of OBS in hyperuricemia further.

Association between the serum uric acid/serum creatinine ratio and cognitive function in older adults: NHANES in the United States.

Cognitive impairment can potentially become a significant health concern in older adults. However, early effective diagnostic methods are still lacking. Therefore, we utilized the NHANES database in the US to investigate the relationship between serum uric acid to serum creatinine (SUA/SCR) ratio and cognitive impairment. In our study, a total of 3874 participants were included (2001-2002, 2011-2014). Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the SUA/SCR and cognitive impairment. In this study, the SUA/SCR was significantly lower in individuals with cognitive impairment. The logistic regression model, after adjusting for all covariates, revealed that the Q2-Q4 were 0.65 (95% CI 0.49, 0.86), 0.60 (95% CI 0.40, 0.90), 0.55 (95% CI 0.39, 0.77) respectively. This indicates that participants in the Q4 had a 45% reduced risk of cognitive impairment. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between SUA/SCR and cognitive impairment, with a turning point at 4.13. Subgroup analysis showed no statistically significant differences in the relationship between SUA/SCR and cognitive impairment among different subgroups (P > 0.05). Our findings indicate a negative correlation between the SUA/SCR and the risk of cognitive impairment in the population of adults aged 60 and above in the US. This suggests that the SUA/SCR holds promise as a potential indicator for cognitive impairment.

Benefits of uric acid-lowering medication after bariatric surgery in patients with gout.

BACKGROUND/PURPOSE: Patients with gout are at risk for increased serum uric acid (SUA) levels and gout attacks in the short term after undergoing bariatric surgery, and the purpose of this study was to evaluate the benefits of short-term treatment with uric acid-lowering medication after bariatric surgery for the control of gout attacks and SUA levels in patients with gout. METHODS: 71 patients who underwent SG from January 2020 to December 2022 were prospectively included. These patients were diagnosed with hyperuricemia before surgery and had a history of gout attacks. Patients were classified into a drug-treatment group (DTG, n = 32) and a non-drug-treatment group (NDTG, n = 39) according to whether they took uric acid-lowering medication after surgery. Changes in the number of gout attacks, body mass index (BMI), and SUA levels at 1 week, 1 month, 3 months, and 6 months after bariatric surgery were measured in both groups. RESULTS: In the DTG, 22 patients (68.8%) experienced an increase in SUA within 1 week, 3 patients (9.4%) had an acute attack of gout within the first month, and no patients had a gout attack thereafter. In the NDTG, 35 patients (89.7%) experienced an increase in SUA within 1 week, 7 patients (17.9%) had an acute gout attack within the first month, and 4 patients (10.3%) experienced gout attacks between month 1 and month 3 postoperatively. Both groups were free of gout attacks between the 3rd and 6th postoperative month and showed a significant decrease in SUA and BMI by the sixth month. CONCLUSION: In patients with gout, continued use of uric acid-lowering medication after bariatric surgery is beneficial in reducing the number of gout attacks and the risk of rising SUA.

Association between the serum uric acid levels and prostate cancer: evidence from National Health and Nutrition Examination Survey (NHANES) 1999-2010.

Background: Uric acid may play a critical role in protection against cancer by the suppression of inflammation. The association between serum uric acid (SUA) levels and prostate cancer risk is debatable yet has received little attention in the American population. Therefore, we used data from the National Health and Nutrition Examination Survey (NHANES) to determine their correlation. Methods: Using information from NHANES 1999-2010, a total of 62,160 individuals from the general population were included in this cross-sectional study. Additionally, a number of covariates were acquired. Prostate cancer was used to divide the participants into two groups: prostate cancer group (n=315) and non-prostate cancer group (n=7,545). A weighted adjusted logistic regression analysis was conducted to examine the potential correlation between SUA and prostate cancer. Results: Our study comprised a total of 7,860 participants. After full adjustment for confounders, SUA was not significantly associated with prostate cancer [odds ratio (OR) 0.91, 95% confidence interval (CI): 0.82-1.00, P=0.058]. In participants aged 60 years and above (≥60 years), a higher SUA was significantly associated with a lower risk of prostate cancer (OR 0.88, 95% CI: 0.80-0.96, P=0.003). However, among those younger than 60 years (<60 years), there was no association between SUA and prostate cancer risk (OR 1.29, 95% CI: 0.69-2.42, P=0.42). In addition, in the subgroup analysis stratified by body mass index, hypertension and diabetes, there was no significant correlation between SUA and prostate cancer. Conclusions: SUA is negatively associated with the risk of prostate cancer in older men, especially for those 60 years of age and beyond.

Association of serum uric acid with all-cause and cardiovascular mortality in chronic kidney disease stages 3-5.

BACKGROUND AND AIMS: The role of serum uric acid (SUA) in the prognosis of chronic kidney disease (CKD) is inconclusive. To explore the association of SUA level with all-cause and cardiovascular disease (CVD) mortality in patients with CKD. METHODS AND RESULTS: Leveraging data from the National Health and Nutritional Examination Survey (NHANES) and linked national death records up to December 31 2019, we explored the association of SUA with all-cause and CVD mortality using weighted cox proportional hazards regression models and restricted cubic spline (RCS) models in patients with CKD stages 3-5. The study finally included 2644 patients with CKD stages 3-5, with a median SUA level of 6.5 mg/dL. After a median follow-up of 55 months, a total of 763 deaths were recorded, with 279 of them attributed to CVD. In the fully adjusted model, per 1 mg/dL increment in SUA concentration was found to be associated with increased HRs (95% CIs) of 1.07 (1.00, 1.14) for all-cause mortality and 1.11 (1.00, 1.24) for CVD mortality. Compared to Q2 (reference), those in Q4 had adjusted HRs of 1.72 (1.36, 2.17) for all-cause mortality and 2.17 (1.38, 3.41) for CVD mortality, while those in Q1 had adjusted HRs of 1.49 (1.19, 1.85) for all-cause mortality and 1.93 (1.26, 2.98) for CVD mortality. CONCLUSIONS: Both higher and lower SUA levels were associated with increased risks of all-cause and CVD mortality in patients with CKD stages 3-5.

Association between serum uric acid and cardiovascular fitness among US adults: A cross-sectional study.

Background: While serum uric acid (SUA) is known as a cardiovascular disease risk factor and is associated with increased cardiovascular mortality, the relationship between SUA and cardiovascular adaptability under exercise stress remains unclear. Aims: This study aims to elucidate the relationship between SUA levels and cardiovascular fitness, particularly as manifested during cardiopulmonary exercise testing. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, this study included 5765 participants aged 12-49 years. Heart rate recovery (HRR) during cardiopulmonary exercise testing was measured as an indicator of cardiovascular fitness. Multivariate linear regression analysis was used to explore the association between SUA levels and heart rate recovery at 1 min (HRR1) and 2 min (HRR2) post-exercise. Results: After adjusting for potential confounders, an inverse relationship was found between SUA levels and both HRR1 and HRR2. Multivariate adjusted smoothing spline plots demonstrated a decrease in HRR1 and HRR2 with increasing SUA levels. This negative correlation was observed across nearly all subgroups. Conclusions: Elevated SUA levels are indicative of poorer cardiovascular adaptability in the adult US population.

Zerumbone reduces TLR2 stimulation-induced M1 macrophage polarization pattern via upregulation of Nrf-2 expression in murine macrophages.

Hyperuricemia contributes significantly to gout arthritis pathogenesis, which promotes urate crystal deposition in the joints and activates joint-resident macrophages and circulating monocytes to initiate a state of inflammatory arthritis. In the joint, macrophages have an immune defense role where the presence of urate crystals results in the inflammatory mediators secretion, inflammatory cells recruitment to the joint, and shift macrophage population toward M1 pro-inflammatory phenotypes. Current treatment modalities of gout arthritis have side effects that limit their use in the elderly. A novel treatment that targets macrophage polarization to re-establish homeostasis may initiate a drug discovery program of novel disease-modifying agents for gout. Zerumbone (Zer) is a sesquiterpenoid bioactive compound found in the rhizome of Zingiberaceae family and possesses anti-inflammatory, antioxidant, and anti-proliferative activity. Our study hypothesized that soluble uric acid (sUA) and Pam3CSK4 (TLR2 agonist) reduce the anti-inflammatory function of murine M2 bone marrow-derived macrophages and change the expression of M2 genetic markers toward M1 phenotypes. We observed that priming of M2 macrophages with sUA and Pam3CSK4 significantly decreased M2 specific markers expression, e.g., Arg-1, Ym-1, and Fizz-1, enhanced mRNA expression of IL-1ß, TNF-α, CXCL2, and iNOS and increased oxidative stress in M2 macrophages, as exhibited by a reduction in Nrf2 expression. We also aimed to study the impact of Zer on reducing the pro-inflammatory effect of sUA in TLR2-stimulated M2 macrophages. We noticed that Zer treatment significantly reduced L-1ß and TNF-α production following Pam3CSK4 + sUA treatment on M2 macrophages. Furthermore, Zer reduced the caspase-1 activity without altering cytosolic NLRP3 content in challenged M2 BMDMs. We also observed that Zer significantly enhanced M2-associated marker's expression, e.g., Arg-1, Ym-1, and Fizz-1, and augmented Nrf-2 and other antioxidant proteins, including HMOX1 and srxn1expression following Pam3CSK4 + sUA treatment. We draw the conclusion that Zer is a potentially effective anti-inflammatory treatment for gout arthritis linked to hyperuricemia.

The association between serum uric acid / serum creatinine ratio and in-hospital outcomes in elderly patients with acute myocardial infarction.

BACKGROUND: The role of Serum uric acid (SUA) in acute myocardial infarction (AMI) was controversial, which might be influenced by the renal clearance function of the patients. The present study aimed to explore the association between serum uric acid to serum creatinine ratio (SUA/Scr), reflecting a net production of SUA, and the in-hospital outcomes of elderly patients with AMI. METHODS: In this retrospective study, a total of 330 elderly AMI patients (≥ 75 years) were enrolled. Data of SUA and Scr on admission were collected to calculate SUA/Scr ratio. Logistic regression analysis and receiver-operating curves were performed to assess the association between SUA/Scr ratio and in-hospital major adverse cardiovascular events (MACEs) and all-cause death. RESULTS: Among the 330 patients, 68 patients had MACEs and 44 patients died. Patients with MACEs or died had lower SUA/Scr values compared with those without MACEs or survival (P < 0.05). Univariate logistic analysis showed that a lower value of SUA/Scr (< 3.45) was significantly associated with in-hospital MACEs (odd ratios (OR): 2.359, 95% confidential interval (CI): 1.369-4.065, P = 0.002) and death (OR: 2.424, 95% CI: 1.275-4.608, P = 0.007). After correcting for confounding factors, a lower SUA/Scr value was still independently associated with in-hospital MACEs (OR: 2.144, 95% CI: 1.169-3.934, P = 0.014) and death (OR: 2.125, 95% CI: 1.050-4.302, P = 0.036). Subgroup analysis showed that the association between a lower SUA/Scr ratio and increased risk of in-hospital outcomes could observed only in males (OR: 2.511, 95%CI: 1.211-5.207, P = 0.013 for MACEs; OR: 2.730, 95% CI: 1.146-6.502, P = 0.023 for death). CONCLUSIONS: A lower SUA/Scr ratio was associated with an increased risk of in-hospital adverse events in elderly patients with AMI, especially in males, which maybe a marker of poor outcomes for elderly AMI patients.

Sua5 catalyzing universal t6A tRNA modification is responsible for multifaceted functions of the KEOPS complex in Cryptococcus neoformans.

The N6-threonylcarbamoyl adenosine (t6A) tRNA modification is critical for ensuring translation fidelity across three domains of life. Our prior work highlighted the KEOPS complex, organized in a Pcc1-Kae1-Bud32-Cgi121 linear arrangement, not only serves an evolutionarily conserved role in t6A tRNA modification but also exerts diverse functional impacts on pathobiological characteristics in Cryptococcus neoformans, a leading cause of fungal meningitis worldwide. However, the extent to which the pleiotropic functions of the KEOPS complex are specifically tied to tRNA modification remains uncertain. To address this, we undertook a functional characterization of Sua5, responsible for generating the precursor threonylcarbamoyl-adenylate (TC-AMP) for t6A tRNA modification, using a reverse genetics approach. Comparative phenotypic analyses with KEOPS mutants revealed that Sua5 plays a vital role in multiple cellular processes, such as t6A tRNA modification, growth, sexual development, stress response, and virulence factor production, thus reflecting the multifaceted functions of the KEOPS complex. In support of this, sua5Δ bud32Δ double mutants showed phenotypes comparable to those of the corresponding single mutants. Intriguingly, a SUA5 allele lacking a mitochondria targeting sequence (SUA5MTSΔ) was sufficient to restore the wild-type phenotypes in the sua5Δ mutant, suggesting that Sua5's primary functional locus may be cytosolic, akin to the KEOPS complex. Further supporting this, the deletion of Qri7, a mitochondrial paralog of Kae1, had no discernible phenotypic impact on C. neoformans. We concluded that cytosolic t6A tRNA modifications, orchestrated by Sua5 and the KEOPS complex, are central to the regulation of diverse pathobiological functions in C. neoformans.IMPORTANCEUnderstanding cellular functions at the molecular level is crucial for advancing disease treatments. Our research reveals a critical connection between the KEOPS complex and Sua5 in Cryptococcus neoformans, a significant cause of fungal meningitis. While the KEOPS complex is known for its versatile roles in cellular processes, Sua5 is specialized in t6A tRNA modification. Our key finding is that the diverse roles of the KEOPS complex, ranging from cell growth and stress response to virulence, are fundamentally linked to its function in t6A tRNA modification. This conclusion is supported by the remarkable similarities between the impacts of Sua5 and KEOPS on these processes, despite their roles in different steps of the t6A modification pathway. This newfound understanding deepens our insight into fungal biology and opens new avenues for developing potential therapies against dangerous fungal diseases.

The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications.

Changes in lifestyle induce an increase in patients with hyperuricemia (HUA), leading to gout, gouty arthritis, renal damage, and cardiovascular injury. There is a strong inflammatory response in the process of HUA, while dysregulation of immune cells, including monocytes, macrophages, and T cells, plays a crucial role in the inflammatory response. Recent studies have indicated that urate has a direct impact on immune cell populations, changes in cytokine expression, modifications in chemotaxis and differentiation, and the provocation of immune cells by intrinsic cells to cause the aforementioned conditions. Here we conducted a detailed review of the relationship among uric acid, immune response, and inflammatory status in hyperuricemia and its complications, providing new therapeutic targets and strategies.

Allopurinol versus Febuxostat: A New Approach for the Management of Hepatic Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes patients with hepatic steatosis and at least one of five cardiometabolic risk factors. Xanthine oxidase (XO) represents a treatment target for MASLD. We aimed to evaluate the effect of two xanthine oxidase inhibitors, allopurinol and febuxostat, plus lifestyle modifications compared to lifestyle modifications alone on improving steatosis. Ninety MASLD patients were assigned to one of three groups for three months. Patients with hyperuricemia were given either allopurinol 100 mg or febuxostat 40 mg daily, along with lifestyle modifications. The third control group was only given lifestyle modifications, excluding all patients with hyperuricemia due to ethical concerns. The primary outcome was to measure the change in the controlled attenuation parameter (CAP) score as an indicator of steatosis from baseline after three months. The secondary outcome was to measure the change in serum uric acid (SUA) three months from baseline. The study found that the CAP score decreased significantly in the allopurinol group (p = 0.009), but the decline in the febuxostat or lifestyle groups was non-significant (p = 0.189 and 0.054, respectively). The SUA levels were significantly reduced in both the allopurinol and febuxostat groups (p < 0.001), with no statistical difference between the two groups (p = 0.496).

Treatment Patterns of Monoclonal Antibodies in Patients With Severe Uncontrolled Asthma Treated by Pulmonologists in Spain.

Introduction and objectives: The use of monoclonal antibody (mAb)-based therapies is becoming the new standard of care for severe uncontrolled asthma (SUA). Even though patients may qualify for one or more of these targeted treatments, based on different clinical criteria, a global vision of mAb prescription management in a large sample of hospitals is not well characterised in Spain.The objective was to give a global vision of mAb prescription management in a large sample of hospitals in Spain. Materials and methods: We used an aggregate data survey method to interview pulmonology specialists in a large sample of Spanish centres (90). The following treatment-related information was obtained on patients treated with mAbs: specific mAbs prescribed, treatment interruption, switch and restart and the reasons for these treatment changes. Results: mAb prescription was more frequent in females (13.3% females vs 7.4% males; p < 0.001). There were no differences in prevalence by hospital complexity level. In contrast, there were differences by geographical area. Omalizumab was the most prescribed mAb (6.2%), followed by mepolizumab (2.9%). Discontinuation of Omalizumab (due to a lack of effectivity) and switches from this mAb to mepolizumab were more frequent. Very few restarts to the first treatment were observed after a switch from ≥2 mAbs. Conclusions: Omalizumab appeared as the most prescribed mAb in SUA but was also the most withdrawn; a specific and objective characterisation of patients with SUA, along with asthma phenotyping, and together with further evaluation of safety and effectiveness profiles, will lead to future progress in the management of SUA with mAbs.

Introducción y objetivos: El uso de terapias basadas en anticuerpos monoclonales (mAb) se está convirtiendo en el nuevo estándar de atención para el asma grave no controlada (AGNC). A pesar de que los pacientes pueden optar a uno o varios de estos tratamientos dirigidos, con base en diferentes criterios clínicos, en España no se ha caracterizado bien una visión global de la gestión de la prescripción de mAb en una gran muestra de hospitales.El objetivo fue dar una visión global de la gestión de la prescripción de mAB en una amplia muestra de hospitales en España. Materiales y métodos: Se utilizó un método basado en una encuesta de datos agregados para entrevistar a especialistas en Neumología en una amplia muestra de centros españoles (90). Se obtuvo la siguiente información relacionada con el tratamiento de los casos tratados con mAbs: mAbs específicos prescritos, interrupción del tratamiento, cambio y reinicio, y las razones de estos cambios de tratamiento en consultas de Neumología. Resultados: La prescripción de mAB fue más frecuente en mujeres (13,3% mujeres vs. 7,4% hombres; p < 0,001). No hubo diferencias de prevalencia por nivel hospitalario. En cambio, hubo diferencias por área geográfica. Omalizumab fue el mAb más prescrito (6,2%), seguido de mepolizumab (2,9%). La interrupción y los cambios (debido a la falta de efectividad) también fueron más frecuentes para omalizumab. Conclusiones: Omalizumab fue el mAb más prescrito en el manejo de AGNC, pero también fue el mAB que presentó más retiradas; una caracterización específica y objetiva de los pacientes con AGNC, mediante fenotipificación de asma, junto con una evaluación adicional de los perfiles de seguridad y efectividad, conducirá a nuevos avances en el manejo del AGNC con mABs.

Higher ratio of serum uric acid to serum creatinine (SUA/SCr) increases the risk of metabolic unhealthy phenotype.

BACKGROUND AND AIM: It is very important to understand which factors play roles in switching from a healthy to an unhealthy metabolism. It is unclear if SUA/SCr is an independent risk factor for metabolic unhealthy phenotype. We examined whether SUA/SCr is associated with an increased risk for metabolic unhealthy phenotype in the Chinese population. METHODS AND RESULTS: As many as 3158 subjects aged 25-75 years who had a metabolic healthy phenotype at baseline were included in the retrospective cohort study. They were assigned to four groups based on the quartile of SUA/SCr. We compared the demographic and clinical characteristics among the four groups. The correlation between SUA/SCr and the risk of metabolic unhealthy phenotype in the overall population and stratified by subgroups was examined by logistic regression analyses. Greater SUA/SCr values were correlated with greater BMI, systolic and diastolic BP, TC, TG, RBC, WBC, HB, ALT, SUA and eGFR. During the two-year follow-up, 632 of the study subjects (20.01%) developed new-onset metabolic unhealthy phenotype from the total of 3158 study subjects. A statistically significant increase in the rates of metabolic unhealthy phenotype was observed with increasing SUA/SCr levels within each group. After multivariate adjustment, the adjusted ORs and 95% CIs were 1.44 (1.03-2.00) and 2.11 (1.52-2.94) in the Q3 group and Q4 group, respectively. CONCLUSION: SUA/SCr was positively related to the risk of metabolic unhealthy phenotype in the Chinese subjects, suggesting the potential of SUA/SCr to serve as an independent risk predictor in the development of metabolic unhealthy phenotype.

The universal Sua5/TsaC family evolved different mechanisms for the synthesis of a key tRNA modification.

TsaC/Sua5 family of enzymes catalyzes the first step in the synthesis of N6-threonyl-carbamoyl adenosine (t6A) one of few truly ubiquitous tRNA modifications important for translation accuracy. TsaC is a single domain protein while Sua5 proteins contains a TsaC-like domain and an additional SUA5 domain of unknown function. The emergence of these two proteins and their respective mechanisms for t6A synthesis remain poorly understood. Here, we performed phylogenetic and comparative sequence and structure analysis of TsaC and Sua5 proteins. We confirm that this family is ubiquitous but the co-occurrence of both variants in the same organism is rare and unstable. We further find that obligate symbionts are the only organisms lacking sua5 or tsaC genes. The data suggest that Sua5 was the ancestral version of the enzyme while TsaC arose via loss of the SUA5 domain that occurred multiple times in course of evolution. Multiple losses of one of the two variants in combination with horizontal gene transfers along a large range of phylogenetic distances explains the present day patchy distribution of Sua5 and TsaC. The loss of the SUA5 domain triggered adaptive mutations affecting the substrate binding in TsaC proteins. Finally, we identified atypical Sua5 proteins in Archaeoglobi archaea that seem to be in the process of losing the SUA5 domain through progressive gene erosion. Together, our study uncovers the evolutionary path for emergence of these homologous isofunctional enzymes and lays the groundwork for future experimental studies on the function of TsaC/Sua5 proteins in maintaining faithful translation.

Association between serum uric acid levels and cardiovascular risk factors among adults in India.

BACKGROUND AND AIM: The objective of this study was to explore the association between serum uric acid (SUA) levels and cardiovascular risk factors in the Indian population. METHODS AND RESULTS: This was a cross-sectional, population-based study. The study enrolled adults aged 20 years and above residing in rural, sub-urban, and urban. All participants completed a detailed questionnaire, underwent anthropometric measurements, and had blood samples collected. Participants were divided into three tertiles based on their SUA concentrations. A total of 2976 participants were included in this study, with 865 from rural, 1030 from sub-urban, and 1081 from urban populations. The mean values of cardiovascular risk factors were significantly higher in tertile 3 (p < 0.001) as compared to the other tertiles. However, we observed a negative trend between the increase of SUA and SUA/Scr ratio and HbA1c levels (Pearson correlation r = -0.068; p < 0.001 and r = -0.140; p < 0.001, respectively). The healthy and prediabetic groups did not show any significant change in HbA1c with increasing SUA levels, while an inverse trend was observed in diabetics. In the diabetic population, both men and women showed an inverse trend between increasing SUA levels and HbA1c in both known and newly diagnosed diabetes (p < 0.001). CONCLUSIONS: The study found a positive association between SUA levels and cardiovascular risk factors. However, HbA1c was inversely correlated with increasing SUA tertiles in both known and newly diagnosed diabetes, as compared to the general population. Additionally, both men and women with diabetes consistently showed an inverse relationship between increasing SUA/SCr ratio and HbA1c levels.

Association of N, N-diethyl-m-toluamide (DEET) with hyperuricemia among adult participants.

BACKGROUND: N,N-diethyl-m-toluamide (DEET) is a widely used active ingredient in insect repellents, and its effects on human health have been a matter of debate. This study aims to investigate the relationship between DEET exposure and hyperuricemia in the adult population. METHODS: Our study utilized a cross-sectional design and analyzed data from adult participants of the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. 3-diethyl-carbamoyl benzoic acid (DCBA) was used as a specific indicator of DEET exposure. DCBA was categorized using quartiles based on its distribution within the study population. Multiple linear regression models were employed to examine the association between DCBA exposure and serum uric acid (SUA) levels in adults. The relationship between DCBA and the prevalence of hyperuricemia in adults was assessed using multiple logistic regression models. Dose-response relationships were analyzed using restricted cubic spline regression. RESULTS: A total of 8708 participants were included in the study. The mean age of the participants was 46.49 years, and the total number of male participants was 50.93%. The median levels of DCBA and SUA were 2.07 ng/mL and 5.40 mg/dL, respectively. Hyperuricemia was found in 19.99% of the participants. In multivariate-adjusted linear regression models, it was found that higher SUA levels were associated with the highest quartile of DCBA compared with the lowest quartile of DCBA (ß [95% CI]: 0.19 [0.08, 0.30], Ptrend<0.001). After adjusting for confounders, a positive association was found between the prevalence of hyperuricemia and DCBA levels (OR [95% CI] quartile 4 vs. 1: 1.41 [1.14-1.74], Ptrend<0.001). Furthermore, linear associations were observed between DCBA concentrations and SUA levels (P for nonlinearity = 0.479) and the prevalence of hyperuricemia (P for nonlinearity = 0.755). CONCLUSION: Higher DCBA concentrations were found to have a positive association with the prevalence of hyperuricemia in the general adult population.

Sex-specific association of serum uric acid trajectories with risk of incident retinal arteriosclerosis in Chinese population: A population-based longitudinal study.

Background: The impact of serum uric acid (SUA) trajectories on the development of retinal arteriosclerosis is uncertain. The purpose of this study was to identify adult SUA trajectories by sex and determine their association with risk of retinal arteriosclerosis. Methods: In this longitudinal study, 4,324 participants who were aged between 18 and 60 years without retinal arteriosclerosis at or before baseline (from January 1, 2010, through December 31, 2010) were included. Group-based trajectory modeling was used to identify SUA trajectories during the exposure period (from January 1, 2006, through December 31, 2010). Cox proportional-hazards models were applied to evaluate the associations between SUA trajectories and the risk of incident retinal arteriosclerosis during the outcome period (from January 1, 2011, through December 31, 2019). Results: 4 distinct SUA trajectories were identified in both women and men: low, moderate, moderate-high, and high. During a median follow-up of 9.54 years (IQR 9.53-9.56), 97 women and 295 men had developed retinal arteriosclerosis. In the fully adjusted model, a significant association between the moderate-high SUA trajectory group and incidence of retinal arteriosclerosis was observed only in men (HR: 1.76, 95% CI: 1.17-2.65) compared with the low trajectory group, but not in women (HR: 0.77, 95% CI: 0.39-1.52). Also, the high SUA trajectory group had the highest risk with an adjusted HR of 1.81 (95% CI, 1.04-3.17) in men. However, they did not exhibit a substantially increased risk in women. Conclusion: Higher SUA trajectory groups were significantly associated with an increased risk of incident retinal arteriosclerosis in men but not in women.