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1.
Parasit Vectors ; 17(1): 235, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778423

RESUMO

BACKGROUND: "Regeneration time" (RT) denotes the time required to obtain a stable mortality rate for mosquitoes exposed to insecticide-treated nets (ITNs) after three consecutive washes of a net in a day. The RT informs the wash interval used to artificially age ITNs to simulate their lifetime performance under user conditions (20 washes). RT was estimated following World Health Organization (WHO) longitudinal method (LM) procedures. Longitudinal evaluation may introduce heterogeneity due to mosquito batch variability, complicating RT determination. To overcome this, nets at each stage of regeneration (i.e., 1, 2, 3, 5 and 7 days post wash) were prepared in advance and refrigerated; then, a complete regeneration series was tested with a single mosquito batch on 1 testing day, completing four series over 4 days. This study compared the complete series method (CSM) against the LM. METHODS: The overall heterogeneity in the methods for estimating RT of one incorporated alpha-cypermethrin and piperonyl butoxide (PBO) and one incorporated permethrin with PBO ITNs was determined using laboratory-reared resistant Anopheles arabiensis under standard laboratory conditions. LM methods and CSM were compared in two experiments with refrigerated nets acclimated for (i) 2 h (test 1) and (ii) 3 h (test 2). Four regeneration replicates per day were tested per ITN product with 50 mosquitoes exposed per replicate (equivalent sample size to LM). The heterogeneity from these methods was compared descriptively. RESULTS: The intra-method variability for unwashed pieces was minimal, with variance of 1.26 for CSM and 1.18 for LM. For unwashed nets, LM had substantially greater variance and ratio of LM:CSM was 2.66 in test 1 and 2.49 in test 2. The magnitude of mortality measured in bioassays depended on sample acclimation after refrigeration. CONCLUSIONS: The CSM is a convenient method for determining the regeneration times. ITNs are prepared in advance, reducing pressure to prepare all samples to start on a single day. A complete regeneration series of samples is removed from the refrigerator, defrosted and evaluated on a single day with one mosquito batch reducing the influence of mosquito batch heterogeneity on results. Replicates can be conducted over several days but do not have to be conducted on consecutive days, allowing easy facility scheduling.


Assuntos
Anopheles , Mosquiteiros Tratados com Inseticida , Inseticidas , Controle de Mosquitos , Animais , Anopheles/fisiologia , Anopheles/efeitos dos fármacos , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Fatores de Tempo , Piretrinas/farmacologia , Permetrina/farmacologia , Malária/prevenção & controle , Malária/transmissão , Butóxido de Piperonila/farmacologia
2.
Cureus ; 16(4): e57985, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738140

RESUMO

Acute respiratory distress syndrome (ARDS) presents a formidable challenge in critical care, often resulting in high mortality rates, particularly in severe cases or those compounded by preexisting conditions. Despite substantial advancements in critical care, the heterogeneous nature of ARDS necessitates nuanced clinical approaches. ARDS is generally diagnosed through clinical evaluation, radiographic imaging, and laboratory tests, as well as acute onset, bilateral lung infiltrates on imaging, and a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspiratory oxygen concentration (FiO2) ratio of less than 300 mmHg. Management involves measurements to improve oxygenation and provide mechanical ventilation to assist breathing. The typical manifestation of ARDS is diffuse lung involvement, which affects multiple lobes symmetrically. Here, we report an unusual case of ARDS in a 53-year-old female who was brought into the hospital in an unresponsive state, exhibiting hypoxic and hypotension requiring intubation. Subsequent imaging revealed a distinctive pattern: the preservation of the right middle lobe, diverging from the conventional diffuse pulmonary affliction. This case underscores the need for clinical vigilance and adaptability, as such atypical presentations can confound diagnosis and management, posing unique clinical challenges. This case highlights the importance of recognizing ARDS' diverse presentations. Moreover, understanding the mechanisms behind the lobar sparing could provide greater insight into the disease heterogeneity and guide tailored therapeutic approaches. The imperative for further research into these uncommon presentations is clear, as it may be vital to improving outcomes for a broader spectrum of ARDS patients.

3.
Sci Rep ; 14(1): 11476, 2024 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769342

RESUMO

Entomological evaluations of vector control tools often use human landing catches (HLCs) as a standard measure of a direct human-vector contact. However, some tools have additional characteristics, such as mortality, and HLCS are not sensitive for measuring other effects beyond landing inhibition. Therefore, additional measures may need to be considered when evaluating these tools for public health use. This study has two main aims (1) the evaluate the accuracy of HLCs as a proxy for feeding and (2) to compare the predicted reduction in vectorial capacity when we do and do not consider these additional characteristics. To achieve this, we analyse previously published semi-field data from an experiment which used HLCs and another where mosquitoes were allowed to feed in the presence of different dosages of the volatile pyrethroid spatial repellent, transfluthrin. We compare results for two mathematical models: one which only considers the reduction in feeding effect and one which also considers mortality before and after feeding (using data gathered by the aspiration of mosquitoes after the semi-field feeding/landing period and 24 h survival monitoring). These Bayesian hierarchical models are parameterised using Bayesian inference. We observe that, for susceptible mosquitoes, reduction in landing is underestimated by HLCs. For knockdown resistant mosquitoes the relationship is less clear; with HLCs sometimes appearing to overestimate this characteristic. We find HLCs tend to under-predict the relative reduction in vectorial capacity in susceptible mosquitoes while over-predicting this impact in knockdown-resistant mosquitoes. Models without secondary effects have lower predicted relative reductions in vectorial capacities. Overall, this study highlights the importance of considering additional characteristics to reduction in biting of volatile pyrethroid spatial repellents. We recommend that these are considered when evaluating novel vector control tools.


Assuntos
Mordeduras e Picadas de Insetos , Controle de Mosquitos , Mosquitos Vetores , Animais , Humanos , Controle de Mosquitos/métodos , Mosquitos Vetores/fisiologia , Mosquitos Vetores/efeitos dos fármacos , Mordeduras e Picadas de Insetos/prevenção & controle , Comportamento Alimentar , Repelentes de Insetos/farmacologia , Ciclopropanos/farmacologia , Fluorbenzenos/farmacologia , Inseticidas/farmacologia , Modelos Teóricos
4.
Pediatr Dermatol ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38770539

RESUMO

BACKGROUND: Ultraviolet (UV)-exposure behaviors can directly impact an individual's skin cancer risk, with many habits formed during childhood and adolescence. We explored the utility of a photoaging smartphone application to motivate youth to improve sun safety practices. METHODS: Participants completed a preintervention survey to gather baseline sun safety perceptions and behaviors. Participants then used a photoaging mobile application to view the projected effects of chronic UV exposure on participants' self-face image over time, followed by a postintervention survey to assess motivation to engage in future sun safety practices. RESULTS: The study sample included 87 participants (median [interquartile (IQR)] age, 14 [11-16] years). Most participants were White (50.6%) and reported skin type that burns a little and tans easily (42.5%). Preintervention sun exposure behaviors among participants revealed that 33 (37.9%) mostly or always used sunscreen on a sunny day, 48 (55.2%) experienced at least one sunburn over the past year, 26 (30.6%) engaged in outdoor sunbathing at least once during the past year, and zero (0%) used indoor tanning beds. Non-skin of color (18 [41.9%], p = .02) and older (24 [41.4%], p = .007) participants more often agreed they felt better with a tan. Most participants agreed the intervention increased their motivation to practice sun-protective behaviors (wear sunscreen, 74 [85.1%]; wear hats, 64 [74.4%]; avoid indoor tanning, 73 [83.9%]; avoid outdoor tanning, 68 [79%]). CONCLUSION: The findings of this cross-sectional study suggest that a photoaging smartphone application may serve as a useful tool to promote sun safety behaviors from a young age.

5.
J Exp Biol ; 227(9)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38634230

RESUMO

Distantly related mammals (e.g. jerboa, tarsiers, kangaroos) have convergently evolved elongated hindlimbs relative to body size. Limb elongation is hypothesized to make these species more effective jumpers by increasing their kinetic energy output (through greater forces or acceleration distances), thereby increasing take-off velocity and jump distance. This hypothesis, however, has rarely been tested at the population level, where natural selection operates. We examined the relationship between limb length, muscular traits and dynamics using Longshanks mice, which were selectively bred over 22 generations for longer tibiae. Longshanks mice have approximately 15% longer tibiae and 10% longer femora compared with random-bred Control mice from the same genetic background. We collected in vivo measures of locomotor kinematics and force production, in combination with behavioral data and muscle morphology, to examine how changes in bone and muscle structure observed in Longshanks mice affect their hindlimb dynamics during jumping and clambering. Longshanks mice achieved higher mean and maximum lunge-jump heights than Control mice. When jumping to a standardized height (14 cm), Longshanks mice had lower maximum ground reaction forces, prolonged contact times and greater impulses, without significant differences in average force, power or whole-body velocity. While Longshanks mice have longer plantarflexor muscle bodies and tendons than Control mice, there were no consistent differences in muscular cross-sectional area or overall muscle volume; improved lunge-jumping performance in Longshanks mice is not accomplished by simply possessing larger muscles. Independent of other morphological or behavioral changes, our results point to the benefit of longer hindlimbs for performing dynamic locomotion.


Assuntos
Membro Posterior , Locomoção , Animais , Membro Posterior/fisiologia , Membro Posterior/anatomia & histologia , Fenômenos Biomecânicos , Camundongos/fisiologia , Músculo Esquelético/fisiologia , Músculo Esquelético/anatomia & histologia , Masculino , Feminino , Tíbia/fisiologia , Tíbia/anatomia & histologia , Fêmur/fisiologia , Fêmur/anatomia & histologia
6.
JOR Spine ; 7(2): e1333, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38660017

RESUMO

Background: Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Methods: Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. Results: CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells. Conclusion: There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

7.
J Obstet Gynaecol Can ; 46(6): 102463, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38631434

RESUMO

OBJECTIVES: It is unclear if use of cesarean delivery in people with inflammatory bowel disease (IBD) is guideline-concordant. We compared the odds of cesarean delivery among primiparous individuals with IBD versus without, overall, and by disease characteristics, as well as time to subsequent delivery. METHODS: Retrospective matched population-based cohort study between 1 April 1994 and 31 March 2020. Primiparous individuals aged 15-55 years with IBD were matched to those without IBD on age, year, hospital, and number of newborns delivered. Primary outcome was cesarean delivery versus vaginal delivery. Multivariable conditional logistic regression analyses were performed to estimate the odds of cesarean delivery among individuals with and without IBD as a binary exposure, and a categorical exposure based on IBD-related indications for cesarean delivery. Time to subsequent delivery was evaluated using a Cox proportional hazard model. RESULTS: We matched 7472 individuals with IBD to 37 360 individuals without (99.02% match rate). Individuals with IBD were categorised as having perianal (PA) disease (IBD-PA, n = 764, 10.2%), prior ileal pouch-anal anastomosis (n = 212, 2.8%), or IBD-Other (n = 6496, 86.9%). Cesarean delivery rates were 35.4% in the IBD group versus 30.4% in their controls (adjusted odds ratio 1.27; 95% CI 1.20-1.34). IBD-ileal pouch-anal anastomosis had a cesarean delivery rate of 66.5%, compared to 49.9% in IBD-PA and 32.7% in IBD-Other. There was no significant difference in the rate of subsequent delivery in those with and without IBD (adjusted hazard ratio 1.03,;95% CI 1-1.07). CONCLUSIONS: The higher risk of cesarean delivery in people with IBD reflects guideline-concordant use. Individuals with and without IBD were equally likely to have a subsequent delivery with similar timing.

8.
BMJ Open ; 14(4): e085850, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631827

RESUMO

INTRODUCTION: Improving sustainable transportation options will help cities tackle growing challenges related to population health, congestion, climate change and inequity. Interventions supporting active transportation face many practical and political hurdles. Implementation science aims to understand how interventions or policies arise, how they can be translated to new contexts or scales and who benefits. Sustainable transportation interventions are complex, and existing implementation science frameworks may not be suitable. To apply and adapt implementation science for healthy cities, we have launched our mixed-methods research programme, CapaCITY/É. We aim to understand how, why and for whom sustainable transportation interventions are successful and when they are not. METHODS AND ANALYSIS: Across nine Canadian municipalities and the State of Victoria (Australia), our research will focus on two types of sustainable transportation interventions: all ages and abilities bicycle networks and motor vehicle speed management interventions. We will (1) document the implementation process and outcomes of both types of sustainable transportation interventions; (2) examine equity, health and mobility impacts of these interventions; (3) advance implementation science by developing a novel sustainable transportation implementation science framework and (4) develop tools for scaling up and scaling out sustainable transportation interventions. Training activities will develop interdisciplinary scholars and practitioners able to work at the nexus of academia and sustainable cities. ETHICS AND DISSEMINATION: This study received approval from the Simon Fraser University Office of Ethics Research (H22-03469). A Knowledge Mobilization Hub will coordinate dissemination of findings via a website; presentations to academic, community organisations and practitioner audiences; and through peer-reviewed articles.


Assuntos
Fortalecimento Institucional , Ciência da Implementação , Humanos , Cidades , Canadá , Vitória
9.
Front Vet Sci ; 11: 1359016, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566749

RESUMO

Introduction: Modic changes (MC) are signs of vertebral pathology visible on magnetic resonance (MR) images that have been associated with low back pain (LBP) and disc degeneration in people. Multiple breeds of dogs also develop MCs and coincident back pain. However, the association between breed, MC, and spinal pathologies has yet to be fully elucidated. This study aimed to identify the prevalence of MC that occur spontaneously in the lumbar vertebral column of dogs diagnosed with intervertebral disc disease (IVDD) and examine their association with demographic criteria and the disc width index (DWI). Methods: Medical records and lumbar vertebral column MR images were examined from 104 dogs (831 intervertebral disc spaces and adjacent vertebrae), which were divided into three groups: chondrodystrophic dogs (CD; n =54) and non-chondrodystrophic dogs (NCD; n =30) with IVDD as the primary diagnosis, and control dogs (n =20) with other spinal diseases as their primary diagnosis. Results: Increasing age and a diagnosis of IVDD were significantly associated with MC in dogs (p < 0.001 and p = 0.0062, respectively). In CD dogs with IVDD, Type 2 MC were most prevalent, whereas, in NCD dogs, Type 3 MC were the most prevalent type. Type 2 MC were distributed nearly equally across the lumbar vertebral column, while Type 3 MC were primarily detected at the level of L7-S1. Discussion: This study demonstrated that MC developed spontaneously in dogs, are common in dogs diagnosed with IVDD, and the type observed varies by breed. Further research is needed to understand the pathogenesis of MC; however, the increased presence of Type 2 MC in CD dogs, similar to what is found in people with disc degeneration, suggests that CD dogs could serve as models for MC in people.

10.
Cureus ; 16(2): e54837, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38533166

RESUMO

The celiacomesenteric trunk (CMT), an exceedingly rare anatomic variant uniting the celiac artery and superior mesenteric artery (SMA), holds significant clinical and surgical implications. Despite its rarity, understanding these implications is crucial for effective management. This report outlines the case of a 99-year-old female presenting with septic shock and abdominal pain, with imaging revealing an incidental CMT. This paper aims to elucidate the surgical implications associated with CMT through a comprehensive case review and literature search. A 99-year-old female with multiple cardiovascular comorbidities presented with altered mental status and right lower quadrant abdominal pain. Upon arrival, the patient exhibited disorientation, an inability to follow commands, hypoxia, and hypotension. Significant laboratory findings included a white count of 20.6 x 109/L, lactate of 6.1 mmol/L, glucose of 53 mg/dL, alanine transaminase (ALT)/aspartate aminotransferase (AST) of 186/336 U/L, and creatinine of 4.2 mg/dL. Immediate interventions involved high-flow oxygen, fluid resuscitation, intravenous antibiotics, and admission to the ICU for septic shock. A CT angiogram (CTA) revealed an incidental large common trunk comprising the celiac trunk and superior mesenteric artery (SMA). There was a high-grade stenosis at the origin of the SMA. However, all the vessels were widely patent distally, and acute mesenteric occlusion was ruled out. By day 12, the patient achieved clinical stability after conservative management and was discharged. Complications such as aneurysm, dissection, stenosis, thrombosis, or acute occlusion of a CMT may necessitate complex surgical interventions, including endovascular procedures or open hepatic surgery. Understanding these technical complexities is vital for avoiding surgical complications in critically ill patients.

11.
Addict Sci Clin Pract ; 19(1): 18, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500166

RESUMO

BACKGROUND: Pharmacists remain an underutilized resource in the treatment of opioid use disorder (OUD). Although studies have engaged pharmacists in dispensing medications for OUD (MOUD), few studies have evaluated collaborative care models in which pharmacists are an active, integrated part of a primary care team offering OUD care. METHODS: This study seeks to implement a pharmacist integrated MOUD clinical model (called PrIMO) and evaluate its feasibility, acceptability, and impact across four diverse primary care sites. The Consolidated Framework for Implementation Research is used as an organizing framework for study development and interpretation of findings. Implementation Facilitation is used to support PrIMO adoption. We assess the primary outcome, the feasibility of implementing PrIMO, using the Stages of Implementation Completion (SIC). We evaluate the acceptability and impact of the PrIMO model at the sites using mixed-methods and combine survey and interview data from providers, pharmacists, pharmacy technicians, administrators, and patients receiving MOUD at the primary care sites with patient electronic health record data. We hypothesize that it is feasible to launch delivery of the PrIMO model (reach SIC Stage 6), and that it is acceptable, will positively impact patient outcomes 1 year post model launch (e.g., increased MOUD treatment retention, medication regimen adherence, service utilization for co-morbid conditions, and decreased substance use), and will increase each site's capacity to care for patients with MOUD (e.g., increased number of patients, number of prescribers, and rate of patients per prescriber). DISCUSSION: This study will provide data on a pharmacist-integrated collaborative model of care for the treatment of OUD that may be feasible, acceptable to both site staff and patients and may favorably impact patients' access to MOUD and treatment outcomes. TRIAL REGISTRATION: The study was registered on Clinicaltrials.gov (NCT05310786) on April 5, 2022, https://www. CLINICALTRIALS: gov/study/NCT05310786?id=NCT05310786&rank=1.


Assuntos
Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Adesão à Medicação , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Farmacêuticos , Atenção Primária à Saúde , Projetos de Pesquisa
12.
Parasit Vectors ; 17(1): 159, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549097

RESUMO

BACKGROUND: The WHO cone bioassay is routinely used to evaluate the bioefficacy of insecticide-treated nets (ITNs) for product pre-qualification and confirmation of continued ITN performance during operational monitoring. Despite its standardized nature, variability is often observed between tests. We investigated the influence of temperature in the testing environment, mosquito feeding status and mosquito density on cone bioassay results. METHODS: Cone bioassays were conducted on MAGNet (alphacypermethrin) and Veeralin (alphacypermethrin and piperonyl butoxide (PBO)) ITNs, using laboratory-reared pyrethroid-resistant Anopheles funestus sensu stricto (FUMOZ strain) mosquitoes. Three experiments were conducted using standard cone bioassays following WHO-recommended test parameters, with one variable changed in each bioassay: (i) environmental temperature during exposure: 22-23 °C, 26-27 °C, 29-30 °C and 32-33 °C; (ii) feeding regimen before exposure: sugar starved for 6 h, blood-fed or sugar-fed; and (iii) mosquito density per cone: 5, 10, 15 and 20 mosquitoes. For each test, 15 net samples per treatment arm were tested with four cones per sample (N = 60). Mortality after 24, 48 and 72 h post-exposure to ITNs was recorded. RESULTS: There was a notable influence of temperature, feeding status and mosquito density on An. funestus mortality for both types of ITNs. Mortality at 24 h post-exposure was significantly higher at 32-33 °C than at 26-27 °C for both the MAGNet [19.33% vs 7%; odds ratio (OR): 3.96, 95% confidence interval (CI): 1.99-7.87, P < 0.001] and Veeralin (91% vs 47.33%; OR: 22.20, 95% CI: 11.45-43.05, P < 0.001) ITNs. Mosquito feeding status influenced the observed mortality. Relative to sugar-fed mosquitoes, The MAGNet ITNs induced higher mortality among blood-fed mosquitoes (7% vs 3%; OR: 2.23, 95% CI: 0.94-5.27, P = 0.068) and significantly higher mortality among starved mosquitoes (8% vs 3%, OR: 2.88, 95% CI: 1.25-6.63, P = 0.013); in comparison, the Veeralin ITNs showed significantly lower mortality among blood-fed mosquitoes (43% vs 57%; OR: 0.56, 95% CI: 0.38-0.81, P = 0.002) and no difference for starved mosquitoes (58% vs 57%; OR: 1.05, 95% CI: 0.72-1.51, P = 0.816). Mortality significantly increased with increasing mosquito density for both the MAGNet (e.g. 5 vs 10 mosquitoes: 7% vs 12%; OR: 1.81, 95% CI: 1.03-3.20, P = 0.040) and Veeralin (e.g. 5 vs 10 mosquitoes: 58% vs 71%; OR 2.06, 95% CI: 1.24-3.42, P = 0.005) ITNs. CONCLUSIONS: The results of this study highlight that the testing parameters temperature, feeding status and mosquito density significantly influence the mortality measured in cone bioassays. Careful adherence to testing parameters outlined in WHO ITN testing guidelines will likely improve the repeatability of studies within and between product testing facilities.


Assuntos
Anopheles , Mosquiteiros Tratados com Inseticida , Inseticidas , Piretrinas , Animais , Inseticidas/farmacologia , Temperatura , Controle de Mosquitos/métodos , Piretrinas/farmacologia , Bioensaio/métodos , Açúcares , Resistência a Inseticidas
13.
Parasit Vectors ; 17(1): 103, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431631

RESUMO

BACKGROUND: Increasing metabolic resistance in malaria vector mosquitoes resulted in the development of insecticide-treated nets (ITNs) with active ingredients (AI) that target them. Bioassays that accurately measure the mortality induced by these AIs on ITNs are needed. Mosquito metabolic enzyme expression follows a circadian rhythm. Thus, this study assessed (i) influence of the time of day of mosquito exposure and (ii) timing of assessment of mortality post exposure (24 and 72 h) to ITNs against vectors that are susceptible to pyrethroids and those with metabolic and knockdown resistance mechanisms. METHODS: Two cone bioassay experiments were conducted following World Health Organization (WHO) guidelines. Firstly, on ITNs incorporated with 2 g AI/kg of deltamethrin (DM) alone, or combined with 8 g AI/kg piperonyl butoxide (PBO) synergist, during the day (9:00-14:00 h) and repeated in the evening (18:00-20:00 h). This was followed by a confirmatory experiment during the afternoon (12:00-14:00 h) and repeated in the night (22:00-24:00 h) using mosquitoes unexposed or pre-exposed to PBO for 1 h before exposure to DM ITNs. Each net piece was tested with a minimum of eight cones per time (N = 24). The outcome was mortality after 24 h (M24) or 72 h (M72) of holding. RESULTS: The cone bioassays performed using metabolic resistant mosquitoes during the evening showed significantly lower M24 than those performed in the day for DM: odds ratio (OR) 0.14 [95% confidence interval (CI) 0.06-0.30, p < 0.0001] and DM PBO [OR 0.29 (95% CI 0.18-0.49, p < 0.0001). M72 was higher than M24 for metabolic resistant mosquitoes exposed to DM [OR 1.44 (95% CI 1.09-1.88), p = 0.009] and DM PBO [OR 1.82 (95% CI 1.42-2.34), p < 0.0001]. An influence of hour of experiment and time of assessment was not observed for mosquitoes that had knockdown resistance or that were pyrethroid-susceptible. CONCLUSIONS: Time of day of experiment and hour of assessment of delayed mortality after exposure of mosquitoes are important considerations in evaluating insecticides that interact with mosquito metabolism to counter metabolic resistant mosquitoes. This is important when evaluating field-aged ITNs that may have lower concentrations of AI.


Assuntos
Anopheles , Mosquiteiros Tratados com Inseticida , Inseticidas , Malária , Piretrinas , Animais , Inseticidas/farmacologia , Controle de Mosquitos/métodos , Mosquitos Vetores , Piretrinas/farmacologia , Butóxido de Piperonila/farmacologia , Resistência a Inseticidas
14.
Front Vet Sci ; 11: 1359546, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444781

RESUMO

Introduction: Veterinary biobanks store samples for future use and distribute samples to academic researchers and industry entities; however, informed consent provided by owners for pets contributing to biobanks can be complicated by limited understanding of goals, purpose, and logistics of biobanking. Methods: This survey-based study aimed to gather feedback from pet owners on how they viewed allowing their pet to contribute to a veterinary biobank, with the goal of identifying opportunities to improve education, awareness of veterinary biobanking initiatives, and the consent processes. An electronic survey was distributed to a listserv of 2,119 pet owners and responses were received from 118 respondents (5.6%). Results: Most respondents (67%) were not familiar with the concept of veterinary biobanking prior to having responded to the survey. Most (89%) were willing to allow their healthy pet to contribute samples to a veterinary biobanking program. Ninety-five percent would allow their sick pet to contribute. Most were neutral about financial incentives as a motivator to participate, although 40% indicated that if their pet's condition resulted in a decision to humanely euthanize, they would be more likely to contribute to the biobank if the veterinary biobanking program covered the cost of euthanasia. Common concerns included security/confidentiality (36%), that results would not be shared with them (33%) or that samples would be used for other purposes beyond those advertised (22%). Discussion: These results suggest veterinary biobanking initiatives are well received by owners and most are willing to allow their pets to participate. Respondent concerns represent opportunities for veterinary biobanks to improve messaging and dissemination of results from work they support.

15.
J Surg Res ; 296: 281-290, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38301297

RESUMO

INTRODUCTION: Transportation databases have limited data regarding injury severity of pedestrian versus automobile patients. To identify opportunities to reduce injury severity, transportation and trauma databases were integrated to examine the differences in pedestrian injury severity at street crossings that were signalized crossings (SCs) versus nonsignalized crossings (NSCs). It was hypothesized that trauma database integration would enhance safety analysis and pedestrians struck at NSC would have greater injury severity. METHODS: Single-center retrospective review of all pedestrian versus automobile patients treated at a level 1 trauma center from 2014 to 2018 was performed. Patients were matched to the transportation database by name, gender, and crash date. Google Earth Pro satellite imagery was used to identify SC versus NSC. Injury severity of pedestrians struck at SC was compared to NSC. RESULTS: A total of 512 patients were matched (median age = 41 y [Q1 = 26, Q3 = 55], 74% male). Pedestrians struck at SC (n = 206) had a lower injury severity score (ISS) (median = 9 [4, 14] versus 17 [9, 26], P < 0.001), hospital length of stay (median = 3 [0, 7] versus 6 [1, 15] days, P < 0.001), and mortality (21 [10%] versus 52 [17%], P = 0.04), as compared to those struck at NSC (n = 306). The transportation database had a sensitivity of 63.4% (55.8%-70.4%) and specificity of 63.4% (57.7%-68.9%) for classifying severe injuries (ISS >15). CONCLUSIONS: Pedestrians struck at SC were correlated with a lower ISS and mortality compared to those at NSC. Linkage with the trauma database could increase the transportation database's accuracy of injury severity assessment for nonfatal injuries. Database integration can be used for evidence-based action plans to reduce pedestrian morbidity, such as increasing the number of SC.


Assuntos
Pedestres , Ferimentos e Lesões , Humanos , Masculino , Adulto , Feminino , Acidentes de Trânsito/prevenção & controle , Meios de Transporte , Centros de Traumatologia , Bases de Dados Factuais , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/epidemiologia
16.
Cureus ; 16(1): e52954, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38406046

RESUMO

Sweet's syndrome (SS), or acute febrile neutrophilic dermatosis, characteristically presents with fever, dermal neutrophilic infiltrates, and neutrophilia. It typically manifests as tender erythematous plaques; however, various variants are documented, including bullous. Malignancy-associated Sweet's syndrome (MASS) can present as a paraneoplastic syndrome in those with established cancers or with undiagnosed malignancies. We present a 72-year-old male with a three-day history of a progressive bullous, erythematous papular rash starting on his right forearm and spreading to his extremities, trunk, palms, and soles. It was mildly pruritic but nontender. He had no recent febrile illnesses. On examination, the rash was violaceous with tense bullae overlying edematous targetoid papules coalescing into plaques. Histopathologic analysis of punch biopsies from his abdomen and thigh demonstrated dense inflammatory infiltrates of neutrophils, eosinophils, histiocytes, and lymphocytes, suggestive of neutrophilic dermatosis, or Sweet's syndrome. He was treated with prednisone 1 mg/kg with improvement in his cutaneous symptoms, and a malignancy workup was initiated. Blood work showed elevated free kappa, lambda light chains, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. A positron emission tomography (PET) scan revealed lesions in the esophagus and kidney. He was referred to Heme/Onc, GI, and Urology. He was diagnosed with esophageal adenocarcinoma stage IIb and a renal mass. He has since completed neoadjuvant chemotherapy and radiation, is s/p robotic Ivor-Lewis esophagectomy with no evidence of residual carcinoma on pathology, and is undergoing surveillance with imaging every three months for his renal mass. This case highlights the importance of rapid identification of MASS and the impact dermatologists can make in getting these patients the potentially lifesaving care they need.

17.
Cureus ; 16(1): e52859, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38406142

RESUMO

Mesothelioma is a rare and aggressive malignancy typically associated with asbestos exposure. We present the clinical and diagnostic journey of a 63-year-old male carpenter, who presented with concerning symptoms of shortness of breath and total right lung "white-out" on imaging. Comprehensive medical evaluation revealed the presence of malignant pleural mesothelioma. This study underscores the importance of considering mesothelioma as a potential diagnosis in individuals with occupational asbestos exposure and highlights patterns in diagnosing and managing this devastating disease. Early recognition and intervention are essential in improving outcomes for patients diagnosed with mesothelioma.

18.
Cell Rep Med ; 5(2): 101422, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38350450

RESUMO

The emergence of immune escape is a significant roadblock to developing effective chimeric antigen receptor (CAR) T cell therapies against hematological malignancies, including acute myeloid leukemia (AML). Here, we demonstrate feasibility of targeting two antigens simultaneously by combining a GRP78-specific peptide antigen recognition domain with a CD123-specific scFv to generate a peptide-scFv bispecific antigen recognition domain (78.123). To achieve this, we test linkers with varying length and flexibility and perform immunophenotypic and functional characterization. We demonstrate that bispecific CAR T cells successfully recognize and kill tumor cells that express GRP78, CD123, or both antigens and have improved antitumor activity compared to their monospecific counterparts when both antigens are expressed. Protein structure prediction suggests that linker length and compactness influence the functionality of the generated bispecific CARs. Thus, we present a bispecific CAR design strategy to prevent immune escape in AML that can be extended to other peptide-scFv combinations.


Assuntos
Leucemia Mieloide Aguda , Receptores de Antígenos Quiméricos , Humanos , Linfócitos T , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Chaperona BiP do Retículo Endoplasmático , Receptores de Antígenos Quiméricos/metabolismo , Leucemia Mieloide Aguda/patologia
20.
Trauma Surg Acute Care Open ; 9(Suppl 1): e001126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38196934

RESUMO

Objectives: Trauma-induced coagulopathy (TIC) occurs in a subset of severely injured trauma patients. Despite having achieved surgical hemostasis, these individuals can have persistent bleeding, clotting, or both in conjunction with deranged coagulation parameters and typically require transfusion support with plasma, platelets, and/or cryoprecipitate. Due to the multifactorial nature of TIC, targeted interventions usually do not have significant clinical benefits. Therapeutic plasma exchange (TPE) is a non-specific modality of removing and replacing a patient's plasma in a euvolemic manner that can temporarily normalize coagulation parameters and remove deleterious substances, and may be beneficial in such patients with TIC. Methods: In a prospective case series, TPE was performed in severely injured trauma patients diagnosed with TIC and transfusion requirement. These individuals all underwent a series of at least 3 TPE procedures performed once daily with plasma as the exclusive replacement fluid. Demographic, injury, laboratory, TPE, and outcome data were collected and analyzed. Results: In total, 7 patients received 23 TPE procedures. All patients had marked improvements in routine coagulation parameters, platelet counts, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activities, inflammatory markers including interleukin-6 concentrations, and organ system injuries after completion of their TPE treatments. All-cause mortality rates at 1 day, 7 days, and 30 days were 0%, 0%, and 43%, respectively, and all patients for whom TPE was initiated within 24 hours after injury survived to the 30-day timepoint. Surgical, critical care, and apheresis nursing personnel who were surveyed were universally positive about the utilization of TPE in this patient population. These procedures were tolerated well with the most common adverse event being laboratory-diagnosed hypocalcemia. Conclusion: TPE is feasible and tolerable in severely injured trauma patients with TIC. However, many questions remain regarding the application of TPE for these critically ill patients including identification of the optimal injured population, ideal time of treatment initiation, appropriate treatment intensity, and concurrent use of adjunctive treatments. Level of evidence: Level V.

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