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1.
Invest Ophthalmol Vis Sci ; 65(5): 41, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38809543

RESUMO

Purpose: The rat controlled elevation of intraocular pressure (CEI) model allows study of in vivo responses to short-term exposure to defined intraocular pressures (IOP). In this study, we used NanoString technology to investigate in vivo IOP-related gene responses in the trabecular meshwork (TM) and optic nerve head (ONH) simultaneously from the same animals. Methods: Male and female rats (N = 35) were subjected to CEI for 8 hours at pressures simulating mean, daytime normotensive rat IOP (CEI-20), or 2.5× IOP (CEI-50). Naïve animals that received no anesthesia or surgical interventions served as controls. Immediately after CEI, TM and ONH tissues were dissected, RNA was isolated, and samples were analyzed with a NanoString panel containing 770 genes. Postprocessing, raw count data were uploaded to ROSALIND for differential gene expression analyses. Results: For the TM, 45 IOP-related genes were significant in the CEI-50 versus CEI-20 and CEI-50 versus naïve comparisons, with 15 genes common to both comparisons. Bioinformatics analysis identified Notch and transforming growth factor beta (TGFß) pathways to be the most up- and downregulated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. For ONH, 22 significantly differentially regulated genes were identified in the CEI-50 versus naïve comparison. Pathway analysis identified defense response and immune response as two significantly upregulated biological process pathways. Conclusions: This study demonstrated the ability to assay short-term IOP-responsive genes in both TM and ONH tissues simultaneously. In the TM, downregulation of TGFß pathway genes suggests that TM responses may reduce TGFß-induced extracellular matrix synthesis. For ONH, the initial response to short-term elevated IOP may be protective.


Assuntos
Modelos Animais de Doenças , Pressão Intraocular , Hipertensão Ocular , Disco Óptico , Malha Trabecular , Animais , Malha Trabecular/metabolismo , Pressão Intraocular/fisiologia , Ratos , Masculino , Feminino , Disco Óptico/metabolismo , Hipertensão Ocular/genética , Hipertensão Ocular/fisiopatologia , Regulação da Expressão Gênica/fisiologia , Perfilação da Expressão Gênica , Ratos Sprague-Dawley
2.
Fish Shellfish Immunol ; 149: 109613, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710341

RESUMO

Aporocotylids (Trematoda: Digenea), also known as fish blood flukes infect the circulatory system of fish leading to serious health problems and mortality. Aporocotylids are a particular concern for farmed fish as infection intensity can increase within the farming environment and lead to mortalities. In the context of managing these infections, one of the most crucial aspects to consider is the host response of the infected fish against these blood flukes. Understanding the response is essential to improving current treatment strategies that are largely based on the use of anthelmintic praziquantel to manage infections in aquaculture. This review focuses on the current knowledge of farmed fish host responses against the different life stages of aporocotylids. New treatment strategies that are able to provide protection against reinfections should be a long-term goal and is not possible without understanding the fish response to infection and the interactions between host and parasite.


Assuntos
Aquicultura , Doenças dos Peixes , Peixes , Trematódeos , Infecções por Trematódeos , Animais , Infecções por Trematódeos/veterinária , Infecções por Trematódeos/imunologia , Infecções por Trematódeos/parasitologia , Infecções por Trematódeos/tratamento farmacológico , Doenças dos Peixes/imunologia , Doenças dos Peixes/parasitologia , Trematódeos/fisiologia , Peixes/imunologia , Peixes/parasitologia , Interações Hospedeiro-Parasita , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/farmacologia
3.
medRxiv ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38746281

RESUMO

Background: Dengue cases can progress to severe ant life-threating forms particularly in subsequent heterologous infections. However, recent studies had explored additional risk factors, including underlying health conditions, even in individuals without prior exposure to dengue, notably, in patients with endothelial dysfunction and chronic inflammation. This study examines the link between diabetes and the development of severe dengue disease in dengue-naive patients during the 2019 dengue outbreak in São Jose do Rio Preto, Brazil. Methodology: We enrolled 529 laboratory-confirmed dengue cases, identified through DENV RT-PCR or NS1 antigen assays in a hospital cohort of acute febrile illness. Subsequently, we investigated the presence of anti-dengue and anti-Zika IgG antibodies. Samples testing positive for Zika were excluded from the analyses. Two groups were analyzed: naïve (DV-), and dengue history (DV+). Results: Initially, presence of diabetes and kidney disease, as well as being dengue-naive, were associated with a higher frequency of severe and potentially severe clinical outcomes. Multivariate analysis identified diabetes as a risk factor, while the presence of anti-dengue antibodies was considered protective. Analysis of dengue naïve samples, highlighted diabetes as an independent risk factor to severe forms of dengue disease. In DV+ patients, no condition was highlighted as a risk factor by univariate analysis or multivariate analysis. Conclusions: We investigated and confirmed diabetes as a risk factor for severe dengue disease in individuals without prior dengue or Zika exposure. Our conclusions raise significant concerns given diabetes' ever increasing global prevalence and its potential impact on patients with or previous dengue exposure.

4.
Toxicol Sci ; 200(1): 95-113, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38603619

RESUMO

Organophosphate esters (OPEs), used as flame retardants and plasticizers, are present ubiquitously in the environment. Previous studies suggest that exposure to OPEs is detrimental to female fertility in humans. However, no experimental information is available on the effects of OPE mixtures on ovarian granulosa cells, which play essential roles in female reproduction. We used high-content imaging to investigate the effects of environmentally relevant OPE mixtures on KGN human granulosa cell phenotypes. Perturbations to steroidogenesis were assessed using ELISA and qRT-PCR. A high-throughput transcriptomic approach, TempO-Seq, was used to identify transcriptional changes in a targeted panel of genes. Effects on lipid homeostasis were explored using a cholesterol assay and global lipidomic profiling. OPE mixtures altered multiple phenotypic features of KGN cells, with triaryl OPEs in the mixture showing higher potencies than other mixture components. The mixtures increased basal production of steroid hormones; this was mediated by significant changes in the expression of critical transcripts involved in steroidogenesis. Further, the total-OPE mixture disrupted cholesterol homeostasis and the composition of intracellular lipid droplets. Exposure to complex mixtures of OPEs, similar to those found in house dust, may adversely affect female reproductive health by altering a multitude of phenotypic and functional endpoints in granulosa cells. This study provides novel insights into the mechanisms of actions underlying the toxicity induced by OPEs and highlights the need to examine the effects of human relevant chemical mixtures.


Assuntos
Poeira , Ésteres , Retardadores de Chama , Células da Granulosa , Lipidômica , Organofosfatos , Fenótipo , Transcriptoma , Humanos , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Transcriptoma/efeitos dos fármacos , Organofosfatos/toxicidade , Ésteres/toxicidade , Retardadores de Chama/toxicidade , Linhagem Celular , Metabolismo dos Lipídeos/efeitos dos fármacos , Plastificantes/toxicidade , Colesterol/metabolismo
5.
J Voice ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38688779

RESUMO

OBJECTIVES: Despite evidence for the validity of using client-led outcome measures in gender-affirming voice training (GAVT), the existing body of research on voice feminization relies heavily on acoustic-perceptual measures without additional qualitative exploration of client experience. Additionally, the authors are not aware of any existing studies prompting client input on the voice feminization methods they find most helpful in achieving their voice goals. The current study focuses on crucial client perceptions of GAVT for voice feminization and identifies the methods clients find most helpful. METHODS: Using a mixed-methods approach, we gathered numeric and qualitative survey data from 21 individuals who engaged in GAVT supporting voice feminization. We conducted follow-up interviews with five survey participants to gather additional qualitative data on client experiences and perceptions of GAVT. RESULTS: Quantitative and qualitative data reveal that clients are satisfied with GAVT supporting voice feminization, perceive their clinicians as being culturally inclusive, and identify oral/forward resonance work as one of the most helpful voice training methods. Interestingly, however, frequency of work on oral/forward resonance during training did not predict voice satisfaction post-training. CONCLUSIONS: Clients identified oral/forward resonance as one of the most helpful methods of voice feminization and found their GAVT experiences to be supportive of their voice goals. These findings emphasize the importance and value of client-led outcome measures when investigating effective approaches to GAVT.

6.
Environ Pollut ; 348: 123730, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38458524

RESUMO

A sensitive modified QuEChERS extraction method was developed to assess the levels of free and conjugated bisphenols (BPs) in human milk collected between 2018 and 2019 from two regions of South Africa (the Limpopo Province Vhembe district, n = 194; Pretoria, n = 193) and Canada (Montreal, n = 207). Total BPA (free and conjugated) and BPS were the predominant bisphenols detected in samples from Vhembe and Pretoria, whereas total BPS was the predominant bisphenol detected in Montreal samples. The levels of total BPA in samples from Vhembe and Pretoria ranged between < MDL-18.61 and

Assuntos
Monitoramento Biológico , Leite Humano , Fenóis , Humanos , África do Sul , Leite Humano/química , Compostos Benzidrílicos/análise , Canadá
7.
Toxicol Sci ; 199(2): 261-275, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38518089

RESUMO

Exposure to the organophosphate esters (OPEs), used as flame retardants and plasticizers, is associated with a variety of adverse health effects including an increase in the incidence of fatty liver diseases. The goal of this study was to investigate the effects of six OPEs, all detected in Canadian house dust, on the phenotype and function of HepG2 liver cells. We used high-content imaging to investigate the effects of these OPEs on cell survival, mitochondria, oxidative stress, lipid droplets, and lysosomes. Effects on the autophagy/lipophagy pathway were evaluated using confocal microscopy. The triaryl OPEs (isopropylated triphenylphosphate [IPPP], tris(methylphenyl) phosphate [TMPP], and triphenyl phosphate [TPHP]) were more cytotoxic than non-triaryl OPEs (tris(2-butoxyethyl) phosphate [TBOEP], tris(1-chloro-2-propyl) phosphate [TCIPP], and tris(1,3-dichloro-2-propyl) phosphate [TDCIPP]). Exposure to most OPEs increased total mitochondria, reduced reactive oxygen species, and increased total lipid droplet areas and lysosomal intensity. Potency ranking was done using the lowest benchmark concentration/administered equivalent dose method and toxicological prioritization index analyses to integrate all phenotypic endpoints. IPPP, TBOEP, and TPHP ranked as the most potent OPEs, whereas TMPP, TCIPP, and TDCIPP were relatively less bioactive. Confocal microscopic analysis demonstrated that IPPP reduced the colocalization of lipid droplets (PLIN2), lysosomes (LAMP1), and autophagosomes (p62), disrupting autophagy. In contrast, TBOEP rescued cells from bafilomycin A1-induced inhibition of autophagy and/or increased autophagic flux. Together, these data demonstrate that OPEs have adverse effects on HepG2 cells. Further, OPE-induced dysregulation of autophagy may contribute to the association between OPE exposure and adverse effects on liver lipid homeostasis.


Assuntos
Autofagia , Retardadores de Chama , Organofosfatos , Estresse Oxidativo , Plastificantes , Humanos , Retardadores de Chama/toxicidade , Plastificantes/toxicidade , Células Hep G2 , Organofosfatos/toxicidade , Autofagia/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenótipo , Sobrevivência Celular/efeitos dos fármacos , Gotículas Lipídicas/efeitos dos fármacos , Gotículas Lipídicas/metabolismo , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Ésteres/toxicidade
8.
J Med Chem ; 67(9): 7276-7282, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38465973

RESUMO

Glucagon-like peptide receptor (GLP-1R) agonists (e.g., semaglutide, liraglutide, etc.) are efficient treatment options for people with type 2 diabetes and obesity. The manufacturing method to produce semaglutide, a blockbuster GLP-1 drug on the market, involves multistep synthesis. The large peptide has a hydrophobic fatty acid side chain that makes it sparingly soluble, and its handling, purification, and large-scale production difficult. The growing demand for semaglutide that the manufacturer is not capable of addressing immediately triggered a worldwide shortage. Thus, we have developed a potential alternative analogue to semaglutide by replacing the hydrophobic fatty acid with a hydrophilic human complex-type biantennary oligosaccharide. Our novel glycoGLP-1 analogue was isolated in an ∼10-fold higher yield compared with semaglutide. Importantly, our glycoGLP-1 analogue possessed a similar GLP-1R activation potency to semaglutide and was biologically active in vivo in reducing glucose levels to a similar degree as semaglutide.


Assuntos
Peptídeo 1 Semelhante ao Glucagon , Glicosilação , Humanos , Animais , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Peptídeo 1 Semelhante ao Glucagon/química , Peptídeos Semelhantes ao Glucagon/farmacologia , Peptídeos Semelhantes ao Glucagon/química , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Masculino , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Engenharia de Proteínas , Camundongos
9.
Clin Neurophysiol ; 161: 17-26, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38432185

RESUMO

OBJECTIVE: Both blinking and walking are altered in Parkinson's disease and both motor outputs have been shown to be linked in healthy subjects. Additionally, studies suggest an involvement of basal ganglia activity and striatal dopamine in blink generation. We investigated the role of the basal ganglia circuitry on spontaneous blinking and if this role is dependent on movement state and striatal dopamine. METHODS: We analysed subthalamic nucleus (STN) activity in seven chronically implanted patients for deep brain stimulation (DBS) with respect to blinks and movement state (resting state and unperturbed walking). Neurophysiological recordings were combined with individual molecular brain imaging assessing the dopamine reuptake transporter (DAT) density for the left and right striatum separately. RESULTS: We found a significantly higher blink rate during walking compared to resting. The blink rate during walking positively correlated with the DAT density of the left caudate nucleus. During walking only, spontaneous blinking was followed by an increase in the right STN beta power and a bilateral subthalamic phase reset in the low frequencies. The right STN blink-related beta power modulation correlated negatively with the DAT density of the contralateral putamen. The left STN blink-related beta power correlated with the DAT density of the putamen in the less dopamine-depleted hemisphere. Both correlations were specific to the walking condition and to beta power following a blink. CONCLUSION: Our findings show that spontaneous blinking is related to striatal dopamine and has a frequency specific deployment in the STN. This correlation depends on the current movement state such as walking. SIGNIFICANCE: This work indicates that subcortical activity following a motor event as well as the relationship between dopamine and motor events can be dependent on the motor state. Accordingly, disease related changes in brain activity should be assessed during natural movement.


Assuntos
Ritmo beta , Piscadela , Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Caminhada , Humanos , Núcleo Subtalâmico/fisiopatologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Masculino , Pessoa de Meia-Idade , Caminhada/fisiologia , Feminino , Piscadela/fisiologia , Idoso , Ritmo beta/fisiologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo
10.
Endocrinology ; 165(4)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38376928

RESUMO

Organophosphate esters (OPEs) are used primarily as flame retardants and plasticizers. Previously, we reported that adrenal cells are important targets of individual OPEs. However, real-life exposures are to complex mixtures of these chemicals. To address this, we exposed H295R human adrenal cells to varying dilutions (1/1000K to 1/3K) of a Canadian household dust-based OPE mixture for 48 hours and evaluated effects on phenotypic, lipidomic, and functional parameters. Using a high-content screening approach, we assessed phenotypic markers at mixture concentrations at which there was greater than 70% cell survival; the most striking effect of the OPE mixture was a 2.5-fold increase in the total area of lipid droplets. We then determined the response of specific lipid species to OPE exposures with novel, nontargeted lipidomic analysis of isolated lipid droplets. These data revealed that house dust OPEs induced concentration-dependent alterations in the composition of lipid droplets, particularly affecting the triglyceride, diglyceride, phosphatidylcholine, and cholesterol ester subclasses. The steroid-producing function of adrenal cells in the presence or absence of a steroidogenic stimulus, forskolin, was determined. While the production of 17ß-estradiol remained unaffected, a slight decrease in testosterone production was observed after stimulation. Conversely, a 2-fold increase in both basal and stimulated cortisol and aldosterone production was observed. Thus, exposure to a house dust-based mixture of OPEs exerts endocrine-disrupting effects on adrenal cells, highlighting the importance of assessing the effects of environmentally relevant mixtures.


Assuntos
Retardadores de Chama , Lipidômica , Humanos , Canadá , Poeira/análise , Organofosfatos , Fenótipo , Monitoramento Ambiental
11.
bioRxiv ; 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38370622

RESUMO

Purpose: The rat Controlled Elevation of Intraocular pressure (CEI) model allows study of in vivo responses to defined intraocular pressures (IOP). In this study, we use Nanostring technology to investigate in vivo IOP-related gene responses in the trabecular meshwork (TM) and optic nerve head (ONH) simultaneously from the same animals. Methods: Male and female rats (N=35) were subject to CEI for 8-hours at pressures simulating mean, daytime normotensive rat IOP (CEI-20), or 2.5x IOP (CEI-50). Naïve animals, receiving no anesthesia or surgical interventions, served as controls. Immediately after CEI, TM and ONH tissues were dissected, RNA isolated, and samples were analyzed with a Nanostring panel containing 770 genes. Post-processing, raw count data were uploaded to Rosalind® for differential gene expression analyses. Results: For the TM, 45 IOP-related genes were significant in the "CEI-50 vs. CEI-20" and "CEI-50 vs. naïve" comparisons, with 15 genes common to both comparisons. Bioinformatics analysis identified Notch and TGFß pathways to be the most up- and down-regulated KEGG pathways, respectively. For ONH, 22 significantly regulated genes were identified in the "CEI-50 vs. naïve" comparison. Pathway analysis identified 'defense response' and 'immune response' as two significantly upregulated biological process pathways. Conclusions: This study demonstrates the ability to assay IOP-responsive genes in both TM and ONH tissues simultaneously. In the TM, downregulation of TGFß pathway genes suggest that TM responses may prevent TGFß-induced extracellular matrix synthesis. For ONH, the initial response to elevated IOP may be protective, with astrocytes playing a key role in these gene responses.

12.
Environ Pollut ; 344: 123415, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38246216

RESUMO

The use of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to analyse soft tissues is limited because of the lack of suitable certified reference materials resulting in difficulties with calibration. In this study, several laboratory-prepared thin agarose sections were tested as matrix-specific standards. Our results showed 1 mm thin agarose sections were suitable as calibration standards for LA-ICP-MS Zn analyses in fish muscle, especially when the signal intensity of 66Zn was normalised to 13C. The thin agarose standard sections were used for LA-ICP-MS Zn analyses in the muscle of melanised and non-melanised sand flathead collected from a polluted estuary and assigned with different melanisation scores. Zn levels in melanised regions of fish muscle were determined to be significantly higher than non-melanised regions across all melanisation scores, though Zn levels in the melanised regions of muscle were not significantly different between sand flathead with different melanisation scores. In non-melanised regions of muscle from fish with melanisation and fish unaffected by melanisation, Zn levels were around baseline levels. Overall, this study has successfully developed matrix-specific standards for LA-ICP-MS analysis of soft tissues, thus allowing broader application of this analytical technique in future environmental pollution studies.


Assuntos
Terapia a Laser , Perciformes , Animais , Zinco , Sefarose , Músculos
13.
Am J Physiol Endocrinol Metab ; 326(1): E61-E72, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37991451

RESUMO

Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood ß-OHB to ∼2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted.NEW & NOTEWORTHY Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days.


Assuntos
Diabetes Mellitus Tipo 2 , Cetonas , Humanos , Adulto , Cetonas/farmacologia , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Controle Glicêmico , Ácido 3-Hidroxibutírico , Ensaios Clínicos Controlados Aleatórios como Assunto , Suplementos Nutricionais
14.
Neuropsychologia ; 193: 108743, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38096980

RESUMO

Walking and minimized movement restriction has a positive effect on creativity, such as divergent thinking. Walking is further known to reduce occipital alpha activity. We used mobile EEG during free and restricted movement, while subjects (N = 23) solved a Guilford's alternate uses test, to understand if occipital alpha power is also affected by movement restriction and if it is a neural marker for creativity. We found that, independent of the task, relative occipital alpha power was higher during movement restriction and showed a negative relationship with creativity scores even though the task was purely based on auditory information. Alpha lateralization was only modulated during the task related think-time (mainly during sitting) and showed a positive relationship with creativity scores but no correlation with the relative alpha power. This indicates that the ongoing alpha power and alpha lateralization mark two independent processes. Overall, our work shows that movement and movement restriction leads to a general change in state which affects cognitive processes. Specifically, limiting one's movements e.g. due to sitting and fixating on a screen can introduce a state of increased occipital alpha power and lowered creativity.


Assuntos
Criatividade , Pensamento , Humanos , Ritmo alfa , Eletroencefalografia , Movimento
15.
Pathogens ; 12(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38133326

RESUMO

Aporocotylid blood flukes Cardicola forsteri and C. orientalis are an ongoing health concern for the Southern Bluefin Tuna (Thunnus maccoyii, SBT) industry, where infections can lead to morbidity and mortality in ranched SBT populations. This study compared blood fluke infection in SBT from two companies during the 2021 ranching season. Both companies administered the same dosage of praziquantel approximately 5 weeks after transfer, feeding with frozen baitfish daily; the only difference in the company's practices was that the pontoons were located 2.5 km apart. Infection severity was measured as prevalence and intensity by quantifying adult C. forsteri in SBT heart and copy numbers of C. forsteri and C. orientalis ITS-2 DNA in SBT heart and gills. Data from the 2018 and 2019 harvests of SBT were used to make comparisons with 2021 harvest data. Cardicola orientalis was detected at transfer and no longer detected after treatment with praziquantel. Cardicola spp. were present in 83% of sampled SBT in 2021. Both companies demonstrated similar patterns of infection, and Company A had higher prevalence and intensity of Cardicola spp. infection. Based on C. forsteri ITS-2 DNA, infection intensity at harvest was significantly greater for both companies in 2021 when compared to 2018 and 2019. Continued monitoring of Cardicola spp. in SBT and improvements in diagnostics contribute to our understanding of Cardicola spp. epizootiology and the detection of changes in treatment efficacy.

16.
Toxicol Sci ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37941476

RESUMO

Despite the growing number of studies reporting potential risks associated with exposure to organophosphate esters (OPEs), their molecular mechanisms of action remain poorly defined. We used the high-throughput TempO-Seq™ platform to investigate the effects of frequently detected OPEs on the expression of ∼3000 environmentally responsive genes in KGN human ovarian granulosa cells. Cells were exposed for 48 h to one of five OPEs (0.1 to 50 µM): tris(methylphenyl) phosphate (TMPP), isopropylated triphenyl phosphate (IPPP), tert-butylphenyl diphenyl phosphate (BPDP), triphenyl phosphate (TPHP), or tris(2-butoxyethyl) phosphate (TBOEP). The sequencing data indicate that four OPEs induced transcriptional changes, whereas TBOEP had no effect within the concentration range tested. Multiple pathway databases were used to predict alterations in biological processes based on differentially expressed genes. At lower concentrations, inhibition of the cholesterol biosynthetic pathway was the predominant effect of OPEs; this was likely a consequence of intracellular cholesterol accumulation. At higher concentrations, BPDP and TPHP had distinct effects, primarily affecting pathways involved in cell cycle progression and other stress responses. Benchmark concentration (BMC) modelling revealed that BPDP had the lowest transcriptomic point of departure. However, in vitro to in vivo extrapolation modeling indicated that TMPP was bioactive at lower concentrations than the other OPEs. We conclude that these new approach methodologies provide information on the mechanism(s) underlying the effects of data-poor compounds and assist in the derivation of protective points of departure for use in chemical read-across and decision-making.

17.
Front Mol Biosci ; 10: 1242879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37916189

RESUMO

Fish gills are not only the respiratory organ, but also essential for ion-regulation, acid-base control, detoxification, waste excretion and host defense. Multifactorial gill diseases are common in farmed Atlantic salmon, and still poorly understood. Understanding gill pathophysiology is of paramount importance, but the sacrifice of large numbers of experimental animals for this purpose should be avoided. Therefore, in vitro models, such as cell lines, are urgently required to replace fish trials. An Atlantic salmon gill epithelial cell line, ASG-10, was established at the Norwegian Veterinary institute in 2018. This cell line forms a monolayer expressing cytokeratin, e-cadherin and desmosomes, hallmarks of a functional epithelial barrier. To determine the value of ASG-10 for comparative studies of gill functions, the characterization of ASG-10 was taken one step further by performing functional assays and comparing the cell proteome and transcriptome with those of gills from juvenile freshwater Atlantic salmon. The ASG-10 cell line appear to be a homogenous cell line consisting of epithelial cells, which express tight junction proteins. We demonstrated that ASG-10 forms a barrier, both alone and in co-culture with the Atlantic salmon gill fibroblast cell line ASG-13. ASG-10 cells can phagocytose and express several ATP-binding cassette transport proteins. Additionally, ASG-10 expresses genes involved in biotransformation of xenobiotics and immune responses. Taken together, this study provides an overview of functions that can be studied using ASG-10, which will be an important contribution to in vitro gill epithelial research of Atlantic salmon.

18.
PLoS Negl Trop Dis ; 17(11): e0011710, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37943879

RESUMO

BACKGROUND: The co-circulation of flaviviruses in tropical regions has led to the hypothesis that immunity generated by a previous dengue infection could promote severe disease outcomes in subsequent infections by heterologous serotypes. This study investigated the influence of antibodies generated by previous Zika infection on the clinical outcomes of dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 1,043 laboratory confirmed dengue patients and investigated their prior infection to Zika or dengue. Severe forms of dengue disease were more frequent in patients with previous Zika infection, but not in those previously exposed to dengue. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that previous Zika infection may represent a risk factor for subsequent severe dengue disease, but we did not find evidence of antibody-dependent enhancement (higher viral titer or pro-inflammatory cytokine overexpression) contributing to exacerbation of the subsequent dengue infection.


Assuntos
Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Humanos , Anticorpos Antivirais , Reações Cruzadas
19.
J Interprof Care ; 37(sup1): S1-S3, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37655717
20.
Viruses ; 15(9)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37766255

RESUMO

Lower respiratory tract infections (LRIs) are a significant cause of disability-adjusted life-years (DALYs) across all age groups, especially in children under 9 years of age, and adults over 75. The main causative agents are viruses, such as influenza and respiratory syncytial virus (RSV). Viral LRIs in adults have historically received less attention. This study investigated the incidence of RSV and influenza in adult patients admitted to a referral hospital, as well as the clinical profile of these infections. Molecular testing was conducted on nasopharyngeal samples taken from a respiratory surveillance cohort comprising adult (15-59 years) and elderly (60+ years) hospitalized patients who tested negative for SARS-CoV-2, to determine the prevalence for influenza and RSV. Influenza was found to be less frequent among the elderly. The main symptoms of RSV infections were cough, fever, dyspnea, malaise, and respiratory distress, while headache, nasal congestion, a sore throat, and myalgia were most frequent in influenza. Elderly patients with RSV were not found to have more severe illness than adults under age 60, underscoring the importance of providing the same care to adults with this viral infection.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Idoso , Adulto , Humanos , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Doenças Negligenciadas , Influenza Humana/epidemiologia , SARS-CoV-2
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