Diagnostic Dose Research Articles

Insecticide Resistance in Aedes aegypti from the National Capital Region of the Philippines.

Human arboviral diseases such as dengue, chikungunya, and Zika can be transmitted by the mosquito Aedes aegypti. The insecticide-based vector control strategy is critical in reducing transmission of these Aedes-borne diseases but is threatened mainly by the emergence of insecticide resistance. Adult Ae. aegypti from the National Capital Region (NCR), Philippines, were subjected to bioassays to determine their susceptibility to diagnostic doses of pyrethroid, organochlorine, and organophosphate insecticides following the standard World Health Organization insecticide susceptibility test. This study reports the detection of insecticide resistance to pyrethroids and organochlorine in Ae. aegypti from the Philippines for the first time. Most of the Ae. aegypti populations from NCR exhibited phenotypic resistance to permethrin, etofenprox, and DDT. Varying resistance levels to deltamethrin, cyfluthrin, and lambda-cyhalothrin were observed in the different mosquito populations, while all populations tested to malathion were susceptible to this organophosphate. This finding should alert public health authorities to consider modifying the existing vector management package for greater control efficacy. Best practices proven to prevent or delay the development of insecticide resistance, such as insecticide rotation, should also be implemented, while alternative chemicals with a different mode of action should be explored to ensure the continuing efficacy of program interventions.

TCT-678 Angina Severity and Symptom Improvement Are Associated With Diagnostic Acetylcholine Provocation Dose in Vasospastic Angina

TCT-678 Angina Severity and Symptom Improvement Are Associated With Diagnostic Acetylcholine Provocation Dose in Vasospastic Angina

Conventional versus cone-beam computed tomography in lung biopsy: diagnostic performance, risks, and the advantages of tract embolization with gelfoam particle suspension.

With the widespread adoption of computed tomography (CT) technology, the number of detected pulmonary nodules has gradually increased. CT-guided percutaneous needle biopsy has become the primary method for qualitative diagnosis of pulmonary nodules. Benefiting from its three-dimensional (3D) reconstruction capability, cone-beam CT (CBCT) technology has also been widely adopted. Nevertheless, pneumothorax remains the most common complication of these diagnostic and therapeutic procedures. This study assessed the diagnostic accuracy of conventional CT (CCT)- and CBCT-guided coaxial core needle biopsy (CCNB) and the effectiveness of gelfoam particle suspension in reducing complications through tract embolization. A retrospective analysis was conducted on 320 patients who had undergone CCNB for nodules ≤3 cm from January 2020 to June 2022 at Zhongshan People's Hospital, comprising 325 biopsies (145 CCT-guided and 180 CBCT-guided). Gelfoam tract embolization was specifically used in biopsies of patients identified with a high risk of complications. Comparative statistics involved diagnostic outcomes (sensitivity, specificity, accuracy), procedural lengths, complication occurrences, and radiation doses. Diagnostically, both CCT (sensitivity 93.3%, specificity 100%, accuracy 94.1%) and CBCT (sensitivity 92.8%, specificity 100%, accuracy 93.8%) offered a similarly high performance. The CCT technique was preferable in terms of shorter median operational times (19 vs. 24 minutes; P<0.001) and greater radiation exposure (13.9 vs. 10.1 mSv; P<0.001). The complication rates of CBCT and CCT, such as those of pneumothorax (18.9% vs. 20.7%; P=0.69) and hemorrhage (23.9% vs. 18.6%; P=0.25), were comparable. Of note, the comparison of biopsies with and without gelfoam embolization revealed a marked reduction in postoperative pneumothorax incidence (1.24% vs. 7.9%; P=0.004) and the requirement for drainage (0% vs. 4.27%; P=0.02), indicating the effectiveness of this procedure. CCT- and CBCT-guided lung biopsies demonstrate equivalent diagnostic capacities, with CCT providing shorter median operational times. Importantly, gelfoam embolization substantially diminishes the risk of postoperative pneumothorax, underscoring its value in high-risk patients.

Establishing Diagnostic Reference Levels and Radiation Dose for Pediatric Head Age-Based Using Computed Tomography in Khartoum State

Computed tomography (CT) is a powerful clinical tool for the diagnosis and management of patients, enabling faster and more accurate diagnosis and the avoidance of interventional surgical techniques. A diagnostic reference level (DRL) is a tool used to aid in optimization of protection in the medical exposure of patients for diagnostic and interventional procedures. It is used in medical imaging with ionizing radiation to indicate whether, in routine conditions, the patient dose or administered activity (amount of radioactive material) from a specified procedure is unusually high or low for that procedure. Radiation dosage variance is one of the topics that arise when dealing with CT devices within medical imaging centers. Diagnostic reference levels have not been established in Sudan. The aim of this study is to propose DRLs for CT of the head for 4 pediatric age groups. The 2 levels that this study covers are volume CT dose index based on a 16-cm phantom (CTDIvol [mGy]) and the dose-length products (DLPs [mGy • cm]). These levels were investigated by conducting a survey to 6 healthcare facilities. The survey consists of questions focused on pediatric exposure parameters, CT protocols, and radiation doses for pediatric age groups &lt;1, 1-5, 5-10, and 10-16 years. For the 4 age groups in the 6 facilities that responded, the mean, 25th, 50th, and 75th percentile values of CTDIvol (mGy) for head CT were for infants (&lt;1 year), 21.2, 14.4, 17.6, and 27.0, respectively; for 1-5 years, 36.5, 15.7, 34.5, and 38.1, respectively; for 5- to 10-year group, the CTDIvol was found to be 40, 15.7, 33.5, and 47.6, respectively, and for the last group of 10-16 years, 41.6, 15.7, 37.4, and 58.3, respectively. The corresponding DLP (mGy • cm) for head CT, the mean, 25th, 50th, and 75th percentile values were as follows: for infants (&lt;1 year), 472.9, 326.9, 385.3, and 545.5, respectively; for 1-5 years, 742.9, 509.1, 689.3, and 902.9, respectively; for 5-10 years, 1,130.4, 501.7, 924.2, and 1,667.4, respectively; for 10-16 years, 1,226.4, 595.4, 870.1, and 1,255.3, respectively. The total mean CTDIvol (mGy) was 38.0, and the total mean DLP (mGy · cm) was 1,001.6. These values have been compared with other values from other similar studies; the summary for these comparisons concluded that the majority of CTDIvol 16-cm phantom and DLP 16-cm phantom values for the head were higher than DRLs reported from other studies in other countries. Therefore, for risk reduction, it is necessary to establish DRLs for pediatric CT in Sudan.

Monitoring detoxification enzyme levels and resistance of Tetranychus urticae against some METI-group chemicals in Türkiye cotton fields.

Acaricides used against Tetranychus urticae Koch, 1836 (Acari: Tetranychidae) in cotton fields cause control failure over time. To determine the resistance status of T. urticae populations to tebufenpyrad and bifenazate, different populations collected from Aydın (AYD), Adana (ADA), Şanlıurfa (SAN), and Diyarbakır (DIY) provinces of Türkiye, between 2019 and 2020, were subjected to diagnostic dose bioassays. Firstly, the spider mites were eliminated with a discriminating dose. Afterwards, LC50 and LC90 of the remaining populations were determined and the ten highest resistant populations were selected. The highest phenotypic resistance to bifenazate was observed in AYD4 and DIY2 (LC50 57.14 mg L- 1 with 85.01-fold and LC50 30.15 mg L- 1with 44.86-fold, respectively), while the lowest phenotypic resistance was found in SAN6 (LC50 1.5 mg L- 1; 2.28-fold). Considering the phenotypic resistance to tebufenpyrad, the highest resistance was found in AYD4 population (LC50 96.81 mg L- 1; 12.92-fold), while the lowest - in DIY28 population (LC50 21.23 mg L- 1; 2.83-fold). In pharmacokinetic studies, the ADA16 population was compared with the sensitive German Susceptible Strain population and it was determined that carboxylesterase activity was statistically higher (1.46 ± 0.04 nmol/min/mg protein enzyme activation 2.70-fold). The highest activation of glutathione S-transferase was detected in ADA16 (1.49 ± 0.01 nmol/min/mg protein; 2.32-fold). No mutations were found in PSST (METI 1), the point mutation site for tebufenpyrad, and Cytb (METI 3), the point mutation site for bifenazate. In terms of phenotypic resistance, bifenazate was found to be moderately resistant in two populations (85.01 and 44.86-fold), while tebufenpyrad was moderately resistant in one population (12.92-fold). This study showed that both acaricides are still effective against T. urticae populations.

Insecticide susceptibility status of Anopheles albimanus populations in historical malaria foci in Quintana Roo, Mexico

BackgroundMexico has experienced a significant reduction in malaria cases over the past two decades. Certification of localities as malaria-free areas (MFAs) has been proposed as a steppingstone before elimination is achieved throughout the country. The Mexican state of Quintana Roo is a candidate for MFA certification. Monitoring the status of insecticide susceptibility of major vectors is crucial for MFA certification. This study describes the susceptibility status of Anopheles albimanus, main malaria vector, from historically important malaria foci in Quintana Roo, using both phenotypic and genotypic approaches.MethodsAdult mosquito collections were carried out at three localities: Palmar (Municipality of Othon P. Blanco), Buenavista (Bacalar) and Puerto Morelos (Puerto Morelos). Outdoor human-landing catches were performed by pairs of trained staff from 18:00 to 22:00 during 3-night periods at each locality during the rainy season of 2022. Wild-caught female mosquitoes were exposed to diagnostic doses of deltamethrin, permethrin, malathion, pirimiphos-methyl or bendiocarb using CDC bottle bioassays. Mortality was registered at the diagnostic time and recovery was assessed 24 h after exposure. Molecular analyses targeting the Voltage-Gated Sodium Channel (vgsc) gene and acetylcholinesterase (ace-1) gene were used to screen for target site polymorphisms. An SNP analysis was carried out to identify mutations at position 995 in the vgsc gene and at position 280 in the ace-1 gene.ResultsA total of 2828 anophelines were collected. The main species identified were Anopheles albimanus (82%) and Anopheles vestitipennis (16%). Mortalities in the CDC bottle bioassay ranged from 99% to 100% for all the insecticides and mosquito species. Sequence analysis was performed on 35 An. albimanus across the three localities; of those, 25 were analysed for vgsc and 10 for ace-1 mutations. All individuals showed wild type alleles.ConclusionThe results demonstrated that An. albimanus populations from historical malaria foci in Quintana Roo are susceptible to the main insecticides used by the Ministry of Health.

Identifying suitable methods for evaluating the sterilizing effects of pyriproxyfen on adult malaria vectors: a comparison of the oviposition and ovary dissection methods

BackgroundNets containing pyriproxyfen, an insect growth regulator that sterilizes adult mosquitoes, have become available for malaria control. Suitable methods for investigating vector susceptibility to pyriproxyfen and evaluating its efficacy on nets need to be identified. The sterilizing effects of pyriproxyfen on adult malaria vectors can be assessed by measuring oviposition or by dissecting mosquito ovaries to determine damage by pyriproxyfen (ovary dissection).MethodLaboratory bioassays were performed to compare the oviposition and ovary dissection methods for monitoring susceptibility to pyriproxyfen in wild malaria vectors using WHO bottle bioassays and for evaluating its efficacy on nets in cone bioassays. Blood-fed mosquitoes of susceptible and pyrethroid-resistant strains of Anopheles gambiae sensu lato were exposed to pyriproxyfen-treated bottles (100 μg and 200 μg) and to unwashed and washed pieces of a pyriproxyfen long-lasting net in cone bioassays. Survivors were assessed for the sterilizing effects of pyriproxyfen using both methods. The methods were compared in terms of their reliability, sensitivity, specificity, resources (cost and time) required and perceived difficulties by trained laboratory technicians.ResultsThe total number of An. gambiae s.l. mosquitoes assessed for the sterilizing effects of pyriproxyfen were 1745 for the oviposition method and 1698 for the ovary dissection method. Fertility rates of control unexposed mosquitoes were significantly higher with ovary dissection compared to oviposition in both bottle bioassays (99–100% vs. 34–59%, P < 0.05) and cone bioassays (99–100% vs. 18–33%, P < 0.001). Oviposition rates of control unexposed mosquitoes were lower with wild pyrethroid-resistant An. gambiae s.l. Cové, compared to the laboratory-maintained reference susceptible An gambiae sensu stricto Kisumu (18–34% vs. 58–76%, P < 0.05). Sterilization rates of the Kisumu strain in bottle bioassays with the pyriproxyfen diagnostic dose (100 μg) were suboptimal with the oviposition method (90%) but showed full susceptibility with ovary dissection (99%). Wild pyrethroid-resistant Cové mosquitoes were fully susceptible to pyriproxyfen in bottle bioassays using ovary dissection (> 99%), but not with the oviposition method (69%). Both methods showed similar levels of sensitivity (89–98% vs. 89–100%). Specificity was substantially higher with ovary dissection compared to the oviposition method in both bottle bioassays (99–100% vs. 34–48%) and cone tests (100% vs.18–76%). Ovary dissection was also more sensitive for detecting the residual activity of pyriproxyfen in a washed net compared to oviposition. The oviposition method though cheaper, was less reliable and more time-consuming. Laboratory technicians preferred ovary dissection mostly due to its reliability.ConclusionThe ovary dissection method was more accurate, more reliable and more efficient compared to the oviposition method for evaluating the sterilizing effects of pyriproxyfen on adult malaria vectors in susceptibility bioassays and for evaluating the efficacy of pyriproxyfen-treated nets.

Can neonicotinoid and pyrrole insecticides manage malaria vector resistance in high pyrethroid resistance areas in Côte d'Ivoire?

BackgroundAnopheles mosquito resistance to insecticide remains a serious threat to malaria vector control affecting several sub-Sahara African countries, including Côte d’Ivoire, where high pyrethroid, carbamate and organophosphate resistance have been reported. Since 2017, new insecticides, namely neonicotinoids (e.g.; clothianidin) and pyrroles (e.g.; chlorfenapyr) have been pre-qualified by the World Health Organization (WHO) for use in public health to manage insecticide resistance for disease vector control.MethodsClothianidin and chlorfenapyr were tested against the field-collected Anopheles gambiae populations from Gagnoa, Daloa and Abengourou using the WHO standard insecticide susceptibility biossays. Anopheles gambiae larvae were collected from several larval habitats, pooled and reared to adulthood in each site in July 2020. Non-blood-fed adult female mosquitoes aged 2 to 5 days were exposed to diagnostic concentration deltamethrin, permethrin, alpha-cypermethrin, bendiocarb, and pirimiphos-methyl. Clothianidin 2% treated papers were locally made and tested using WHO tube bioassay while chlorfenapyr (100 µg/bottle) was evaluated using WHO bottle assays. Furthermore, subsamples of exposed mosquitoes were identified to species and genotyped for insecticide resistance markers including the knock-down resistance (kdr) west and east, and acetylcholinesterase (Ace-1) using molecular techniques.ResultsHigh pyrethroid resistance was recorded with diagnostic dose in Abengourou (1.1 to 3.4% mortality), in Daloa (15.5 to 33.8%) and in Gagnoa (10.3 to 41.6%). With bendiocarb, mortality rates ranged from 49.5 to 62.3%. Complete mortality (100% mortality) was recorded with clothianidin in Gagnoa, 94.9% in Daloa and 96.6% in Abengourou, while susceptibility (mortality > 98%) to chlorfenapyr 100 µg/bottle was recorded at all sites and to pirimiphos-methyl in Gagnoa and Abengourou. Kdr-west mutation was present at high frequency (0.58 to 0.73) in the three sites and Kdr-east mutation frequency was recorded at a very low frequency of 0.02 in both Abengourou and Daloa samples and absent in Gagnoa. The Ace-1 mutation was present at frequencies between 0.19 and 0.29 in these areas. Anopheles coluzzii represented 100% of mosquitoes collected in Daloa and Gagnoa, and 72% in Abengourou.ConclusionsThis study showed that clothianidin and chlorfenapyr insecticides induce high mortality in the natural and pyrethroid-resistant An. gambiae populations in Côte d’Ivoire. These results could support a resistance management plan by proposing an insecticide rotation strategy for vector control interventions.

Impact of age on tumor characteristics and treatment outcomes in pediatric Differentiated Thyroid Carcinoma.

There is a tendency to use data generated for adults in the management of pediatric Differentiated Thyroid Carcinoma, neglecting the clinical peculiarities of this condition in childhood. This study aimed to assess and compare the clinical-epidemiological characteristics and their significance in the evolution of thyroid carcinoma diagnosed in childhood across different age groups. Seventy-seven patients diagnosed with Differentiated Thyroid Carcinoma (DTC) up to 21 years old were selected and divided into different age groups: up to 10 years, 11 to 18 years, and 19 to 21 years old. Clinical-epidemiological data and their influence in the disease progression were analyzed and compared across age groups. Patients diagnosed below 10 years of age were associated with tumors showing extrathyroidal extension, metastasis in regional lymph nodes, higher levels of stimulated thyroglobulin in the diagnostic iodine-131 whole-body scan (WBS), and under TSH suppression in the last assessment. Additionally, pulmonary metastasis were associated in both diagnostic and post-radioiodine dose WBSs in these younger patients. Analysis of findings in the post-radioiodine therapy WBS revealed significant differences between all age groups (p = 0.0029). The time of diagnosis was identified as a factor associated with an excellent response in subgroups up to 18 years and up to 21 years. No factors associated with dynamic responses over the 1st, 3rd and 5th years of follow-up and the persistence/recurrence of the disease were identified in the subgroup up to 18 years. In the subgroup up to 21 years, having an incomplete structural response in the 3rd year of follow-up increased the chances of recurrent or persistent response by 5.5 times, and by 32.6 times if found in the 5th year of follow-up. Younger patients exhibited more aggressive tumor characteristics and underwent more rigorous treatment. However, treatment response and disease status in the last assessment, whether free or recurrent/persistence, were similar when comparing the age groups of 11 to 18 and 19 to 21 years. Nonetheless, responses obtained in the 3rd and 5th years post-treatment emerged as factors associated with the persistence/recurrence of the disease in the last assessment in the age group up to 21 years but not in patients diagnosed up to 18 years, a relevant distinction considering the tumor behavior in defining the pediatric age range in thyroid cancer.

Metabolic Resistance and Not Voltage-Gated Sodium Channel Gene Mutation Is Associated with Pyrethroid Resistance of Aedes albopictus (Skuse, 1894) from Cambodia.

(1) Background: In Cambodia, Aedes albopictus is an important vector of the dengue virus. Vector control using insecticides is a major strategy implemented in managing mosquito-borne diseases. Resistance, however, threatens to undermine the use of insecticides. In this study, we present the levels of insecticide resistance of Ae. albopictus in Cambodia and the mechanisms involved. (2) Methods: Two Ae. albopictus populations were collected from the capital, Phnom Penh city, and from rural Pailin province. Adults were tested with diagnostic doses of malathion (0.8%), deltamethrin (0.03%), permethrin (0.25%), and DDT (4%) using WHO tube assays. Synergist assays using piperonyl butoxide (PBO) were implemented before the pyrethroid assays to detect the potential involvement of metabolic resistance mechanisms. Adult female mosquitoes collected from Phnom Penh and Pailin were tested for voltage-gated sodium channel (VGSC) kdr (knockdown resistance) mutations commonly found in Aedes sp.-resistant populations throughout Asia (S989P, V1016G, and F1534C), as well as for other mutations (V410L, L982W, A1007G, I1011M, T1520I, and D1763Y). (3) Results: The two populations showed resistance against all the insecticides tested (<90% mortality). The use of PBO (an inhibitor of P450s) strongly restored the efficacy of deltamethrin and permethrin against the two resistant populations. Sequences of regions of the vgsc gene showed a lack of kdr mutations known to be associated with pyrethroid resistance. However, four novel non-synonymous mutations (L412P/S, C983S, Q1554STOP, and R1718L) and twenty-nine synonymous mutations were detected. It remains to be determined whether these mutations contribute to pyrethroid resistance. (4) Conclusions: Pyrethroid resistance is occurring in two Ae. albopictus populations originating from urban and rural areas of Cambodia. The resistance is likely due to metabolic resistance specifically involving P450s monooxygenases. The levels of resistance against different insecticide classes are a cause for concern in Cambodia. Alternative tools and insecticides for controlling dengue vectors should be used to minimize disease prevalence in the country.

Impact of the exposure of sublethal dose of mosquito coil on the development of insecticide resistance in Aedes aegypti (L.) (Diptera: Culicidae).

Mosquito coil is commonly used in many African households for protection against mosquito bites. The coil usually has semi-volatile pyrethroids as an active ingredient, which usually diffuse across open space, and the cloud either kills mosquitoes that are exposed, or mosquitoes can be exposed to sublethal doses of the insecticides. This study was conducted to assess the impact of sublethal doses of mosquito coil on the development of insecticide resistance in Aedes aegypti, a major vector for dengue fever and several other arboviral diseases. A laboratory colony of Ae. aegypti was exposed to sublethal doses of a meperfluthrin-based mosquito coil in a Peet-Grady chamber once per generation for 16 generations. The susceptibility of the exposed colony to a diagnostic dose of the mosquito coil as well as to three other insecticides was determined. Three different kdr mutations and five enzyme activities were evaluated in both the exposed and control colonies. After 16 generations of sublethal exposure to mosquito coils, the full diagnostic dose of the coil caused 68% mortality to the exposed colony compared to 100% mortality in the control colony. Mortality caused by deltamethrin (0.05%) was also significantly lower in the exposed colony. The frequency of 1016I kdr mutation as well as MFO and alpha esterase activities were higher in the exposed colony compared to the control colony. This study provides evidence of the development of pyrethroid resistance in an Ae. aegypti population due to sublethal exposure to mosquito coil for 16 generations. Given the large-scale use of mosquito coils in many African households, its role as a pyrethroid resistance selection source should be taken into consideration when designing resistance management strategies.

Photon-counting computed tomography for paediatric congenital heart defects yields images of high diagnostic quality with low radiation doses at both 70 kV and 90 kV

BackgroundPhoton-counting computed tomography (PCCT) is a new clinical method that may show better diagnostic quality at lower radiation doses than conventional CT.ObjectiveTo investigate the diagnostic quality and radiation dose of paediatric cardiovascular PCCT for diagnosis of congenital heart defects at 70 kV and 90 kV.Materials and methodsThis retrospective assessment included clinical non-gated paediatric PCCT examinations for assessment of congenital heart defects. Radiation doses were recorded, and overall and specific diagnostic quality (1–4) were scored by four paediatric radiologists. Agreement, differences, and trends were assessed by percent rater agreement, intraclass correlation, Mann–Whitney tests, and Jonckheere-Terpstra tests.ResultsSeventy children with congenital heart defects were examined at 70 kV (n = 35; age 2 days–16 years; 63% boys) or 90 kV (n = 35; age 2 days–17 years; 51% boys). All observers gave a median score of 4 (high diagnostic quality) for both 70 kV and 90 kV, with no difference in median values between tube voltages (all P > 0.06). Agreement for overall scores was 66–94% for 70 kV and 60–77% for 90 kV. Agreement for specific scores was 80–97% for 70 kV and 83–89% for 90 kV. Size-dependent dose estimate was 0.68 mGy (0.25–2.02 mGy) for 70 kV and 1.10 mGy (0.58–2.71 mGy; P < 0.001) for 90 kV. Effective dose was 0.30 mSv (0.15–0.82 mSv) for 70 kV and 0.39 mSv (0.22–1.51 mSv; P = 0.01) for 90 kV.ConclusionPaediatric cardiovascular PCCT yields images for congenital heart defects of high diagnostic quality with low radiation dose at both 70 kV and 90 kV.

Investigating knowledge of DRLs, image quality and radiation dose in PET/CT and CT imaging among medical imaging professionals

ObjectiveTo investigate the knowledge of diagnostic reference levels (DRLs), image quality, radiation dose and protocol parameters among Jordanian medical imaging professionals (MIPs) involved in PET/CT and CT scan procedures. Materials and methodsA questionnaire was designed and distributed to MIPs in Jordan. The survey comprised four sections: demographic data, MIP knowledge on dose/protocol parameters, image quality, and DRLs. Statistical analyses were performed utilizing Pearson's correlation, t-tests, ANOVA, and linear regression, with a significance level of 95 % and a p-value threshold of <0.05. ResultsThe study involved 147 participants. Most respondents were male (76.2 %), and most were aged 26–35 years (44.2 %). Approximately 51 % held a bachelor's degree, and the most common range of experience was 3–5 years (28.6 %). Participants showed a moderate level of knowledge regarding dose and protocol parameters, with a mean score of 61.8 %. The mean scores for knowledge of image quality and DRLs were 45.2 % and 44.8 %, respectively. The age group of the MIPs and the total experience were found to have a significant impact on the knowledge of the dose and protocol parameters, as well as the DRLs. Additionally, experience was found to have a significant influence on knowledge of the dose and protocol parameters. The study revealed a positive and significant effect of MIPs' knowledge of dose/protocol parameters and image quality on their knowledge of DRLs. ConclusionsThis study indicates that professionals across five specialties who are engaged in PET/CT and CT imaging possess a moderate understanding of dosage and protocol parameters. However, there is a notable gap in knowledge regarding DRLs and image quality. To address this issue, it is recommended that MIPs actively engage in educational programs emphasizing exposure parameters and their impact on image quality. Additionally, access to comprehensive education and training programs will enable MIPs to grasp the complexities of DRLs and their implications, facilitating their implementation in clinical practice.

Insecticide Resistance in Aedes aegypti Mosquitoes: Possible Detection of kdr F1534C, S989P, and V1016G Triple Mutation in Benin, West Africa.

Epidemics of arboviruses in general, and dengue fever in particular, are an increasing threat in areas where Aedes (Ae.) aegypti is present. The effectiveness of chemical control of Ae. aegypti is jeopardized by the increasing frequency of insecticide resistance. The aim of this study was to determine the susceptibility status of Ae. aegypti to public health insecticides and assess the underlying mechanisms driving insecticide resistance. Ae. aegypti eggs were collected in two study sites in the vicinity of houses for two weeks using gravid Aedes traps (GATs). After rearing the mosquitoes to adulthood, female Ae. aegypti were exposed to diagnostic doses of permethrin, deltamethrin and bendiocarb, using Centers for Disease Control and Prevention (CDC) bottle bioassays. Unexposed, un-engorged female Ae. aegypti were tested individually for mixed-function oxidase (MFO), glutathione-S-transferase (GST) and α and β esterase activities. Finally, allele-specific PCR (AS-PCR) was used to detect possible kdr mutations (F1534C, S989P, and V1016G) in the voltage-gated sodium channel gene in insecticide-exposed Ae. aegypti. Most traps were oviposition positive; 93.2% and 97% of traps contained Ae. aegypti eggs in the 10ème arrondissement of Cotonou and in Godomey-Togoudo, respectively. Insecticide bioassays detected resistance to permethrin and deltamethrin in both study sites and complete susceptibility to bendiocarb. By comparison to the insecticide-susceptible Rockefeller strain, field Ae. aegypti populations had significantly higher levels of GSTs and significantly lower levels of α and β esterases; there was no significant difference between levels of MFOs. AS-PCR genotyping revealed the possible presence of 3 kdr mutations (F1534C, S989P, and V1016G) at high frequencies; 80.9% (228/282) of the Ae. aegypti tested had at least 1 mutation, while the simultaneous presence of all 3 kdr mutations was identified in 13 resistant individuals. Study findings demonstrated phenotypic pyrethroid resistance, the over-expression of key detoxification enzymes, and the possible presence of several kdr mutations in Ae. aegypti populations, emphasizing the urgent need to implement vector control strategies targeting arbovirus vector species in Benin.

Toxicity of isocycloseram, an isoxazoline insecticide, against laboratory and field-collected German cockroaches (Blattodea: Ectobiidae).

Isocycloseram is a new insecticide in the isoxazoline class that targets insect GABA-gated chloride channels. In this study, we evaluated a cockroach gel bait formulation containing 1% isocycloseram against a susceptible strain (UCR) and 5 field-collected strains (WM, RG386, Ryan, CDR, and SY) of the German cockroach, Blattella germanica (L.) (Blattodea: Ectobiidae), and compared it with several commercial insecticide baits in the laboratory. Using the Ebeling choice box method, we also tested a residual deposit of an SC formulation of isocycloseram against the UCR, RG386, and Ryan strains. The isocycloseram bait was among the fastest-performing treatments against adult males (mean survival time: 0.9-2.7 days) and mixed stages and sexes (mean survival time: 1.4-5.4 days) across all strains. Secondary transfer effects of the bait were demonstrated in the UCR strain by exposing new adult males to individuals killed by direct bait treatment. Physiological resistance was not detected in the WM, CDR, and RG386 strains with topical treatment of a diagnostic dose (3× LD95) of isocycloseram developed using the UCR strain. However, topical assays revealed resistance ratios (RR50) of 1.6 and 3.0× in the Ryan and SY strains, respectively. The performance of a 0.05% isocycloseram residual application against the Ryan strain was improved with the addition of piperonyl butoxide.

Overexpression of cytochrome P450 gene CYP6K1 is associated with pyrethroid resistance in German cockroaches (Blattodea: Ectobiidae) from California.

We investigated the expression of 4 cytochrome P450 genes (CYP4G19, CYP6J1, CYP6K1, and CYP4C21) in 4 field-collected strains (WM, RG386, CDR, and Ryan) of the German cockroach, Blattella germanica (L.), collected from California. The UCR susceptible strain was used as a comparison. Topical assays using a diagnostic dose (3× LD95) of deltamethrin revealed decreased sensitivity in all field-collected strains with mortality ranging from 0% to 58%, and the addition of PBO before deltamethrin treatment increased mortality to 52.5%-87.5%. Using qPCR to investigate the expression levels of CYP4G19, CYP4C21, CYP6J1, and CYP6K1, we found that only CYP6K1 was significantly overexpressed (2.1-5.8× higher) in all field-collected strains when compared to the UCR strain. Next, we investigated the role of the CYP6K1 gene by performing gene knockdown using RNAi. After dsCYP6K1 treatment, the expression levels of CYP6K1 in WM and Ryan strains were significantly reduced (P < 0.01) by 91%-94% vs. those treated with dsEGFP (control) on the third and sixth day posttreatment. RG386, CDR, and Ryan strains were more susceptible compared to their respective controls to topically applied deltamethrin 6 days after treatment with dsCYP6K1. This study provides evidence of the involvement of the P450 CYP6K1 gene in pyrethroid resistance in some populations of German cockroaches.

Pharmacokinetics, safety, and tolerability of the novel tetrameric gadolinium-based MRI contrast agent gadoquatrane in healthy Chinese and Japanese men: Two randomized dose-escalation studies including concentration–QTc modeling

PurposeTo investigate the pharmacokinetics, safety, and tolerability of the novel tetrameric high-relaxivity gadolinium-based contrast agent gadoquatrane in Japanese (Study 1) and Chinese men (Study 2). Participants and methodsIn two similarly designed single-center, randomized, single-blind, placebo-controlled, consecutive-cohort dose-escalation studies, healthy volunteers were randomly assigned to intravenous administration of gadoquatrane (0.01–0.1 mmol gadolinium/kg body weight) or placebo. Study procedures included blood sampling and collection of urine for pharmacokinetic analyses and safety assessments. ResultsTwenty-five healthy Japanese men (mean age ± standard deviation: 26±5.9 years) and 23 healthy Chinese men (31±7.6 years old) were evaluated. In both studies, the pharmacokinetic profile of gadoquatrane was characterized by rapid distribution of the drug into the extracellular space and fast renal elimination. Postdose gadolinium concentrations rapidly declined with a geometric mean effective half-life of 1.3–1.4 h. The exposure increased approximately dose-proportionally with dose. The body weight-normalized volume of distribution was constant across dose levels (0.21–0.24 L/kg). Total recovery of gadolinium in urine amounted to 82–95 % (Study 1) and 96–99 % (Study 2) of the dose administered.Only a few mild, transient adverse events were reported, none of which gave rise to any safety concerns. Exploratory drug concentration–QTc modeling indicated no risk of a clinically relevant QT/QTc prolongation at the anticipated diagnostic dose. ConclusionGadoquatrane was safe and well tolerated at all doses tested. The pharmacokinetic profile was essentially the same as that of other extracellular macrocyclic gadolinium-based contrast agents and was consequentially also similar for Japanese and Chinese participants.

Low-dose, high-pitch, spiral (FLASH) mode versus conventional sequential method for coronary artery calcium scoring: A derivation-validation study.

The present study sought to compare the diagnostic accuracy and radiation dose of ECG-gated, ultra-fast, low-dose, high-pitch, spiral (FLASH) mode versus conventional, ECG-gated, sequential coronary artery calcium (CAC) scoring in patients with suspected coronary artery disease (CAD). The study included 120 patients who underwent both conventional scanning and FLASH mode scanning and were subdivided into derivation and validation cohorts. In the conventional sequential (step-and-shoot) protocol, prospective ECG-gated, non-contrast acquisition was performed at 70% of R-R interval. The spiral (FLASH) mode utilized a high-pitch and high-speed gantry rotation scanning mode where acquisition of the entire heart was done within a single cardiac cycle with prospective ECG-gating at 70% of R-R interval. Correlation between CAC scores derived from conventional (cCAC) and FLASH mode (fCAC) in derivation cohort was excellent (r=0.99; P<0.001). A linear regression model was used to develop a formula for deriving the estimated CAC score (eCAC) from fCAC (eCAC=0.978 x fCAC). In validation cohort, eCAC showed excellent agreement with cCAC (ICC=0.9983; 95%CI: 0.9972 - 0.9990). Excellent agreement for risk classification (weighted kappa=0.93898; 95%CI: 0.86833 - 1.0000) was observed with 95% (57/60) scores falling within the same risk category. Effective dose was significantly lower in FLASH mode (conventional, 0.58±0.21 mSv vs. FLASH, 0.34±0.12 mSv; P<0.0001). CAC scoring using FLASH mode is feasible with high accuracy and shows excellent agreement with conventional CAC scores at significantly reduced radiation doses.

The Biocidal capacity of Datura (Datura stramonium L.) leaves and flowers and Cannabis (Cannabis sativa L.) seeds on some Mosquito’s larvae (Diptera: Culicidae)

Plant-based alternative pesticides are safe, effective, eco-friendly and can be used instead of synthetic pesticides. The aim of this study was to evaluate the biocidal capacity of Datura stramonium leaves (DL) and flowers (DF) and Cannabis sativa seeds (CS) on Anopheles arabiensis, Culex quiquefasciatus and Aedes aegypti larvae. The selected plant parts were collected from the experimental farm, the University garden. The LC50s of A. arabinoses larvae towards the ethanol extract of each plant part were taken to estimate the single diagnostic dose for the survival and deformities tests. GC-MS analysis for the selected plant parts was investigated. The results show that DL ethanol extract detected 14 compounds of which butanol,3-methyl is the main component (79.76%) followed by toluene (6.14%). Phytol was also detected (3.9%). 14 compounds were detected from DF of which formic acid,3-methylbut-2-yl ester was the main component (82.22%) followed by dodecanoic acid, ethyl ester (3.3%) and toluene (2.86%). Also, from CS, Dronabinol (41.4%) was the main component, followed by Cannabinol (10.38%), Phytol (10.38%) and Caryophylene (2.07%). The susceptibility test of An. arabiensis larvae revealed the LC50’s of 562.95 mg/L for DL, 424.41 mg/L for DF and 175.40 mg/L for CS. It was noticed that 3-6% of An. arabiensis and 1-28% of Culex quiquefasciatus and 12-22% of Aedes aegypti larvae developed to pupae and some of them developed to adult stage after one week. In the survival test, more than 70% of the larvae were killed by a concentration supposed to kill 50% or less of the larvae. Some deformations were monitored on Anopheles, Culex and Aedes larvae including swelled body, separated alimentary canal. Field assessment should be run and the concept of LC50 should be re-written.

Kdr mutations and deltamethrin resistance in house flies in Abu Dhabi, UAE

BackgroundThe house fly, Musca domestica, is a significant carrier of diseases that can impact public health. Repeated use of pyrethroid insecticides may act as a selection pressure for mutations and amino acid substitutions in the house fly voltage-sensitive sodium channel (VSSC), which ultimately confers resistance. The objectives of this study were to determine the presence of knockdown resistance (kdr) mutations using molecular tools and to set up a CDC bottle bioassay specific for house flies in the United Arab Emirates (UAE) to screen for deltamethrin resistance.MethodsAdult flies were collected from 19 locations in Abu Dhabi, UAE, and DNA was extracted, followed by PCR amplification of specific alleles (PASA) and conventional PCR using several primers to amplify regions of the VSSC gene. Sanger sequencing was performed on PCR products. We also designed primers that detect four kdr mutations using complementary DNA (cDNA) in reverse transcriptase (RT)-PCR followed by Sanger sequencing. Additionally, a CDC bottle bioassay was set up for detecting deltamethrin resistance in adult house flies.ResultsIn PASA, the primers successfully amplified the target bands (480, 280 and 200 bp). The kdr allele was found in flies collected from 18 of the 19 locations, at the highest and lowest prevalence of 46.9% and 9.4%, respectively. Resistant homozygous (RR) insects constituted 5.0% of the tested populations, and heterozygous (RS) insects accounted for 36.5%. The RR genotype was prevalent in house flies collected at 10 of 19 sampling locations. House fly populations were mostly in Hardy–Weinberg equilibrium, except in three locations. In addition to verifying the presence of the previously identified kdr mutation L1014F, in this study we detected two kdr mutations, L1014H and T929I, that have not previously been reported in the UAE. Also, for the first time in the UAE, a CDC bottle bioassay for deltamethrin resistance was used, which found that 60 min and 4.5 µg/ml were the diagnostic time and dose, respectively. Using this assay, we detected deltamethrin resistance in house flies from two of 16 locations, with a resistance level of 12.5%.ConclusionsUsing DNA sequencing, we confirmed the presence of a known kdr mutation and uncovered two new kdr mutations in house flies from Abu Dhabi. Additionally, we detected deltamethrin resistance in these flies using a CDC bottle bioassay. Further research is recommended to comprehensively identify more kdr mutations in UAE house fly populations and assess their impacts on control strategies.Graphical