Bcl2-Expressing Quiescent Type B Neural Stem Cells in the Ventricular-Subventricular Zone Are Resistant to Concurrent Temozolomide/X-Irradiation.

The ventricular-subventricular zone (V-SVZ) of the mammalian brain is a site of adult neurogenesis. Within the V-SVZ reside type B neural stem cells (NSCs) and type A neuroblasts. The V-SVZ is also a primary site for very aggressive glioblastoma (GBM). Standard-of-care therapy for GBM consists of safe maximum resection, concurrent temozolomide (TMZ), and X-irradiation (XRT), followed by adjuvant TMZ therapy. The question of how this therapy impacts neurogenesis is not well understood and is of fundamental importance as normal tissue tolerance is a limiting factor. Here, we studied the effects of concurrent TMZ/XRT followed by adjuvant TMZ on type B stem cells and type A neuroblasts of the V-SVZ in C57BL/6 mice. We found that chemoradiation induced an apoptotic response in type A neuroblasts, as marked by cleavage of caspase 3, but not in NSCs, and that A cells within the V-SVZ were repopulated given sufficient recovery time. 53BP1 foci formation and resolution was used to assess the repair of DNA double-strand breaks. Remarkably, the repair was the same in type B and type A cells. While Bax expression was the same for type A or B cells, antiapoptotic Bcl2 and Mcl1 expression was significantly greater in NSCs. Thus, the resistance of type B NSCs to TMZ/XRT appears to be due, in part, to high basal expression of antiapoptotic proteins compared with type A cells. This preclinical research, demonstrating that murine NSCs residing in the V-SVZ are tolerant of standard chemoradiation therapy, supports a dose escalation strategy for treatment of GBM. Stem Cells 2019;37:1629-1639.

Persistence and shedding of senecavirus A in naturally infected boars.

Senecavirus A (SVA) infection in pigs causes vesicular disease and results in a short viremia and transient shedding of the virus, mainly in oral fluids and feces. Here we describe the consistent prolonged shedding of SVA in the semen of 2 boars, and persistence of SVA within the tonsils and testes of 3 adult boars. Two SVA-infected boars that were identified on a Minnesota sow farm in 2017 shed SVA RNA in semen for >3 mo after an outbreak of vesicular disease had occurred on the farm. SVA was isolated from 1 semen sample collected 9 d after clinical disease began on the farm. The third SVA-infected boar was identified on an Indiana sow farm in 2020. All boars had SVA RNA detected in the testes and tonsils by RT-rtPCR, with lower Ct values obtained for the testes than from the tonsils. All boars had multifocal lymphocytic orchitis with segmental degeneration and atrophy of the germinal epithelium within the seminiferous tubules. One boar also had areas of seminiferous tubule collapse and interstitial fibrosis within the testes. In all boars, in situ hybridization demonstrated the presence of SVA mRNA within cells located basally in the seminiferous tubules of the testes, and within the basal surface epithelial cells, crypt epithelial cells, and subepithelial and parafollicular lymphocytes and histiocytes of the tonsil.

Rodent Model of Brain Radionecrosis Using Clinical LINAC-Based Stereotactic Radiosurgery.

Purpose: Our purpose was to develop a rodent model of brain radionecrosis using clinical linear accelerator based stereotactic radiosurgery. Methods and Materials: Single fraction maximum prescription points in the mouse's left hemisphere were irradiated using linear accelerator-based stereotactic radiosurgery with multiple arcs at 60 (n = 5), 100 (n = 5), and 140 (n = 5) Gy. Rats (n = 6) were similarly treated with 140 Gy. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) was used to track radiation injury in mice over weeks (100 and 140 Gy) or months (60 Gy). Target accuracy was measured by the distance from the prescription point to the center of the earliest Gd-MRI enhancement. Confirmation of necrosis via histology was performed at the subject endpoints. Results: Radiation injury as indicated by Gd-MRI was first identified at 2 weeks (140 Gy), 4 to 6 weeks (100 Gy), and 8 months (60 Gy). A volumetric time course showed rapid growth in the volume of Gd-MRI signal enhancement after the appearance of apparent necrosis. Histopathologic features were consistent with radionecrosis. Conclusions: The presented method uses a commonly available clinical linear accelerator to induce radiation necrosis in both mice and rats. The treatment is modeled after patient therapy for a more direct model of human tissue under a range of doses used in clinical neuro-ablation techniques. The short time to onset of apparent necrosis, accurate targeting of the prescription point, high incidence of necrosis, and similar pathologic features make this a suitable animal model for further research in radionecrosis.

Investigating the potential of conical scintillation detectors for patient-specific verification of intensity-modulated radiotherapy plans.

BACKGROUND AND PURPOSE: Conical scintillation detectors are frequently used to measure geometric characteristics of radiotherapy modalities. However, their application to verify intensity-modulated radiotherapy plan delivery has not been investigated and requires a more detailed understanding of device response. This work evaluated the novel application of a conical scintillation detector to plan-specific quality assurance (QA) for intensity-modulated photon plans by evaluating device dependence on beam delivery and device acquisition parameters. MATERIALS AND METHODS: Measurements were made with a conical scintillation detector using beam delivery parameters of five photon beams (6-15 MV, including flattening filter free), three field sizes (1 × 1-5 × 5 cm2), and several dose rates (100-2000 MU/min) combined with device acquisition parameters of two frame rates (10 and 20 fps) and three gains (18-22 dB). A standardization equation to correct for gain and frame rate was investigated, and the remaining dose rate dependence was characterized. Device precision was evaluated using replicate measurements, and spatial uniformity was determined by irradiating different parts of the device. RESULTS: For each parameter combination, measurement reproducibility was 1.3%, and spatial uniformity was 1-2%. Scintillation intensity varied with gain, frame rate, and dose rate. Standardizing measurements for gain and frame rate was effective, but a dependence on dose rate caused errors at non-reference conditions (root mean squared error, RMSE: 0-152%). An additional dose rate correction specific to each combination of gain and frame rate improved accuracy (RMSE 0-17%). CONCLUSIONS: To consider the detector for plan-specific QA of intensity-modulated radiotherapy plans, correction factors are imperative to mitigate effects of delivery and acquisition parameters.

Detection of Mycoplasma hyopneumoniae in piglet processing fluids.

Processing fluid (PF) is a sample type composed of fluids obtained from testicles and tails as the product of piglet processing. Mycoplasma hyopneumoniae is a bacterium that colonises the respiratory tract of pigs and has rarely been detected in tissues outside the respiratory system. No data exist in the literature regarding detection of M hyopneumoniae in PF or its use for herd monitoring of this pathogen. The main goal of this study was to evaluate the feasibility of detecting M hyopneumoniae in PF. Testicles and tails of 21 conveniently selected litters from a commercial sow farm were collected, by litter, and tested for M hyopneumoniae by real time-PCR. Daily aggregated processing tissues were collected for a two-month period to assess the detection of M hyopneumoniae in PF. The comparison in the percentage of positive samples in fluids from testicles (38 per cent, 8/21) or tails (4.8 per cent, 1/21) was significantly different (P=0.023). The percentage of daily aggregated PF with cycle threshold values up to 37 was 52.9 per cent (9/17) and 26.7 per cent (4/15) for December and January, respectively. Overall, these data show detection of M hyopneumoniae in PF for the first time and points at the potential use of this sample for monitoring of this bacterium in breeding farms.

Africa is on the verge of a major health crisis and the need for nutrition and health surveys is imperative.

The African region may be reaching a tipping point for a major health crisis. Over the last few decades for example, there has been a significant increase in the prevalence of obesity and associated comorbidities. This alarming trend is attributed to the rapid urbanization, increase in income, and unhealthy lifestyles among many others. Most importantly, managing and treating non-communicable diseases (NCDs) is expensive and proving to be beyond the reach of ordinary Africans. Interestingly, Africa has not fully eradicated undernutrition particularly micronutrient malnutrition especially among women and children. Additionally, HIV/AIDs, malaria, diarrheal diseases and other preventable infectious diseases continue to pose serious threat to the health of the populace. The management of NCDs is challenging and costly as most healthcare systems on the continent are largely built for the provision of curative care for communicable diseases. This article proposes the institution of nutrition and health surveys in individual countries to monitor trends. We believe this approach, in addition to addressing lifestyle and behavioral factors, may be effective in curbing the rising phenomenon of obesity and NCDs.

Comparison of U.S. Environmental Protection Agency's CAP88 PC Versions 3.0 and 4.0.

The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (U.S. EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with U.S. EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within its corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective dose. A detailed summary for select radionuclides of concern at the Savannah River Site (60Co, 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes U.S. EPA made in the external ground shine calculations.