Efficacy and safety of pulsed field ablation for accessory pathways: a pilot study.

AIMS: Radiofrequency ablation is used as a first-line therapy for accessory pathways (APs). However, data regarding the effects of pulsed field ablation (PFA) on APs are limited. We sought to evaluate the acute procedural and 6-month success and safety of PFA in a cohort of patients with APs. METHODS AND RESULTS: A focal contact force-sensing PFA catheter was used for patients with APs. Pulsed field ablation generator generated a bipolar and biphasic waveform (±1000 V) with a duration of 100 ms from the tip of the PFA catheter. A 100% acute procedural success was achieved in 10 conscious patients with APs (7 left anterolateral, 2 left inferolateral, and 1 right posteroseptal APs) including 6 (60%) patients after an initial application. The average total ablation time was 6.3 ± 4.9 s for 4.7 ± 1.8 ablation sites (ASs), including 3.1 ± 2.4 s at targets and 3.2 ± 2.9 s at 3.2 ± 2 bolus ASs. The mean skin-to-skin time was 59.3 ± 15.5 min, and PFA catheter dwell time was 29.4 ± 7.8 min. One patient encountered transient sinus arrest during PFA due to parasympathetic overexcitation. Sinus rhythm was restored in all patients without any significant adverse events during the short-term follow-up. CONCLUSION: Pulsed field ablation of APs was feasible, effective, and safe. Its efficiency was remarkable for its ultrarapid termination of AP conduction. Further studies are warranted to prove whether utilization of PFA with current parameters can extend to manifold AP ablation.

Interactive Effects of Salinity and Mosquito Larvicides Toxicity to Larvae of Aedes Taeniorhynchus.

Understanding the influence of salinity on the efficacy of mosquito larvicides in brackish water habitats is crucial for effective salt-marsh Aedes taeniorhynchus control. This study investigated the interactive effects of salinity on the toxicity of 3 commonly used mosquito larvicides: Bacillus thuringiensis israelensis (VectoBac® 12AS), spinosad (Natular® SC), and S-methoprene (Altosid® 12AS) against Ae. taeniorhynchus larvae. Four salinity levels (0 ppt [parts per thousand], 8 ppt, 16 ppt, and 32 ppt) were tested in laboratory bioassays. The results revealed distinct responses of these larvicides to varying salinity levels. VectoBac 12AS displayed consistent efficacy across all salinity levels, indicating its suitability for brackish water habitats. In contrast, Natular 2EC exhibited increased effectiveness with higher salinity, making it a preferable choice for saline environments. Altosid 12AS showed its highest efficacy in freshwater, with reduced effectiveness as salinity increased. These findings underscore the need to consider salinity levels when selecting and applying mosquito larvicides in diverse aquatic habitats. Understanding the complex interplay between salinity and larvicide performance is essential for optimizing mosquito control strategies and mitigating mosquito-borne diseases in various environments.

Outcomes of Focal Pulsed Field Ablation for Paroxysmal Supraventricular Tachycardia.

BACKGROUND: Pulsed field ablation (PFA) is primarily used for treatment of atrial fibrillation as it provides better safety and efficacy. However, there are limited data available on the use of PFA for paroxysmal supraventricular tachycardia (PSVT). The study sought to describe the outcomes of PSVT ablation with a novel focal contact force (CF)-sensing PFA. METHODS: In this first-in-human pilot study, a focal CF-sensing PFA catheter was used for mapping and ablation navigated with an electroanatomic mapping system (EAMS). Pulsed field energy was delivered as biphasic/bipolar electrical pulse trains with 2000 V/delivery. CF was controlled from 2 g to 10 g during PFA. RESULTS: Procedural acute success was achieved without general anaesthesia or conscious sedation in all 10 patients, including 7 patients diagnosed with typical atrioventricular nodal re-entrant tachycardias and 3 patients with orthodromic reciprocating tachycardias. Successful target ablation time was 2.0 ± 0.5 seconds per patient, and the acute procedural success at the first single site was achieved in 5 patients. The mean skin-to-skin procedure time was 79.4 ± 15 minutes, PFA catheter dwell time was 50.1 ± 14 minutes, and fluoroscopy time was 6.2 ± 7 minutes. Maintenance of sinus rhythm was observed in all patients within 6-month follow-up. No serious adverse events occurred in any subjects during PFA or during the 6-month follow-up. CONCLUSIONS: A focal CF-sensing PFA catheter could effectively, rapidly, and safely ablate PSVT in conscious patients. CLINICAL TRIAL REGISTRATION: NCT05770921.

Adult Mosquito and Butterfly Exposure to Permethrin and Relative Risk Following ULV Sprays from a Truck-Mounted Sprayer.

Ground applications of adulticides via a specialized truck-mounted sprayer are one of the most common practices for control of flying adult mosquitoes. Aerosols released to drift through a targeted area persist in the air column to contact and kill flying mosquitoes, but may also drift into adjacent areas not targeted by the applications where it may affect nontarget insects such as imperiled butterflies. This study compared the risk of permethrin to adult mosquitoes and adult butterflies to assess the likelihood that the butterflies would be affected following such sprays. Permethrin toxicity values were determined for Aedes aegypti and Culex quinquefasciatus (LD50s of 81.1 and 166.3 ng/g dw, respectively) and then combined with published toxicity data in a species sensitivity distribution for comparison with published permethrin toxicity data for adult butterflies. The sensitivity distributions indicated adult butterflies and mosquitoes are similarly sensitive, meaning relative risk would be a function of exposure. Exposure of adult butterflies and adult mosquitoes to permethrin was measured following their exposure to ULV sprays in an open field. Average permethrin concentrations on adult mosquitoes (912-38,061 ng/g dw) were typically an order of magnitude greater than on adult butterflies (110-11,004 ng/g dw) following each spray, indicating lower risk for butterflies relative to mosquitoes. Despite lower estimated risk, 100% mortality of adult butterflies occurred following some of the sprays. Additional studies could help understand exposure and risk for butterflies in densely vegetated habitats typical near areas treated by ULV sprays.

Insecticide Susceptibility Status of Lab and Field Populations of Aedes albopictus from Gainesville, Florida, to Organophosphates and Pyrethroids.

Previous unpublished results from 2 open-field studies in South Florida evaluated the effectiveness of 4 ultra-low volume malathion formulations, applied by ground application against a USDA (Gainesville) laboratory-colonized strain of Aedes albopictus. Field results of the bioassays indicated that the species was highly resistant to malathion compared with other insecticide-susceptible mosquito species concurrently tested. Unfortunately, when the Ae. albopictus colony was initially started in 2003 from a field collection in Gainesville, FL, susceptibility to insecticides was not determined. Since that time, this species has been in constant production without exposure to pesticides by the Center for Medical, Agricultural, and Veterinary Entomology, Gainesville, FL. In order to determine its susceptibility level to malathion and compare it with 3 current field-collected Ae. albopictus populations, 3 organophosphates (malathion, chlorpyrifos, naled) and 2 pyrethroids (permethrin, deltamethrin) were tested in the laboratory, using the Centers for Disease Control and Prevention bottle bioassays. Results of the study confirmed that the USDA-Gainesville Ae. albopictus was still highly resistant to malathion even after being maintained in the laboratory for 16 years without exposure to pesticides. The 3 field-collected populations were also resistant to malathion but slightly less so than the USDA-Gainesville population. Rotation of pyrethroid products 16 years ago did not result in any significant reduction of malathion resistance in the field populations. Neither the USDA-Gainesville nor the field-collected Ae. albopictus populations showed cross-resistance to chlorpyrifos and naled. Lower mortalities were observed in the 10-min diagnostic time from the 3 field-collected populations against permethrin but rose significantly at 15-min exposure. Resistance was not detected for deltamethrin in any of the 4 Gainesville Ae. albopictus populations.

Displacement of Aedes albopictus by Aedes aegypti in Gainesville, Florida.

Aedes aegypti and Ae. albopictus are invasive mosquitoes, capable of vectoring arboviruses such as dengue, chikungunya, yellow fever, and Zika. Recent shifts in spatial distribution indicate there is a resurgence of Ae. aegypti in certain regions of Florida. After a 26-year absence, Ae. aegypti larvae were collected in a downtown neighborhood in Gainesville, Florida, in November 2019. Subsequent surveys confirmed that Ae. albopictus was completely displaced by Ae. aegypti in this neighborhood, whereas Ae. albopictus and Ae. aegypti coexisted around this community focus, and Ae. albopictus alone has been found elsewhere in the city and county since the 1990s. Field surveys revealed that Ae. aegypti is resurging in the downtown area of Gainesville and is actively dispersing to adjacent neighborhoods. Thus, Ae. aegypti could potentially replace Ae. albopictus across more of urban Gainesville in north-central Florida, as reported recently in coastal cities of northeastern Florida.

Sonodynamic therapy reduces iron retention of hemorrhagic plaque.

Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased atherosclerotic burden, positively altered atherosclerotic lesion composition, and alleviated iron retention in rabbit hemorrhagic plaques. Furthermore, SDT reduced iron retention by stimulating ferroportin 1 (Fpn1) expression in apolipoprotein E (ApoE)-/- mouse plaques with high susceptibility to IPH. Subsequently, SDT inhibited iron-overload-induced foam-cell formation and pro-inflammatory cytokines secretion in vitro. Moreover, SDT reduced levels of the labile iron pool and ferritin expression via the reactive oxygen species (ROS)-nuclear factor erythroid 2-related factor 2 (Nrf2)-FPN1 pathway. SDT exerted therapeutic effects on hemorrhagic plaques and reduced iron retention via the ROS-Nrf2-FPN1 pathway in macrophages, thereby suggesting that it is a potential translational strategy for patients with advanced atherosclerosis in clinical practice.

Rapid reduction in plaque inflammation by sonodynamic therapy inpatients with symptomatic femoropopliteal peripheral artery disease:A randomized controlled trial.

BACKGROUND: Inflammation is actively involved in the clinical manifestation of peripheral artery disease (PAD). Sonodynamic therapy (SDT), a novel non-invasive, plaque-based, macrophage-targeted anti-inflammatory regimen for atherosclerosis has the potential to improve walking performance by reducing plaque inflammation. METHODS: This phase-2, randomized, sham-controlled, double-blind clinical trial enrolled 32 participants with symptomatic femoropopliteal PAD. The primary outcome was the 30-day change in the target-to-background ratio (TBR) within the most diseased segment (MDS) of the femoropopliteal artery assessed through positron emission tomography/computed tomography (PET/CT). The secondary outcomes were changes in walking performance, limb perfusion, lesional morphology and quality of life measurements. RESULTS: The mean age was 64.7 years and 63% were male. Thirty-one completed follow-up. SDT significantly decreased the MDS TBR by 0.53 (95% CI, -0.70 to -0.36, P < 0.001) compared with control. Furthermore, SDT increased peak walking time by 118.6 s (95% CI, 74.3 to 163.0, P < 0.001), increased ankle-brachial index by 0.11 (95% CI, 0.07 to 0.14, P < 0.001), decreased lesional diameter and area stenosis by 7.2% (95% CI, -8.6 to -4.5, P < 0.001) and 9.6% (95% CI, -24.5 to -5.3, P = 0.005), respectively, and increased the walking speed score of the Walking Impairment Questionnaire by 16.1 (95% CI, 2.6 to 29.5, P = 0.021) and the physical functioning score of the 36-item Short-Form Health Survey by 10.0 (95% CI, 5.0 to 20.0, P = 0.003) compared with control. These improvements were maintained in the SDT group up to 6-month. CONCLUSIONS: SDT rapidly reduced plaque inflammation and improved walking performance among patients with symptomatic PAD. TRIAL REGISTRATION: Clinical Trials NCT03457662.

Sonodynamic Therapy Suppresses Neovascularization in Atherosclerotic Plaques via Macrophage Apoptosis-Induced Endothelial Cell Apoptosis.

During atherosclerosis plaque progression, pathological intraplaque angiogenesis leads to plaque rupture accompanied by thrombosis, which is probably the most important cause of arteries complications such as cerebral and myocardial infarction. Even though few treatments are available to mitigate plaque rupture, further investigation is required to develop a robust optimized therapeutic method. In this study using rabbit and mouse atherosclerotic models, sinoporphyrin sodium (DVDMS)-mediated sonodynamic therapy reduced abnormal angiogenesis and plaque rupture. Briefly, DVDMS is injected to animals, and then the plaque was locally exposed to pulse ultrasound for a few minutes. Furthermore, a small size clinical trial was conducted on patients with atherosclerosis. Notably, a significant reduction of arterial inflammation and angiogenesis was recorded following a short period of DVDMS-mediated sonodynamic therapy treatment. This beneficial outcome was almost equivalent to the therapeutic outcome after 3-month intensive statin treatment.

Efficacy of Residual Pesticide-Treated Plant Saucers Against Aedes albopictus Larvae Under Semi-Field and Field Conditions.

Plant saucers are ubiquitous, outdoor water-holding receptacles and are one of the most productive domestic mosquito habitats in the urban environment. Two kinds of commonly used plant saucers, clay and plastic, were manually treated with 3 residual insecticides, bifenthrin (Talstar® Professional), lambda-cyhalothrin (Lambda 9.7 CS), and tau-fluvalinate (Mavrik® Perimeter), at their maximum rates to assess their residual efficacy against Aedes albopictus larvae under semi-field and field conditions. Both clay and plastic saucers treated with bifenthrin and lambda-cyhalothrin provided weeks of control of 3rd instars of Ae. albopictus, whereas tau-fluvalinate provided only 1 day of control. Results from this study show that bifenthrin and lambda-cyhalothrin can provide good control of Ae. albopictus larvae for a considerable period of time and have great potential with regard to container mosquito management in the future.

Transcriptomic Analysis of Aedes aegypti Innate Immune System in Response to Ingestion of Chikungunya Virus.

Aedes aegypti (L.) is the primary vector of emergent mosquito-borne viruses, including chikungunya, dengue, yellow fever, and Zika viruses. To understand how these viruses interact with their mosquito vectors, an analysis of the innate immune system response was conducted. The innate immune system is a conserved evolutionary defense strategy and is the dominant immune system response found in invertebrates and vertebrates, as well as plants. RNA-sequencing analysis was performed to compare target transcriptomes of two Florida Ae. aegypti strains in response to chikungunya virus infection. We analyzed a strain collected from a field population in Key West, Florida, and a laboratory strain originating from Orlando. A total of 1835 transcripts were significantly expressed at different levels between the two Florida strains of Ae. aegypti. Gene Ontology analysis placed these genes into 12 categories of biological processes, including 856 transcripts (up/down regulated) with more than 1.8-fold (p-adj (p-adjust value) ≤ 0.01). Transcriptomic analysis and q-PCR data indicated that the members of the AaeCECH genes are important for chikungunya infection response in Ae. aegypti. These immune-related enzymes that the chikungunya virus infection induces may inform molecular-based strategies for interruption of arbovirus transmission by mosquitoes.

Rapid inhibition of atherosclerotic plaque progression by sonodynamic therapy.

Aims: Currently, efficient regimens to reverse atherosclerotic plaques are not available in the clinic. Herein, we present sonodynamic therapy (SDT) as a novel methodology to rapidly inhibit progression of atherosclerotic plaques. Methods and results: In atherosclerotic rabbit and apoE-deficient mouse models, SDT efficiently decreased the atherosclerotic burden within 1 week, revealing a decrease in the size of the atherosclerotic plaque and enlarged lumen. The shrunken atherosclerotic plaques displayed compositional alterations, with a reduction in lesional macrophages and lipids. The rapid efficacy of SDT may be due to its induction of macrophage apoptosis, enhancement of efferocytosis, and amelioration of inflammation in the atherosclerotic plaque. Compared with atorvastatin, the standard of care for atherosclerosis, SDT showed more significant plaque shrinkage and lumen enlargement during 1 week treatment. Furthermore, SDT displayed good safety without obvious side effects. In a pilot clinical trial recruiting the patients suffering atherosclerotic peripheral artery disease, combination therapy of SDT with atorvastatin efficiently reduced progression of atherosclerotic plaque within 4 weeks, and its efficacy was able to last for at least 40 weeks. Conclusion: SDT is a non-invasive and efficacious regimen to inhibit atherosclerotic plaque progression.

Survival of Overwintering Aedes albopictus Eggs Under Natural Conditions In North-Central Florida.

Aedesalbopictus mosquitoes overwinter as eggs in north-central Florida. Knowledge of this species' overwintering survival rate is of great interest to local mosquito control districts. In this study, field-collected Ae. albopictus eggs were exposed to natural conditions during winter 2016-17 in Gainesville, FL, to determine the overwintering survival rate. Individual strips of germination paper containing eggs of this species were collected from ovitraps in November 2016 then later clipped to the inner edge of empty flowerpots and placed in the Department of Public Works compound, City of Gainesville, in December. Egg strips that remained outdoors were later brought back to the laboratory and hatched in late March 2017. Significant differences were found among the 5 ambient environmental exposure methods (configurations) in terms of egg survival rate, egg collapsed rate, and egg unaccounted rate, whereas no significant difference was observed on the egg intact rate. Egg strips stored in flowerpots with the drainage hole sealed had the highest survival rate (18.3%), whereas eggs stored in an open covered area had the least survival rate (2.4%). The effect of different storage conditions on the survivorship of overwintering Ae. albopictus eggs in north-central Florida is discussed.

Non-Lethal Sonodynamic Therapy Inhibits Atherosclerotic Plaque Progression in ApoE-/- Mice and Attenuates ox-LDL-mediated Macrophage Impairment by Inducing Heme Oxygenase-1.

BACKGROUND: Previous studies from our group showed that low-intensity sonodynamic therapy (SDT) has protective effects on atherosclerosis (AS). However, because the intensity of ultrasound passing through tissue is attenuated, the consequences of very low-intensity SDT, referred to as non-lethal SDT (NL-SDT), on atherosclerotic plaques are unclear. The aim of this study was to determine whether NL-SDT affects atherosclerotic plaques and to elucidate the possible underlying mechanisms. METHODS: An AS model was established using ApoE-/- mice fed a western diet. En face Oil Red O staining was used to measure atherosclerotic plaque size. Hematoxylin and eosin staining and immunohistochemical staining were used to observe plaque morphology and assess the location of macrophages and heme oxygenase 1 (HO-1). HO-1 mRNA and protein levels in AS plaques were evaluated by real-time PCR and western blotting. Human THP-1 cells and mouse peritoneal macrophages were used in this study. Western blotting was used to investigate the expression of cellular proteins after NL-SDT. Macrophage apoptosis was evaluated by TUNEL assays and flow cytometry with Annexin V/PI double staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were measured with 2'-7'-dichlorofluorescein diacetate (DCFH-DA) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazolyl carbocyanine iodide (JC-1) staining, respectively. RESULTS: NL-SDT significantly inhibited AS progression and reduced the necrotic core area. NL-SDT induced HO-1 expression in lesional macrophages and in cultured macrophages. NL-SDT activated the protein kinase B (AKT) and extracellular signal-related protein kinase (ERK) pathways and the transcription factor NF-E2-related factor 2 (Nrf2).NL-SDT significantly reduced oxidized LDL (ox-LDL)-induced macrophage MMP collapse, ROS production and cell apoptosis. Zinc protoporphyrin (ZnPP), a HO-1-specific inhibitor, reversed the protective effects of NL-SDT. CONCLUSION: NL-SDT inhibits atherosclerotic plaque progression and increases plaque stability. In vitro, NL-SDT has a protective effect on ox-LDL-induced macrophage impairment via HO-1.

Laboratory and field evaluation of spinosad, a biorational natural product, against larvae of Culex mosquitoes.

Spinosad, a fermentation product from the naturally occurring soil actinomycete bacterium Saccharopolyspora spinosa, has been reported to have a high level of activity against phytophagous insects and insects impacting human and animal health. It has low mammalian toxicity and a favorable environmental profile, including low persistence and no toxicity to fish and wildlife at mosquito larvicidal rates. In order to determine the activity and efficacy of spinosad against larvae of Culex mosquitoes, technical powder and liquid formulations of spinosad were tested against mosquito larvae under laboratory and field conditions. In the laboratory, spinosad powder was highly active against 2nd and 4th instars of Culex quinquefasciatus after 24 h of exposure. The extent of mortality increased slightly after 48 h of exposure. Second instars were slightly more susceptible than 4th instars. The liquid formulation showed somewhat higher activity (about 2x) than the technical powder material at both the LCs50 and LC90 levels. In field microcosm tests against natural populations of mosquitoes, the liquid formulation yielded excellent control of immature Culex spp. for 21 days at concentrations of 0.05 mg (AI)/liter and 35 days at 0.1 to 0.5 mg (AI)/liter in outdoor tubs. This formulation also yielded excellent control of natural Culex mosquitoes for 14 days or longer at 0.025 to 0.1 mg (AI)/liter in outdoor ponds. From our data, it appears that spinosad as a new mode of action has a good potential for controlling mosquito larvae.

Susceptibility of the adult eye gnat Liohippelates collusor (Diptera: Chloropidae) to neonicotinoids and spinosad insecticides.

Imidacloprid, thiamethoxam (first and second generation neonicotinoid insecticides), and spinosad (a naturally derived biorational insecticide) were evaluated in the laboratory against adult eye gnats, Liohippelates collusor (Townsend), using two modes of exposure. Ingestion experiments revealed that toxicity was the highest for thiamethoxam (Platinum soluble concentrate) followed by technical thiamethoxam, imidacloprid (Admire 2 flowable concentrate), and spinosad (Success* soluble concentrate). When incorporated into 5% sucrose solutions, eye gnat mortality was significantly increased compared to the same concentrations of aqueous insecticide solutions. Contact toxicity experiments revealed that thiamethoxam formulation (Platinum) was the most toxic, followed by technical thiamethoxam, imidacloprid, and spinosad. Increasing the duration of exposure time from 15 min to 30 min significantly increased adult eye gnat mortality, but no further mortality occurred by extending exposure from 30 min to 60 min. Our results suggest that Platinum has good ingestion and contact activity against adult eye gnats. Admire and Success have appreciable ingestion toxicity but low contact activity against adult eye gnats.