Gout risk in adults with pre-diabetes initiating metformin.

OBJECTIVE: Despite the strong association between gout and pre-diabetes, the role of metformin in gout among individuals with pre-diabetes remains uncertain. We compared the incidence rates of gout in adults with pre-diabetes starting metformin with those not using antidiabetic treatments. METHODS: We conducted a new-user, propensity score-matched cohort study using electronic health records from an academic health system (2007-2022). Pre-diabetes was defined based on haemoglobin A1c levels. Metformin users were identified and followed from the first metformin prescription date. Non-users of antidiabetic medications were matched to metformin users based on propensity score and the start of follow-up. The primary outcome was incident gout. Cox proportional hazards models estimated the HR for metformin. Linear regression analyses assessed the association between metformin use and changes in serum urate (SU) or C-reactive protein (CRP). RESULTS: We identified 25 064 individuals with pre-diabetes and propensity score-matched 1154 metformin initiators to 13 877 non-users. Baseline characteristics were well balanced (all standardised mean differences <0.1). The median follow-up was 3.9 years. The incidence rate of gout per 1000 person-years was lower in metformin users 7.1 (95% CI 5.1 to 10) compared with non-users 9.5 (95% CI 8.8 to 10.2). Metformin initiation was associated with a reduced relative risk of gout (HR 0.68, 95% CI 0.48 to 0.96). No relationship was found between metformin and changes in SU or CRP. CONCLUSIONS: Metformin use was associated with a reduced risk of gout among adults with pre-diabetes, suggesting that metformin may be important in lowering gout risk in individuals with pre-diabetes.

Changes in alcohol intake and serum urate changes: longitudinal analyses of annual medical examination database.

INTRODUCTION: Despite the established cross-sectional association between alcohol intake and serum urate (SU), its longitudinal association remains unknown. This study aimed to determine whether changes in alcohol intake have a clinically relevant association with SU change. METHOD: We conducted retrospective analyses using systematically collected annual medical examination data from October 2012 to October 2022 in a Japanese preventive medicine centre. The exposure was changes in alcohol intake between two consecutive visits. The association of SU changes with alcohol intake changes was estimated by mixed-effect linear regression with adjustment for relevant covariates. RESULTS: We analysed 63 486 participants (median age, 47.0 years; 55% women; 58.6% regular alcohol drinkers with a median of 1.4 drinks/day) with 370 572 visits. The median SU level was 5.3 mg/dL, and 506 (0.8%) participants had diagnoses of gout or hyperuricemia without medication use during the study period. Decreasing one daily alcohol intake had a clinically small association with SU changes (-0.019 (95% CI: -0.021 to -0.017) mg/dL). Beer had the largest association with SU (-0.036 (95% CI: -0.039 to -0.032) mg/dL for one beer decrease). Complete discontinuation of any alcohol from a mean of 0.8 drinks/day was associated with -0.056 mg/dL (95% CI: -0.068 to -0.043) decrease in SU; the association became larger in hyperuricemic participants (-0.110 mg/dL (95% CI: -0.154 to -0.066) for alcohol discontinuation from a mean of 1.0 drinks/day). CONCLUSIONS: This study revealed changes in alcohol intake had small associations with SU change at the general Japanese population level. Complete discontinuation of alcohol in hyperuricemic participants had only modest improvement in SU.

Fractures in Patients With Acute Calcium Pyrophosphate Crystal Arthritis Versus Matched Comparators in a Large Cohort Study.

OBJECTIVE: Calcium pyrophosphate deposition (CPPD) disease was associated with osteopenia in two cross-sectional studies. We compared fracture risks in patients with acute calcium pyrophosphate (CPP) crystal arthritis versus matched comparators. METHODS: We performed a longitudinal cohort study using electronic health record data from a single large academic health system, with data from 1991 to 2023. Patients with one or more episodes of acute CPP crystal arthritis were matched to comparators on the index date (first documentation of "pseudogout" or synovial fluid CPP crystals or matched encounter) and first encounter in the health system. The primary outcome was first fracture at the humerus, wrist, hip, or pelvis. We excluded patients with fracture before the index date. Covariates included demographics, body mass index, smoking, comorbidities, health care use, glucocorticoids, and osteoporosis treatments. We estimated incidence rates and adjusted hazard ratios for fracture. Sensitivity analyses excluded patients prescribed glucocorticoids, patients prescribed osteoporosis treatments, or patients with rheumatoid arthritis and additionally adjusted for chronic kidney disease. RESULTS: We identified 1,148 patients with acute CPP crystal arthritis matched to 3,730 comparators, with a mean age of 73 years. Glucocorticoids and osteoporosis treatments were more frequent in the acute CPP crystal arthritis cohort. Fracture incidence rates were twice as high in the acute CPP crystal arthritis cohort (11.7 per 1,000 person-years) versus comparators (5.5 per 1,000 person-years). After multivariable adjustment, fracture relative risk was twice as high in the acute CPP crystal arthritis cohort (hazard ratio 1.8 [95% confidence interval 1.3-2.3]); results were similar in sensitivity analyses. CONCLUSION: In this first published study of fractures and CPPD, fracture risk was nearly doubled in patients with acute CPP crystal arthritis.

Patterns of genetic diversity in Colombia for 38 indels used in human identification.

The current population of Colombia has a genetic heterogeneity resulting from different migrations from other continents and within the country. In addition, there are small groups in their territory that have remained isolated and therefore have a different genetic pool in relation to that of the neighbouring urban populations. This population stratification must be considered in forensic analysis, being more complex for markers with marked intercontinental differentiation. In this study, population differentiation in Colombian admixed, native, and Afro-descendant populations was evaluated for a group of 38 indels described for forensic use. Allelic frequencies and parameters of forensic relevance were determined in each of the groups defined based on population differentiation analyses. In addition to the differences found between population groups, the results show that the set of 38 indels analysed could be useful in studies of individual identification in Colombia. The exclusion power presented by this set of markers suggests the need for joint use with other markers, being able to complement the STRs in paternity cases. High levels of both power of discrimination and exclusion were found when complementing the 38 HID-indels with a second multiplex, for a total of 83 indels.

Searching for the roots of the first free African American community.

San Basilio de Palenque is an Afro-descendant community near Cartagena, Colombia, founded in the sixteenth century. The recognition of the historical and cultural importance of Palenque has promoted several studies, namely concerning the African roots of its first inhabitants. To deepen the knowledge of the origin and diversity of the Palenque parental lineages, we analysed a sample of 81 individuals for the entire mtDNA Control Region as well as 92 individuals for 27 Y-STRs and 95 for 51 Y-SNPs. The results confirmed the strong isolation of the Palenque, with some degree of influx of Native American maternal lineages, and a European admixture exclusively mediated by men. Due to the high genetic drift observed, a pairwise FST analysis with available data on African populations proved to be inadequate for determining population affinities. In contrast, when a phylogenetic approach was used, it was possible to infer the phylogeographic origin of some lineages in Palenque. Contradicting previous studies indicating a single African origin, our results evidence parental genetic contributions from widely different African regions.

Robust automated reading of the skin prick test via 3D imaging and parametric surface fitting.

The conventional reading of the skin prick test (SPT) for diagnosing allergies is prone to inter- and intra-observer variations. Drawing the contours of the skin wheals from the SPT and scanning them for computer processing is cumbersome. However, 3D scanning technology promises the best results in terms of accuracy, fast acquisition, and processing. In this work, we present a wide-field 3D imaging system for the 3D reconstruction of the SPT, and we propose an automated method for the measurement of the skin wheals. The automated measurement is based on pyramidal decomposition and parametric 3D surface fitting for estimating the sizes of the wheals directly. We proposed two parametric models for the diameter estimation. Model 1 is based on an inverted Elliptical Paraboloid function, and model 2 on a super-Gaussian function. The accuracy of the 3D imaging system was evaluated with validation objects obtaining transversal and depth accuracies within ± 0.1 mm and ± 0.01 mm, respectively. We tested the method on 80 SPTs conducted in volunteer subjects, which resulted in 61 detected wheals. We analyzed the accuracy of the models against manual reference measurements from a physician and obtained that the parametric model 2 on average yields diameters closer to the reference measurements (model 1: -0.398 mm vs. model 2: -0.339 mm) with narrower 95% limits of agreement (model 1: [-1.58, 0.78] mm vs. model 2: [-1.39, 0.71] mm) in a Bland-Altman analysis. In one subject, we tested the reproducibility of the method by registering the forearm under five different poses obtaining a maximum coefficient of variation of 5.24% in the estimated wheal diameters. The proposed method delivers accurate and reproducible measurements of the SPT.

Assembly of a pan-genome from deep sequencing of 910 humans of African descent.

We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.

Author Correction: Assembly of a pan-genome from deep sequencing of 910 humans of African descent.

In the version of this article initially published, the statement "there are no pan-genomes for any other animal or plant species" was incorrect. The statement has been corrected to "there are no reported pan-genomes for any other animal species, to our knowledge." We thank David Edwards for bringing this error to our attention. The error has been corrected in the HTML and PDF versions of the article.

A continuum of admixture in the Western Hemisphere revealed by the African Diaspora genome.

The African Diaspora in the Western Hemisphere represents one of the largest forced migrations in history and had a profound impact on genetic diversity in modern populations. To date, the fine-scale population structure of descendants of the African Diaspora remains largely uncharacterized. Here we present genetic variation from deeply sequenced genomes of 642 individuals from North and South American, Caribbean and West African populations, substantially increasing the lexicon of human genomic variation and suggesting much variation remains to be discovered in African-admixed populations in the Americas. We summarize genetic variation in these populations, quantifying the postcolonial sex-biased European gene flow across multiple regions. Moreover, we refine estimates on the burden of deleterious variants carried across populations and how this varies with African ancestry. Our data are an important resource for empowering disease mapping studies in African-admixed individuals and will facilitate gene discovery for diseases disproportionately affecting individuals of African ancestry.

[Distribution of three polymorphisms of the TSLP gen in African-descendent population from San Basilio de Palenque, Colombia]. / Distribución de tres polimorfismos del gen TSLP en población afrodescendiente de San Basilio de Palenque, Colombia.

INTRODUCTION: Thymic stromal lymphopoietin (TSLP) has been linked as a susceptibility gene for the development of allergic diseases. It is known that the population of Cartagena is a triethnic mix, in which the component of African ancestry was significantly associated with risk of asthma and high total serum IgE levels. This component comes from African slaves brought into the continent and settled in "palenques", one of them is San Basilio de Palenque, in the Colombian Caribbean Coast. OBJECTIVE: To analyze the distribution of single nucleotide polymorphisms (SNP) rs1837253, rs17551370 and rs2289276 located in TSLP gene, in the African-descendent population of San Basilio de Palenque. MATERIALS AND METHODS: By real time-PCR and probes TaqMan SNP Genotyping™, we genotyped three polymorphisms in 80 individuals of African-descent aged 5 to 18 years of age. RESULTS: The frequency of the rs1837253 allele T was 41.9%, for the allele A, 14.3% for rs17551370, and 22.5% for the allele T of rs2289276. The rs17551370 and rs2289276 distribution remained in Hardy- Weinberg genetic equilibrium. The allele frequency of each SNP did not show statistically significant differences with those reported for other African and African-descendent populations. CONCLUSION: The three polymorphisms in the TSLP were present in the sample population of San Basilio de Palenque and its distribution is similar to that reported for African populations and African ancestry in America.

Distribución de tres polimorfismos del gen TSLP en población afrodescendiente de San Basilio de Palenque, Colombia / Distribution of three polymorphisms of theTSLPgen in African-descendent population from San Basilio de Palenque, Colombia

Introducción. La linfopoyetina tímica del estroma ( Thymic Stromal Lymphopoietin, TSLP) se ha vinculado como un gen de propensión al desarrollo de enfermedades alérgicas. Se sabe que la población de Cartagena es una mezcla triétnica, en la cual el componente de herencia africana se asoció con el riesgo de asma y altos niveles séricos de IgE total. Este componente provino de esclavos africanos que lograron organizarse en "palenques", uno de ellos es San Basilio de Palenque, en la Costa Caribe colombiana. Objetivo. Determinar la distribución de los polimorfismos de nucleótido simple ( Single Nucleotide Polymorphism, SNP) rs1837253, rs17551370 y rs2289276 del gen TSLP en individuos afrodescendientes de San Basilio de Palenque. Materiales y métodos. Mediante PCR en tiempo real y sondas TaqMan SNP Genotyping ™ se genotipificaron estos SNP en 80 individuos afrodescendientes entre los 5 y 18 años de edad. Resultados. El alelo de menor frecuencia para el polimorfismo rs1837253 fue el alelo T (41,9 %), para el rs17551370, el alelo A (14,3 %), y para el rs2289276, el alelo T (22,5 %). La distribución de los polimorfismos rs17551370 y rs2289276 se mantuvo en equilibrio genético de Hardy-Weinberg. Las frecuencias alélicas de cada SNP no mostraron diferencias significativas con las reportadas para poblaciones africanas. Conclusiones. Los tres polimorfismos analizados en el gen TSLP estuvieron presentes en la muestra de población de San Basilio de Palenque y su distribución es similar a la reportada para poblaciones africanas y para poblaciones americanas de ancestro africano. Palabras clave: frecuencia de los genes, afroamericanos, polimorfismo de nucleótido simple, citocinas, endogamia, Colombia.

Introduction: Thymic stromal lymphopoietin (TSLP) has been linked as a susceptibility gene for the development of allergic diseases. It is known that the population of Cartagena is a triethnic mix, in which the component of African ancestry was significantly associated with risk of asthma and high total serum IgE levels. This component comes from African slaves brought into the continent and settled in "palenques", one of them is San Basilio de Palenque, in the Colombian Caribbean Coast. Objective: To analyze the distribution of single nucleotide polymorphisms (SNP) rs1837253, rs17551370 and rs2289276 located in TSLP gene, in the African-descendent population of San Basilio de Palenque. Materials and methods: By real time-PCR and probes TaqMan SNP Genotyping ™ , we genotyped three polymorphisms in 80 individuals of African-descent aged 5 to 18 years of age. Results: The frequency of the rs1837253 allele T was 41.9%, for the allele A, 14.3% for rs17551370, and 22.5% for the allele T of rs2289276. The rs17551370 and rs2289276 distribution remained in Hardy- Weinberg genetic equilibrium. The allele frequency of each SNP did not show statistically significant differences with those reported for other African and African-descendent populations. Conclusion: The three polymorphisms in the TSLP were present in the sample population of San Basilio de Palenque and its distribution is similar to that reported for African populations and African ancestry in America.

Anticuerpos contra proteínas del cristalino en pacientes con cataratas

Con el fin de establecer la prevalencia de los anticuerpos contra antígenos del cristalino en diversos grupos de pacientes con y sin cataratas y si existen diferencias significativas entre éstos y un grupo control, estudiamos por la técnica de doble inmunodifusión de Oucherlony los sueros de 37 pacientes con cataratas seniles, dos pacientes diabéticos con cataratas, 11 diabéticos sin cataratas, seis afáquicos y como controles 33 personas sanas, encontrándose la presencia de anticuerpos en 18.1 por ciento de individuos sanos, en 81.08 por ciento y 81.8 por ciento de pacientes con cataratas seniles y diabéticos sin cataratas respectivamente (P=0.001). Además el análisis molecular del extracto antigénico por medio de la técnica de SDS-PAGE reveló la presencia de nueve fracciones con pesos moleculares comprendidos entre 80KD y 16 KD siendo el de 50KD el más antigénico con los sueros probados por western-blot