Discovery of super-insecticide-resistant dengue mosquitoes in Asia: Threats of concomitant knockdown resistance mutations.

Aedes aegypti (Linnaeus, 1762) is the main mosquito vector for dengue and other arboviral infectious diseases. Control of this important vector highly relies on the use of insecticides, especially pyrethroids. The high frequency (>78%) of the L982W substitution was detected at the target site of the pyrethroid insecticide, the voltage-gated sodium channel (Vgsc) of A. aegypti collected from Vietnam and Cambodia. Alleles having concomitant mutations L982W + F1534C and V1016G + F1534C were also confirmed in both countries, and their frequency was high (>90%) in Phnom Penh, Cambodia. Strains having these alleles exhibited substantially higher levels of pyrethroid resistance than any other field population ever reported. The L982W substitution has never been detected in any country of the Indochina Peninsula except Vietnam and Cambodia, but it may be spreading to other areas of Asia, which can cause an unprecedentedly serious threat to the control of dengue fever as well as other Aedes-borne infectious diseases.

A first, naturally occurring substitution at the second pyrethroid receptor of voltage-gated sodium channel of Aedes aegypti.

BACKGROUND: Aedes aegypti is a remarkably effective mosquito vector of epidemiologically important arboviral diseases including dengue fever, yellow fever and Zika. The present spread of resistance against pyrethroids, the primary insecticides used for mosquito control, in global populations of this species is of great concern. The voltage-gated sodium channel (VGSC) in the nervous system is the known target site of pyrethroids in insects. Past studies have revealed several amino-acid substitutions in this channel that confer pyrethroid resistance, which are known as knockdown resistance (kdr) mutations. RESULTS: This study investigated a laboratory colony of Ae. aegypti, MCNaeg, established from larvae collected in Rio de Janeiro, Brazil in 2016. The MCNaeg colony showed strong resistance against pyrethroids without laboratory selection. Of the two VGSC gene haplotypes present within this colony, one harbored three known kdr mutations, V410L, V1016I, and F1534C, and the other harbored only the known F1534C mutation. In latter haplotype, we also found novel amino-acid substations including V253F. Previous molecular modeling and electrophysiological studies suggest that this residue serves a pyrethroid-sensing site in the second receptor, PyR2. Our genetical analysis showed that the haplotype harboring V253F and F1534C is associated with equal or slightly stronger resistance than the other triple kdr haplotype to both Type I and Type II pyrethroids. CONCLUSION: The novel substitution V253F is potentially involved in pyrethroid resistance in Ae. aegypti. Further studies are needed to elucidate the role of this substitution in the pyrethroid susceptibility of VGSC. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Preeclampsia as a Manifestation of New-Onset Systemic Lupus Erythematosus during Pregnancy: A Case-Based Literature Review.

Introduction New-onset systemic lupus erythematosus (SLE) during pregnancy is rare and difficult to diagnose, especially in cases that manifest as preeclampsia. We report a patient with new-onset SLE that manifested as preeclampsia during pregnancy and provide a review of the literature to identify factors for a rapid diagnosis. Case A 32-year-old primigravid Japanese woman was diagnosed with severe preeclampsia and underwent emergent cesarean section at 29 weeks of gestation. Her hypertension and renal disorder gradually improved after the operation, but her thrombocytopenia and anemia worsened. SLE was diagnosed on postoperative day 5 by a comprehensive autoimmune workup. She was discharged on postoperative day 34 with remission. Conclusion Our case and previous reports suggest that distinguishing underlying SLE from preeclampsia in the third trimester is particularly difficult. Helpful factors for diagnosis of suspected SLE in these cases were persistence of symptoms and new atypical symptoms for preeclampsia revealed after delivery (e.g., fever, renal disorder, and thrombocytopenia).

18F-FLT PET performs better than 18F-FDG PET in differentiating malignant uterine corpus tumors from benign leiomyoma.

PURPOSE: The aim of this study is to test the hypothesis that positron emission tomography (PET) with 3'-deoxy-3'-[(18)F]-fluorothymidine ((18)F-FLT) can differentiate malignancy from benign leiomyoma better than PET with 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG), and to evaluate whether (18)F-FLT and (18)F-FDG uptake correlate with immunohistochemical index of cell proliferation. METHODS: The protocol of this prospective study was approved by the institutional ethics committee, and all patients gave written informed consent. Fifteen patients (aged 26-65 years, median 44 years) with uterine corpus tumor which has the possibility of being leiomyosarcoma underwent (18)F-FLT and (18)F-FDG PET scans. Maximum standard uptake value (SUV(max)) of PET scans and Ki-67 labeling index of surgical specimens were evaluated. Mann-Whitney's U test was used for comparing uptakes between benign and malignant, and linear regression analysis was used for evaluating the correlation between Ki-67 labeling index and SUV(max). RESULTS: Five cases were diagnosed as malignant (leiomyosarcoma for 3 cases, and carcinoma for 2 cases), and the others were benign leiomyoma. Sensitivity and negative predictive value of both tracers for detecting malignancy was 100%. Specificity, positive predictive value and accuracy of (18)F-FLT PET were higher than those of (18)F-FDG PET. Difference in SUV(max) between malignant and benign was significant for (18)F-FLT PET (P < 0.01), but not for (18)F-FDG PET. While all the malignant cases showed positive uptake in both tracers, a case of leiomyosarcoma with huge necrosis showed relatively low uptake. Uptake of (18)F-FLT showed better correlation with Ki-67 labeling index compared with (18)F-FDG (R(2) = 0.91 vs. R(2) = 0.26). CONCLUSION: Negative findings on additional (18)F-FDG or (18)F-FLT PET may rule out the possibility of malignancy for the patients with suspected leiomyosarcoma diagnosed by conventional methods. (18)F-FLT PET is superior to (18)F-FDG PET in differentiating malignant from benign leiomyoma. Moreover, (18)F-FLT uptake correlated well with the immunohistochemical index of cell proliferation.