Polymeric stenting in the porcine coronary artery model: Differential outcome of exogenous fibrin sleeves versus polyurethane-coated stents

AbstractObjectives. In a porcine coronary model, fibrin film soaked for 3 h in heparin was used as a circumferential coating on a tantalum stent to assess the effect of this naturally occurring biopolymer on arterial healing. The results were compared with those obtained with medical grade polyurethane-coated stainless steel stents.Background. Thrombus plays an important role in healing after arterial injury and may affect the development of neointimal hyperplasia. Manipulation of the initial thrombus may alter the healing response. To study this, we placed a template of fibrin in a porcine coronary artery restenosis model.Methods. Thirty-four fibrin film stents were delivered in 20 swine. Oversizing was avoided, to prevent deep arterial injury, by placement of optimally sized stents. Initial patency of the syented vessel was confirmed by angiography.Results. Three fibrin-stented swine died within 48 h; in each, the stent was occluded with a fibrin/red blood cell mass. In two of these three, a portion of the exogenous fibrin had become detached from the stent and partially occluded the lumen. Of the remaining 31 stents, all were patent at elective sacrifice at 28 days. Eightyfour percent had a diameter stenosis <50%, and the mean (± SD) diameter stenosis was 32.3 ± 13%. There was no evidence of significant foreign-body giant-cell reaction. These results contrasted with the medical grade polyurethane-coated stents placed according to the same protocol without oversizing. Twelve of these stents were placed; six swine died of thrombotic occlusion within the 1st 48 h. At elective sacrifice at 28 days, the remaining polyurethane-coated stents were occluded by marked neointimal hyperplasia.Conclusions. Fibrin film-coated stents seem promising as a template for modifying the local response to arterial injury and for potentially decreasing restenosis rates

Inverse lichen planus

A Case of Inverse Lichen Planus Lichen planus (LP) is a pruritic, papular eruption characterized by its violaceous color and polygonal shape. It is most commonly found on the flexor surfaces of the upper extremities, on the genitalia, and on the mucous membranes. We herein report a classic case of LP in an inverse distribution

Healthcare choice: Discourses, perceptions, experiences and practices

Policy discourse shaped by neoliberal ideology, with its emphasis on marketisation and competition, has highlighted the importance of choice in the context of healthcare and health systems globally. Yet, evidence about how so-called consumers perceive and experience healthcare choice is in short supply and limited to specific healthcare systems, primarily in the Global North. This special issue aims to explore how choice is perceived and utilised in the context of different systems of healthcare throughout the world, where choice, at least in policy and organisational terms, has been embedded for some time. The articles are divided into those emphasising: embodiment and the meaning of choice; social processes associated with choice; the uncertainties, risks and trust involved in making choices; and issues of access and inequality associated with enacting choice. These sociological studies reveal complexities not always captured in policy discourse and suggest that the commodification of healthcare is particularly problematic

Tumor‐stroma interactions differentially alter drug sensitivity based on the origin of stromal cells

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large‐scale coculture assay optimized to measure drug‐induced cell death, we identify tumor–stroma interactions that modulate drug sensitivity. Our data show that the chemo‐insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts. Furthermore, we find that fibroblasts influence drug responses in two distinct and divergent manners, associated with the tissue from which the fibroblasts were harvested. These divergent phenotypes occur regardless of the drug tested and result from modulation of apoptotic priming within tumor cells. Our study highlights unexpected diversity in tumor–stroma interactions, and we reveal new principles that dictate how fibroblasts alter tumor drug responses

Electromyography Data Processing Impacts Muscle Synergies during Gait for Unimpaired Children and Children with Cerebral Palsy

Muscle synergies calculated from electromyography (EMG) data identify weighted groups of muscles activated together during functional tasks. Research has shown that fewer synergies are required to describe EMG data of individuals with neurologic impairments. When considering potential clinical applications of synergies, understanding how EMG data processing impacts results and clinical interpretation is important. The aim of this study was to evaluate how EMG signal processing impacts synergy outputs during gait. We evaluated the impacts of two common processing steps for synergy analyses: low pass (LP) filtering and unit variance scaling. We evaluated EMG data collected during barefoot walking from five muscles of 113 children with cerebral palsy (CP) and 73 typically-developing (TD) children. We applied LP filters to the EMG data with cutoff frequencies ranging from 4 to 40 Hz (reflecting the range reported in prior synergy research). We also evaluated the impact of normalizing EMG amplitude by unit variance. We found that the total variance accounted for (tVAF) by a given number of synergies was sensitive to LP filter choice and decreased in both TD and CP groups with increasing LP cutoff frequency (e.g., 9.3 percentage points change for one synergy between 4 and 40 Hz). This change in tVAF can alter the number of synergies selected for further analyses. Normalizing tVAF to a z-score (e.g., dynamic motor control index during walking, walk-DMC) reduced sensitivity to LP cutoff. Unit variance scaling caused comparatively small changes in tVAF. Synergy weights and activations were impacted less than tVAF by LP filter choice and unit variance normalization. These results demonstrate that EMG signal processing methods impact outputs of synergy analysis and z-score based measures can assist in reporting and comparing results across studies and clinical centers

Cemented Endoprosthetic Reconstruction of the Proximal Tibia: How Long Do They Last?

The few available studies documenting the long-term survival of cemented proximal tibial endoprostheses for musculoskeletal tumors do not differentiate between stem designs or patient diagnosis. There is wide variation in survival rates reported, possibly a result of this heterogeneity in patient population and implant design. We therefore asked: (1) How long do proximal tibial endoprostheses last? (2) What is the typical long-term functional result after proximal tibial replacement? And (3) what are the short- and long-term complications associated with endoprosthetic reconstruction of the proximal tibia, particularly with respect to the soft tissue reconstruction? We retrospectively reviewed 52 patients with 52 proximal tibial endoprosthetic reconstructions for a tumor-related diagnosis. Kaplan-Meier survivorship analysis was performed using revision of the stemmed components for any reason as an endpoint for implants, and death due to disease progression for patients. Function was assessed using the MSTS scoring system. The minimum followup was 1 month (mean, 96 months: range, 1–284 months; median, 69 months). Using revision of the stemmed components for any reason as an end point, overall prosthesis survival at 5, 10, 15, and 20 years was 94%, 86%, 66%, and 37%, respectively. The 29 modular implants demonstrated a trend toward improved survival compared to the 23 custom-designed components, with a 15-year survivorship of 88% versus 63%. The mean postoperative Musculoskeletal Tumor Society score at most recent followup was 82% of normal function (mean raw score, 24.6; range, 4–29). Cemented endoprosthetic reconstruction of the proximal tibia provides a reliable method of reconstruction following tumor resection. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence

Robust Detection of Rare Species Using Environmental DNA: the Importance of Primer Specificity

Environmental DNA (eDNA) is being rapidly adopted as a tool to detect rare animals. Quantitative PCR (qPCR) using probe-based chemistries may represent a particularly powerful tool because of the method\u27s sensitivity, specificity, and potential to quantify target DNA. However, there has been little work understanding the performance of these assays in the presence of closely related, sympatric taxa. If related species cause any cross-amplification or interference, false positives and negatives may be generated. These errors can be disastrous if false positives lead to overestimate the abundance of an endangered species or if false negatives prevent detection of an invasive species. In this study we test factors that influence the specificity and sensitivity of TaqMan MGB assays using co-occurring, closely related brook trout (Salvelinus fontinalis) and bull trout (S. confluentus) as a case study. We found qPCR to be substantially more sensitive than traditional PCR, with a high probability of detection at concentrations as low as 0.5 target copies/ml. We also found that number and placement of base pair mismatches between the Taqman MGB assay and non-target templates was important to target specificity, and that specificity was most influenced by base pair mismatches in the primers, rather than in the probe. We found that insufficient specificity can result in both false positive and false negative results, particularly in the presence of abundant related species. Our results highlight the utility of qPCR as a highly sensitive eDNA tool, and underscore the importance of careful assay design

Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

<p>Abstract</p> <p>Background</p> <p>Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA) and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM) and impaired glucose metabolism (IGM).</p> <p>Methods</p> <p>Forty-five severely obese adults (36 women) without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS) and pancreatic beta-cell function (HOMA-B).</p> <p>Results</p> <p>Both increases in apnea-hypopnea index (AHI) and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (<it>P </it>= 0.003). In subjects with NGM (n = 30), OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS) independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; <it>P </it>= 0.001) in women with NGM and with IL-6 (rho=-0.55; <it>P </it>= 0.035) in women with IGM (n = 15) matched individually for age, adiposity, and AHI.</p> <p>Conclusions</p> <p>OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly nocturnal oxyhemoglobin desaturations are associated with chronic metabolic fluxes and specific cytokine stressors that reflect links between sleep apnea and glucose metabolism. The study may help illuminate potential mechanisms for glucose dysregulation in OSA, and resolve some controversy over the associations of OSA with TNF-α and IL-6 in previous studies.</p

Biobehavioral effects of Tai Chi Qigong in men with prostate cancer: Study design of a three-arm randomized clinical trial.

Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment &amp; Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov