Dexamethasone potentiates in vitro blood-brain barrier recovery after primary blast injury by glucocorticoid receptor-mediated upregulation of ZO-1 tight junction protein

Owing to the frequent incidence of blast-induced traumatic brain injury (bTBI) in recent military conflicts, there is an urgent need to develop effective therapies for bTBI-related pathologies. Blood-brain barrier (BBB) breakdown has been reported to occur after primary blast exposure, making restoration of BBB function and integrity a promising therapeutic target. We tested the hypothesis that treatment with dexamethasone (DEX) after primary blast injury potentiates recovery of an in vitro BBB model consisting of mouse brain endothelial cells (bEnd.3). DEX treatment resulted in complete recovery of transendothelial electrical resistance and hydraulic conductivity 1 day after injury, compared with 3 days for vehicle-treated injured cultures. Administration of RU486 (mifepristone) inhibited effects of DEX, confirming that barrier restoration was mediated by glucocorticoid receptor signaling. Potentiated recovery with DEX treatment was accompanied by stronger zonula occludens (ZO)-1 tight junction immunostaining and expression, suggesting that increased ZO-1 expression was a structural correlate to BBB recovery after blast. Interestingly, augmented ZO-1 protein expression was associated with specific upregulation of the α⁺ isoform but not the α⁻ isoform. This is the first study to provide a mechanistic basis for potentiated functional recovery of an in vitro BBB model because of glucocorticoid treatment after primary blast injury.     

Growth of the Social #RadOnc Network on Twitter

PurposeTwitter is an increasingly popular social media platform within the health care community. The objective of this analysis is to characterize the profile of radiation oncology–related tweets and Twitter users over the past 6 years.Methods and MaterialsUsing the web-based social media analytics platform Symplur Signals, we filtered tweets containing at least 1 of the following hashtags or key words: #radonc, #radiationoncology, "rad onc," or "radiation oncology." We evaluated radiation oncology–related Twitter activity between October 2014 and March 2020 for tweet frequency, tweet content, and individuals or groups posting tweets. We identified the most influential Twitter users contributing to radiation oncology–related tweets.ResultsFrom 2014 to 2020, the quarterly volume of radiation oncology–related tweets increased from 5027 to 29,763. Physicians contributed the largest growth in tweet volume. Academic radiation oncologists comprise 60% of the most influential Twitter accounts responsible for radiation oncology–related content. The number of radiation-oncology resident physicians on Twitter increased from 25 to 328 over the past 6 years, and 20% of radiation-oncology residency programs have a Twitter account. Seventy-one percent of radiation oncology–related tweets generated direct communication via mentions, and 59% of tweets contain links to external sources, including scientific articles.ConclusionsThe number of physicians contributing radiation oncology–related Twitter content has increased significantly in recent years. Academic radiation oncologists are the primary influencers of radiation oncology–related Twitter activity. Twitter is used by radiation oncologists to both professionally network and discuss findings related to the field. There remains the opportunity for radiation oncologists to broaden their audience on Twitter to encompass a more diverse community, including patients.     

Stability of transverse expansion in the mandibular arch.

This was a retrospective, longitudinal cephalometric and cast study of 29 white patients at pretreatment, posttreatment, and an average of 6 years 3 months postretention. The goal was to assess changes with treatment and retention with the expanding mandibular lingual arch appliance in conjunction with fixed edgewise treatment. Seven mandibular cast measurements were assessed, including arch crowding, arch perimeter, arch length, and arch width at the permanent canines, first premolars, second premolars, and first molars. Cephalometric radiographs were digitized, and 16 cephalometric measurements were made. Repeated-measures analysis of variance and 2-sample t tests were used to determine statistically significant changes. It was found that the expanding lingual arch used for less than 6 months with the mandibular fixed edgewise appliance caused an increase in both the transverse and sagittal dimensions of the mandibular dental arch. Transverse expansion was more stable in the posterior region of the mandibular dental arch than in the anterior region. Mandibular intercanine width increase could be maintained only by fixed retention. Although the maxillary and mandibular incisors were advanced and proclined, lip protrusion did not occur.     

Specification of the Dose to Organs at Risk in External Beam Radiotherapy

Reporting of the clinical relevant dose to organs at risk (OR) and other normal tissues is crucial in trials and protocols where the aim is to assess late complications and to increase the therapeutic ratio for external beam radiotherapy. The dose distribution in normal tissues and ORs are, however, most often heterogeneous, at least when more than two opposing beams are applied. To decide the most clinical relevant dose with respect to late occurring complications is therefore not a straight forward problem. In this work we discuss what parameters characterise the dose-volume-histogram (DVH) best by calculating normal tissue complication probabilities (NTCPs) by using the Lyman model and various sets of statistical parameters drawn out from the DVHs. These NTCPs are compared to NTCPs calculated from the full DVHs, when the sets of parameters are evaluated. Our calculations indicate that the NTCP based on the Lyman model is best correlated to the D_max value, for serially organised tissues such as the spinal cord. For organs, described largely as tissues organised in parallel, the D_median or D_mean of the DVH may be applied. Our calculations reveal that D_mean is the parameter of choice when D_meclian is quite small, but when the two parameters approach each other, D_mediarl will be a better choice, using a unity volume fraction. For ORs characterised by a mixed serial and parallel functional structure, as the heart, neither D_max, D_median, nor D_mi,_an may predict the actual NTCP.     

Xenogeneic bone marrow transplantation: II. Porcine-specific growth factors enhance porcine bone marrow engraftment in an in vitro primate microenvironment

Abstract: Establishment of mixed bone marrow chimerism in pig-to-primate transplantation, as a means of inducing specific immune tolerance, will require that both immune and nonimmune barriers be overcome. As a preliminary step in evaluating nonimmune barriers in this system, we have developed an in vitro model of engraftment in which long-term culture of porcine bone marrow-derived hematopoietic cells is supported on preformed primate bone marrow stromal layers. In the absence of cytokine supplementation, primate stromal cells were unable to support long-term porcine hematopoiesis in these cultures. Supplementation with porcine Steel Factor was required for long-term maintenance of hematopoietic progenitor cell content and total hematopoietic activity. Addition of porcine IL-3, in combination with porcine Steel Factor, increased long-term progenitor cell content and hematopoietic activity on primate stroma to levels comparable to that obtained in cultures on porcine stroma. The combination of porcine GM-CSF and Steel Factor increased progenitor cell content and hematopoietic activity early in the cultures, but had little effect in long-term cultures. The Steel Factor and IL-3 combination was species-specific in its action in these cultures, as the corresponding human cytokines were unable to effectively support long-term porcine hematopoiesis. Likewise, the combination of porcine cytokines had only minimal effects on long-term bone marrow culture of primate CD34+ cells I on primate stroma.     

Diastolic function in children and adolescents on dialysis and after kidney transplantation: an echocardiographic assessment

Thirty-seven children and adolescents on renal replacement therapy (11 on haemodialysis, 14 on continuous ambulatory peritoneal dialysis and 12 after renal transplantation) were studied by echocardiography, echo-Doppler and phonocardiography. Right and left ventricular (R/L V) diastolic functions were measured by transmitral and transtricuspid flow velocities and by LV isovolumic relaxation time (LVIRT). Thirty-seven age- and sex-matched healthy subjects served as controls. R/L V diastolic dysfunction was only observed in the dialysis patients. In these patients LVIRT was prolonged. LV and RV peak inflow velocities were increased both in early (E) and late (A) diastole with a reduction in the E/A ratios. This pattern of diastolic dysfunction is compatible with the combined effects of a hypercirculatory state (volume overload, anaemia, arteriovenous fistula) and an abnormality of cardiac relaxation. The transplant patients showed no major cardiac abnormalities.     

Vitrectomy for idiopathic epiretinal membranes causing macular pucker.

We used vitreous surgery to remove idiopathic epiretinal membranes from the macular area in 70 consecutive cases. The abnormal tissue was successfully removed in each case. Vision improved postoperatively in 61 eyes (87%), remained unchanged in six eyes (9%), and worsened in three eyes (4%). However, at the time of final examination vision was improved in only 47 eyes (67%), primarily because of the occurrence or progression of nuclear sclerosis, which occurred in 38 of 60 phakic eyes (63%). Four preoperative factors were associated with final visual acuity of 20/60 or better: (1) initial vision of 20/100 or better, (2) shorter preoperative duration of blurred vision, (3) thin epiretinal membrane, and (4) absence of traction retinal detachment.     

Rapid adenosine release in the nucleus tractus solitarii during defence response in rats: real-time measurement in vivo

We have measured the release of adenosine and inosine from the dorsal surface of the brainstem and from within the nucleus tractus solitarii (NTS) during the defence response evoked by hypothalamic stimulation in the anaesthetised rat. At the surface of the brainstem, only release of inosine was detected on hypothalamic defence area stimulation. This inosine signal was greatly reduced by addition of the ecto-5'-nucleotidase inhibitor α,β-methylene ADP (200 μM), suggesting that the inosine arose from adenosine that was produced in the extracellular space by the prior release of ATP. By placing a microelectrode biosensor into the NTS under stereotaxic control we have recorded release of adenosine within this nucleus. By contrast to the brainstem surface, a fast increase in adenosine, accompanied only by a much smaller change in inosine levels, was seen following stimulation of the hypothalamic defence area. The release of adenosine following hypothalamic stimulation was mainly confined to a narrow region of the NTS some 500 μm in length around the level of the obex. Interestingly the release of adenosine was depletable: when the defence reaction was evoked at short time intervals, much less adenosine was released on the second stimulus. Our novel techniques have given unprecedented real-time measurement and localisation of adenosine release in vivo and demonstrate that adenosine is released at the right time and in sufficient quantities to contribute to the cardiovascular components of the defence reaction.