Cysteinyl-leukotriene pathway as a new therapeutic target for the treatment of atherosclerosis related to obstructive sleep apnea syndrome.

Aims: Obstructive sleep apnea (OSA) characterized by nocturnal intermittent hypoxia (IH) is associated with atherosclerosis and cysteinyl-leukotrienes (CysLT) pathway activation. We aimed to identify the determinants of CysLT pathway activation and the role of CysLT in OSA-related atherosclerosis.

Methods And Results: Determinants of the urinary excretion of LTE (U-LTE) including history of cardiovascular events, polysomnographic and biological parameters were studied in a cohort of 170 OSA patients and 29 controls, and in a subgroup of OSA patients free of cardiovascular event (n = 136).

Comorbidities, risk factors and outcomes in patients with heart failure and an ejection fraction of more than or equal to 40% in primary care- and hospital care-based outpatient clinics.

Objective: The aim of this study is to describe patients with heart failure and an ejection fraction (EF) of more than or equal to 40%, managed in both Primary- and Hospital based outpatient clinics separately with their prognosis, comorbidities and risk factors. Further to compare the heart failure medication in the two groups.

Design: We used the prospective Swedish Heart Failure Registry to include 9654 out-patients who had HF and EF ≥40%, 1802 patients were registered in primary care and 7852 in hospital care.

Morphological Classification of Corrupted Colonic Crypts in Ulcerative Colitis.

Background/aim: In ulcerative colitis (UC) the colonic mucosa shows, in addition to a high number of inflammatory cells, crypts with architectural distortions, called corrupted colonic crypts (CCC). Here we classify the histologic repertoire and assess the frequency of CCC in UC.

Patients And Methods: Five-hundred and sixteen histologic sections from 29 colectomy specimens with UC (24 having adenocarcinoma and five, high-grade dysplasia, HGD) were reviewed.

Expression of Progesterone and Androgen Receptors in the Breast of Premenopausal Women, Considering Menstrual Phase.

Background: Progesterone and androgens are important for normal development and tumorigenesis of the breast.

Patients And Methods: Breast tissue samples from 49 premenopausal women were obtained. The progesterone receptors (PRA, PRB, PGRMC1 and PGRMC2) and the androgen receptor (AR) were determined in malignant and benign breast tumors and control tissues.

Exome sequencing of primary breast cancers with paired metastatic lesions reveals metastasis-enriched mutations in the A-kinase anchoring protein family (AKAPs).

Background: Tumor heterogeneity in breast cancer tumors is today widely recognized. Most of the available knowledge in genetic variation however, relates to the primary tumor while metastatic lesions are much less studied. Many studies have revealed marked alterations of standard prognostic and predictive factors during tumor progression.

Influence of peanut matrix on stability of allergens in gastric-simulated digesta: 2S albumins are main contributors to the IgE reactivity of short digestion-resistant peptides.

Background: Most food allergens sensitizing via the gastrointestinal tract are stable proteins that are resistant to pepsin digestion, in particular major peanut allergens, Ara h 2 and Ara h 6. Survival of their large fragments is essential for sensitizing capacity. However, the immunoreactive proteins/peptides to which the immune system of the gastrointestinal tract is exposed during digestion of peanut proteins are unknown.

Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

Background: In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours.

Flt3 ligand expands bona fide innate lymphoid cell precursors in vivo.

A common helper-like innate lymphoid precursor (CHILP) restricted to the innate lymphoid cells (ILC) lineage has been recently characterized. While specific requirements of transcription factors for CHILPs development has been partially described, their ability to sense cytokines and react to peripheral inflammation remains unaddressed. Here, we found that systemic increase in Flt3L levels correlated with the expansion of Lineage (Lin)α4β7 precursors in the adult murine bone marrow.

Structural connections in the brain in relation to gender identity and sexual orientation.

Both transgenderism and homosexuality are facets of human biology, believed to derive from different sexual differentiation of the brain. The two phenomena are, however, fundamentally unalike, despite an increased prevalence of homosexuality among transgender populations. Transgenderism is associated with strong feelings of incongruence between one's physical sex and experienced gender, not reported in homosexual persons.

Host DNases prevent vascular occlusion by neutrophil extracellular traps.

Platelet and fibrin clots occlude blood vessels in hemostasis and thrombosis. Here we report a noncanonical mechanism for vascular occlusion based on neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during inflammation. We investigated which host factors control NETs in vivo and found that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in circulation during sterile neutrophilia and septicemia.

Updated Histologic Classification of Adenomas and Carcinomas in the Colon of Carcinogen-treated Sprague-Dawley Rats.

Background: Recent studies have disclosed novel histological phenotypes of colon tumours in carcinogen-treated rats. The aim of this study was to update the current histological classification of colonic neoplasias in Sprague-Dawley (SD) rats.

Materials And Methods: Archival sections from 398 SD rats having 408 neoplasias in previous experiments were re-evaluated.

Intestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system.

Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined.

An HIF-1α/VEGF-A Axis in Cytotoxic T Cells Regulates Tumor Progression.

Cytotoxic T cells infiltrating tumors are thought to utilize HIF transcription factors during adaptation to the hypoxic tumor microenvironment. Deletion analyses of the two key HIF isoforms found that HIF-1α, but not HIF-2α, was essential for the effector state in CD8 T cells. Furthermore, loss of HIF-1α in CD8 T cells reduced tumor infiltration and tumor cell killing, and altered tumor vascularization.

Partial to complete abrogation of the subepithelial macrophage barrier against the gut microbiota in patients with ulcerative colitis and Crohn's colitis.

Aims: The integrity of the band of indigenous macrophages in the subepithelial layer of the lamina propria (SLP) is crucial in preventing the commensal gut microbiota from attacking the host. The breakdown of the SLP macrophage barrier results in microbiota inflow and improper immune responses; this might lead to inflammatory bowel disease (IBD). During inflammation, the SLP macrophage barrier is reinforced by inflammation-elicited macrophages (IEMs), which are derived from blood-circulating monocytes.

IGF-1 as a Drug for Preterm Infants: A Step-Wise Clinical Development.

Background: Insulin-like growth factor 1 (IGF-1) is a mitogenic hormone involved in many processes such as growth, metabolism, angiogenesis and differentiation. After very preterm birth, energy demands increase while maternal supplies of nutrients and other factors are lost and the infant may become dependent on parenteral nutrition for weeks. Low postnatal IGF-1 concentrations in preterm infants are associated with poor weight gain, retinopathy of prematurity (ROP) and other morbidities.

Clustering of conformational IgE epitopes on the major dog allergen Can f 1.

Immunoglobulin E (IgE)-associated allergy affects more than 25% of the population. Can f 1 is the major dog allergen associated with respiratory symptoms but the epitopes recognized by allergic patients IgE on Can f 1 are unknown. To characterize IgE epitopes of Can f 1 recognized by dog allergic patients, six overlapping peptides spanning the Can f 1 sequence were synthesized.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology.

The third pathway of colorectal carcinogenesis.

Aims: The majority of the colorectal carcinomas (CRC) arise in a vast mucosal area built with columnar cells and mucus-producing goblet cells. These carcinomas evolve via the conventional (tubular/villous) adenoma-carcinoma pathway, or the serrated adenoma-carcinoma pathway. Much less frequently CRC arise in the gut-associated lymphoid tissue (GALT) mucosal domain via the third pathway of colorectal carcinogenesis.

Corrupted Colonic Crypts Bordering Regenerating Mucosal Ulcers in Ulcerative Colitis.

Background/aim: Histology in protracted ulcerative colitis (UC) discloses high numbers of chronic inflammatory cells and crypts with architectural distortions. In severe cases, ulcerations are frequently found. The histogenesis of colonic crypts with architectural distortions in UC remains elusive.

Are Corrupted Non-dysplastic Colonic Crypts the First Histological Event in Experimental Colonic Carcinogenesis?

Background: The colonic crypts in rats replicate by symmetric fission at the base of the crypts, and proceeds upwards, to generate two separate identical crypts. Recently, anomalous crypts (called corrupted colonic crypts, CCCs) were found in the colonic mucosa of Sprague-Dawley rats treated with the carcinogen dimethylhydrazine. Here it was investigated whether CCCs develop in the colonic mucosa of another rat strain, treated with a different carcinogen.

Expression of Nestin associates with BRCA1 mutations, a basal-like phenotype and aggressive breast cancer.

We here examined whether Nestin, by protein and mRNA levels, could be a predictor of BRCA1 related breast cancer, a basal-like phenotype, and aggressive tumours. Immunohistochemical staining of Nestin was done in independent breast cancer hospital cohorts (Series I-V, total 1257 cases). Also, TCGA proteomic data (n = 103), mRNA microarray data from TCGA (n = 520), METABRIC (n = 1992), and 6 open access breast cancer datasets (n = 1908) were analysed.

The Histogenesis of the Third Pathway of Colonic Carcinogenesis in Rats.

Background/aim: Conventional (tubular or villous) adenomas, and the more recently described serrated adenomas, are non-invasive neoplasias that precede colon carcinomas in carcinogen-treated rats. In contrast, the histological steps antedating carcinomas in gut-associated lymphoid tissue (GALT) in rats, i.e.

Corrupted colonic crypt fission in carcinogen-treated rats.

Background: The colonic crypts in rats reproduce themselves by symmetric fission at the base of the crypts, and proceeding upwards, generate two separate identical crypts. Recently we reported corrupted colonic crypt fission (CCCF) in rats with colonic carcinoma. Here we investigated whether CCCF also occurred in the colonic mucosa without carcinoma in carcinogen-treated rats.

Cannabis Edibles: Blood and Oral Fluid Cannabinoid Pharmacokinetics and Evaluation of Oral Fluid Screening Devices for Predicting Δ-Tetrahydrocannabinol in Blood and Oral Fluid following Cannabis Brownie Administration.

Background: Roadside oral fluid (OF) Δ-tetrahydrocannabinol (THC) detection indicates recent cannabis intake. OF and blood THC pharmacokinetic data are limited and there are no on-site OF screening performance evaluations after controlled edible cannabis.

Content: We reviewed OF and blood cannabinoid pharmacokinetics and performance evaluations of the Draeger DrugTest5000 (DT5000) and Alere™ DDS2 (DDS2) on-site OF screening devices.