Mcclurehealy2042

Starting from Röntgen's discovery and the first radiograph of his wife's hand, the curtain was raised on a new technique with remarkable possibilities for contributing to human health. While growth in applications proceeded rapidly, it was accompanied by significant harms to those involved and by inappropriate opportunistic application. This paper places the attempts to deal with the harms and inappropriate activities side by side with the positive developments. It attempts a narrative on the development of medical radiation protection over the 125-year period and places it in the context of a commentary on governance and ethics. The substance of the narrative is based on the recommendations of ICRP as they developed and altered over time. The governance commentary is based on assessing the independence of ICRP and its attention to medical exposures. In terms of ethics, the recommendations at each stage are reviewed in the light of values that are deemed appropriate to both medical ethics and radiation protection. The paper, while celebrating Röntgen-125, also hopefully provides a perspective for discussion as ICRP's centenary in 2028 approaches. This is an important part of ensuring continued acceptance and confident use of X-Rays, and helps underwrite the possibility of further developments in the area.Charge carrier transport through the probe-sample junction can have substantial consequences for outcomes of electrical and electromechanical atomic-force-microscopy (AFM) measurements. For understanding physical processes under the probe, we carried out conductive-AFM (C-AFM) measurements of local current-voltage (I-V) curves as well as their derivatives on samples of a mixed ionic-electronic conductor Li1-xMn2O4 and developed an analytical framework for the data analysis. The implemented approach discriminates between contributions the highly resistive sample surface layer and the bulk with the account of ion redistribution in the field of the probe. It was found that, with increasing probe voltage, the conductance mechanism in the surface layer transforms from Pool-Frenkel to space-charge-limited current. The surface layer significantly alters the ion dynamics in the sample bulk under the probe, which leads, in particular, to a decrease of the effective electromechanical AFM signal associated with the ionic motion in the sample. The framework can be applied for the analysis of electronic transport mechanisms across the probe/sample interface as well as to uncover the role of the charge transport in the electric field distribution, mechanical, and other responses in AFM measurements of a broad spectrum of conducting materials.Cells respond to the mechanical properties of the extracellular matrix (ECM) through formation of focal adhesions (FAs), re-organization of the actin cytoskeleton and adjustment of cell contractility. These are energy-demanding processes, but a potential causality between mechanical cues (matrix stiffness) and cellular (energy) metabolism remains largely unexplored. Here, we cultured human mesenchymal stem cells (hMSCs) on stiff (20 kPa) or soft (1 kPa) substrate and demonstrate that cytoskeletal reorganization and FA formation spreading on stiff substrates lead to a drop in intracellular ATP levels, correlating with activation of AMP-activated protein kinase (AMPK). The resulting increase in ATP levels further facilitates cell spreading and reinforces cell tension of the steady state, and coincides with nuclear localization of YAP/TAZ and Runx2. While on soft substrates (1 kPa), lowered ATP levels limit these cellular mechanoresponses. Furthermore, genetic ablation of AMPK lowered cellular ATP levels on stiff substrate and strongly reduced responses to substrate stiffness. Amlexanox Together, these findings reveal a hitherto unidentified relationship between energy expenditure and the cellular mechanoresponse, and point to AMPK as a key mediator of stem cell fate in response to ECM mechanics.Titanium surface mediated immunomodulation may address compromised post-implantation bone healing in diabetes mellitus. To assess in vitro phenotypic changes, M1 and M2 polarised Type 2 diabetic rat (Goto Kakizaki, GK) macrophages were cultured on micro-rough (SLA) or hydrophilic nanostructured SLA (modSLA) titanium. The in vivo effects of the SLA and modSLA surfaces on macrophage phenotype, wound-associated protein expression and bone formation were investigated using a critical-sized calvarial defect model. Compared to healthy macrophages, GK M2 macrophage function was compromised, secreting significantly lower levels of the anti-inflammatory cytokine IL-10. The modSLA surface attenuated the pro-inflammatory cellular environment, reducing pro-inflammatory cytokine production and promoting M2 macrophage phenotype differentiation. ModSLA also suppressed gene expression associated with macrophage multinucleation and giant cell formation and stimulated pro-osteogenic genes in co-cultured osteoblasts. In vivo, modSLA enhanced osteogenesis compared to SLA in GK rats. During early healing, proteomic analysis of both surface adherent and wound exudate material showed that modSLA promoted an immunomodulatory pro-reparative environment. The modSLA surface therefore successfully compensated for the compromised M2 macrophage function in Type 2 diabetes by attenuating the pro-inflammatory response and promoting M2 macrophage activity, thus restoring macrophage homeostasis and resulting in a cellular environment favourable for enhanced osseous healing.The crucial balance of stability in blood-circulation and tumor-specific delivery has been suggested as one of the challenges for effective bench-to-bedside translation of nanomedicines (NMs). Herein, we developed a supramolecularly enabled tumor-extracellular (Tex) pH-triggered NM that can maintain the micellar structure with the entrapped-drug during systemic circulation and progressively release drug in the tumor by rightly sensing heterogeneous tumor-pH. Desacetylvinblastine hydrazide (DAVBNH), a derivative of potent anticancer drug vinblastine, was conjugated to an aliphatic ketone-functionalized poly(ethylene glycol)-b-poly(amino acid) copolymer and the hydrolytic stability of the derived hydrazone bond was efficiently tailored by exploiting the compartmentalized structure of polymer micelle. We confirmed an effective and safe therapeutic application of Tex pH-sensitive DAVBNH-loaded micelle (Tex-micelle) in orthotopic glioblastoma (GBM) models, extending median survival to 1.4 times in GBM xenograft and 2.6 times in GBM syngeneic model, compared to that of the free DAVBNH. The work presented here offers novel chemical insights into the molecular design of smart NMs correctly sensing Tex-pH via programmed functionalities. The practical engineering strategy based on a clinically relevant NM platform, and the encouraging therapeutic application of Tex-micelle in GBM, one of the most lethal human cancers, thus suggests the potential clinical translation of this system against other types of common cancers, including GBM.Meniscus injuries are prevalent in orthopedic diagnosis. The reconstruction of the structural inhomogeneity and anisotropy of the meniscus is a major challenge in clinical practice. Meniscal tissue engineering has emerged as a potential alternative for the treatment of various meniscal diseases and injuries. In this study, we developed three-dimensional (3D) cell-printed meniscus constructs using a mixture of polyurethane and polycaprolactone polymers and cell-laden decellularized meniscal extracellular matrix (me-dECM) bioink with high controllability and durable architectural integrity. The me-dECM bioink provided 3D cell-printed meniscus constructs with a conducive biochemical environment that supported growth and promoted the proliferation and differentiation of encapsulated stem cells toward fibrochondrogenic commitment. In addition, we investigated the in vivo performance of the 3D cell-printed meniscus constructs, which exhibited biocompatibility, excellent mechanical properties, and improved biological functionality. These attributes were similar to those of the native meniscus. Collectively, the 3D cell-printing technology and me-dECM bioink facilitate the recapitulation of meniscus tissue specificity in the aspect of the shape and microenvironment for meniscus regeneration. Further, the developed constructs can potentially be applied in clinical practice.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.

To describe a novel and practical volumetric modulated arc therapy (VMAT) planning approach for grid therapy.

Dose is prescribed to 1.5-cm diameter spherical contours placed throughout the gross tumor volume (GTV). Placement of spheres is variable, but they must maintain at least a 3-cm (center to center) separation, and the edge of any sphere must be at least 1 cm from any organ at risk (OAR). Three concentric ring structures are used during optimization to confine the highest doses to the center of the spheres and maximize dose sparing between them. The end result is alternating regions of high and low dose throughout the GTV and minimal dose to OARs. High-intensity flattening filter-free (FFF) modes are used to efficiently deliver the plans, and entire treatments typically take only 15 to 20 minutes.

The approach is illustrated with 2 examples treated at our institution. Patient #1 had a 1703-cm

mediastinal mass and was prescribed 20 Gray (Gy) to 24 spherical regions within the GTV. Patient #2 had any centers offer VMAT treatments, the approach is widely accessible and can be readily implemented once appropriate patient selection and delivery processes are established.

Abdominal compression (COMP) and breath-hold with an active breathing coordinator (ABC) device are 2 different respiratory motion management techniques used in lung stereotactic body radiation therapy (SBRT) practice. We compared local failure (LF) results for COMP versus ABC.

We surveyed our institutional review board-approved prospective registry for patients who were treated with SBRT for either a primary lung cancer (PRIME) or an oligometastatic (OLIGO) diagnosis with a minimum of 6 months' follow-up to determine their rates of local failure by motion management modality.

From October 2003 to July 2014, 873 patients with 931 lesions were treated. Patient characteristics included 455 (52.1%) female; median age of 73 years (range, 37-97); median Karnofsky performance status (KPS) of 80 (range, 40-100); and median BMI of 26.2 (range, 12.1-56.3). Tumor characteristics included median tumor size of 2.2 cm (range, 0.7-10.0); median maximum standardized uptake value from positron emission tomography PET SUVmax of 7.