Search

Purpose: In March 2020, a 1-week adjuvant breast radiotherapy schedule, 26 Gy in 5 fractions, was adopted to reduce the risk of COVID19 for staff and patients. This study quantifies acute toxicity rates and the effect on linac capacity. Materials and methods: This is a report of consecutive patients receiving ultrafractionated breast radiotherapy ( ± sequential boost) Mar–Aug 2020. Virtual consultations assessed acute skin toxicity during treatment and weeks 1, 2, 3 and 4 post treatment using CTCAE V5 scoring criteria. The number of linac minutes saved was estimated accounting for boost and DIBH use. Results: In total, 128/135 (95%) patients, including 31/33 boost patients, completed at least 3/5 assessments. 0/128 (0%) reported moist desquamation not confined to skin folds or minor bleeding (Grade 3), 41/128 (32%) reported brisk erythema, moist desquamation confined to skin folds or breast swelling (Grade 2), 62/128 (48%) reported faint erythema or dry desquamation (Grade 1) as their worst skin toxicity, with the remaining 20% reporting no skin toxicity. The highest prevalence of grade 2 toxicity occurred week 1 following treatment (20%), reducing to 3% by week 4. There was no difference in toxicity between those who received a boost versus not (p = 1.00). Delivering this schedule to 135 patients over six months saved 21,300 linac minutes and 1485 hospital visits compared to a 3-week schedule. Conclusion: Rapidly implementing ultrahypofractionated breast radiotherapy is feasible and acute toxicity rates are acceptable even when followed by boost.

This study brings together plot-scale growing season fluxes of carbon dioxide (CO2) and methane (CH4) from six Canadian peatlands restored by the moss layer transfer technique (MLTT) and compares them with fluxes from adjacent unrestored and natural peatlands to determine: 1) if CO2 and CH4 fluxes return to natural-site levels and 2) whether the ecohydrological controls (e.g. water table, plant cover) on these fluxes are similar between treatments. We also examine differences between eastern (humid/maritime climate) and western (sub-humid climate) Canadian plots, and between restoration of former horticultural peat extraction sites and oil industry well-pads. Our results indicate that restored site fluxes of CO2 and CH4 are not significantly different between eastern and western Canada or between a restored well-pad and restored horticultural peat extraction sites. Restoration resulted in gross primary production rates similar to those at natural plots and significantly greater than those at unrestored plots. Ecosystem respiration was not significantly different at restored and unrestored plots, and was lower at both than at natural plots. Methane emission was significantly greater at restored plots than at unrestored plots, but remained significantly lower on average than at natural plots. Water table was a significant control on CH4 flux across restored and natural plots. Vascular plant cover was significantly related to CO2 uptake (gross photosynthesis) at restored and unrestored plots, but not at natural plots, while higher moss cover resulted in significantly greater net uptake of CO2 at natural plots but not at restored and unrestored plots. Overall, MLTT restoration greatly alters CO2 and CH4 dynamics compared to unrestored areas but fluxes remain, on average, significantly different from those in natural peatlands, in both the magnitude of mean growing season fluxes and controls on variation in these fluxes among plots. Peatland restoration by MLTT results in reduced CO2 emissions and higher CH4 emissions; however, more year-round measurements in more restored peatlands over longer periods post-restoration are needed to improve greenhouse gas emission estimates for restored Canadian peatlands.

We present a case of acute hemolytic anemia, renal failure, and Clostridium perfringens bacteremia in a patient with acute myelogenous leukemia. The high fatality of C. perfringens bacteremia requires that clinicians recognize and rapidly treat patients at risk for this infection. Although other hemolytic processes are in the differential diagnosis of these events, the presence of high fever, chills, and rapidly positive blood cultures may help narrow the diagnosis. Most cases of C. perfringens bacteremia have a concomitant coinfection, which makes broad spectrum empiric therapy essential. There is a high mortality rate of C. perfringens infections associated with leukemia.

Objective: To determine the activity of fucoidan from Undaria pinnatifida (UPF) and Fucus vesiculosus (FVF) when given in combination of chemotherapy drugs using selected human breast or ovarian cancer orthotopic mouse models. Methods: Mice were inoculated with 1 × 10 6 cells of TOV-112d, MCF-7, or ZR-75 subcutaneously or SKOV 3 -GFP-Luc intraperitoneally on day 0. MCF-7 and ZR-75 mice were administered with estradiol valerate 2 mg/kg in 0.2 mL castor oil subcutaneously two days prior to cell inoculation. Mice were randomized to one of six arms (N = 10/arm) paclitaxel, UPF/paclitaxel, FVF/paclitaxel, tamoxifen, UPF/tamoxifen, or FVF/tamoxifen. Tumors were measured three times per week for 28 days. Results: Improved activity was observed with UPF or FVF in combination with tamoxifen in both the MCF-7 and ZR-75D breast cancer mouse models. Decreased activity of paclitaxel was observed when given in combination with UPF or FVF in both breast cancer mouse models. The combination of FVF/tamoxifen in the TOV-112d ovarian cancer mouse model had improved activity but no there was difference observed with the UPF/tamoxifen in either ovarian cancer mouse model. No difference was observed with combination of UPF or FVF with paclitaxel in human ovarian cancer SKOV 3 or TOV-112d orthotopic mouse models. Conclusion: This study did confirm that UPF/FVF in combination with tamoxifen did not decrease tamoxifen activity in both breast and ovarian cancer, with some potential to improve activity compared to tamoxifen alone in breast cancers. Previous in vitro studies had suggested UPF and FVF had overall synergistic activity with paclitaxel; however, in the current in vivo human cancer mouse model studies there was no change in paclitaxel activity when given in combination with UPF or FVF in either of the two human ovarian cancer models. Furthermore, this study demonstrated that UPF or FVF given in combination with paclitaxel had a potential antagonistic effect in breast cancer models. Additional studies are warranted to delineate mechanisms contributing to variation in the in vivo activity when given in combination with paclitaxel. As a first step, a clinical pharmacokinetic study evaluating impact of FVF/UPF given in combination with chemotherapy in patients with solid tumors is underway.

Objectives: To evaluate potential hepatic metabolism-mediated drug interactions with fucoidan from Undaria pinnatifida (UPF) or Fucus vesiculosus (FVF) and potential growth inhibition activity with either fucoidan alone or with chemotherapy. In vivo studies were done to confirm safety and investigate fucoidan-mediated immune modulation. Methods: Cytochrome P450 (CYP450) 3A4, 2C8, 2C9, and 2D6 inhibition experiments were conducted in vitro followed by an ex vivo human hepatocytes model to evaluate the CYP450 induction potential of each fucoidan at highest theoretical concentrations. Four hepatic metabolism phase II pathways—glutathione S transferase (GST), quinone oxidoreductase (QOR), catechol-O-methyltransferases (COMT), and uridine di-phosphate (UDP)-glucuronosyltransferase (UGT)—were evaluated with validated immunoassays. Growth inhibition assays were performed with each fucoidan alone and in combination with chemotherapy agents in a panel of human cancer cell lines. In vivo studies evaluated safety and immune modualtion. Results: CYP450 inhibition was observed with FVF. The GST, QOR, and UGT pathways had no changes. UPF and FVF both interacted with COMT. No growth inhibitory activity in cancer cell lines was observed. UPF and FVF had synergistic activity with paclitaxel or tamoxifen and additive activity with topotecan. In vivo, FVF decreased HeLa human cervical tumor growth and both FVF and UPF decreased TOV-112D human ovarian tumor growth. Otherwise, no significant change in tumor growth was observed. FVF immune modulation of IgG and IL-6 was observed (p

Objective. To determine the impact on antitumor activity when active hexose correlated compound (AHCC) in combination with anticancer hormonal agents in orthotopic mouse models of human estrogen receptor positive breast cancer and evaluate impact of AHCC on aromatase activity. Methods. The study consisted of 7 treatment arms (n=10) conducted in 2 breast cancer mouse models: MCF-7 and ZR-75. Treatment groups included untreated, vehicle, AHCC 50 mg/kg, AHCC 50 mg/kg + tamoxifen 10 mg/kg, tamoxifen 10 mg/kg, AHCC 50 mg/kg + letrozole 10 µg/mouse, or letrozole 10 µg/mouse. All treatments were administered daily by oral gavage for 12 weeks. Tumors were measured 3 times a week. In vitro estrone and 17β-estradiol enzyme immunoassay was used to evaluate aromatase activity. Results. There was no difference in the activity with the combination of AHCC + tamoxifen compared with tamoxifen ( P = 0.29). In the ZR-75 model (catechol- O -methyltransferase [COMT] wild-type), there was no difference in activity with the letrozole + AHCC compared with letrozole. However, in the MCF-7 model (COMT variant), AHCC + letrozole resulted in a decrease in activity compared with letrozole ( P < 0.01). Immunoassay data suggested that AHCC is a potential inducer of aromatase activity. In both tumor models, there was cytotoxicity observed with AHCC compared with untreated ( P < 0.02). Conclusion. AHCC did not change the activity of tamoxifen. AHCC may have some interaction with letrozole in patients with COMT variant genotype. AHCC had cytotoxicity that warrents additional studies to evaluate its potential role for consolidation/prevention of breast cancer.

Promoting youth representation in parliaments is a growing global priority. To promote youth leadership and more inclusive politics, youth organizations in Nigeria mobilized successfully for a constitutional reform to lower the eligibility age to run for political office. In this paper, we draw on global data to assess whether lower eligibility ages will in fact lead to higher levels of youth participation. We find that lower age requirements positively affect the representation of the youngest and next youngest cohorts in parliament. We draw on qualitative interviews and gender literature to theorize that lower age limits have immediate and longer-term “mobilizing effects”, shifting the calculations of potential candidates in terms of the age at which they first decide to run for office.

Promoting youth representation in parliaments is a growing global priority. To promote youth leadership and more inclusive politics, youth organizations in Nigeria mobilized successfully for a constitutional reform to lower the eligibility age to run for political office. In this paper, we draw on global data to assess whether lower eligibility ages will in fact lead to higher levels of youth participation. We find that lower age requirements positively affect the representation of the youngest and next youngest cohorts in parliament. We draw on qualitative interviews and gender literature to theorize that lower age limits have immediate and longer-term “mobilizing effects”, shifting the calculations of potential candidates in terms of the age at which they first decide to run for office.