Age-related influence of hypothyroidism on caveolins and nitric oxide modulation

Introduction: Hypothyroidism and age impact on cardiac and renal nitricoxide (NO) production. Caveolins, which are negativemodulators of NO synthase (NOS) activity, are affected byboth factors. Objectives: The aim of this study was to evaluate caveolin (CAV) participationin the modulation of renal and cardiac NOS activityin adult hypothyroid animals. Methods: Euthyroid and hypothyroid [methimazole 0.02% (v/v) in thedrinking water during 28 days] male Sprague-Dawley ratswere used. Animals were sacrificed to remove the heart andkidneys. Results: Right atrial NOS activity decreased with age and hypothyroidism.Caveolin-1 expression increased with age andhypothyroidism. Conversely, left ventricular NOS activityincreased with aging and hypothyroidism and the expressionof both CAV isoforms decreased in adult and hypothyroidgroups. In the renal medulla, hypothyroidism reducedNOS activity in young and raised it in adult animals andCAV-1 expression decreased with age and in hypothyroidyoung animals. Caveolin-3 protein levels decreased in adulthypothyroid animals. Conclusions: Hypothyroidism impacts on NOS activity and on that ofits modulators, caveolins, in the cardiovascular and renalsystems. Hypothyroidism enhances the effects of aging inboth systems.Fil: Detomaso, Florencia M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Braga, Paula. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Rodríguez, Lourdes. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Arreche, Noelia Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Sarati, Lorena Ivonne. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Balaszczuk, Ana María. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Fellet, Andrea L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentin

Molecular analysis of pancreatic cystic neoplasm in routine clinical practice

BACKGROUND Cystic pancreatic lesions consist of a wide variety of lesions that are becoming increasingly diagnosed with the growing use of imaging techniques. Of these, mucinous cysts are especially relevant due to their risk of malignancy. However, morphological findings are often suboptimal for their differentiation. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) with molecular analysis has been suggested to improve the diagnosis of pancreatic cysts. AIM To determine the impact of molecular analysis on the detection of mucinous cysts and malignancy. METHODS An 18-month prospective observational study of consecutive patients with pancreatic cystic lesions and an indication for EUS-FNA following European clinical practice guidelines was conducted. These cysts included those > 15 mm with unclear diagnosis, and a change in follow-up or with concerning features in which results might change clinical management. EUS-FNA with cytological, biochemical and glucose and molecular analyses with next-generation sequencing were performed in 36 pancreatic cysts. The cysts were classified as mucinous and non-mucinous by the combination of morphological, cytological and biochemical analyses when surgery was not performed. Malignancy was defined as cytology positive for malignancy, high-grade dysplasia or invasive carcinoma on surgical specimen, clinical or morphological progression, metastasis or death related to neoplastic complications during the 6-mo follow-up period. Next-generation sequencing results were compared for cyst type and malignancy. RESULTS Of the 36 lesions included, 28 (82.4%) were classified as mucinous and 6 (17.6%) as non-mucinous. Furthermore, 5 (13.9%) lesions were classified as malignant. The amount of deoxyribonucleic acid obtained was sufficient for molecular analysis in 25 (69.4%) pancreatic cysts. The amount of intracystic deoxyribonucleic acid was not statistically related to the cyst fluid volume obtained from the lesions. Analysis of KRAS and/or GNAS showed 83.33% [95% confidence interval (CI): 63.34-100] sensitivity, 60% (95%CI: 7.06-100) specificity, 88.24% (95%CI: 69.98-100) positive predictive value and 50% (95%CI: 1.66-98.34) negative predictive value (P = 0.086) for the diagnosis of mucinous cystic lesions. Mutations in KRAS and GNAS were found in 2/5 (40%) of the lesions classified as non-mucinous, thus recategorizing those lesions as mucinous neoplasms, which would have led to a modification of the follow-up plan in 8% of the cysts in which molecular analysis was successfully performed. All 4 (100%) malignant cysts in which molecular analysis could be performed had mutations in KRAS and/or GNAS, although they were not related to malignancy (P > 0.05). None of the other mutations analyzed could detect mucinous or malignant cysts with statistical significance (P > 0.05). CONCLUSION Molecular analysis can improve the classification of pancreatic cysts as mucinous or non-mucinous. Mutations were not able to detect malignant lesion

Greater basal skeletal muscle AMPKalpha phosphorylation in men than in women: associations with anaerobic performance

This study was designed to investigate the association of gender, fibre type composition, and anaerobic performance with the basal skeletal muscle signalling cascades regulating muscle phenotype

Comment on 'Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system'

This work was funded by Projects PI13/01741, PI13/01273, PI16/01920 and PI16/01650 from the Spanish Ministry of Health and Consumer Affairs and FEDER, and Mutua Madrileña Foundation (2012-0036), and was approved by the Ethics Committee of our Institution.Peer Reviewe

mRNA Detection in Anal Cytology: A Feasible Approach for Anal Cancer Screening in Men Who Have Sex with Men Living With HIV

There is growing interest in anal cancer screening strategies. However, cytological/molecular evaluation of anal samples is challenging. We aimed to determine the feasibility of detecting, in anal liquid-based cytologies, the expression of biomarkers involved in the cell cycle disturbance elicited by human papillomavirus (HPV). The accuracy of this approach in the identification of high-grade squamous intraepithelial lesions/anal intraepithelial neoplasia grade2-3 (HSIL/AIN2-3) was also evaluated. 215 anal cytologies from men having sex with men living with human immunodeficiency virus were evaluated. Patients showing concordant cytological and anoscopy-directed biopsy diagnosis were selected: 70 with negative cytology and HPV test, 70 with low-grade SIL (LSIL/AIN1) cytology and biopsy, and 75 with cytology and biopsy of HSIL/AIN2-3. CDKN2A/p16, MKI67 and TOP2A mRNA expression was analyzed. HPV detection was performed with Xpert HPV Assay (Cepheid, Sunnyvale, CA, USA). HSIL/AIN2-3 showed higher expression for the biomarkers than LSIL/AIN1 or negative samples. The specificity for HSIL/AIN2-3 detection for a sensitivity established at 70% was 44.7% (95%confidence interval [CI] 36.5-53.2) for TOP2A and MKI67 and 54.5% (95%CI 46.0-62.8%) for CDKN2A/p16. mRNA detection of cell biomarkers in anal liquid-based cytology is feasible. Further studies are warranted to confirm if strategies based on mRNA detection have any role in anal cancer screening

Four spot megrim (Lepidorhombus boscii) weight-length and weight-weight relationships in northern Iberian waters (stock 8.c, 9.a)

Total weight-length, gutted weight-length and total weight-gutted weight relationships were fitted for the Iberian Atlantic stock of four spot megrim (Lepidorhombus boscii) and their temporal variations were analyzed. The large sample size, size range and timeseries available allowed obtaining robust somatic parameters of combined sexes for the total weight-length relationships (a=0.0043, b=3.2008), for the gutted weight-length relationships (a=0.0055, b=3.1139), and the weight conversion factors (1.062). They are considered to best fit the current biometric relationships and most appropriate to be used in the stock assessment of the status of the stock and they contribute to a deeper knowledge of the life history traits of this species

Intermediate-onset colorectal cancer: A clinical and familial boundary between both early and late-onset colorectal cancer

Comparative studies of colorectal cancer (CRC) according to the age of onset have found differences between early-onset CRC (EOCRC) and late-onset CRC (LOCRC). Using this as a starting point, we wished to determine whether intermediate-onset CRC (IOCRC) might also be considered as an independent group within CRC. We performed a retrospective comparative study of the clinicopathological and familial features, as well as of the symptoms and their duration, of a total of 272 subjects diagnosed with CRC classified into three groups according to the age-of-onset (98 EOCRC, 83 IOCRC and 91 LOCRC). The results show that from a clinicopathological point of view, IOCRC shared certain features with EOCRC (gender, prognosis), and with LOCRC (multiple primary CRCs), whereas it also had characteristics that were specific for IOCRC (mean number of associated polyps). A gradual progression was observed from EOCRC to LOCRC from a greater family aggregation to sporadic cases, in parallel with a change of Lynch Syndrome cases to the sporadic microsatellite instability pathway, with the IOCRC being a boundary group that is more related to EOCRC. With respect to symptoms, duration and correlation with stages, IOCRC appeared more similar to EOCRC. Clinically, IOCRC behaves as a transitional group between EOCRC and LOCRC, with features in common with both groups, but also with IOCRC-specific features. Excluding cases with familial cancer history, the awareness for EOCRC diagnosis should be extended to IOCRC.Wethank the Tumor Registry of the Pathology Department of the 12 de Octubre University Hospita lfor providing the paraffinembedded tissues,and Ron Hartong for his help with the English revision of this manuscript.S

Megrim (Lepidorhombus whiffiagonis) weight-length relationships in the northern Bay of Biscay and Celtic Sea

The weight-length relationships are of a great interest in fish biology, stock assessment and fishery management, by predicting weight from length information and allowing to estimate the stock biomass. Weight-length relationships of megrim (Lepidorhombus whiffiagonis), an economically relevant flatfish species, are studied for two decades (2001 to 2019) in northern Bay of Biscay and Celtic Sea (ICES stock Div. 7.b-k, 8.abd), two important European fishing areas. More than 22000 specimens collected from commercial landings by AZTI and IEO were sampled. Total fish length, total weight and commercial gutted weight were obtained. Four five-year periods (quinquennium) (2000-04; 2005-09; 2010-14; 2015-19) were defined in the studied time-series. Both the large sample size and time-series available, as well as the collaboration between both institutions collecting complementary information from this stock, allowed obtaining robust somatic parameters and analyzing their temporal variations. A weight-length relationship model was fitted and the quinquennium and semester factors, which are of interest biologically and for assessment purposes, and their interactions were significant in the preliminary model. The weight-length relationships, both for total and gutted weight and for the combined sexes of the most recent quinquennium are presented in this work and considered the most suitable to be used in the oncoming annual assessment process of the status of this stock in northern Bay of Biscay and Celtic Sea in ICES

Criterios de Interpretación de la Edad en los Otolitos del Lirio o Bacaladilla del Atlántico Nordeste (Micromesistius poutassou) (versión 2)

Este manual tiene como objetivo describir los métodos para la determinación de la edad anual del lirio o bacaladilla (Micromesistius poutassou), centrándose en los criterios utilizados y estandarizados a nivel europeo para la interpretación de los anillos de crecimiento anual en los otolitos del lirio del Atlántico Nordeste. Este manual tiene como finalidad servir de referencia para los lectores de edad del lirio en los laboratorios del IEO y se basa en los últimos intercambios, talleres y publicaciones sobre la determinación de la edad del lirio (ICES 2005, 2013, 2017)