Polypharmacy is defined as concurrent use of multiple drugs for one or more conditions. The occurrence of polypharmacy in vulnerable populations, particularly the elderly, is frequent. Increased incidents of adverse drug reactions and drug-drug interactions plus high costs are not offset by a noticeable improvement in outcome.
View Article and Find Full Text PDFHuman mesenchymal stem cells/multipotent stromal cells (MSCs) hold great promise in aiding wound healing through their ability to modulate all phases of repair and regeneration, most notably their secretion of pro-regenerative paracrine factors. However, MSC clinical utility is hindered by poor survival rates post-transplantation due to the harsh microenvironment in injured tissue. Previous work has shown that the matricellular protein Tenascin-C (TNC) provides survival signaling to MSCs via the epidermal growth factor receptor by restricting its activation at the plasma membrane, resulting in enhanced prosurvival signals.
View Article and Find Full Text PDFChronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways.
View Article and Find Full Text PDFCutaneous wound healing is an intricate orchestration of three overlapping phases of repair that encompass numerous cell types, signalling cascades, and microenvironment modifications to reach a successful resolution. Disruption of any of these steps will create an abnormal healing response resulting in either ulceration or excessive scarring. It has become evident that the extracellular matrix and its associated components are key orchestrators during this process.
View Article and Find Full Text PDFDiabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia as a result of insufficient insulin levels and/or impaired function as a result of autoimmune destruction or insulin resistance. While Type 1 DM (T1DM) and Type 2 DM (T2DM) occur through different pathological processes, both result in β-cell destruction and/or dysfunction, which ultimately lead to insufficient β-cell mass to maintain normoglycemia. Therefore, therapeutic agents capable of inducing β-cell proliferation is crucial in treating and reversing diabetes; unfortunately, adult human β-cell proliferation has been shown to be very limited (~0.
View Article and Find Full Text PDFCancer Biol Med
October 2021
Objective: Early prostate cancer micrometastatic foci undergo a mesenchymal to epithelial reverting transition, not only aiding seeding and colonization, but also rendering the tumor cells generally chemoresistant. We previously found that upregulated E-cadherin in the epithelial micrometastases activated canonical survival pathways, including PI3K-Akt, that protected the tumor cells from death; however, the extent of protection from blocking the pathway in its entirety was modest, because different isoforms may have alternately affected cell functioning. Here, we characterized Akt isoform expressions in primary and metastatic prostate cancers, as well as their individual contributions to chemoresistance.
View Article and Find Full Text PDFBackground: The use of dietary supplements by young warfighters is pervasive and comes with a readiness cost, especially in the deployed setting. Predatory targeting and marketing by various unscrupulous companies put this population at risk for a higher than baseline risk for adverse events.
Methods: We report on 6 serious adverse events experienced by warfighters while deployed in Kuwait and Afghanistan.
Pancreatic islet transplantation to restore insulin production in Type 1 Diabetes Mellitus patients is commonly performed by infusion of islets into the hepatic portal system. However, the risk of portal vein thrombosis or elevation of portal pressure after transplantation introduces challenges to this procedure. Thus, alternative sites have been investigated, among which the omentum represents an ideal candidate.
View Article and Find Full Text PDFThe origins of low-temperature tissue storage research date back to the late 1800s. Over half a century later, osmotic stress was revealed to be a main contributor to cell death during cryopreservation. Consequently, the addition of cryoprotective agents (CPAs) such as dimethyl sulfoxide (DMSO), glycerol (GLY), ethylene glycol (EG), or propylene glycol (PG), although toxic to cells at high concentrations, was identified as a necessary step to protect against rampant cell death during cryopreservation.
View Article and Find Full Text PDFBackground: In the setting of recurrent cancer, there is no standard methodology regarding the technical aspects of repeat sentinel lymph node (rSLN) surgery. We analyzed our institutional experience with attempted rSLN surgery to determine the optimal injection technique.
Materials And Methods: Single site, retrospective review of patients with prior lumpectomy for breast cancer who presented with recurrent or new ipsilateral breast cancer and underwent attempt at rSLN surgery from 2008 to 2017.
Ultrasound-guided breast biopsies can be challenging to perform, especially when the target is adjacent to the nipple, skin, or implant or when the target is small and in very posterior, dense fibroglandular tissue. Oftentimes, a slightly modified approach can result in a diagnostic biopsy specimen with minimal complications. After a brief review of basic techniques for ultrasound-guided breast biopsies that includes a review of conventional breast biopsy devices, a presentation of procedural modifications and techniques to consider for more challenging cases is described.
View Article and Find Full Text PDFCancer Epidemiol Biomarkers Prev
August 2019
Background: Mammographic breast density declines during menopause. We assessed changes in volumetric breast density across the menopausal transition and factors that influence these changes.
Methods: Women without a history of breast cancer, who had full field digital mammograms during both pre- and postmenopausal periods, at least 2 years apart, were sampled from four facilities within the San Francisco Mammography Registry from 2007 to 2013.
Background: Breast density and body mass index (BMI) are used for breast cancer risk stratification. We evaluate whether the positive association between volumetric breast density and breast cancer risk is strengthened with increasing BMI.
Methods: The San Francisco Mammography Registry and Mayo Clinic Rochester identified 781 premenopausal and 1850 postmenopausal women with breast cancer diagnosed between 2007 and 2015 that had a screening digital mammogram at least 6 months prior to diagnosis.
Islet transplantation has been shown to restore normoglycemia in animal models and for type 1 diabetic patients in clinical trials. One method of storing islets intended for transplantation is via cryobanking at very low temperatures (-196 °C). Cryobanking islets without the use of cryoprotecting agents (CPAs) contributes to cellular shear stress and cell death.
View Article and Find Full Text PDFPurpose: Background parenchymal uptake (BPU), which describes the level of radiotracer uptake in normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor. Our objective was to develop and validate a deep learning model using image convolution to automatically categorize BPU on MBI.
Methods: MBI examinations obtained for clinical and research purposes from 2004 to 2015 were reviewed to classify the BPU pattern using a standardized five-category scale.
Background: Metastasis in breast cancer foreshadows mortality, as clinically evident disease is aggressive and generally chemoresistant. Disseminated breast cancer cells often enter a period of dormancy for years to decades before they emerge as detectable cancers. Harboring of these dormant cells is not individually predictable, and available information suggests that these micrometastatic foci cannot be effectively targeted by existing therapies.
View Article and Find Full Text PDFPurpose To identify phenotypes of mammographic parenchymal complexity by using radiomic features and to evaluate their associations with breast density and other breast cancer risk factors. Materials and Methods Computerized image analysis was used to quantify breast density and extract parenchymal texture features in a cross-sectional sample of women screened with digital mammography from September 1, 2012, to February 28, 2013 (n = 2029; age range, 35-75 years; mean age, 55.9 years).
View Article and Find Full Text PDFBackground: Background parenchymal uptake (BPU), which refers to the level of Tc-99m sestamibi uptake within normal fibroglandular tissue on molecular breast imaging (MBI), has been identified as a breast cancer risk factor, independent of mammographic density. Prior analyses have used subjective categories to describe BPU. We evaluate a new quantitative method for assessing BPU by testing its reproducibility, comparing quantitative results with previously established subjective BPU categories, and determining the association of quantitative BPU with breast cancer risk.
View Article and Find Full Text PDFBackground: Understanding factors that influence physical activity (PA) and sedentary behavior is crucial to develop interventions to improve adolescents' health-related behaviors.
Purpose: To compare the influence of friends and psychosocial factors on moderate-to-vigorous physical activity (MVPA) and screen time (ST) between normal weight (NW) and overweight (OW) adolescents.
Methods: In all, 21 OW and 21 NW adolescents wore accelerometers and completed questionnaires assessing MVPA, ST, and psychosocial variables.
Background: Over the past two decades, changes in mission and expectations of deployed medical assets are requiring adaptations of pharmacy services. Specifically, the Department of Defense (DOD)-deployed contractors in theater are now eligible for varying levels of care from DOD-deployed assets. Pharmacy must now stock and maintain a complex medication footprint.
View Article and Find Full Text PDFBackground: Breast lesions closer than 2 cm to the chest wall are difficult to position in the field of view of dedicated breast PET (db-PET) systems. This inability to detect such lesions is a significant limitation of these systems. The primary objective of this study was to determine if modifications to the design of the imaging table and detector used for a db-PET system would enable improved visualization of breast tissue close to the chest wall.
View Article and Find Full Text PDFBackground: Transplantation of mesenchymal stem cells (MSC) has been proposed to improve wound healing. However, as these cells only transiently survive in the implantation site, the mechanisms underlying this beneficial healing response are associated with restorative paracrine effects of MSC matricellular factors on resident stromal cells. However, this requires that the recipient has a robust reservoir of viable cells.
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