[Analysis on infection risk in secondary close contacts of COVID-19 patients].

Objective: To study the infection rate of secondary close contacts of COVID-19 patients, and assess the infection risk in the contacts. Methods: COVID-19 patients' close contacts (with a clear exposure time to index case) with negative nucleic acid test results and secondary close contacts were surveyed in continuous isolation and medical observation in this prospective study. The dynamic nucleic acid test results of the close contacts and secondary contacts of COVID-19 patients were collected to assess their risk of infection. Results: A total of 4 533 close contacts were surveyed, in whom 14 were confirmed as COVID-19 patients with overall secondary attack rate of 0.31%, and 4 201 secondary contacts were tracked, in whom no subsequent infections occurred. Conclusion: Close contacts of COVID-19 patients entered in centralized isolation for medical observation with negative nucleic acid tese results,the secondary close contacts of COVID-19 patients have no risk of infection.

[Analysis on infectivity of COVID-19 patients before and after last negative nucleic acid test].

Objective: To investigate the infection rate in close contacts of COVID-19 patients before and after the last negative nucleic acid test, evaluate the effect of dynamic nucleic acid test in determining the infectivity of COVID-19 patients. Methods: Dynamic nucleic acid test results of COVID-19 cases were collected in a retrospective cohort study. COVID-19 cases with negative nucleic acid test results before their first positive nucleic acid tests were selected as study subjects. Close contacts of the index cases and the secondary close contacts were kept isolation for medical observation to assess their risk of infection. Results: This study included 89 confirmed cases from two local COVID-19 epidemics in Ningbo. A total of 5 609 close contacts were surveyed, the overall infection rate was 0.20%. No close contacts of the COVID-19 cases before the last negative nucleic acid test were infected, and the infection rate in the close contacts of the COVID-19 cases after the last negative nucleic acid test was 1.33%, all of these close contacts lived together with the index cases. No secondary close contacts were infected. Conclusion: COVID-19 patient becomes infectious after the last nucleic acid is negative, and has no infectivity before the last nucleic acid negative.

Neoplastic transformation in vitro by mixed beams of high-energy iron ions and protons.

The radiation environment in space is complex in terms of both the variety of charged particles and their dose rates. Simulation of such an environment for experimental studies is technically very difficult. However, with the variety of beams available at the National Space Research Laboratory (NSRL) at Brookhaven National Laboratory (BNL) it is possible to ask questions about potential interactions of these radiations. In this study, the end point examined was transformation in vitro from a preneoplastic to a neoplastic phenotype. The effects of 1 GeV/n iron ions and 1 GeV/n protons alone provided strong evidence for suppression of transformation at doses ≤5 cGy. These ions were also studied in combination in so-called mixed-beam experiments. The specific protocols were a low dose (10 cGy) of protons followed after either 5-15 min (immediate) or 16-24 h (delayed) by 1 Gy of iron ions and a low dose (10 cGy) of iron ions followed after either 5-15 min or 16-24 h by 1 Gy of protons. Within experimental error the results indicated an additive interaction under all conditions with no evidence of an adaptive response, with the one possible exception of 10 cGy iron ions followed immediately by 1 Gy protons. A similar challenge dose protocol was also used in single-beam studies to test for adaptive responses induced by 232 MeV/n protons and (137)Cs γ radiation and, contrary to expectations, none were observed. However, subsequent tests of 10 cGy of (137)Cs γ radiation followed after either 5-15 min or 8 h by 1 Gy of (137)Cs γ radiation did demonstrate an adaptive response at 8 h, pointing out the importance of the interval between adapting and challenge dose. Furthermore, the dose-response data for each ion alone indicate that the initial adapting dose of 10 cGy used in the mixed-beam setting may have been too high to see any potential adaptive response.

Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions.

Neoplastic transformation of HeLa x skin fibroblast human hybrid cells by doses of 1 GeV/nucleon iron ions in the range 1 cGy to 1 Gy to exposed cultures has been examined. The data indicate a threshold-type dose-response curve with no increase in transformation frequency until doses above 20 cGy. At doses <10 cGy, not all exposed cells receive a direct traversal of an iron-ion track core, but all exposed cells receive up to several mGy of low-LET radiation associated with the delta-ray penumbra. It is proposed that the threshold-type response seen is a consequence of an adaptive response associated with the delta-ray exposure. For comparison purposes, the dose response for (137)Cs gamma rays over the same dose range was examined using the same experimental procedure. As we have shown previously, the dose response for (137)Cs gamma radiation was J-shaped. The iron ions were 1.5 to 1.7 times more biologically effective than the gamma radiation over the dose range examined.

Low doses of very low-dose-rate low-LET radiation suppress radiation-induced neoplastic transformation in vitro and induce an adaptive response.

The purpose of this study was to determine whether adaptation against neoplastic transformation could be induced by exposure to very low-dose-rate low-LET radiation. HeLa x skin fibroblast human hybrid cells were irradiated with approximately 30 kVp photons from an array of (125)I seeds. The initial dose rate was 4 mGy/day. Cell samples were taken at four intervals at various times over a period of 88 days and assayed for neoplastic transformation and the presence of reactive oxygen species (ROS). The dose rate at the end of this treatment period was 1.4 mGy/day. Transformation frequencies and ROS levels were compared to those of parallel unirradiated controls. At the end of 3 months and an accumulated dose of 216 mGy, cells treated with very low-dose-rate radiation were exposed to a high-dose-rate 3-Gy challenge dose of (137)Cs gamma rays, and the effects compared with the effect of 3 Gy on a parallel culture of previously unirradiated cells. Cells exposed to very low-dose-rate radiation exhibited a trend toward a reduction in neoplastic transformation frequency compared to the unirradiated controls. This reduction seemed to diminish with time, indicating that the dose rate, rather than accumulated dose, may be the more important factor in eliciting an adaptive response. This pattern was in general paralleled by a reduction of ROS present in the irradiated cultures compared to controls. The very low-dose-rate-treated cells were less sensitive to the high challenge dose than unirradiated controls, suggesting the induction of an adaptive response. Since there was a suggestion of a dose-rate threshold for induction suppression, a second experiment was run with a fresh batch of cells at an initial dose rate of 1 mGy/day. These cells were allowed to accumulate 40 mGy over 46 days (average dose rate=0.87 mGy/day), and there was no evidence for suppression of transformation frequency compared to parallel unirradiated controls. It is concluded that doses of less than 100 mGy delivered at very low dose rates in the range 1 to 4 mGy/day can induce an adaptive response against neoplastic transformation in vitro. When the dose rate drops below approximately 1 mGy/day, this suppression is apparently lost, suggesting a possible dose-rate-dependent threshold for this process.

The effect of dose rate on radiation-induced neoplastic transformation in vitro by low doses of low-LET radiation.

The dependence of the incidence of radiation-induced cancer on the dose rate of the radiation exposure is a question of considerable importance to the estimation of risk of cancer induction by low-dose-rate radiation. Currently a dose and dose-rate effectiveness factor (DDREF) is used to convert high-dose-rate risk estimates to low dose rates. In this study, the end point of neoplastic transformation in vitro has been used to explore this question. It has been shown previously that for low doses of low-LET radiation delivered at high dose rates, there is a suppression of neoplastic transformation frequency at doses less than around 100 mGy. In the present study, dose-response curves up to a total dose of 1000 mGy have been generated for photons from (125)I decay (approximately 30 keV) delivered at doses rates of 0.19, 0.47, 0.91 and 1.9 mGy/min. The results indicate that at dose rates of 1.9 and 0.91 mGy/min the slope of the induction curve is about 1.5 times less than that measured at high dose rate in previous studies with a similar quality of radiation (28 kVp mammographic energy X rays). In the dose region of 0 to 100 mGy, the data were equally well fitted by a threshold or linear no-threshold model. At dose rates of 0.19 and 0.47 mGy/min there was no induction of transformation even at doses up to 1000 mGy, and there was evidence for a possible suppressive effect. These results show that for this in vitro end point the DDREF is very dependent on dose rate and at very low doses and dose rates approaches infinity. The relative risks for the in vitro data compare well with those from epidemiological studies of breast cancer induction by low- and high-dose-rate radiation.

Neoplastic transformation in vitro by low doses of ionizing radiation: role of adaptive response and bystander effects.

The shape of the dose-response curve for cancer induction by low doses of ionizing radiation is of critical importance to the assessment of cancer risk at such doses. Epidemiologic analyses are limited by sensitivity to doses typically greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the examination of lower doses using cancer-relevant endpoints. One such endpoint is neoplastic transformation in vitro. It is known that this endpoint is responsive to both adaptive response and bystander effects. The relative balance of these processes is likely to play an important role in determining the shape of the dose-response curve at low doses. A factor that may influence this balance is cell density at time of irradiation. The findings reported in this paper indicate that the transformation suppressive effect of low doses previously seen following irradiation of sub-confluent cultures, and attributed to an adaptive response, is reduced for irradiated confluent cultures. However, even under these conditions designed to optimize the role of bystander effects the data do not fit a linear no-threshold model and are still consistent with the notion of a threshold dose for neoplastic transformation in vitro by low LET radiation.

Neoplastic transformation in vitro induced by low doses of 232 MeV protons.

The aim was to define the dose--response curve for high-energy proton-induced neoplastic transformation in vitro. The HeLa x skin fibroblast human hybrid cell assay was used to determine the frequency of neoplastic transformation following doses of 232 MeV protons (mean linear energy transfer, LET=0.44 keV microm(-1)) in the range 5-600 mGy. Proton irradiations were carried out at the Loma Linda University Proton Treatment Facility, CA, USA. The data indicate no evidence for induction of transformation below a dose of 100 mGy. At doses of 5 and 50 mGy, there is evidence for a possible suppression of transformation frequencies below that for spontaneous transformation. The shape of the dose--response curve for high-energy proton-induced transformation of the human hybrid cell line CGL1 does not follow a linear no-threshold model and shows evidence for a threshold as well as for possible suppression of transformation at doses <100 mGy, similar to that seen for other low-LET radiations.

Intraperitoneal cisplatin with sodium thiosulfate protection in rats with intestinal anastomoses.

Intraperitoneal (IP) cisplatin administered at the time of intraabdominal malignancies such as gastric cancer may prevent or delay intraabdominal recurrence. Perioperative IP cisplatin raises concerns regarding systemic toxicity and retardation of wound healing. Systemic cisplatin toxicity may be reduced by administering its antidote, sodium thiosulfate (STS). A preclinical study of IP cisplatin in rats undergoing a small intestinal anastomosis was carried out. All animals that had received only cisplatin died in the postoperative period as a consequence of cisplatin toxicity. Tensile strength of the intestinal anastomoses was determined on the tenth postoperative day in the surviving animals. Animals that had received intravenous (IV) cisplatin with STS had significantly lower tensile strengths than both those receiving IP cisplatin with STS and STS alone. This study demonstrates the safety of perioperative cisplatin with STS protection by the avoidance of systemic toxicity and minimizing the cisplatin-related retardation of wound healing.