Basic Science and Pathogenesis.

Background: Mechanisms driving cerebrovascular decline during Alzheimer's disease and related dementias (ADRD) are poorly understood. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme in the folate/methionine pathway. Variants in MTHFR, notably 677C>T, are associated with ADRD.

Characterizing molecular and synaptic signatures in mouse models of late-onset Alzheimer's disease independent of amyloid and tau pathology.

Introduction: MODEL-AD (Model Organism Development and Evaluation for Late-Onset Alzheimer's Disease) is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to capture the trajectory and progression of late-onset Alzheimer's disease (LOAD) more accurately.

Methods: We created the LOAD2 model by combining apolipoprotein E4 (APOE4), Trem2*R47H, and humanized amyloid-beta (Aβ). Mice were subjected to a control diet or a high-fat/high-sugar diet (LOAD2+HFD).

Renal hyperparathyroidism- a risk factor in the development of encapsulating peritoneal sclerosis.

Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS.

Characterizing Molecular and Synaptic Signatures in mouse models of Late-Onset Alzheimer's Disease Independent of Amyloid and Tau Pathology.

Introduction: MODEL-AD is creating and distributing novel mouse models with humanized, clinically relevant genetic risk factors to more accurately mimic LOAD than commonly used transgenic models.

Methods: We created the LOAD2 model by combining APOE4, Trem2*R47H, and humanized amyloid-beta. Mice aged up to 24 months were subjected to either a control diet or a high-fat/high-sugar diet (LOAD2+HFD) from two months of age.

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions.

Peritoneal adhesions commonly occur after abdominal or pelvic surgery. These scars join internal organs to each other or to the cavity wall and can present with abdominal or pelvic pain, and bowel obstruction or female infertility. The mechanisms underlying adhesion formation remain unclear and thus, effective treatments are not forthcoming.

-Host Interactions Mediating Airway Wall Remodelling in Asthma.

Asthma is a chronic heterogeneous respiratory condition that is mainly associated with sensitivity to airborne agents such as pollen, dust mite products and fungi. Key pathological features include increased airway inflammation and airway wall remodelling. In particular, goblet cell hyperplasia, combined with excess mucus secretion, impairs clearance of the inhaled foreign material.

Ongoing Exposure to Peritoneal Dialysis Fluid Alters Resident Peritoneal Macrophage Phenotype and Activation Propensity.

Peritoneal dialysis (PD) is a more continuous alternative to haemodialysis, for patients with chronic kidney disease, with considerable initial benefits for survival, patient independence and healthcare costs. However, long-term PD is associated with significant pathology, negating the positive effects over haemodialysis. Importantly, peritonitis and activation of macrophages is closely associated with disease progression and treatment failure.

The use of mesenchymal stem cells in animal models for gastrointestinal anastomotic leak: A systematic review.

Aim: Anastomotic leak is the most feared complication of gastrointestinal surgery. Mesenchymal stem cell technology is used clinically to promote wound healing; however, the safety and efficacy of this technology on anastomotic healing has yet to be defined. The aim of this study was to investigate whether mesenchymal stem cells confer any benefit when applied to animal models for gastrointestinal anastomotic leak, identify the methodology and how efficacy is assessed.

Differential Proinflammatory Responses to by Airway Epithelial Cells In Vitro Are Protease Dependent.

is an important human respiratory mould pathogen. In addition to a barrier function, airway epithelium elicits a robust defence against inhaled by initiating an immune response. The manner by which initiates this response and the reasons for the immunological heterogeneity with different isolates are unclear.

Post-Surgical Peritoneal Scarring and Key Molecular Mechanisms.

Post-surgical adhesions are internal scar tissue and a major health and economic burden. Adhesions affect and involve the peritoneal lining of the abdominal cavity, which consists of a continuous mesothelial covering of the cavity wall and majority of internal organs. Our understanding of the full pathophysiology of adhesion formation is limited by the fact that the mechanisms regulating normal serosal repair and regeneration of the mesothelial layer are still being elucidated.

The Effects of an Acute Bout of Self-Myofascial Release on the Physiological Parameters of Running.

This study examined changes in the physiological parameters of running performance when self-myofascial release (SMR) was used prior to a submaximal run. A total of 16 male recreational runners, between the ages of 27 and 50 years old volunteered for the study. Participants had to complete a running event measuring a 10K or longer in the past 12 months and obtained a O value of 45 mL·kg · min to be included in the study.

Regulation of Peritoneal Inflammatory Response to Implant Material Using an Ex Vivo Model System.

Background: Implants used in abdominal wall reconstruction are associated with intra-abdominal inflammation that can cause complications such as adhesions, fistulae, or failure of the implant. This study analyzed the inflammatory response of human peritoneum explants when exposed to different implant materials including synthetic and biological (cross-linked and non-cross-linked).

Materials And Methods: Human peritoneum explants (parietal and visceral) were incubated in culture with implants used for abdominal wall reconstruction.

Endothelin-1 mediates Aspergillus fumigatus-induced airway inflammation and remodelling.

Background: Asthma is a chronic inflammatory condition of the airways and patients sensitized to airborne fungi such as Aspergillus fumigatus have more severe asthma. Thickening of the bronchial subepithelial layer is a contributing factor to asthma severity for which no current treatment exists. Airway epithelium acts as an initial defence barrier to inhaled spores, orchestrating an inflammatory response and contributing to subepithelial fibrosis.

Functional molecules in mesothelial-to-mesenchymal transition revealed by transcriptome analyses.

Peritoneal fibrosis is a common complication of abdominal and pelvic surgery, and can also be triggered by peritoneal dialysis, resulting in treatment failure. In these settings, fibrosis is driven by activated myofibroblasts that are considered to be partly derived by mesothelial-to-mesenchymal transition (MMT). We hypothesized that, if the molecular signature of MMT could be better defined, these insights could be exploited to block this pathological cellular transition.

Differential susceptibility of Dectin-1 isoforms to functional inactivation by neutrophil and fungal proteases.

Patients with cystic fibrosis (CF) experience chronic or recurrent bacterial and fungal lung infections. Many patients with CF cannot effectively clear Aspergillus from their lungs. This may result in IgE sensitization and the development of allergic bronchopulmonary aspergillosis, or invasive infections, such as Aspergillus bronchitis.

High-density lipoprotein particle pattern and overall lipid responses to a short-term moderate-intensity aerobic exercise training intervention in patients with chronic kidney disease.

Background: Chronic kidney disease (CKD) is associated with abnormal lipid profiles and altered high-density lipoprotein (HDL) particle size patterns. Lower levels of the larger, cardioprotective HDL particles found in CKD may play a role in the increased risk for cardiovascular disease in these patients. The current study was designed to assess the effects of short-term moderate-intensity aerobic exercise training on the HDL particle pattern and overall lipid profiles in stage 3 CKD patients.

Characterization of TLR-induced inflammatory responses in COPD and control lung tissue explants.

Purpose: Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD). They activate toll-like receptors (TLRs) 3, 7, and 8, leading to a pro-inflammatory response. We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers.

Mesothelial cells and peritoneal homeostasis.

The mesothelium was traditionally thought to be a simple tissue with the sole function of providing a slippery, nonadhesive, and protective surface to allow easy movement of organs within their body cavities. However, our knowledge of mesothelial cell physiology is rapidly expanding, and the mesothelium is now recognized as a dynamic cellular membrane with many other important functions. When injured, mesothelial cells initiate a cascade of processes leading either to complete regeneration of the mesothelium or the development of pathologies such as adhesions.

Mesothelial cells in tissue repair and fibrosis.

Mesothelial cells are fundamental to the maintenance of serosal integrity and homeostasis and play a critical role in normal serosal repair following injury. However, when normal repair mechanisms breakdown, mesothelial cells take on a profibrotic role, secreting inflammatory, and profibrotic mediators, differentiating and migrating into the injured tissues where they contribute to fibrogenesis. The development of new molecular and cell tracking techniques has made it possible to examine the origin of fibrotic cells within damaged tissues and to elucidate the roles they play in inflammation and fibrosis.

Encapsulating peritoneal sclerosis-a rare but devastating peritoneal disease.

Encapsulating peritoneal sclerosis (EPS) is a devastating but, fortunately, rare complication of long-term peritoneal dialysis. The disease is associated with extensive thickening and fibrosis of the peritoneum resulting in the formation of a fibrous cocoon encapsulating the bowel leading to intestinal obstruction. The incidence of EPS ranges between 0.

Genetic Polymorphisms and Peritoneal Membrane Function.

Background: Outcomes for peritoneal dialysis (PD) patients are affected by the characteristics of the peritoneal membrane, which may be determined by genetic variants. We carried out a systematic review of the literature to identify studies which assessed the association between genetic polymorphisms, peritoneal membrane solute transport, and clinical outcomes for PD patients.

Methods: The National Library of Medicine was searched using a variety of strategies.

The role of mouse strain differences in the susceptibility to fibrosis: a systematic review.

In humans, a number of genetic factors have been linked to the development of fibrosis in a variety of different organs. Seeking a wider understanding of this observation in man is ethically important. There is mounting evidence suggesting that inbred mouse strains with different genetic backgrounds demonstrate variable susceptibility to a fibrotic injury.

TGF-β₂ decreases baseline and IL-13-stimulated mucin production by primary human bronchial epithelial cells.

Introduction: Mucus hypersecretion is a major contributor to asthma pathology and occurs as part of a spectrum of structural changes termed airway wall remodeling. Transforming growth factor (TGF)-β is proposed to play a key role in regulating airway matrix remodeling although less is known about the specific action of TGF-β isoforms in regulating mucus production.

Methods: Primary human bronchial epithelial (HBE) cells cultured at air-liquid interface were treated with exogenous TGF-β(1), TGF-β(2), and/or a Th2 cytokine, interleukin (IL)-13.