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Caterpillars of the genus Spodoptera are the main pests in soybean and cotton crops and Spodoptera cosmioides causes more severe losses than other caterpillars in these agricultural crops. However, there are few recommended insecticides for controlling this pest. Lambda-cyhalothrin is a pyrethroid used to control a wide spectrum of arthropods including lepidopterans. Therefore, the objective of this study was to evaluate the potential of lambda-cyhalothrin for the control of S. cosmioides. Specifically, toxicity and histopathological changes in the midgut were evaluated. The effectiveness of the insecticide was determined by estimating the different lethal concentrations (LCs) ​​in the laboratory upon S. cosmioides. Lambda-cyhalothrin was found toxic to S. cosmioides (LC50 = 23.03 mg L-1 and LC90 = 174.8 mg L-1), with the survival reduced from 83.33% in the control to 37.89%, 16.66%, 0%, and 0% after 72 h of exposure to the LC25, LC50, LC75, and LC90 of lambda-cyhalothrin, respectively. Histopathological studies revealed that lambda-cyhalothrin caused damage to midgut cells, including epithelial disorganization, increased cytoplasmic vacuolization, brush border degeneration, nuclear chromatin condensation, and cell fragmentation, indicating cell death by apoptosis. It was concluded that lambda-cyhalothrin, a neurotoxic insecticide, caused damage to the midgut of S. cosmioides, compromising its physiology and indicating that it has potential to be used to control this pest.

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Ductal carcinomas, a variant of salivary gland cancer, are characterized by concurrent androgen receptor (AR) positivity and overexpression of HER2, making them potential targets for tailored therapies extensively explored in literature. We present two consecutive cases of patients diagnosed with inoperable metastatic ductal carcinoma, both displaying HER2 overexpression and AR positivity, who underwent combination therapy involving chemotherapy and dual targeted agents. Both patients diagnosed with centralized inoperable ductal carcinoma were retrospectively analyzed and received trastuzumab, docetaxel, leuprolide and bicalutamida as first-line therapy until progression, defined by RECIST criteria. The first patient exhibited a partial response, with a 34% reduction in nodal metastases, remaining progression-free for 20 months. Despite rapid progression on initial treatment lines, the second patient achieved a partial response with a 35% reduction in metastases upon receiving third-line therapy, sustaining a progression-free interval. Importantly, both patients tolerated the treatment regimen well without severe acute toxicities. Although they responded favorably to the combined therapy, the addition of antiandrogen, anti-HER2, and chemotherapy did not appear to enhance efficacy. The use of combined target therapy seems to be effective in selected patients, but this indication requires further investigation through prospective studies.

Los carcinomas ductales son una variante histológica de cáncer de glándula salival que frecuentemente expresan el receptor androgénico a nivel nuclear y sobre expresan HER2 en inmunohistoquímica, mostrando sensibilidad a terapias dirigidas a estos blancos en múltiples series de casos. En este trabajo, se presentan 2 casos consecutivos de pacientes con estos marcadores, tratados con terapia combinada de quimioterapia y doble terapia dirigida. Ambos pacientes con carcinoma ductal metastásico no operable, con sobreexpresión de HER2 y receptor androgénico positivo por inmunohistoquímica, recibieron como primera línea trastuzumab, docetaxel, leuprolide y bicalutamida hasta la progresión, los criterios progresión y respuesta fueron adecuados a RECIST 1.1. El primer paciente mostró una respuesta parcial, con una reducción del 34% de las metástasis ganglionares, permaneciendo libre de progresión durante 20 meses. A pesar de la rápida progresión en las líneas de tratamiento iniciales, el segundo paciente logró una respuesta parcial con una reducción del 35% de las metástasis al recibir la terapia de tercera línea, manteniendo un intervalo libre de progresión. Es importante destacar que ambos toleraron bien el régimen de tratamiento sin toxicidades agudas graves. A pesar de la respuesta observada en ambos pacientes, la combinación de dos o más agentes no aumentaría la efectividad del tratamiento dirigido solo monoterapia. La terapia con múltiples drogas dirigidas puede ser efectiva en pacientes muy seleccionados, pero se requiere mayor investigación para respaldar su indicación.

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Aedes albopictus (Skuse) is a competent vector of dengue and Zika viruses in Mexico. Monitoring the level of resistance of local population is essential due to its epidemiological significance. This study aimed to identify mutations in the voltage-gated sodium channel (VGSC) as one of the mechanisms responsible for pyrethroid insecticide resistance in Ae. albopictus. Immature samples were collected in a rural town in Yucatan, Mexico, from May to October 2021. The pyrethroid insecticide lambda-cyhalothrin was impregnated in CDC bottles and bioassays were conducted on Ae. albopictus populations 3-5 days after emergence. The mosquitoes were susceptible to the insecticide. Females were taken for total DNA extraction. Fragments of domains II, III, and IV of the voltage-gated sodium channel (VGSC) were amplified and sequenced. The presence of synonymous and non-synonymous mutations was found in positions 1532 and 1534 of domain III of the sodium channel gene (VGSC). No mutant alleles in domain IV were detected. A homozygous mutant (ACG) coding for the amino acid threonine (1008Thr) was identified in domain II. Domain III included three heterozygous alleles (P1528S, L1530S, and Ile1410Thr). This last heterozygous allele is reported for the first time in Mexico. Homozygous mutants encoding the amino acids serine/serine and serine/proline in domain III were observed. These have been reported in Aedes aegypti from Mexico, but not yet in Ae. albopictus. This represents new findings for the region, as Ae. albopictus has only been introduced there for approximately five years. In conclusion, non-synonymous mutations were found in Ae. albopictus in a rural area of Yucatan, emphasizing the importance of integrated vector control to prevent Asian tiger mosquitoes from spreading these resistant alleles.

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BACKGROUND: Visceral leishmaniasis (VL) is a zoonotic disease caused by Leishmania infantum and transmitted by the sand fly Lutzomyia longipalpis. Dogs are the major domestic reservoir of L. infantum. To prevent the spread of the disease, dog collars impregnated with 4% deltamethrin have been effectively used in VL endemic areas. However, this approach may contribute to the emergence of insecticide resistance in sand flies. Therefore, it is important to characterize the susceptibility of different populations of Lu. longipalpis to deltamethrin in areas where insecticide-impregnated dog collars are used. METHODS: Six field sand fly populations from Brazil were exposed to deltamethrin in CDC bottle bioassays at the diagnostic doses (DD) of 21.9 µg/bottle and 30 µg/bottle. For the dose-response (DR) experiments, doses of 1, 3, 5, 7, 9 and 11 µg/bottle of deltamethrin were used to impregnate bottles; control group bottles were impregnated with acetone only. Each bottle contained an average of 20 sand flies, both male and female, and they were exposed to either deltamethrin or acetone for 60 min. RESULTS: Based on the DD of 21.9 µg/bottle, three populations were susceptible to deltamethrin. In contrast, two populations collected from the states of Ceará and Minas Gerais exhibited mortality rates of 94.9% and 95.7%, indicating possible resistance, and one population from the state of Ceará showed resistance, with a mortality rate of 87.1%. At the DD of 30 µg/bottle, two populations from the states of Ceará and Piauí showed possible resistance, while the other four populations were susceptible. The resistance ratio (RR50) ranged from 2.27 to 0.54, and RR95 ranged from 4.18 to 0.33, indicating a low resistance intensity. CONCLUSIONS: This study established a DD for Lu. longipalpis using the CDC bottle bioassay. We found that Lu. longipalpis populations in three Brazilian states where insecticide-impregnated dog collars were used for VL control were susceptible to deltamethrin. However, one population in Ceará State was classified as resistant to deltamethrin. These results contribute to the current knowledge on sand fly resistance and surveillance, and highlight the need for a better understanding of the resistance mechanisms of Lu. longipalpis in areas where insecticide-impregnated dog collars have been widely used.

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Triatoma species from the phyllosoma subcomplex are sympatrically distributed and include some of the main vectors of Chagas disease in Mexico. Species within this subcomplex, including Triatoma pallidipennis, T. mazzottii, T. picturata, and T. longipennis, have shown resistance to pyrethroid insecticides, associated with mutations in the para gene of the voltage gate sodium channel (VGSC) and the activity of detoxifying enzymes such as ß-esterases and glutathione s-transferases (GST). In this study, we evaluated resistance to deltamethrin in hybrids of T. pallidipennis × T. mazzottii (T.pal × T.maz) and T. pallidipennis × T. picturata (T.pal × T.pic) under laboratory conditions, and the inheritance was determined based on the degree of dominance (DO). Additionally, associated resistance mechanisms were analyzed, including detoxifying enzymes and knockdown resistance (kdr) mutations. High levels of resistance to deltamethrin were found in the hybrids of T.pal × T.maz when compared with the susceptible strain of T. mazzottii (RR50 = 17.50). Dominance levels calculated for each hybrid showed values < - 1, confirming that resistance to deltamethrin was recessive. Hybrids exhibited reduced α-, ß-esterases, and cytochrome P450 mixed-function oxidases (MFO) activity. However, both hybrids showed significantly increased GST activity, particularly in T.pal × T.pic, suggesting enhanced detoxification through this pathway. The kdr mutation A943V, present in T. mazzottii, was found in T.pal × T.maz hybrids. These results emphasize the importance of considering hybridization in resistance management programs and its potential impact on the success of insecticide-based control measures.

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BACKGROUND: One bioassay for detecting acaricide resistance in livestock ticks is the adult immersion test (AIT), wherein engorged ticks are briefly immersed into a solution of a particular acaricidal compound and examined for mortality, their egg-laying capacity and offspring hatchability in vitro. Usually, the recommended label dose or an established discriminating dose of an acaricide is used to determine high mortality (≥ 95%) of susceptible tick strains. Such a test intends to detect the presence of resistance in a tick population. However, the adult immersion test does not directly translate the bioassay results to the predicted efficacy in the field. In this paper, we used the AIT as an initial screening bioassay supplemented with the resistance intensity test (RIT), a novel larval-based bioassay, wherein the resistance level can be determined and translated to the expected field efficacy. This was done by adopting World Health Organisation (WHO) guidelines for resistance detection in mosquitoes, which combines a 1 × recommended dose with 5 × and 10 × concentrated doses to reveal low, moderate and high resistance intensity, respectively. METHODS: Engorged Rhipicephalus microplus ticks were collected from cattle at six different ranches across Rio Grande do Sul, Brazil, as part of the state's acaricide resistance surveillance program. Groups of adult ticks from each field collection were subjected to the AIT from each field sample. Additionally, engorged female ticks from each ranch were allowed to lay eggs, and their larval progeny aged 14 to 28 days were then used in the RIT. Deltamethrin and a combination of cypermethrin, chlorpyrifos and piperonyl butoxide were used in both tests, and the results were statistically analysed. RESULTS: The in vitro efficacy of deltamethrin against adult ticks in the AIT ranged between 8.74% and 25.38%. The corresponding RIT results on their larval progeny indicated a high resistance level. In the immersion test, the in vitro efficacy of the combination of cypermethrin, chlorpyrifos, and piperonyl butoxide against adult ticks ranged between 49.31% and 100%. The corresponding RIT results on their larval progeny indicated a similar response ranging from fully susceptible to low or moderate resistance. The Pearson correlation coefficient (r = 0.883) showed a high correlation between tick mortality at the 1 × recommended concentrations of acaricides in both tests. CONCLUSIONS: The resistance intensity test is a valuable addition to the range of bioassays currently available for detecting acaricide resistance by determining the level of acaricide resistance. This is relevant to whether or not to continue using a particular acaricidal class for controlling cattle ticks.

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The widespread and extensive use of pesticides in European crop production to reduce losses from weeds, diseases, and insects may have serious consequences on the ecosystem and human health. This study aimed to identify 20 active substances of high health risk, based on their detection frequency within and across the environmental matrices (soil, crop, water, and sediment) and to identify their associated hazardous effects. A sampling campaign was conducted across 10 case study sites in Europe and 1 in Argentina and included conventional and organic farming systems. In 31% of cases, the detected substances were found at a higher concentration in the soil than in the corresponding crops, 93% of the compounds were fungicides, and the remainder were insecticides. 43% of the substances, 57% of which were insecticides, were detected only in soil. There was a clear relationship between soils and crops in terms of contamination, but not between water and sediment. Portuguese soil (wine grapes) had the highest number of substances (12) with average concentrations (AC) varying between 1 and 162 µg/kg, followed by French (11 substances in wine grapes) (1≤AC≤64 µg/kg) and Spanish soils (9 substances in vegetables) (3≤AC≤59 µg/kg). The crops corresponding to these soils contained a relatively high number of detected substances and several in high average concentrations (AC). The risk quotient was consistently higher for conventional farms than for organic farms. For the soils from conventional farms, 5 active substances (chlorpyrifos, glyphosate, boscalid, difenoconazole, lambda-cyhalothrin, and one metabolite: AMPA) were considered high risk. For water samples, 2 substances (dieldrin and terbuthylazine) found were high risk, and for sediment, there were 3 substances (metalaxyl-M, spiroxamine, and lambda-cyhalothrin). There were 6 substances detected in crops that are suspected to cause human health effects. Uncontaminated soil is a prerequisite for the adoption of sustainable alternatives to pesticides. Efforts are needed to elucidate the unknown effects of mixtures, including biocides and banned compounds in addition to the substances used in agriculture.

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The sugarcane weevil (Sphenophorus levis Vaurie, 1978) is currently considered the most important sugarcane pest in Brazil, causing significant yield losses. Application methods of insecticides for S. levis control have not been effective, mostly due to the insect's cryptic behavior below the soil surface which suppresses the correct placement of insecticide active ingredients on target. Two experiments were conducted using an innovative bioassay methodology that simulates sugarcane field conditions to effectively evaluate S. levis adult mortality and insecticide residues in the soil under different treatments. The first experiment aimed to assess the efficacy of two liquid- and solid-applied insecticides, while the second aimed to examine the effect of increasing the dose of lambda-cyhalothrin + thiamethoxam on S. levis adult control. The novel bioassays simulated liquid and solid insecticide applications on sugarcane by exposing S. levis adults to chemical residuals on rhizomes and in soil after insecticide application. In the first experiment, low S. levis adult control was detected (< 53% mortality) across all treatments, where both solid and liquid applications of lambda-cyhalothrin + thiamethoxam provided greater efficacy levels than imidacloprid and control treatments, respectively. Solid applications maintained higher insecticide concentrations in the soil for longer periods than liquid insecticide applications, providing maximum insect control levels 7 days after application. The second experiment revealed that solid applications at higher insecticide doses significantly improved control of S. levis adult (76.7% mortality) and resulted in greater insecticide concentrations in the soil compared to the recommended label rate (58.8% mortality).

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Chlorothalonil (CTL) is a pesticide widely used in Brazil, yet its mutagenic potential is not fully determined. Thus, we assessed the mutagenicity of CTL and its bioactivation metabolites using the somatic mutation and recombination test (SMART) in Drosophila melanogaster, by exposing individuals, with basal and high bioactivation capacities (standard and high bioactivation cross offspring, respectively), from third instar larval to early adult fly stages, to CTL-contaminated substrate (0.25, 1, 10 or 20 µM). This substrate served as food and as physical medium. Increased frequency of large single spots in standard cross flies' wings exposed to 0.25 µM indicates that, if CTL is genotoxic, it may affect Drosophila at early life stages. Since the total spot frequency did not change, CTL cannot be considered mutagenic in SMART. The same long-term exposure design was performed to test whether CTL induces oxidative imbalance in flies with basal (wild-type, WT) or high bioactivation (ORR strain) levels. CTL did not alter reactive oxygen species and antioxidant capacity against peroxyl radicals levels in adult flies. However, lipid peroxidation (LPO) levels were increased in WT male flies exposed to 1 µM CTL. SMART and LPO alterations were observed only in flies with basal bioactivation levels, pointing to direct CTL toxicity to DNA and lipids. Survival, emergence and locomotor behavior were not affected, indicating no bias due to lethality, developmental and behavioral impairment. We suggest that, if related to CTL exposure, DNA and lipid damages may be residual damage of earlier life stages of D. melanogaster.

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Little information is available on the adverse effects of expired pesticides on the environment, so it is essential to characterize the risk of these chemicals to non-target organisms. Therefore, this work aims to estimate and compare the acute toxicity (LD50) of unexpired and expired formulations of malathion, chlorpyrifos, and lambda-cyhalothrin in rats and to determine their residues in the liver and kidneys of treated rats. This is the first study to investigate the toxic effects of expired pesticides on rats. The acute toxicity of expired lambda-cyhalothrin was higher than that of non-expired rats, while the opposite was observed in rats treated with malathion and chlorpyrifos. All formulations tested caused clinical signs of toxicity in the treated rats. The data showed that some expired formulations significantly affected body weight and estimated vital signs compared to non-expired pesticides. The data showed that the highest residues were found in the liver and kidneys of rats treated with both malathion formulations, followed by chlorpyrifos; however, the lowest residues were found in rats treated with lambda-cyhalothrin, which can be referred to as LD50 values of the insecticides tested. The residues detected after the 10th dose gradually decreased at the end of the recovery period, and their losses ranged from 80.0 to 95.4% in the liver and from 92.3 to 99.99% (undetectable). The results show that the toxic effects of expired and non-expired formulations are different. This underlines the need to dispose of expired compounds carefully to prevent their discharge into the ecosystem.

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In recent years, heterogeneous photocatalysis has emerged as a promising alternative for the treatment of organic pollutants. This technique offers several advantages, such as low cost and ease of operation. However, finding a semiconductor material that is both operationally viable and highly active under solar irradiation remains a challenge, often requiring materials of nanometric size. Furthermore, in many processes, photocatalysts are suspended in the solution, requiring additional steps to remove them. This can render the technique economically unviable, especially for nanosized catalysts. This work demonstrated the feasibility of using a structured photocatalyst (ZnO, g-C3N4, and carbon xerogel) optimized for this photodegradation process. The synthesized materials were characterized by nitrogen adsorption and desorption, X-ray diffraction (XRD), and diffuse reflectance spectroscopy (DRS). Adhesion testing demonstrated the efficiency of the deposition technique, with film adhesion exceeding 90%. The photocatalytic evaluation was performed using a mixture of three textile dyes in a recycle photoreactor, varying pH (4.7 and 10), recycle flow rate (2, 4, and 6 L h-1), immobilized mass (1, 2, and 3 mg cm-2), monolith height (1.5, 3.0, and 4.5 cm), and type of radiation (solar and visible artificials; and natural solar). The structured photocatalyst degraded over 99% of the dye mixture under artificial radiation. The solar energy results are highly promising, achieving a degradation efficiency of approximately 74%. Furthermore, it was possible to regenerate the structured photocatalyst up to seven consecutive times using exclusively natural solar light and maintain a degradation rate of around 70%. These results reinforce the feasibility and potential application of this system in photocatalytic reactions, highlighting its effectiveness and sustainability.

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BACKGROUND: Acaricide resistance in cattle ticks is a significant concern in (sub)tropical regions, particularly Brazil. The Larval Packet Test (LPT) is the standard laboratory bioassay for resistance diagnosis, which requires triplicates of seven acaricidal dilutions plus controls to cover larval mortalities ranging between 0 and 100%. The value of the LPT lies in providing resistance ratios based on the ratio between the LC50 calculated with potentially resistant and susceptible ticks. However, LC50 ratios are difficult to translate into practical advice for farmers. Moreover, LPT requires laboratory facilities to maintain susceptible tick colonies, and it takes 6 weeks to obtain the larvae to be tested by LPT derived from engorged female ticks collected from cattle in the field. Our novel approach was twofold: first, we upgraded the LPT to the Resistance Intensity Test (RIT) by adopting the latest WHO guidelines for resistance detection in mosquitoes, which combines a 1 × recommended dose with 5 × and 10 × concentrated doses to reveal low, moderate and high resistance intensity, respectively. This reduced the number of test papers and tick larvae and, more importantly, provided relevant information on the resistance level. Our second innovative step was to abolish testing larvae entirely and expose partly engorged adult ticks to the same acaricidal doses immediately after removing them from cattle in the field. This resulted in the Rapid Tick exposure Test (RaTexT®), wherein partly engorged adult ticks were exposed to an acaricide-impregnated, specially designed matrix providing test results within 24 h. This approach directly compared resistance detection in tick larvae in the RIT with resistance in adult ticks in RaTexT®. METHODS: Laboratory validation was conducted in Brazil with resistant and susceptible colonies of Rhipicephalus microplus ticks. For field validation, adult R. microplus ticks collected from different cattle farms in Brazil were evaluated for resistance to RaTexT®, and the results regarding their larval progenies were compared with those for the RIT. Partly engorged adult ticks derived from cattle infested with laboratory and field strains of R. microplus were exposed to deltamethrin in RaTexT® containers, which contained six rows of four interconnected compartments, accommodating five to eight semi-engorged female ticks with a preferred size ranging between 5 and 8 mm. The corresponding larvae of each strain were exposed in the RIT to the same deltamethrin concentrations in filter papers. RESULTS: In RaTexT®, mortality in adult ticks from a resistant strain of R. microplus from Seropédica in Brazil was 38.4%, 54.2% and 75.0% at the 1 ×, 5 × and 10 × doses of deltamethrin, respectively. In RIT, mortality of larvae from the same resistant strain was 2.0%, 4.9% and 19.5% at 1 ×, 5 × and 10 × doses, respectively. The results of RaTexT® and RIT agreed since both tests identified a high level of resistance based on a cut-off of 90% mortality. In RaTexT®, mortality of adult ticks from a susceptible strain originating from Porto Alegre was 73.8%, 92.9% and 97.6% at the 1 ×, 5 × and 10 × doses, respectively. In RIT, mortality of larvae from the susceptible strain was 95.2%, 95.2% and 96.8% at the 1 ×, 5 × and 10 × doses, respectively. Interestingly, both tests identified a low number of unexpected resistant individuals in the susceptible strain since the mortality of neither larvae nor adults reached 100%. This effect remained unnoticed in the LPT, wherein a resistance ratio of 159.5 was found based on the LC50 of the resistant strain divided by the LC50 of the susceptible strain. Next, RaTexT® was compared with RIT using adult and larval ticks derived from three field strains of R. microplus in Brazil. RaTexT® detected high levels of resistance to deltamethrin in adult ticks in all strains, which was confirmed in larvae tested by the RIT. Both tests agreed on the same resistance level with significantly lower mortality rates in larvae than in adult ticks. CONCLUSIONS: RaTexT® is a novel rapid pen-site test for detecting acaricide resistance in adult livestock ticks. It potentially replaces laborious tests using larval ticks and provides results within 24 h relevant to acaricide resistance management of livestock ticks.

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The effectiveness of a visceral leishmaniasis (VL) control strategy based on the application of 4 % deltamethrin impregnated collars (DIC) exclusively in seropositive dogs was assessed between 2018 and 2019, through a prospective study. The effectiveness of DIC-collaring was evaluated by comparing the incidence rate of anti-leishmanial antibodies among dogs from two endemic districts in Brazil. In one of the areas, the conventional control measure which is based on the non-compulsory euthanasia of LV seropositive dogs, was practiced by the official healthy service as a regular procedure, whereas strategic collaring, conceived in this study, was carried out in the other. Results of serological tests applied to serum samples collected from all domiciled dogs were evaluated in three consecutive times, spaced by around 200 days. Incidence rates of VL seroreactivity were compared between districts in the same period of time as well as within the same district, in consecutive periods. Based on the results, the risk of infection in the population under conventional control measure was up to four times higher than the risk of infection where DIC-collaring was used. The strategic use of collar proposed here emerged as a promising measure for VL control in dogs from endemic areas. Strategic collaring does not rely on the euthanasia of infected animals, an extremely controversial procedure, and instead of being used in all dogs, as collaring is normally recommended; only seropositive dogs are intervened. Strategic use of DIC has the potential to drastically reduce costs, if compared to mass collaring canine population.

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Wetlands play a crucial role in providing valuable ecosystem services, including the removal of various pollutants. In agricultural basins, wetlands are exposed to agrochemical loads. This study aims to assess the attenuation effect of the ubiquitous macrophyte Azolla spp. on the toxicity of lambda-cyhalothrin to sensitive aquatic organisms. An indoor mesocosm experiment was conducted to compare the concentration of lambda-cyhalothrin at different time points after pesticide application in vegetated and unvegetated treatments, including a control without pesticide addition. Toxicity tests were performed throughout the experiment on three organisms: a fish (Cnesterodon decemmaculatus), a macroinvertebrate (Hyalella curvispina), and an amphibian (Boana pulchella). The results demonstrated that lambda-cyhalothrin concentration and toxicity in water were significantly lower in the Azolla spp. treatment. Furthermore, the half-life of lambda-cyhalothrin decreased from 1.2 days in the unvegetated treatment to 0.4 days in the vegetated treatment. The vegetated treatment also resulted in a significantly lower mortality rate for both H. curvispina and C. decemmaculatus. However, no mortality was observed in B. pulchella for any of the treatments. Sublethal effects were observed in this organism, such as lateral bending of the tail and impairment of the ability to swim, which were attenuated in the vegetated treatment. We conclude that Azolla spp. can effectively reduce the concentration and toxicity of lambda-cyhalothrin, suggesting its potential use in farm-scale best management practices to mitigate the effects of pesticide loads from adjacent crops.

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We compared the effects of lambda-cyhalothrin as the pure active ingredient and as a formulated product (Zero®), on the larval stage of the autochthonous species Boana pulchella. We evaluated ecotoxicological endpoints, behavioral and developmental alterations, and the biochemical detoxifying, neurotoxic, and oxidative stress responses, covering a wide concentration range from environmental to high application levels. Both pyrethroid preparations displayed similar ecotoxicity (median lethal concentration of ~0.5 mg/L), with the lethal effect of Zero® being more pronounced than that of the active ingredient. Sublethal behavioral alterations in natatory activity were observed at 1000 times lower concentrations, indicating the ecological hazard of tadpole exposure to this pyrethroid at environmentally relevant concentrations. Biochemical endpoints in B. pulchella larvae showed significant responses to lambda-cyhalothrin in the ng/L range; these responses were different for the pure or the formulated product, and they were variable at higher concentrations. Principal components analysis confirmed the prevalence of biochemical responses as early endpoints at the lowest lambda-cyhalothrin concentrations; the Integrated Biomarker Response Index proportionally increased with pyrethroid concentration in a similar way for the pure and the formulated products. We conclude that lambda-cyhalothrin is of concern from an environmental perspective, with particular emphasis on autochthonous anuran development. The battery of biochemical biomarkers included in our study showed a consistent integrated biomarker response, indicating that this is a potent tool for monitoring impacts on amphibians. Environ Toxicol Chem 2024;43:2134-2144. © 2024 SETAC.

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Resistance to insecticides is one of the great challenges that vector control programs must face. The constant use of pyrethroid-type insecticides worldwide has caused selection pressure in populations of the Aedes aegypti vector, which has promoted the emergence of resistant populations. The resistance mechanism to pyrethroid insecticides most studied to date is target-site mutations that desensitize the voltage-gated sodium channel (VGSC) of the insect to the action of pyrethroids. In the present study, susceptibility to the pyrethroid insecticides permethrin, lambda-cyhalothrin, and deltamethrin was evaluated in fourteen populations from the department of Córdoba, Colombia. The CDC bottle bioassay and WHO tube methods were used. Additionally, the frequencies of the F1534C, V1016I, and V410L mutations were determined, and the association of resistance with the tri-locus haplotypes was examined. The results varied between the two techniques used, with resistance to permethrin observed in thirteen of the fourteen populations, resistance to lambda-cyhalothrin in two populations, and susceptibility to deltamethrin in all the populations under study with the CDC method. In contrast, the WHO method showed resistance to the three insecticides evaluated in all populations. The frequencies of the mutated alleles ranged from 0.05-0.43 for 1016I, 0.94-1.0 for 1534C, and 0.01-0.59 for 410L. The triple homozygous mutant CIL haplotype was associated with resistance to all three pyrethroids evaluated with the WHO bioassay, while with the CDC bioassay, it was only associated with resistance to permethrin. This study highlights the importance of implementing systematic monitoring of kdr mutations, allowing resistance management strategies to be dynamically adjusted to achieve effective control of Aedes aegypti.

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New mixtures of pesticides are being placed on the market to increase the spectrum of phytosanitary action. Thus, the eco(geno)toxic effects of the new commercial mixture named Platinum Neo, as well as its constituents the neonicotinoid Thiamethoxam and the pyrethroid Lambda-Cyhalothrin, were investigated using the species Daphnia magna, Raphidocelis subcapitata, Danio rerio, and Allium cepa L. The lowest- and no-observed effect concentration (LOEC and NOEC) were measured in ecotoxicological tests. While Thiamethoxam was ecotoxic at ppm level, Lambda-Cyhalothrin and Platinum Neo formulation were ecotoxic at ppb level. The mitotic index (MI), chromosomal aberrations and micronucleus [MN] frequency were measured as indicators of phytogenotoxicity in A. cepa plants exposed for 12 h to the different insecticides and their mixture under different dilutions. There were significant alterations in the MI and MN frequency in comparison with the A. cepa negative control group, with Thiamethoxam, Lambda-Cyhalothrin, and Platinum Neo treatments all significantly reducing MI and increasing MN frequency. Thus, MI reduction was found at 13.7 mg L-1 for Thiamethoxam, 0.8 µg L-1 for Lambda-Cyahalothrin, and 2.7:2 µg L-1 for Platinum Neo, while MN induction was not observed at 14 mg L-1 for Thiamethoxam, 0.8 µg L-1 for Lambda-Cyahalothrin, and 1.4:1 µg L-1 for Platinum Neo. The insecticide eco(geno)toxicity hierarchy was Platinun Neo > Lambda-Cyhalothrin > Thiamethoxam, and the organism sensitivity hierarchy was daphnids > fish > algae > A. cepa. Eco(geno)toxicity studies of new pesticide mixtures can be useful for management, risk assessment, and avoiding impacts of these products on living beings.

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BACKGROUND: Mortality caused by various pyrethroids, and neonicotinoids has been studied for stored-product insects in the past, yet limited information exists on the sublethal effects they can induce to Oryzaephilus surinamensis. In the current study, the sublethal effects of deltamethrin, λ-cyhalothrin, α-cypermethrin, etofenprox, and the mixture of acetamiprid with d-tetramethrin and piperonyl butoxide on the mobility of O. surinamensis in the presence or the absence of a food source was investigated. RESULTS: Lethal concentrations (LCs) were lower for deltamethrin, α-cypermethrin, and λ-cyhalothrin (LC10 = 0.000233, 0.000211, and 0.000271 mg active ingredient (a.i.) cm-2, LC30 = 0.000413, 0.000398, and 0.000447 mg a.i. cm-2, respectively), followed by etofenprox, and the mixture of acetamiprid with d-tetramethrin and piperonyl butoxide (LC10 = 0.00228 and 0.003267 mg a.i. cm-2, LC30 = 0.00437 and 0.01188 mg a.i. cm-2, respectively). Deltamethrin and λ-cyhalothrin negatively impacted adult walking behavior, increasing stop durations compared to controls. Adults exposed to LC10 and LC30 of λ-cyhalothrin, and LC30 of deltamethrin exhibited prolonged periods on their backs compared to the remaining treatments and the controls. The α-cypermethrin LC30-exposed adults exhibited significantly shorter walking and stopping durations than controls but demonstrated prolonged climbing on the arena walls compared to adults exposed to the remaining a.i. and the control. A similar trend was observed for etofenprox. CONCLUSIONS: Under sublethal concentrations, λ-cyhalothrin and deltamethrin increased stop intervals and reduced the duration of climbing attempts of O. surinamensis versus α-cypermethrin. These findings advance comprehension of the underexplored sublethal impacts of the tested a.i. on O. surinamensis adults, holding potential for leveraging insecticide-induced behavioral effects to enhance warehouse pest management. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

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Exploring therapeutic options is crucial in the ongoing COVID-19 pandemic caused by SARS-CoV-2. Nirmatrelvir, which is a potent inhibitor that targets the SARS-CoV-2 Mpro, shows promise as an antiviral treatment. Additionally, Ivermectin, which is a broad-spectrum antiparasitic drug, has demonstrated effectiveness against the virus in laboratory settings. However, its clinical implications are still debated. Using computational methods, such as molecular docking and 100 ns molecular dynamics simulations, we investigated how Nirmatrelvir and Ivermectin interacted with SARS-CoV-2 Mpro(A). Calculations using density functional theory were instrumental in elucidating the behavior of isolated molecules, primarily by analyzing the frontier molecular orbitals. Our analysis revealed distinct binding patterns: Nirmatrelvir formed strong interactions with amino acids, like MET49, MET165, HIS41, HIS163, HIS164, PHE140, CYS145, GLU166, and ASN142, showing stable binding, with a root-mean-square deviation (RMSD) of around 2.0 Å. On the other hand, Ivermectin interacted with THR237, THR239, LEU271, LEU272, and LEU287, displaying an RMSD of 1.87 Å, indicating enduring interactions. Both ligands stabilized Mpro(A), with Ivermectin showing stability and persistent interactions despite forming fewer hydrogen bonds. These findings offer detailed insights into how Nirmatrelvir and Ivermectin bind to the SARS-CoV-2 main protease, providing valuable information for potential therapeutic strategies against COVID-19.

RESUMO

Insecticide resistance is considered a barrier to chemical control of Triatoma infestans, the main vector of Chagas disease in the Southern Cone of South America. Although initiatives to reduce the incidence of the disease in the region have integrated different strategies, they have mainly relied on vector elimination using pyrethroid insecticides such as deltamethrin. Reports of pyrethroid resistance in connection with T. infestans control failures first emerged in northern Argentina and southern Bolivia. Recently, a mosaic pyrethroid-resistant focus has been described in the center of the Argentine Gran Chaco (Department of General Güemes, Chaco Province), characterized by the presence of susceptible and very highly resistant populations in the same area. The involvement of different resistance mechanisms has been proposed, together with the contribution of environmental variables that promote the toxicological heterogeneity described. In the endemic zone of Argentina, however, new questions arise: Are there any other clusters of resistance? Is there a relationship between the distribution of resistance and environmental variables (as has been observed at smaller scale)? We studied toxicological data from insects collected and analyzed at 224 localities between 2010 and 2020 as part of the resistance monitoring conducted by the Chagas National Program. The sites were classified according to the survival rate of insects exposed to a discriminant dose of deltamethrin: 0-0.19 were considered susceptible, 0.2-0.79 low-resistance, and 0.8-1 high-resistance. Localities were georeferenced to describe the spatial distribution of resistance and to identify environmental variables (demographics, land use, urbanization, connectivity, and climate) potentially associated with resistance. We used Generalized Linear Models (GLMs) to examine the association between resistance and environmental predictors, selecting error distributions based on the response variable definition. For the entire period, 197 susceptible localities were distributed across the endemic zone. Localities with different survival rates were found throughout the area; 9 high-resistance localities circled the two previously identified resistant foci, and 18 low-resistance in 6 provinces, highlighting their relevance for control planning. Precipitation variables were linked to resistance in all the GLMs evaluated. Presence/absence models were the most accurate, with precipitation, distance from the capital city, and land use contributing to the distribution of resistance. This information could be valuable for improving T. infestans control strategies in future scenarios characterized by unpredictable changes in land use and precipitation.