Altered expression of the kisspeptin/KISS1R and neurokinin B/NK3R systems in mural granulosa and cumulus cells of patients with polycystic ovarian syndrome.

Purpose: The neurokinin B (NKB)/NK receptor (NK3R) and kisspeptin (KISS1)/kisspeptin receptor (KISS1R), two systems essential for reproduction, are present in human granulosa cells (GCs) of healthy women and contribute to the control of fertility, at least partially, by acting on the gonads. However, little is known about the expression of these systems in GCs of women with polycystic ovarian syndrome (PCOS). The aim of this study was to analyze the expression of NKB/NK3R and KISS1/KISS1R in mural granulosa (MGCs) and cumulus cells (CCs) of PCOS women.

Infections and internal medicine patients: Could a comorbidity score predict in-hospital mortality?

Infectious diseases (ID) are frequently cause of internal medicine wards (IMW) admission. We aimed to evaluate risk factors for in-hospital mortality (IHM) in IMW patients with ID, and to test the usefulness of a comorbidity score (CS).This study included ID hospital admissions between January 2013, and December 2016, recorded in the database of the local hospital.

Role of Anti-inflammatory Interventions in Coronary Artery Disease: Understanding the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS).

Coronary artery disease (CAD) is the leading cause of death worldwide. Despite notable advances in understanding the nature of atherosclerotic processes and the use of effective medications such as statins, there remains a significant residual risk. Even after optimal medical treatments and precise revascularisations, the recurrence of MI remains at approximately one-third for 5 years after an acute coronary syndrome (ACS).

A Knockout IFNL4 Variant Is Associated With Protection From Sexually Transmitted HIV-1 Infection.

An interferon λ4 gene (IFNL4) knockout allele (rs368234815; TT) is associated with spontaneous and IFN-α-dependent cure of hepatitis C virus infection. The role of this polymorphism in the susceptibility to human immunodeficiency virus type 1 (HIV-1) infection is controversial. This study aimed to assess the association of this knockout IFNL4 variant and sexually transmitted HIV-1 infection.

Comparison of Low-Density Lipoprotein Cholesterol Assessment by Martin/Hopkins Estimation, Friedewald Estimation, and Preparative Ultracentrifugation: Insights From the FOURIER Trial.

Importance: Recent studies have shown that Friedewald underestimates low-density lipoprotein cholesterol (LDL-C) at lower levels, which could result in undertreatment of high-risk patients. A novel method (Martin/Hopkins) using a patient-specific conversion factor provides more accurate LDL-C levels. However, this method has not been tested in proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor-treated patients.

Efficacy of the Otago Exercise Programme to reduce falls in community-dwelling adults aged 65-80 years old when delivered as group or individual training.

Aim: This study will compare how falls can be reduced in non-institutionalized older Spanish adults aged 65-80 years by providing group or individual exercise sessions using the Otago Exercise Programme.

Background: The Otago Exercise Programme is a progressive home-based exercise programme, where trained health professionals help people engage in strength, balance and endurance exercises. Its format is based on the evidence from four clinical trials.

Haploidentical transplant in patients with myelodysplastic syndrome.

The only curative treatment in patients with intermediate or high-risk myelodysplastic syndrome (MDS) is allogeneic hematopoietic stem cell transplantation (HSCT), which usually results in a long-term, disease-free survival rate of between 30% and 50%, depending on the disease risk and the type of donor. In patients without an HLA-matched sibling donor, a family haploidentical donor is an alternative option. The present study reports the European Group for Blood and Marrow Transplantation activity for haploidentical transplantation in MDS patients.

High Serum Retinol as a Relevant Contributor to Low Bone Mineral Density in Postmenopausal Osteoporotic Women.

There is controversial information about the impact of vitamin A on bone. Some epidemiological studies show that excessive intake of vitamin A, or an excess of serum vitamin A, has related with adverse impact on bone mass; however, other studies did not find these links, and some authors have proposed that this vitamin might promote a better bone health. The present work aims to contribute to clarify the real role of vitamin A in bone tissue.

Deleting the mouse Hsd17b1 gene results in a hypomorphic Naglu allele and a phenotype mimicking a lysosomal storage disease.

HSD17B1 is a steroid metabolising enzyme. We have previously generated knockout mice that had the entire coding region of Hsd17b1 replaced with lacZ-neo cassette (Hsd17b1-LacZ/Neo mice). This resulted in a 90% reduction of HSD17B1 activity, associated with severe subfertility in the knockout females.

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.

Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter.

Dietary magnesium supplementation prevents and reverses vascular and soft tissue calcifications in uremic rats.

Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.

Cardiovascular disease in immune-mediated inflammatory diseases: A cross-sectional analysis of 6 cohorts.

To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences.Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke.

Hepatic p63 regulates steatosis via IKKβ/ER stress.

p53 family members control several metabolic and cellular functions. The p53 ortholog p63 modulates cellular adaptations to stress and has a major role in cell maintenance and proliferation. Here we show that p63 regulates hepatic lipid metabolism.

Social vulnerability and hypoglycemia among patients with diabetes.

Lower-income populations are hit harder by the diabetes epidemic as regards both prevalence and the risk of complications. Food Insecurity is one of the mechanisms through which poverty may predispose people with low socio-economic status to poorer control and higher complication rates. The United Nations Food and Agriculture Organization defined food security as "the right to have access to sufficient nutritional and culturally acceptable food choices.

Development and validation of a method for precise dating of female puberty in laboratory rodents: The puberty ovarian maturation score (Pub-Score).

Puberty is a key developmental event whose primary regulatory mechanisms remain poorly understood. Precise dating of puberty is crucial for experimental (preclinical) studies on its complex neuroendocrine controlling networks. In female laboratory rodents, external signs of puberty, such as vaginal opening (VO) and epithelial cell cornification (i.

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients.

Background: Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk.

Methods: In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo.

Unmet needs in the management of atherosclerotic cardiovascular disease: Is there a role for emerging anti-inflammatory interventions?

Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Despite extraordinary advances in the understanding of the pathophysiology and the utilization of very effective medications such as statins, there still remains a significant residual risk. In fact, even after optimal interventional and medical therapy, the possibility of recurrent myocardial infarction remains at approximately one third for five years after acute coronary syndromes, thus emphasizing the urgent need for novel therapies to prevent the progress of atherosclerosis.

Klotho Prevents Translocation of NFκB.

Klotho protein is a β-glucuronidase capable of hydrolyzing steroid β-glucuronides. Two molecules are produced by the Klotho gene, a membrane bound form and a circulating form. This protein is recognized as an antiaging gene with pleiotropic functions.

Dissecting the Roles of Gonadotropin-Inhibitory Hormone in Mammals: Studies Using Pharmacological Tools and Genetically Modified Mouse Models.

Reproduction is essential for perpetuation of the species and, hence, is controlled by a sophisticated network of regulatory factors of central and peripheral origin that integrate at the hypothalamic-pituitary-gonadal (HPG) axis. Among the central regulators of reproduction, kisspeptins, as major stimulatory drivers of gonadotropin-releasing hormone (GnRH) neurosecretion, have drawn considerable interest in the last decade. However, the dynamic, if not cyclic (in the female), nature of reproductive function and the potency of kisspeptins and other stimulatory signals of the HPG axis make tenable the existence of counterbalance inhibitory mechanisms, which may keep stimulation at check and would allow adaptation of reproductive maturation and function to different endogenous and environmental conditions.

Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but are Insufficient to Fully Preserve Gonadotropic Axis Activity.

Kisspeptins, ligands of the receptor, Gpr54, are potent stimulators of puberty and fertility. Yet, whether direct kisspeptin actions on GnRH neurons are sufficient for the whole repertoire of their reproductive effects remains debatable. To dissect out direct vs.

Development of Donor-Specific Anti-HLA Antibodies After Restarting Hemodialysis Due to Graft Failure.

Background: Incidents of renal replacement therapy (RRT) from renal transplants are on the rise. Some authors have associated the development of donor-specific anti-HLA antibodies (DSA) with the end of immunosuppression treatment (IS) and/or the performing of a transplantectomy. The objective of this study was to analyze the characteristics of transplant patients having high immunological risk who restarted RRT and the subsequent development of DSA.

[Arteriovenous Malformations - checking and descriptive analysis of 52 AVMs treated for the 2000-2010 period].

Background: To describe our experience in treating AVMs based on age, sex, reasons for consultation and symptoms, localization and clinical diagnosis, size, types, relation with aneurysms, endovascular procedures used, postoperative results and complications.

Methods: We present 52 patients with AVMs, analysing Neurological Exam, Ct, Irm and Brain Arteriography.

Results: Average age: 37.

RF9 Acts as a KISS1R Agonist In Vivo and In Vitro.

RF9, a reported antagonist of the mammalian gonadotropin-inhibitory hormone receptor, stimulates gonadotropin secretion in mammals. Recent studies have suggested that the stimulatory effect of RF9 on gonadotropin secretion relies on intact kisspeptin receptor (KISS1R) signaling, but the underlying mechanisms remain to be elucidated. Using Chinese Hamster Ovary cells stably transfected with KISS1R, we show that RF9 binds specifically to KISS1R, with a Kd of 1.

In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters.

Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes.

Metabolic and Gonadotropic Impact of Sequential Obesogenic Insults in the Female: Influence of the Loss of Ovarian Secretion.

The reproductive impact of persistent energy excess in the female remains incompletely defined, yet the escalating prevalence of obesity calls for better understanding of this phenomenon. Also along this line, the influence of ovarian hormones on the pathophysiology of obesity and its comorbidities merits further investigation. We study here the metabolic and gonadotropic impact of sequential obesogenic insults, namely postnatal overnutrition [by rearing in small litters (SL)] and high-fat diet (HFD) after weaning, in gonadal-intact and ovariectomized (OVX) female rats.