Ainsbury, E. A., Livingston, G. K., Abbott, M. G., Moquet, J. E., Hone, P. A., Jenkins, M. S., Christensen, D. M., Lloyd, D. C. and Rothkamm, K. Interlaboratory Variation in Scoring Dicentric ...Chromosomes in a Case of Partial-Body X-Ray Exposure: Implications for Biodosimetry Networking and Cytogenetic “Triage Mode” Scoring. The international radiation biodosimetry community has recently been engaged in activities focused on establishing cooperative networks for biodosimetric triage for radiation emergency scenarios involving mass casualties. To this end, there have been several recent publications in the literature regarding the potential for shared scoring in such an accident or incident. We present details from a medical irradiation case where two independently validated laboratories found very different yields of dicentric chromosome aberrations. The potential reasons for this disparity are discussed, and the actual reason is identified as being the partial-body nature of the radiation exposure combined with differing criteria for metaphase selection. In the context of the recent networking activity, this report is intended to highlight the fact that shared scoring may produce inconsistencies and that further validation of the scoring protocols and experimental techniques may be required before the networks are prepared to deal satisfactorily with a radiological or nuclear emergency. Also, the findings presented here clearly demonstrate the limitations of the dicentric assay for estimating radiation doses after partial-body exposures and bring into question the usefulness of rapid “triage mode” scoring in such exposure scenarios.
Artificial Lymph Node
In article number 2310043, Hai‐Quan Mao, Jonathan P. Schneck, and co‐workers report an artificial lymph node (aLN) biomatrix composed of a hydrogel conjugated with T cell ...stimulating signals. Following subcutaneous injection, this aLN biomatrix develops into a complex immune niche in vivo. Naïve, adoptively transferred T cells are stimulated within the aLN in an antigen‐specific manner through direct interaction with the matrix. The cover art depicts a novel aLN hydrogel biomatrix which when injected subcutaneously, is capable of simulating adoptively transferred naïve T cells and recruiting an array of endogenous immune cells. Upon entering the porous biomatrix, naïve T cells (green) bind to the antigen‐specific stimulating signals conjugated to the hydrogel matrix and are activated (yellow) and interact with the recruited cells in the dynamic immune microenvironment, which facilitate the expansion and differentiation into effector and memory T‐cells (orange). The activated T cells then emigrate and travel to the tumor where they can directly kill the tumor cells and lead to increased survival of animals with established tumors.
T cells are critical mediators of antigen‐specific immune responses and are common targets for immunotherapy. Biomaterial scaffolds have previously been used to stimulate antigen‐presenting cells to ...elicit antigen‐specific immune responses; however, structural and molecular features that directly stimulate and expand naïve, endogenous, tumor‐specific T cells in vivo have not been defined. Here, an artificial lymph node (aLN) matrix is created, which consists of an extracellular matrix hydrogel conjugated with peptide‐loaded‐MHC complex (Signal 1), the co‐stimulatory signal anti‐CD28 (Signal 2), and a tethered IL‐2 (Signal 3), that can bypass challenges faced by other approaches to activate T cells in situ such as vaccines. This dynamic immune‐stimulating platform enables direct, in vivo antigen‐specific CD8+ T cell stimulation, as well as recruitment and coordination of host immune cells, providing an immuno‐stimulatory microenvironment for antigen‐specific T cell activation and expansion. Co‐injecting the aLN with naïve, wild‐type CD8+ T cells results in robust activation and expansion of tumor‐targeted T cells that kill target cells and slow tumor growth in several distal tumor models. The aLN platform induces potent in vivo antigen‐specific CD8+ T cell stimulation without the need for ex vivo priming or expansion and enables in situ manipulation of antigen‐specific responses for immunotherapies.
Here, an injectable T cell‐stimulating scaffold, the artificial lymph node (aLN), is developed that works with the host immune system to create an immunostimulatory niche. The aLN can activate and expand rare, antigen‐specific CD8+ T cells from fully naïve, endogenous populations. aLN stimulated cells are fully functional and synergize with immune checkpoint blockade to reduce tumor burden and prolong survival.
The tumour microenvironment (TME) has recently drawn much attention due to its profound impact on tumour development, drug resistance and patient outcome. There is an increasing interest in new ...therapies that target the TME. Nonetheless, most established in vitro models fail to include essential cues of the TME. Microfluidics can be used to reproduce the TME in vitro and hence provide valuable insight on tumour evolution and drug sensitivity. However, microfluidics remains far from well-established mainstream molecular and cell biology methods. Therefore, we have developed a quick and straightforward collagenase-based enzymatic method to recover cells embedded in a 3D hydrogel in a microfluidic device with no impact on cell viability. We demonstrate the validity of this method on two different cell lines in a TME microfluidic model. Cells were successfully retrieved with high viability, and we characterised the different cell death mechanisms via AMNIS image cytometry in our model.
Previous research in our laboratory has shown that citric acid (CA) improves phytate P utilization in New Hampshire x Columbian (NHC) crossbred chicks fed a P-deficient corn-soybean meal diet. The ...current study was conducted to determine if CA is also effective in commercial broiler chicks (Ross x Ross). In 3 experiments, 4 replicate groups of 5 male NHC chicks and male commercial chicks were fed corn-soybean meal diets varying in CA and nonphytate P (NPP) from 8 to 22 d of age. In experiment 1, a 2 x 2 x 2 factorial treatment arrangement was used to evaluate the effect of 2 levels of CA (0 and 3%) and NPP (0.13 and 0.28%) in NHC chicks and commercial chicks. The commercial chicks, but not the NHC chicks, fed the 0.13% NPP diet had to be removed from the experiment after 3 to 5 d due to very poor growth and severe leg problems. Chick weight gain and tibia ash were significantly increased (P < 0.05) by CA in both types of chicks. In experiment 2, the same 2 x 2 x 2 factorial treatment arrangement was again used except that the NPP levels were 0.18 and 0.28%. Tibia ash was increased significantly (P < 0.05) with the addition of CA in both breeds of chicks; response was greater at 0.18% NPP than at 0.28% NPP. In experiment 3, graded levels of CA (0, 1, 2, 3, and 4%) were evaluated in commercial chicks fed diets containing 0.18% NPP. Tibia ash increased linearly (P < 0.05) as CA increased from 0 to 4%. The average increase in bone ash resulting from 3% CA supplementation in experiments 2 and 3 was 41%. These results indicate that CA markedly improved phytate P utilization in NHC and Ross x Ross commercial broiler chicks.
Blunt cardiac injury (BCI) can occur after chest trauma and may be associated with sternal fracture (SF). We hypothesized that injuries demonstrating a higher transmission of force to the thorax, ...such as thoracic aortic injury (TAI), would have a higher association with BCI.
We queried the National Trauma Data Bank (NTDB) from 2007-2015 to identify adult blunt trauma patients.
BCI occurred in 15,976 patients (0.3%). SF had a higher association with BCI (OR = 5.52, CI = 5.32–5.73, p < 0.001) compared to TAI (OR = 4.82, CI = 4.50–5.17, p < 0.001). However, the strongest independent predictor was hemopneumothorax (OR = 9.53, CI = 7.80–11.65, p < 0.001) followed by SF and esophageal injury (OR = 5.47, CI = 4.05–7.40, p < 0.001).
SF after blunt trauma is more strongly associated with BCI compared to TAI. However, hemopneumothorax is the strongest predictor of BCI. We propose all patients presenting after blunt chest trauma with high-risk features including hemopneumothorax, sternal fracture, esophagus injury, and TAI be screened for BCI.
Using the National Trauma Data Bank, sternal fracture is more strongly associated with blunt cardiac injury than blunt thoracic aortic injury. However, hemopneumothorax was the strongest predictor.
•The incidence of blunt cardiac injury in adults with blunt trauma is <1%.•The strongest independent risk factor for blunt cardiac injury is hemopneumothorax.•Open sternal fracture has higher risk for blunt cardiac injury compared to closed.
Luminal geometries are common structures in biology, which are challenging to mimic using conventional in vitro techniques based on the use of Petri dishes. In this context, microfluidic systems can ...mimic the lumen geometry, enabling a large variety of studies. However, most microfluidic models still rely on polydimethylsiloxane (PDMS), a material that is not amenable for high-throughput fabrication and presents some limitations compared with other materials such as polystyrene. Thus, we have developed a microfluidic device array to generate multiple bio-relevant luminal structures utilizing polystyrene and micro-milling. This platform offers a scalable alternative to conventional microfluidic devices designed in PDMS. Additionally, the use of polystyrene has well described advantages, such as lower permeability to hydrophobic molecules compared with PDMS, while maintaining excellent viability and optical properties. Breast cancer cells cultured in the devices exhibited high cell viability similar to PDMS-based microdevices. Further, co-culture experiments with different breast cell types showed the potential of the model to study breast cancer invasion. Finally, we demonstrated the potential of the microfluidic array for drug screening, testing chemotherapy drugs and photodynamic therapy agents for breast cancer.
Ionizing radiation exposure can induce profound changes in intracellular components, potentially leading to diverse health effects in exposed individuals. Any cellular component can be damaged by ...radiation, but some components affect cellular viability more profoundly than others. The ionization caused by radiation lasts longer than the initial inciting incident, continuing as 1 ionization incident causes another. In some cases, damage to DNA can lead to cellular death at mitosis. In other cases, activation of the genetic machinery can lead to a genetic cascade potentially leading to mutations or cell death by apoptosis. In the third of 5 articles on the management of injuries and illnesses caused by ionizing radiation, the authors provide a clinically relevant overview of the pathophysiologic process associated with potential exposure to ionizing radiation.
The major populations at risk for developing pressure ulcers are older adults who have multiple risk factors that increase their vulnerability, people who are critically ill and those with spinal ...cord injury/disease. The reported prevalence of pressure ulcers in the United States is 2.5 million. However, this estimate is derived from acute care facilities and does not include people who are living at home or in nursing facilities. Despite the implementation of hospital and facility‐based preventive measures, the incidence of pressure ulcers has not decreased in decades. In addition to the burden of pain, infection and death, it is estimated that hospital‐acquired pressure ulcers cost the health system $26.8 billion annually with over 50% of the cost attributed to treating Stage 3 and 4 pressure injuries. Thus, it is critical to examine the literature and develop guidelines that will improve the outcomes of this complex and costly condition. This guideline update is a compendium of the best available evidence for the treatment of Pressure Ulcers published since the last update in 2015 and includes a new section based on changing demographics entitled ‘Palliative wound care for seriously ill patients with pressure ulcers’. The overall goal of the Wound Healing Society Guideline project is to present clear, concise and commercial free guidelines that clinicians can use to guide care, that researchers can use to develop studies that will improve treatment and that both clinicians and researchers can use to understand the gaps in our knowledge base.
Purpose
More than half a million children experience non-accidental trauma (NAT) annually. Historically, NAT has been associated with an increased hospital length of stay (LOS). We hypothesized that ...in pediatric trauma patients, NAT is associated with longer hospital LOS, independent of injury severity, compared to accidental trauma (AT).
Methods
The Pediatric Trauma Quality Improvement Program (2014–2016) was queried for patients aged 1–16 years. Patients were stratified into two groups: AT and NAT. The median LOS for the entire cohort was identified and used in a multivariable logistic regression analysis.
Results
From 93,089 pediatric trauma patients, 417 (< 0.1%) were involved in NAT. Patients with NAT had a lower median age (3 vs. 9 years,
p
< 0.001) and higher median injury severity score (10 vs. 5,
p
< 0.001), compared to patients with AT. After controlling for covariates, patients with NAT were associated with a longer hospital LOS (≥ 2 days), compared to those with AT (OR = 4.99 CI = 3.55–7.01,
p
< 0.001). In comparison to AT, NAT was also associated with a higher mortality rate (10.3% vs. 0.8%,
p
< 0.001).
Conclusion
Pediatric patients presenting after NAT have a prolonged hospital and ICU LOS, even after adjusting for injury severity. Furthermore, pediatric victims of NAT had a higher mortality rate compared to those presenting after AT.
PDF
