Screening executive function and global cognition with the Nine-Card Sorting Test: healthy participant studies and ageing implications.

Background: The Nine-Card Sorting Test provides valid and reliable scores when screening executive function, intelligence, and academic achievement. It is also useful for detecting cognitive impairment and dementia in the elderly and for assessing disease evolution and treatment effectiveness. It deals with three non-verbal sorting principles, individually and in pairs.

Increased prepubertal body weight enhances leptin sensitivity in proopiomelanocortin and neuropeptide y neurons before puberty onset in female rats.

Pubertal onset may be advanced by obesity, with leptin potentially acting as a permissive factor. We hypothesized that having increased body weight (BW) prepubertally affects the ability of leptin to activate intracellular signaling pathways and modulate the expression of hypothalamic neuropeptides involved in reproduction and metabolism. Because being raised in small litters (SLs) tends to increase BW at weaning, female rats were raised in litters of 4 or large litters (LLs) of 12 pups.

Identification of risk loci for Crohn's disease phenotypes using a genome-wide association study.

Background & Aims: Crohn's disease is a highly heterogeneous inflammatory bowel disease comprising multiple clinical phenotypes. Genome-wide association studies (GWASs) have associated a large number of loci with disease risk but have not associated any specific genetic variants with clinical phenotypes. We performed a GWAS of clinical phenotypes in Crohn's disease.

Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined.

Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells.

Study Question: Are neurokinin B (NKB), NK3 receptor (NK3R), kisspeptin (KISS1) and kisspeptin receptor (KISS1R) expressed in human ovarian granulosa cells?

Summary Answer: The NKB/NK3R and kisspeptin/KISS1R systems are co-expressed and functionally active in ovarian granulosa cells.

What Is Known Already: The NKB/NK3R and KISS1/KISS1R systems are essential for reproduction. In addition to their well-recognized role in hypothalamic neurons, these peptide systems may contribute to the control of fertility by acting directly on the gonads, but such a direct gonadal role remains largely unknown.

Differential impact of selective GH deficiency and endogenous GH excess on insulin-mediated actions in muscle and liver of male mice.

A reciprocal relationship between insulin sensitivity and glucose tolerance has been reported in some mouse models and humans with isolated changes in growth hormone (GH) production and signaling. To determine if this could be explained in part by tissue-specific changes in insulin sensitivity, hyperinsulinemic-euglycemic clamps were performed in mice with adult-onset, isolated GH deficiency and in mice with elevated endogenous GH levels due to somatotrope-specific loss of IGF-I and insulin receptors. Our results demonstrate that circulating GH levels are negatively correlated with insulin-mediated glucose uptake in muscle but positively correlated with insulin-mediated suppression of hepatic glucose production.

Disparate changes in kisspeptin and neurokinin B expression in the arcuate nucleus after sex steroid manipulation reveal differential regulation of the two KNDy peptides in rats.

Kisspeptin, neurokinin B (NKB) and dynorphin A are coexpressed in a population of neurons in the arcuate nucleus (ARC), termed KNDy neurons, which were recently recognized as important elements for the generation of GnRH pulses. However, the topographic distribution of these peptides and their regulated expression by sex steroids are still not well understood. In this study, detailed examination of NKB and kisspeptin immunoreactivity in the rat ARC was carried out, including comparison between sexes, with and without sex steroid replacement.

Physiological roles of gonadotropin-inhibitory hormone signaling in the control of mammalian reproductive axis: studies in the NPFF1 receptor null mouse.

RF-amide-related peptide-3 (RFRP-3), the mammalian ortholog of the avian gonadotropin-inhibiting hormone (GnIH), operates via the NPFF1 receptor (NPFF1R) to repress the reproductive axis, therefore acting as counterpart of the excitatory RF-amide peptide, kisspeptin (ligand of Gpr54). In addition, RFRP-3 modulates feeding and might contribute to the integrative control of energy homeostasis and reproduction. Yet, the experimental evidence supporting these putative functions is mostly indirect, and the physiological roles of RFRP-3 remain debatable and obscured by the lack of proper analytical tools and models.

Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation.

Objectives: The aim of this study was to determine the relationship between lipoprotein(a) [Lp(a)] and cardiovascular disease (CVD) in a large cohort of patients with heterozygous familial hypercholesterolemia (FH).

Background: Lp(a) is considered a cardiovascular risk factor. Nevertheless, the role of Lp(a) as a predictor of CVD in patients with FH has been a controversial issue.

Tuberculosis in solid-organ transplant recipients: disease characteristics and outcomes in the current era.

We determined the characteristics of posttransplant tuberculosis and the impact of rifampin-based antituberculosis regimens on outcomes in the current era. Patients comprised 64 transplant recipients with tuberculosis, divided into 2 consecutive cohorts: an earlier cohort (cases occurring from 2003 to 2007) and a later cohort (cases from 2008 to 2011). Patients from the later versus earlier era had tuberculosis develop later after transplant (odds ratio, 1.

Long- but not short-term adult-onset, isolated GH deficiency in male mice leads to deterioration of β-cell function, which cannot be accounted for by changes in β-cell mass.

Developmental models of GH deficiency (GHD) and excess indicate that GH is positively associated with β-cell mass. Therefore, the reduction in GH levels observed with age and weight gain may contribute to the age-related decline in β-cell function. To test this hypothesis, β-cell mass and function were assessed in a mouse model of adult-onset, isolated GHD (AOiGHD).

Top single nucleotide polymorphisms affecting carbohydrate metabolism in metabolic syndrome: from the LIPGENE study.

Rationale: Metabolic syndrome (MetS) is a high-prevalence condition characterized by altered energy metabolism, insulin resistance, and elevated cardiovascular risk.

Objectives: Although many individual single nucleotide polymorphisms (SNPs) have been linked to certain MetS features, there are few studies analyzing the influence of SNPs on carbohydrate metabolism in MetS.

Methods: A total of 904 SNPs (tag SNPs and functional SNPs) were tested for influence on 8 fasting and dynamic markers of carbohydrate metabolism, by performance of an intravenous glucose tolerance test in 450 participants in the LIPGENE study.

Cardiac condition in young chagasic women.

Rationale: Chagas disease is a complex disorder caused by Trypanosoma cruzi. Most patients remain asymptomatic for several years and 30% of them progress quietly to developing cardiomyopathy. The factors that lead to chronic myocardial lesions are not fully understood.

Nutritional, hormonal, and depot-dependent regulation of the expression of the small GTPase Rab18 in rodent adipose tissue.

There is increasing evidence that proteins associated with lipid droplets (LDs) play a key role in the coordination of lipid storage and mobilization in adipocytes. The small GTPase, RAB18, has been recently identified as a novel component of the protein coat of LDs and proposed to play a role in both β-adrenergic stimulation of lipolysis and insulin-induced lipogenesis in 3T3-L1 adipocytes. In order to better understand the role of Rab18 in the regulation of lipid metabolism in adipocytes, we evaluated the effects of age, fat location, metabolic status, and hormonal milieu on Rab18 expression in rodent white adipose tissue (WAT).

Peripubertal-onset but not adult-onset obesity increases IGF-I and drives development of lean mass, which may lessen the metabolic impairment in adult obesity.

It has been suggested that adult metabolic dysfunction may be more severe in individuals who become obese as children compared with those who become obese later in life. To determine whether adult metabolic function differs if diet-induced weight gain occurs during the peripubertal age vs. if excess weight gain occurs after puberty, male C57Bl/6J mice were fed a low-fat (LF; 10% kcal from fat) or high-fat (HF; 60% kcal from fat) diet starting during the peripubertal period (pHF; 4 wk of age) or as adults (aHF; 12 wk of age).

[Immunological monitoring strategies for cytomegalovirus infection. Immune-based therapies].

T-cell response to cytomegalovirus (CMV) is essential in the control of viral replication. Quantification of functional CD4(+) and CD8(+) T lymphocytes against certain CMV-antigen specificities through flow cytometry, ELISPOT or the QuantiFERON-CMV kit allows fairly accurate estimation of the risk of active infection and CMV disease in solid organ transplantation (SOT). Combined virological and immunological monitoring of CMV infection could allow antiviral treatments to be individually tailored and optimized in SOT, although clinical experience is currently lacking.

Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans.

Components of the innate immune response, including neutrophils and macrophages, are the first line of defense against infections. Their role is to initiate an inflammatory response, phagocyte and kill pathogens, recruit natural killer cells (NK), and facilitate the maturation and migration of dendritic cells that will initiate the adaptive immune response. Extraordinary advances have been made in the last decade on the knowledge of the receptors and mechanisms used by cells of the innate immunity not only to sense and eliminate the pathogen but also to communicate each other and collaborate with cells of adaptive immunity to mount an effective immune response.

Olive oil and haemostasis: platelet function, thrombogenesis and fibrinolysis.

Mediterranean diet is one of the healthiest nutritional models used in developed countries. The actual interest in this dietary model is based in two main premises. First, the high palatability for the consumer, which aids to the adherence to the model on a life-long basis, and second, the mounting evidence on the beneficial properties that its consumption provokes in cardiovascular risk factors, cancer and cognitive age associated decline.

Interleukin 1B variant -1473G/C (rs1143623) influences triglyceride and interleukin 6 metabolism.

Context: IL1b (IL1B or IL1β), a key modulator of the immune response, exerts its functions mainly via IL6 regulation. Fatty meals cause transient hypertriglyceridemia and are considered to be proinflammatory, but the extent of these responses shows high interindividual susceptibility.

Objective: We evaluated the influence of a genetic variant located in the promoter region of IL1B (-1473G/C) on fasting and postprandial lipids and IL6.

Update on genetics of postprandial lipemia.

The relationship between alimentary lipemia and coronary disease is of great interest in view of the epidemiological and experimental evidence that underlies it. The modulation of such phenomena is influenced by both genetic and environmental factors, thus explaining their extraordinary individual variance. Over the last two decades there has been an explosion of research in this area, with often conflicting findings reported in the literature.

[Dermoepidermic junction: a selective, complex and vital barrier].

Dermoepidermic junction (DEJ) is a highly complex region, containing a great variety of cellular elements, which despite of having different embriogenesis, interact with each other, generating different substances that keep the function and homeostasis of the greatest organ of the human body. DEJ is regarded as a highly specialized basal lamina, which acts as a highly selective pathway for the migration of cells and macromolecules, inducing cellular differentiation and micro enviromental metabolism modifications. DEJ may be divided into three zones regarding the basal lamina 1--the nearest to epidermic zone, having tonofilaments and hemidesmosomes, which keep anchored basal cells.

Genetic polymorphism of thiopurine S-methyltransferase in Argentina.

Background: Thiopurine methyltransferase (TPMT) catalyses the S-methylation of 6-thiopurine drugs, which are commonly used in the treatment of autoimmune diseases, leukaemia and organ transplantation. TPMT activity is polymorphic as a result of gene mutations. Ethnic variations in phenotype and genotype have been identified in previous population studies, but no information was available within Latin-American populations.

Generalized eruptive keratoacanthoma (Grzybowski variant).

We describe a patient with generalized eruptive keratoacanthoma (KA) of Grzybowski showing the characteristic features of this extremely rare condition. Since the first description by Grzybowski in 1950, only 28 additional cases (including the present one) have been reported. This variety of KA most commonly affects patients during the fifth to seventh decade of life and appears as a generalized eruption of hundreds to thousands of follicular papules.