- MINOAS: A Single-arm Translational Phase II Trial of FOLFIRI Plus Aflibercept as First-line Therapy in Unresectable, Metastatic Colorectal Cancer. [Journal Article]
- TOTarget Oncol 2019 Jun 15
- CONCLUSIONS: The activity and safety of first-line FOLFIRI/aflibercept merit further evaluation in randomized studies. CLINICALTRIALS.
- Linking microvascular collapse to tissue hypoxia in a multiscale model of pressure ulcer initiation. [Journal Article]
- BMBiomech Model Mechanobiol 2019 Jun 15
- Pressure ulcers are devastating injuries that disproportionately affect the older adult population. The initiating factor of pressure ulcers is local ischemia, or lack of perfusion at the microvascul…
Pressure ulcers are devastating injuries that disproportionately affect the older adult population. The initiating factor of pressure ulcers is local ischemia, or lack of perfusion at the microvascular level, following tissue compression against bony prominences. In turn, lack of blood flow leads to a drop in oxygen concentration, i.e, hypoxia, that ultimately leads to cell death, tissue necrosis, and disruption of tissue continuity. Despite our qualitative understanding of the initiating mechanisms of pressure ulcers, we are lacking quantitative knowledge of the relationship between applied pressure, skin mechanical properties as well as structure, and tissue hypoxia. This gap in our understanding is, at least in part, due to the limitations of current imaging technologies that cannot simultaneously image the microvascular architecture, while quantifying tissue deformation. We overcome this limitation in our work by combining realistic microvascular geometries with appropriate mechanical constitutive models into a microscale finite element model of the skin. By solving boundary value problems on a representative volume element via the finite element method, we can predict blood volume fractions in response to physiological skin loading conditions (i.e., shear and compression). We then use blood volume fraction as a homogenized variable to couple tissue-level skin mechanics to an oxygen diffusion model. With our model, we find that moderate levels of pressure applied to the outer skin surface lead to oxygen concentration contours indicative of tissue hypoxia. For instance, we show that applying a pressure of 60 kPa at the skin surface leads to a decrease in oxygen partial pressure from a physiological value of 65 mmHg to a hypoxic level of 31 mmHg. Additionally, we explore the sensitivity of local oxygen concentration to skin thickness and tissue stiffness, two age-related skin parameters. We find that, for a given pressure, oxygen concentration decreases with decreasing skin thickness and skin stiffness. Future work will include rigorous calibration and validation of this model, which may render our work an important tool toward developing better prevention and treatment tools for pressure ulcers specifically targeted toward the older adult patient population.
- Charcot-Leyden Crystals in Eosinophilic Inflammation: Active Cytolysis Leads to Crystal Formation. [Review]
- CACurr Allergy Asthma Rep 2019 Jun 15; 19(8):35
- Charcot-Leyden crystals (CLCs), slender bipyramidal hexagonal crystals, were first described by Jean-Martin Charcot in 1853, predating Paul Ehrlich's "discovery" of eosinophils by 26 years. To date, …
Charcot-Leyden crystals (CLCs), slender bipyramidal hexagonal crystals, were first described by Jean-Martin Charcot in 1853, predating Paul Ehrlich's "discovery" of eosinophils by 26 years. To date, CLCs are known as a classical hallmark of eosinophilic inflammation. CLC protein expresses palmitate cleaving lysophospholipase activity and is a member of the family of S-type lectins, galectin-10. We summarize current knowledge regarding the pathological observations of CLCs and their mechanism of generation focusing on eosinophil cell death.
- Follicular dendritic cells display microvesicle-associated LMP1 in reactive germinal centers of EBV+ classic Hodgkin lymphoma. [Journal Article]
- VAVirchows Arch 2019 Jun 15
- Expression of the latent membrane protein-1 (LMP1) of Epstein-Barr virus (EBV) was investigated in 153 cases of EBV+ classic Hodgkin lymphoma (cHL); 120 cases were pediatric patients (< 14 years of a…
Expression of the latent membrane protein-1 (LMP1) of Epstein-Barr virus (EBV) was investigated in 153 cases of EBV+ classic Hodgkin lymphoma (cHL); 120 cases were pediatric patients (< 14 years of age) from Iraq, and 33 cases were adult patients from Italy. We describe for the first time the presence of LMP1 protein in EBV-encoded RNA (EBER)-negative follicular dendritic cells (FDCs) of reactive germinal centers (GC) associated with EBV+ cHL. Presence of LMP1+ GCs was independent of geographic region and age of patients. Variable numbers of reactive GCs were present in 22.2% of cases (34 of 153), whereas LMP1 staining of FDCs was present in about a third of cases (10 of 34) with reactive GC. Most cases with LMP1+ GC were mixed-cellularity (MC) subtype, but some nodular sclerosis (NS) was also present. GC cells with LMP1+ FDCs were surrounded by numerous EBV-infected cells which were positive for EBER, LMP1, and CD30. Double immunolocalization analysis revealed that LMP1 was associated with CD63, an exosomal marker, and with CD21. The possibility is discussed that peri-follicular EBV-infected cells release LMP1 protein, perhaps through exosomes, and that the protein is then captured by FDCs and is presented to EBER-negative GC B cells.
- Replication and extension of a model predicting response to psilocybin. [Journal Article]
- PPsychopharmacology (Berl) 2019 Jun 15
- CONCLUSIONS: Mental states of surrender or preoccupation at the time of ingestion explain variance in mystical or adverse psilocybin experiences, and mystical experiences relate to long-term positive change. The capacity to recognize this optimal preparatory mental state may benefit therapeutic use of psilocybin in clinical settings.
- Death notice: Maurice Parker. [News]
- BDBr Dent J 2019; 226(11):822
- The Modifying Effect of Age on Survival in Parkinson's Disease: A Population-Based Cohort Study. [Journal Article]
- NNeuroepidemiology 2019 Jun 14; :1-7
- CONCLUSIONS: Our large-scale cohort enabled us to find an age-differential standardized death risk among PD patients, with the largest increased risk at ages 60-69 years. Comorbidities and other contributory factors warrant further investigation.
- Is Chronic Kidney Disease Progression Influenced by the Type of Renin-Angiotensin-System Blocker Used? [Journal Article]
- NNephron 2019 Jun 14; :1-8
- CONCLUSIONS: In patients with CKD, treatment with ACEI or ARB had a superior effect than no ACEI or ARB treatment on slowing kidney disease progression and on proteinuria reduction. Efficacy of ACEI and ARB was comparable.
- Contemporary Trends in Clinical Outcomes among Dialysis Patients with Medicare Coverage. [Journal Article]
- AJAm J Nephrol 2019 Jun 14; :1-9
- CONCLUSIONS: For the first time since the beginning of this century, rates of both death and hospitalization among dialysis patients with Medicare fee-for-service coverage have stagnated. The reasons for this change are unknown and require detailed assessment. Persistent lack of change in clinical outcomes may alter the future expectations about dialysis patient population growth.
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- Monocyte Chemoattractant Protein-1-Induced Protein in Age-Related Atrial Fibrillation and Its Association with Circulating Fibrosis Biomarkers. [Journal Article]
- CCardiology 2019 Jun 14; :1-6
- CONCLUSIONS: MCPIP expression was higher in age-related AF than in the other patient groups and it was associated with AF-induced fibrosis.