Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus).

Despite the need for safe and effective postoperative analgesia in neonates, research regarding pain management in neonatal rodents is relatively limited. Here, we investigate whether sustained release buprenorphine (Bup SR) effectively attenuates thermal hypersensitivity in a neonatal rat model of incisional pain. Male and female postnatal day 3 Sprague Dawley rat pups (n = 34) were randomly assigned to one of four treatment groups: 1) saline (control), 0.1 mL, once subcutaneously (SC); 2) buprenorphine HCl (Bup HCl), 0.05 mg/kg, once SC; 3) low dose Bup SR (low-SR), 0.5 mg/kg, once SC; 4) high dose Bup SR (high-SR), 1 mg/kg, once SC. Pups were anesthetized with sevoflurane and a 0.5-cm long skin incision was made over the left lateral thigh. The underlying muscle was dissected and closed using surgical glue. Thermal hypersensitivity testing was performed at 24 h prior to surgery and subsequently at 1, 4, 8, 24, and 48 h post-surgery using an infrared diode laser. Thermal hypersensitivity was attenuated at 1 h post-surgery in the Bup HCl group, while it was attenuated through the entire postoperative period in both low-SR and high-SR groups. This data suggests that a single dose of low-SR (0.5 mg/kg) or high-SR (1 mg/kg) effectively attenuates thermal hypersensitivity for at least 8 h in neonatal rat pups.

FLASH Irradiation Results in Reduced Severe Skin Toxicity Compared to Conventional-Dose-Rate Irradiation.

Radiation therapy, along with surgery and chemotherapy, is one of the main treatments for cancer. While radiotherapy is highly effective in the treatment of localized tumors, its main limitation is its toxicity to normal tissue. Previous preclinical studies have reported that ultra-high dose-rate (FLASH) irradiation results in reduced toxicity to normal tissues while controlling tumor growth to a similar extent relative to conventional-dose-rate (CONV) irradiation. To our knowledge this is the first report of a dose-response study in mice comparing the effect of FLASH irradiation vs. CONV irradiation on skin toxicity. We found that FLASH irradiation results in both a lower incidence and lower severity of skin ulceration than CONV irradiation 8 weeks after single-fraction hemithoracic irradiation at high doses (30 and 40 Gy). Survival was also higher after FLASH hemithoracic irradiation (median survival >180 days at doses of 30 and 40 Gy) compared to CONV irradiation (median survival 100 and 52 days at 30 and 40 Gy, respectively). No ulceration was observed at doses 20 Gy or below in either FLASH or CONV. These results suggest a shifting of the dose-response curve for radiation-induced skin ulceration to the right for FLASH, compared to CONV irradiation, suggesting the potential for an enhanced therapeutic index for radiation therapy of cancer.

Diversity of rickettsiae in a rural community in northern California.

Far northern California forests are highly biodiverse in wildlife reservoirs and arthropod vectors that may propagate rickettsial pathogens in nature. The proximity of small rural communities to these forests puts people and domestic animals at risk of vector-borne infection due to spillover from wildlife. The current study was conducted to document exposure to rickettsial pathogens in people and domestic animals in a rural community, and identify which rickettsiae are present in sylvatic and peri-domestic environments near this community. Blood samples from people, domestic animals (dogs, cats, and horses) and wild carnivores were tested for Rickettsia spp. antibodies and DNA (people and domestic animals only) by serology and real time (RT)-PCR, respectively. Ectoparasites were collected from dogs, wild carnivores and from vegetation by flagging, and tested for Rickettsia spp. DNA by RT-PCR. DNA sequencing of the rickettsial 17kDa protein gene or the ompA gene was used for species identification. Despite a seroprevalence of 3% in people, 42% in dogs, 79% in cats, 33% in gray foxes, and 83% in bobcats, RT-PCR on blood was consistently negative, likely because the sensitivity of this test is low, as Rickettsia spp. do not often circulate in high numbers in the blood. Rickettsia spp. DNA was found in four flea species collected from bobcats and Ctenocephalides felis collected from domestic dogs. All amplicons sequenced from fleas were R. felis. Ixodes pacificus collected by flagging were commonly infected with a Rickettsia sp. endosymbiont. Rickettsia rhipicephali DNA was found in Dermacentor variabilis from dogs, black bears, a gray fox, and a D. occidentalis collected by flagging. Dermacentor variabilis from dogs and black bears also contained R. montanensis DNA. Multiple Rickettsia spp. (including species with zoonotic and pathogenic potential) were found among human biting arthropod vectors of both wild and domestic carnivores and on flags. Knowledge of the diversity of Rickettsia spp. that are present within arthropod vectors to which people and domestic animals are exposed is an essential first step is making an accurate diagnosis and in better understanding the epidemiology of these potential pathogens. Within-host and vector interaction among these species may play a role in spillover into human and domestic animals.