New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Una aproximación a la joyería de época tardoantigua en la provincia de Granada

In this paper, we present an approach to the ancient jewellery deposited in the Archaeological and Ethnological Museum of Granada. These materials were recovered by rescue excavations carried out in the rural necropolis of El Cortijo del Chopo (Colomera), El Castillón (Montefrío), El Almendral (Zafarraya), and Las Delicias (Ventas de Zafarraya), belonging to the province of Granada.En este artículo realizamos una aproximación a la joyería tardoantigua depositada en el Museo Arqueológico y Etnológico de Granada. Estos materiales proceden de las intervenciones efectuadas con carácter de urgencia en las necrópolis rurales de El Cortijo del Chopo (Colomera), El Castillón (Montefrío), El Almendral (Zafarraya), y Las Delicias (Ventas de Zafarraya), pertenecientes a la provincia de Granada

Archaeometallurgical characterization of Late Antique personal adornments. The necropolis of Cortijo del Chopo (Granada, Spain)

Objects of personal adornment from Late Antiquity have been extensively studied in the Iberian Peninsula since the 19th century, when the first funerary contexts from that period began to come to light. However, only partial information was available with regard to their production process and chemical composition. This came from the archaeometallurgical studies carried out on funerary assemblages from central and northern Iberia. In order to obtain a more complete picture, a set of 80 copper-based alloy objects were analysed, most of ornaments and parts of them, from the necropolis of Cortijo del Chopo (Granada), in southeastern Spain. The results from the portable X-ray fluorescence reveal the presence of a wide variety of alloys and confirm the practice of recycling metals to make the items, a characteristic of the metallurgy of the period. Lead isotope analysis provide evidence of a local production of brass objects with a high Zn content, similar in appearance to gold.This paper has been supported by a University Teacher Training contract (FPU 2018) awarded by the Ministry of Science, Innovation and Universities, the R&D Group GEA Cultura material e identidad social en la Prehistoria Reciente en el sur de la Península Ibérica (HUM-064), and the R&D Project PID2022-137494NB-I00 funded by MICIU/SRA /10.13039/501100011033 and FEDER, UE. Funding for open access charge: Universidad de Granada / CBUA

Furfural Determination with Disposable Polymer Films and Smartphone-Based Colorimetry for Beer Freshness Assessment

We have developed disposable color-changing polymeric films for quantification of furfurala freshness indicatorin beer using a smartphone-based reader. The films are prepared by radical polymerization of 4-vinylaniline, as a furfural-sensitive indicator monomer, 2-hydroxymethyl methacrylate as a comonomer, and ethylene dimethyl methacrylate (EDMA) as a cross-linker. The sensing mechanism is based on the Stenhouse reaction in which aniline and furfural react in acidic media with the generation of a deep red cyanine derivative, absorbing at 537 nm, which is visible to the naked eye. The colorimetric response has been monitored using either a portable fiber-optic spectrophotometer or the built-in camera of a smartphone. Under the optimized conditions, a linear response to furfural in beer was obtained in the 39 to 500 μg L^–1 range, with a detection limit of 12 μg L^–1, thus improving the performance of other well-established colorimetric or chromatographic methods. The novel films are highly selective to furfural, and no cross-reactivity has been observed from other volatile compounds generated during beer aging. A smartphone application (app), developed for Android platforms, measures the RGB color coordinates of the sensing membranes after exposure to the analyte. Following data processing, the signals are converted into concentration values by preloaded calibration curves. The method has been applied to determination of furfural in pale lager beers with different storage times at room temperature. A linear correlation (<i>r</i> > 0.995) between the storage time and the furfural concentration in the samples has been confirmed; our results have been validated by HPLC with diode-array detection

[18F]DCFPyL PET/CT versus [18F]fluoromethylcholine PET/CT in Biochemical Recurrence of Prostate Cancer (PYTHON): a prospective, open label, cross-over, comparative study

Abstract Purpose Primary objective was to compare the per-patient detection rates (DR) of [ 18 F]DCFPyL versus [ 18 F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM). Methods This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [ 18 F]DCFPyL (investigational medicinal product) or [ 18 F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [ 18 F]DCFPyL and [ 18 F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs. Results A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [ 18 F]DCFPyL- and/or [ 18 F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [ 18 F]DCFPyL- compared to [ 18 F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p  2.0: 50/57 (88%) vs. 39/57 (68%) for [ 18 F]DCFPyL- and [ 18 F]fluoromethylcholine -PET/CT, respectively). [ 18 F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [ 18 F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed. Conclusions The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [ 18 F]DCFPyL compared to [ 18 F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [ 18 F]DCFPyL was safe and well tolerated

Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3-15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7-16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion: Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.Advanced differentiated thyroid cancerEpidemiological studyRadioiodine-refractory differentiated thyroid cancerRelapsing differentiated thyroid cancerRelapsing prognostic factorsSurvival prognostic factor

Data_Sheet_1_Effect of the Mediterranean diet and probiotic supplementation in the management of mild cognitive impairment: Rationale, methods, and baseline characteristics.docx

IntroductionMild cognitive impairment (MCI) can progress to Alzheimer’s disease (AD). When MCI is not properly controlled, the speed of deterioration can dramatically increase. Reduction of oxidative stress/inflammation and the modulation of the gut-brain axis could be new potential therapeutic targets for the prevention and treatment of AD. Consumption of specific nutrients, diets and probiotic supplementation have been evaluated for neurodegenerative disorders. We focus on a detailed description of the study methods and baseline characteristics of a clinical trial aiming to evaluate the efficacy of a combined nutritional intervention, i.e., a Mediterranean diet with probiotics, on cognitive capacity in a population with MCI.MethodsIn this randomized, latin-square crossover, double-blind, and controlled dietary intervention trial (clinicaltrials.gov NCT05029765), 47 MCI patients were randomized to consume three dietary interventions for 24-weeks each: (1) A Mediterranean diet supplemented with probiotics (109 colony-forming units of Lactobacillus rhamnosus and Bifidobacterium longum); (2) A Mediterranean diet + placebo; and (3) A Healthy diet according to the World Health Organization (WHO) recommendations. Participants will be evaluated before and after each of the three intervention periods (each 24-weeks, with a total of 72-weeks) for adherence to the assigned diet, blood tests, cognitive performance, gut microbiota analysis and functional neuroimaging studies.ResultsFifty patients, ≥60 years-old and diagnosed with MCI, underwent randomization. A total of 47 patients completed follow-up dietary interventions (57.4% males), with a good glycemic control (HbA1c 5.8 ± 0.1%, fasting glucose and insulin 99.7 ± 3.3 mg/dL and 10.4 ± 0.9 mU/L, respectively), elevated systolic blood pressure (136.9 ± 2.1 mmHg) and increased degree of inflammation (high-sensitivity C-reactive protein, 8.8 ± 0.9 mg/dL). Baseline adherence to the Mediterranean diet was medium (7.5 ± 0.3 points on the score that ranged from 0 to 14 points).ConclusionThe results of this clinical study would provide more evidence on the need for dietary therapeutic strategies, for clinical and individual practice, in the management of MCI patients to reduce the risk of AD development. Targeting lifestyle modifications in high-risk populations could prevent substantial cases of cognitive decline.Clinical trial registration[ClinicalTrials.gov], identifier [NCT05029765].</p

Quorum sensing network in clinical strains of A. baumannii : AidA is a new quorum quenching enzyme

Acinetobacter baumannii is an important pathogen that causes nosocomial infections generally associated with high mortality and morbidity in Intensive Care Units (ICUs). Currently, little is known about the Quorum Sensing (QS)/Quorum Quenching (QQ) systems of this pathogen. We analyzed these mechanisms in seven clinical isolates of A. baumannii. Microarray analysis of one of these clinical isolates, Ab1 (A. baumannii ST-2-clon-2010), previously cultured in the presence of 3-oxo-C12-HSL (a QS signalling molecule) revealed a putative QQ enzyme (α/β hydrolase gene, AidA). This QQ enzyme was present in all nonmotile clinical isolates (67% of which were isolated from the respiratory tract) cultured in nutrient depleted LB medium. Interestingly, this gene was not located in the genome of the only motile clinical strain growing in this medium (A. baumannii strain Ab421-GEIH-2010 [Ab7], isolated from a blood sample). The AidA protein expressed in E. coli showed QQ activity. Finally, we observed downregulation of the AidA protein (QQ system attenuation) in the presence of HO (ROS stress). In conclusion, most of the A. baumannii clinical strains were not surface motile (84%) and were of respiratory origin (67%). Only the pilT gene was involved in surface motility and related to the QS system. Finally, a new QQ enzyme (α/β hydrolase gene, AidA protein) was detected in these strains

Age at menopause in Latin America

Objective: To assess the age at menopause (AM) in Latin America urban areas. Design: A total of 17,150 healthy women, aged 40 to 59 years, accompanying patients to healthcare centers in 47 cities of 15 Latin American countries, were surveyed regarding their age, educational level, healthcare coverage, history of gynecological surgery, smoking habit, presence of menses, and the use of contraception or hormone therapy at menopause. The AM was calculated using logit analysis. Results: The mean age of the entire sample was 49.4 ± 5.5 years. Mean educational level was 9.9 ± 4.5 years, and the use of hormone therapy and oral contraception was 22.1% and 7.9%, respectively. The median AM of women in all centers was 48.6 years, ranging from 43.8 years in Asuncion (Paraguay) to 53 years in Cartagena de Indias (Colombia). Logistic regression analysis determined that women aged 49 living in cities at 2,000 meters or more above sea level (OR = 2.0, 95% CI: 1.4-2.9, P < 0.001) and those with lower educational level (OR = 1.9, 95% CI: 1.3-2.8, P < 0.001) or living in countries with low gross national product (OR = 2.1, 95% CI: 1.5-2.9, P < 0.001) were more prone to an earlier onset of menopause. Conclusions: The AM varies widely in Latin America. Lower income and related poverty conditions influence the onset of menopause