The relationship of peritubular capillary density with glomerular volume and kidney function in living kidney donors.

Background: Peritubular capillary rarefaction plays an important role in the progression of chronic kidney disease. Little is known about the relation between peritubular capillary density, glomerular volume and filtration rate in the healthy kidney.

Methods: In this single-center study, we included 69 living kidney donors who donated between 2005 and 2008 and had representative renal biopsies available.

The Maastricht Acquisition Platform for Studying Mechanisms of Cell-Matrix Crosstalk (MAPEX): An Interdisciplinary and Systems Approach towards Understanding Thoracic Aortic Disease.

Current management guidelines for ascending thoracic aortic aneurysms (aTAA) recommend intervention once ascending or sinus diameter reaches 5-5.5 cm or shows a growth rate of >0.5 cm/year estimated from echo/CT/MRI.

Visual interstitial fibrosis assessment as continuous variable in protocol renal transplant biopsies.

Aims: In current renal transplant pathology practice, interstitial fibrosis is visually assessed in categories according to the Banff classification. As this has a moderate reproducibility, which is little ameliorated by morphometric analysis, we investigated whether visual renal fibrosis assessment is feasible on a continuous scale, i.e.

SOX2 expression in the pathogenesis of premalignant lesions of the uterine cervix: its histo-topographical distribution distinguishes between low- and high-grade CIN.

SOX2 expression in high-grade cervical intraepithelial neoplasia (CIN3) and cervical squamous cell carcinoma is increased compared to that in the normal cervical epithelium. However, data on the expression and histological distribution of SOX2 in squamous epithelium during progression of CIN are largely lacking. We studied SOX2 expression throughout the epithelium in 53 cases of CIN1, 2, and 3.

Sequential Exposure to Antenatal Microbial Triggers Attenuates Alveolar Growth and Pulmonary Vascular Development and Impacts Pulmonary Epithelial Stem/Progenitor Cells.

Perinatal inflammatory stress is strongly associated with adverse pulmonary outcomes after preterm birth. Antenatal infections are an essential perinatal stress factor and contribute to preterm delivery, induction of lung inflammation and injury, pre-disposing preterm infants to bronchopulmonary dysplasia. Considering the polymicrobial nature of antenatal infection, which was reported to result in diverse effects and outcomes in preterm lungs, the aim was to examine the consequences of sequential inflammatory stimuli on endogenous epithelial stem/progenitor cells and vascular maturation, which are crucial drivers of lung development.

Intestinal Goblet Cell Loss during Chorioamnionitis in Fetal Lambs: Mechanistic Insights and Postnatal Implications.

Chorioamnionitis, an important cause of preterm birth, is linked to necrotizing enterocolitis (NEC). NEC is characterized by a disrupted mucus barrier, goblet cell loss, and endoplasmic reticulum (ER) stress of the intestinal epithelium. These findings prompted us to investigate the mechanisms underlying goblet cell alterations over time in an ovine chorioamnionitis model.

Nerve Fibers in the Tumor Microenvironment Are Co-Localized with Lymphoid Aggregates in Pancreatic Cancer.

B cells and tertiary lymphoid structures (TLS) are reported to be important in survival in cancer. Pancreatic Cancer (PDAC) is one of the most lethal cancer types, and currently, it is the seventh leading cause of cancer-related death worldwide. A better understanding of tumor biology is pivotal to improve clinical outcome.

Chorioamnionitis induces changes in ovine pulmonary endogenous epithelial stem/progenitor cells in utero.

Background: Chorioamnionitis, an intrauterine infection of the placenta and fetal membranes, is a common risk factor for adverse pulmonary outcomes in premature infants including BPD, which is characterized by an arrest in alveolar development. As endogenous epithelial stem/progenitor cells are crucial for organogenesis and tissue repair, we examined whether intrauterine inflammation negatively affects these essential progenitor pools.

Methods: In an ovine chorioamnionitis model, fetuses were intra-amniotically exposed to LPS, 2d or 7d (acute inflammation) before preterm delivery at 125d of gestation, or to intra-amniotic Ureaplasma parvum for 42d (chronic inflammation).

RAGE deficiency does not affect non-alcoholic steatohepatitis and atherosclerosis in Western type diet-fed Ldlr mice.

Non-alcoholic fatty liver disease is a spectrum of liver diseases ranging from steatosis only to non-alcoholic steatohepatitis (NASH). The latter is characterized by hepatic inflammation, which increases the risk of cardiovascular disease. It is poorly understood which factors contribute to the onset of hepatic inflammation characterizing the progression from steatosis to NASH.

Comparability of histological outcomes in rats and humans in a hernia model.

Background: Hernia repair is one of the most frequently performed operations. In search of the ideal mesh for hernia repair, animal research is required. Although rats are most often used in experimental mesh experiments, no correlation with clinical findings in humans has ever been shown.

The influence of anesthetics on substantia nigra tyrosine hydroxylase expression and tau phosphorylation in the hypoxic-ischemic near-term lamb.

BackgroundGeneral anesthetics could protect key neurotransmitter systems, such as the dopaminergic system, from hypoxic-ischemic encephalopathy (HIE) by limiting excessive glutamatergic neurotransmission. However, anesthetics may adversely affect inflammation and tau phosphorylation.MethodsA near-term sheep model of HIE by umbilical cord occlusion (UCO) under anesthesia was used.

Histopathological and Inflammatory Features of Chronically Discharging Open Mastoid Cavities: Secondary Analysis of a Randomized Clinical Trial.

Importance: Many patients with an open radical mastoid cavity experience therapy-resistant otorrhea. Little is known about the underlying histopathological substrate of unstable cavities and the correlation with treatment failure.

Objective: To study the histopathological and inflammatory features of chronically discharging open radical mastoid cavities and the influence of different treatments.

FXR agonism protects against liver injury in a rat model of intestinal failure-associated liver disease.

Background: Intestinal failure-associated liver disease (IFALD) is a clinical challenge. The pathophysiol-ogy is multifactorial and remains poorly understood. Disturbed recirculation of bile salts, due to loss of bile via an enterocutaneous fistula, is considered a major contributing factor.

Whole body and hematopoietic ADAM8 deficiency does not influence advanced atherosclerotic lesion development, despite its association with human plaque progression.

Although A Disintegrin And Metalloproteinase 8 (ADAM8) is not crucial for tissue development and homeostasis, it has been implicated in various inflammatory diseases by regulating processes like immune cell recruitment and activation. ADAM8 expression has been associated with human atherosclerosis development and myocardial infarction, however a causal role of ADAM8 in atherosclerosis has not been investigated thus far. In this study, we examined the expression of ADAM8 in early and progressed human atherosclerotic lesions, in which ADAM8 was significantly upregulated in vulnerable lesions.

Topical Sinecatechins, 10%, Ointment for Superficial Basal Cell Carcinoma: A Randomized Clinical Trial.

This randomized clinical trial compares topical sinecatechins ointment, 10%, vs placebo in the treatment of superficial basal cell carcinoma.

Intermittent pacing therapy favorably modulates infarct remodeling.

Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown.

Diet-induced weight loss decreases adipose tissue oxygen tension with parallel changes in adipose tissue phenotype and insulin sensitivity in overweight humans.

Background/objectives: Although adipose tissue (AT) hypoxia is present in rodent models of obesity, evidence for this in humans is limited. Here, we investigated the effects of diet-induced weight loss (WL) on abdominal subcutaneous AT oxygen tension (pO), AT blood flow (ATBF), AT capillary density, AT morphology and transcriptome, systemic inflammatory markers and insulin sensitivity in humans.

Subjects/methods: Fifteen overweight and obese individuals underwent a dietary intervention (DI), consisting of a 5-week very-low-calorie diet (VLCD, 500 kcal day; WL), and a subsequent 4-week weight stable diet (WS).

Vessel wall and adventitial DCE-MRI parameters demonstrate similar correlations with carotid plaque microvasculature on histology.

Purpose: To assess parameter agreement of volume transfer coefficient (K ) between two vascular regions and to study the correlation with microvessel density on histology. The dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter K is frequently used to study atherosclerotic plaque microvasculature. K has been reported using different descriptive statistics (mean, median, 75 percentile) either for the whole vessel wall or the adventitia in previous studies.

Limited additive value of the Ki-67 proliferative index on patient survival in World Health Organization-classified pulmonary carcinoids.

Aims: Currently pulmonary carcinoids are separated into typical and atypical based on mitotic count and presence of necrosis, according to the World Health Organization. At variance with gastroenteropancreatic neuroendocrine tumours, which are graded based on mitotic count and Ki-67 proliferative index, the use of Ki-67 for grading pulmonary carcinoids is still under debate.

Methods And Results: In this study we evaluated the prognostic impact of Ki-67 assessment in a multicentre cohort of 201 carcinoids [147 typical carcinoids (TCs) and 54 atypical carcinoids (ACs)] using manual analysis (2000 cells counted) and digital image analysis (in-house Leica Qwin program; ≥4500 cells counted).

Osseointegration and implant stability of extraoral implants in Göttingen minipigs after irradiation.

Objectives: The aim of this study was to compare the influence of implant surface treatment and irradiation dose on implant stability and osseointegration of 144 extraoral implants in irradiated frontal bone of minipigs.

Material And Methods: 144 implants with 3 different surface treatments (machined, etched and HAVD-coated) were implanted in the frontal bone of 16 Göttingen minipigs. Three groups of four pigs received radiation with equivalent doses of 25, 50 and 70 Gy, and one group served as control.

Imaging Intraplaque Inflammation in Carotid Atherosclerosis With 18F-Fluorocholine Positron Emission Tomography-Computed Tomography: Prospective Study on Vulnerable Atheroma With Immunohistochemical Validation.

Background: (18)F-fluorocholine ((18)F-FCH) uptake is associated with cell proliferation and activity in tumor patients. We hypothesized that (18)F-FCH could similarly be a valuable imaging tool to identify vulnerable plaques and associated intraplaque inflammation and atheroma cell proliferation.

Methods And Results: Ten consecutive stroke patients (90% men, median age 66.

Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated.

Intra-Section Analysis of Human Coronary Arteries Reveals a Potential Role for Micro-Calcifications in Macrophage Recruitment in the Early Stage of Atherosclerosis.

Background: Vascular calcification is associated with poor cardiovascular outcome. Histochemical analysis of calcification and the expression of proteins involved in mineralization are usually based on whole section analysis, thereby often ignoring regional differences in atherosclerotic lesions. At present, limited information is available about factors involved in the initiation and progression of atherosclerosis.

Hck/Fgr Kinase Deficiency Reduces Plaque Growth and Stability by Blunting Monocyte Recruitment and Intraplaque Motility.

Background: Leukocyte migration is critical for the infiltration of monocytes and accumulation of monocyte-derived macrophages in inflammation. Considering that Hck and Fgr are instrumental in this process, their impact on atherosclerosis and on lesion inflammation and stability was evaluated.

Methods And Results: Hematopoietic Hck/Fgr-deficient, LDLr(-/-) chimeras, obtained by bone marrow transplantation, had smaller but, paradoxically, less stable lesions with reduced macrophage content, overt cap thinning, and necrotic core expansion as the most prominent features.

Angiopoietin-2 blocking antibodies reduce early atherosclerotic plaque development in mice.

Objective: Angiopoietin-2 (Ang-2) blocking agents are currently undergoing clinical trials for use in cancer treatment. Ang-2 has also been associated with rupture-prone atherosclerotic plaques in humans, suggesting a role for Ang-2 in plaque stability. Despite the availability of Ang-2 blocking agents, their clinical use is still lacking.