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The Aedes aegypti mosquito, is an arbovirus vector that can spread dengue, chikungunya, Zika, and yellow fever. Pyrethroids are widely used to control mosquitoes. The voltage-gated sodium channel (Vgsc) is the target of pyrethroids, and amino acid substitutions in this channel attenuate the effects of pyrethroids. This is known as knockdown resistance (kdr). Recently, we found that Ae. aegypti with concomitant Vgsc mutations L982W + F1534C exhibit extremely high levels of pyrethroid resistance. L982 is located in a highly conserved region of Vgsc in vertebrates and invertebrates. This study aimed to evaluate the viability of Ae. aegypti, with concomitant L982W + F1534C mutations in Vgsc. We crossed a resistant strain (FTWC) with a susceptible strain (SMK) and reared it up to 15 generations. We developed a rapid and convenient genotyping method using a fluorescent probe (Eprobe) to easily and accurately distinguish between three genotypes: wild-type and mutant homozygotes, and heterozygotes. As generations progressed, the proportion of wild-type homozygotes increased, and only 2.9% of mutant homozygotes were present at the 15th generation; the allele frequencies of L982W + F1534C showed a decreasing trend over generations. These observations show that these concomitant mutations have some fitness costs, suggesting that mosquitoes can potentially recover pyrethroid susceptibility over time without pyrethroid selection pressure in the field., Competing Interests: Declaration of Competing Interest The authors declare there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Glutamate-gated chloride channels (GluCls) are inhibitory neurotransmitter receptors that are present only in invertebrates such as nematodes and insects. These channels are important targets of insecticidal, acaricidal, and anthelmintic macrolides such as avermectins, ivermectin (IVM), and milbemycins. To identify the amino acid residues that interact with IVM in GluCls, three IVM B1a derivatives with different photoreactive substitutions at C-13 were synthesized in the present study. These derivatives displayed low- or subnanomolar affinity for parasitic nematode (Haemonchus contortus) and silkworm (Bombyx mori) GluCls expressed in COS-1 cells. The derivatives also activated homomeric H. contortus GluCls expressed in Xenopus oocytes. The results indicate that synthesized photoreactive IVM B1a derivatives have superior affinity and functionality for chemically labeling the macrolide-binding site in GluCls. ., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate the long-term results of radical radiation therapy (RT) for cervical cancer in elderly patients., Methods: We reviewed the clinical records of 727 patients with cervical cancer who underwent radical RT at the Tokushima University Hospital and compared the treatment results of three age groups: /=75 years (older group [OG], 132 patients)., Results: At the last follow-up, 155 YG (46%), 77 YOG (30%), and 48 OG patients (36%) had died of cervical cancer; the median follow-up periods were 82, 87, and 68 months, respectively. The 5-/10-year disease-specific survival rates were 60%/52% in YG, 76%/68% in YOG, and 66%/57% in OG. Differences between OG and the other groups were not significant. The 5-/10-year disease-specific survival rate of YOG was significantly superior to that of YG (p<0.001). Clinical stage was the only significant prognostic variable (p<0.001). Late radiation morbidity of grades 2-4 in the bladder and/or rectum occurred in 22% of YG, 31% of YOG, and 8% of OG patients., Conclusions: RT was well tolerated in elderly patients, and age was not a significant prognostic factor. In the management of cervical cancer, advanced age is not a contraindication to radical RT.

Objective: To investigate the incidence, clinical and imaging finding of insufficiency fractures (IF) of the female pelvis following radiation therapy., Methods: We reviewed the radiation oncology records of 158 patients with gynecologic malignancies who underwent external beam radiation therapy of the whole pelvis between April 1993 and March 2004. All patients underwent computed tomography (CT) scan every 6 months in follow-up after radiation therapy and magnetic resonance imaging (MRI) and radionuclide bone scan were added when the patients complained of a pelvic pain., Results: Eighteen of 158 patients (11.4%) developed IF in the irradiated field with a median interval of 6 months (range 3-51) from the completion of external beam radiation therapy. The cumulative incidence of symptomatic IF at 5 years calculated with Kaplan-Meyer methods was 13%. Median age of the patients who developed IF was 70 years (range 48-88), and all of them were postmenopausal. IF occurred in the sacloiliac joints, upper limb of pubic bone, acetabulum, sacral body and 5th lumbar vertebra. Twelve of 18 patients had multiple lesions and 8 had symmetric longitudinal fracture lines parallel to the sacroiliac joints. Avoidance of weight bearing by bed rest and analgesics provided good pain relief in all patients, although symptoms lasted from 3 to 20 months., Conclusions: Radiation-induced pelvic IF following radiation therapy for gynecologic malignancies were frequently observed in the postmenopausal patients within 1 year after external beam radiation therapy. Symmetric fractures of the both sacroiliac joints were the characteristic pattern of pelvic IF. Knowledge of characteristic imaging pattern of IF is essential in order to rule out the bone metastasis. Therapy recommendations are conservative with analgesics.