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1.
bioRxiv ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38979270

RESUMO

TDP-43 proteinopathy, initially disclosed in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coexists with tauopathy in a variety of neurodegenerative disorders, termed multiple etiology dementias (MEDs), including Alzheimer's Disease (AD). While such co-pathology of TDP-43 is strongly associated with worsened neurodegeneration and steeper cognitive decline, the pathogenic mechanism underlying the exacerbated neuron loss remains elusive. The loss of TDP-43 splicing repression that occurs in presymptomatic ALS-FTD individuals suggests that such early loss could facilitate the pathological conversion of tau to accelerate neuron loss. Here, we report that the loss of TDP-43 repression of cryptic exons in forebrain neurons (CaMKII-CreER;Tardbp f/f mice) is necessary to exacerbate tauopathy-dependent brain atrophy by sensitizing vulnerable neurons to caspase 3-dependent cleavage of endogenous tau to promote tauopathy. Corroborating this finding within the human context, we demonstrate that loss of TDP-43 function in iPSC-derived cortical neurons promotes early cryptic exon inclusion and subsequent caspase 3-mediated endoproteolysis of tau. Using a genetic approach to seed tauopathy in CaMKII-CreER;Tardbp f/f mice by expressing a four-repeat microtubule binding domain of human tau, we show that the amount of tau seed positively correlates with levels of caspase 3-cleaved tau. Importantly, we found that the vulnerability of hippocampal neurons to TDP-43 depletion is dependent on the amount of caspase 3-cleaved tau: from most vulnerable neurons in the CA2/3, followed by those in the dentate gyrus, to the least in CA1. Taken together, our findings strongly support the view that TDP-43 loss-of-function exacerbates tauopathy-dependent brain atrophy by increasing the sensitivity of vulnerable neurons to caspase 3-mediated endoproteolysis of tau, resulting in a greater degree of neurodegeneration in human disorders with co-pathologies of tau and TDP-43. Our work thus discloses novel mechanistic insights and therapeutic targets for human tauopathies harboring co-pathology of TDP-43 and provides a new MED model for testing therapeutic strategies.

2.
Pathogens ; 13(6)2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38921806

RESUMO

Haemonchus contortus, a blood-feeding parasite in grazing sheep, causes economic losses. Drug resistance necessitates exploring plant-based anthelmintics like Artemisia cina (Asteraceae). The plant, particularly its ethyl acetate extract, shows anthelmintic activity against H. contortus. However, there is limited information on pharmacodynamic interactions in ethyl acetate compounds. The study aims to identify pharmacodynamic interactions in the ethyl acetate extract of A. cina with anthelmintic effects on H. contortus eggs and L3 larvae using binary mixtures. Bioactive compounds were isolated via chromatography and identified using spectroscopic techniques. Pharmacodynamic interactions were assessed through binary mixtures with a main compound. Four bioactive compounds were identified: 1-nonacosanol, hentriacontane, peruvin, and cinic acid. Binary mixtures, with peruvin as the main compound, were performed. Peruvin/1-nonacosanol-hentriacontane and peruvin/cinic acid mixtures demonstrated 1.42-fold and 4.87-fold increased lethal effects in H. contortus L3 infective larvae, respectively, at a 0.50LC25/0.50LC25 concentration. In this work, we determined the synergism between bioactive compounds isolated from the ethyl acetate extract of A. cina and identified unreported compounds for the specie.

3.
PLoS One ; 19(6): e0305155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865346

RESUMO

Haemonchus contortus is a blood-feeding gastrointestinal parasite that impacts grazing sheep, causing economic losses in animal production. Due to its anthelmintic resistance, alternative antiparasitic treatments like plant-based anthelmintics are necessary to explore. Artemisia cina (Asteraceae) is a plant whose n-hexane extract and ethyl acetate extract exhibit anthelmintic activity against H. contortus, the n-hexane more active. To discover additional bioactive metabolites, a chemical analysis was performed on ethyl acetate extract, which presented an LC90 of 3.30 mg/mL and allowed the isolation of 11-[(1R,5S,7R,8R,10S,)-1,8-dihydroxy-5,10-dimethyl-4-oxodecahydroazulen-7-yl] acrylic acid. This new sesquiterpene was identified through one and two-dimensional NMR. The compound was named cinic acid and displayed an LC50 of 0.13 (0.11-0.14) mg/mL and LC90 of 0.40 (0.37-0.44) mg/mL, which, compared with ethyl acetate extract larvicidal activity, was 256-fold more active at LC50 and 15.71-fold at LC90. In this study, a new sesquiterpene with larvicidal activity against H. contortus L3 infective larvae was isolated from the ethyl acetate extract of Artemisia cina.


Assuntos
Anti-Helmínticos , Artemisia , Haemonchus , Larva , Extratos Vegetais , Sesquiterpenos , Artemisia/química , Haemonchus/efeitos dos fármacos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/química , Larva/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Ovinos , Espectroscopia de Ressonância Magnética
4.
Rev Argent Microbiol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38871623

RESUMO

The aim of this study was to detect vector-borne pathogens (Anaplasmataceae family, Rickettsia genus, and Bartonella genus) in bats from Misiones (Argentina). Thirty-three specimens were captured over 8 days using mist nets. Twenty (60.6%) blood samples were positive (11/13 Artibeus lituratus, 4/10 Desmodus rotundus, 4/8 Carollia perspicillata, and 1/2 Myotis nigricans) by PCR for the gltA gene fragment of Bartonella. All samples were negative by PCR for the Anaplasmataceae family and Rickettsia genus. The phylogenetic analysis showed seven Bartonella genotypes. The three genotypes obtained from A. lituratus, 2 from C. perspicillata, and 1 from D. rotundus were related to Bartonella spp. from New World bats, while the sequence obtained from M. nigricans was related to Old World bats. We identified a considerable diversity of Bartonella genotypes in a small number of bats, thus further research is required to better understand the complex bat-pathogen interaction.

5.
Sci Rep ; 14(1): 11568, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773157

RESUMO

Artemisia cina (Ac) is a plant with anthelmintic compounds such as 3'-demethoxy-6-O-demethylisoguaiacin (D) and norisoguaiacin (N). Three major objectives were proposed: (1) To evaluate biochemical parameters in blood (2) to determine the tissue oxidative stress by biomarkers as TBARS and glutathione peroxidase activity, and (3) to evaluate anatomopathological changes in organs such as the brain, liver, kidney, and lung after oral administration of n-hexane extract of Ac and D and N. D and N were administrated following the OECD guides for acute oral toxicity evaluation (Guide 420). Fifty Wistar rats were distributed into ten groups as follows: Group 1 (G1): 4 mg/Kg; G2: 40 mg/Kg; G3: 240 mg/Kg; G4: 1600 mg/Kg of n-hexane extract of Ac. G5: 2 mg/Kg; G6: 20 mg/Kg; G7: 120 mg/Kg; G8: 800 mg/Kg of D and N, G9: water and G10: polyvinylpyrrolidone at 2000 mg/Kg. At 14 days, the rats were euthanized, and the blood, liver, brain, kidney, and lung were taken for biochemical analysis, anatomopathological changes, and TBARS and GSH evaluation. Glucose, cholesterol, and phosphorus were altered. Histopathological analysis showed multifocal neuronal degeneration in the brain (G2). The kidney and lungs had changes in G7. The GSH and TBARS increased in G6 and G7. The TBARS activity was higher in G1 and G2. In conclusion, extract and D and N of Ac did not have damage at therapeutic doses. D, N, and n-hexane extract of A. cina do not cause histopathological damage at pharmaceutical doses. Still, the brain, kidney, and liver are related to biochemical parameters at higher doses. However, compounds are proposed as antioxidant agents.


Assuntos
Biomarcadores , Estresse Oxidativo , Extratos Vegetais , Ratos Wistar , Animais , Estresse Oxidativo/efeitos dos fármacos , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Masculino , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Glutationa Peroxidase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
6.
Acta Parasitol ; 69(2): 1132-1140, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38568361

RESUMO

PURPOSE: We analysed the possible synergistic activity among active extracts from Artemisia cina and Tagetes lucida combinations on Haemonchus contortus, a nematode parasitising sheep. METHODS: The work was carried out in vitro on eggs and infective larvae (L3) of H. contortus. The results were analysed with SAS 9.1, applying the ANOVA and Tukey test, and the lethal concentration (LC) values LC50 and LC90 were determined with regression analysis, employing Proc Probit of SAS 9.1. Additionally, the lethal concentration (LC) was calculated with LC50 and LC90 to determine the synergistic effect. RESULTS: The results demonstrated a high efficacy of the two plants studied on both nematode eggs and L3 larvae as well as of their combinations. The highest egg hatching inhibition was obtained with a 50/50 combination, and the best larvae mortality was obtained with 25% A. cina and 75% T. lucida at 10 mg/mL. Additionally, this combination showed a synergistic effect. CONCLUSION: The two plant species studied here can be applied as natural anthelmintic alternatives due to their high bioactive effect and synergistic response.


Assuntos
Anti-Helmínticos , Artemisia , Sinergismo Farmacológico , Haemonchus , Larva , Extratos Vegetais , Tagetes , Animais , Haemonchus/efeitos dos fármacos , Artemisia/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Tagetes/química , Larva/efeitos dos fármacos , Anti-Helmínticos/farmacologia , Acetatos/farmacologia , Ovinos , Hemoncose/parasitologia , Hemoncose/veterinária , Hemoncose/tratamento farmacológico , Doenças dos Ovinos/parasitologia , Doenças dos Ovinos/tratamento farmacológico , Óvulo/efeitos dos fármacos , Hexanos
7.
Conserv Biol ; : e14261, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38571408

RESUMO

Amid a global infrastructure boom, there is increasing recognition of the ecological impacts of the extraction and consumption of construction minerals, mainly processed as concrete, including significant and expanding threats to global biodiversity. We investigated how high-level national and international biodiversity conservation policies address mining threats, with a special focus on construction minerals. We conducted a review and quantified the degree to which threats from mining these minerals are addressed in biodiversity goals and targets under the 2011-2020 and post-2020 biodiversity strategies, national biodiversity strategies and action plans, and the assessments of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. Mining appeared rarely in national targets but more frequently in national strategies. Yet, in most countries, it was superficially addressed. Coverage of aggregates mining was greater than coverage of limestone mining. We outline 8 key components, tailored for a wide range of actors, to effectively mainstream biodiversity conservation into the extractive, infrastructure, and construction sectors. Actions include improving reporting and monitoring systems, enhancing the evidence base around mining impacts on biodiversity, and modifying the behavior of financial agents and businesses. Implementing these measures could pave the way for a more sustainable approach to construction mineral use and safeguard biodiversity.


Amenazas de la minería a las políticas de alto nivel para la conservación de la biodiversidad Resumen Enmedio del auge global del desarrollo de infraestructura, hay un mayor reconocimiento de los impactos ecológicos de la extracción y consumo de materiales para construcción, procesados predominantemente como concreto. Estos materiales representan amenazas significativas y en expansión para la biodiversidad global. Investigamos cómo son abordadas las amenazas de la minería por las políticas nacionales e internacionales de alto nivel para la conservación de la biodiversidad, con enfoque especial en los minerales para construcción. Realizamos una revisión exhaustiva y cuantificamos el grado en el cual son abordadas las amenazas de la extracción de estos minerales en los objetivos y metas para la biodiversidad bajo estrategias 2011­2020 y post 2020, las estrategias y planes de acción nacionales para la biodiversidad, y las evaluaciones de la Plataforma Intergubernamental Científico­normativa sobre Diversidad Biológica y Servicios de los Ecosistemas. La minería raramente apareció en los objetivos nacionales, pero fue más frecuente en las estrategias nacionales. Sin embargo, fue abordada superficialmente en la mayoría de los países. La cobertura de minería de agregados fue mayor que la cobertura de la minería de caliza. Describimos ocho componentes clave, adaptados para una amplia gama de actores, para incorporar eficazmente la conservación de la biodiversidad en los sectores extractivo, desarrollo de infraestructura y construcción. Las acciones incluyen la mejora de los sistemas de informes y monitoreo, el reforzamiento de la base de evidencias en torno a los impactos de la minería sobre la biodiversidad y la modificación del comportamiento de los agentes financieros y comerciales. La implementación de estas medidas podría allanar el camino para un enfoque más sostenible en el uso de minerales para la construcción y la salvaguarda de la biodiversidad.

8.
Science ; 384(6694): 458-465, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38662818

RESUMO

Based on an extensive model intercomparison, we assessed trends in biodiversity and ecosystem services from historical reconstructions and future scenarios of land-use and climate change. During the 20th century, biodiversity declined globally by 2 to 11%, as estimated by a range of indicators. Provisioning ecosystem services increased several fold, and regulating services decreased moderately. Going forward, policies toward sustainability have the potential to slow biodiversity loss resulting from land-use change and the demand for provisioning services while reducing or reversing declines in regulating services. However, negative impacts on biodiversity due to climate change appear poised to increase, particularly in the higher-emissions scenarios. Our assessment identifies remaining modeling uncertainties but also robustly shows that renewed policy efforts are needed to meet the goals of the Convention on Biological Diversity.


Assuntos
Biodiversidade , Mudança Climática , Extinção Biológica
9.
Exp Parasitol ; 261: 108768, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38679124

RESUMO

This study describes the anthelmintic efficacy of an organic fraction (EtOAc-F) from Guazuma ulmifolia leaves and the evaluation of its reactive oxidative stress on Haemonchus contortus. The first step was to assess the anthelmintic effect of EtOAc-F at 0.0, 3.5, 7.0 and 14 mg kg of body weight (BW) in gerbil's (Meriones unguiculatus) artificially infected with H. contortus infective larvae (L3). The second step was to evaluate the preliminary toxicity after oral administration of the EtOAc-F in gerbils. Finally, the third step was to determine the relative expression of biomarkers such as glutathione (GPx), catalase (CAT), and superoxide dismutase (SOD) against H. contortus L3 post-exposition to EtOAc-F. Additionally, the less-polar compounds of EtOAc-F were identified by gas mass spectrophotometry (GC-MS). The highest anthelmintic efficacy (97.34%) of the organic fraction was found in the gerbils treated with the 14 mg/kg of BW. Histopathological analysis did not reveal changes in tissues. The relative expression reflects overexpression of GPx (p<0.05, fold change: 14.35) and over expression of SOD (p≤0.05, fold change: 0.18) in H. contortus L3 exposed to 97.44 mg/mL of EtOAc-F compared with negative control. The GC-MS analysis revealed the presence of 4-hydroxybenzaldehyde (1), leucoanthocyanidin derivative (2), coniferyl alcohol (3), ferulic acid methyl ester acetate (4), 2,3,4-trimethoxycinnamic acid (5) and epiyangambin (6) as major compounds. According to these results, the EtOAc-F from G. ulmifolia leaves exhibit anthelmintic effect and increased the stress biomarkers on H. contortus.


Assuntos
Anti-Helmínticos , Catalase , Gerbillinae , Glutationa , Hemoncose , Haemonchus , Estresse Oxidativo , Extratos Vegetais , Folhas de Planta , Superóxido Dismutase , Animais , Haemonchus/efeitos dos fármacos , Folhas de Planta/química , Estresse Oxidativo/efeitos dos fármacos , Hemoncose/veterinária , Hemoncose/tratamento farmacológico , Hemoncose/parasitologia , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Catalase/análise , Glutationa/metabolismo , Glutationa/análise , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Contagem de Ovos de Parasitas/veterinária , Biomarcadores , Glutationa Peroxidase/metabolismo , Feminino
10.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338933

RESUMO

Glaucoma is the leading cause of irreversible blindness, and its pathophysiology includes neuroinflammatory changes. The present therapies for glaucoma target pressure-lowering mechanisms with limited success, making neuroinflammation a target for future interventions. This review summarizes the neuroinflammatory pathways seen in glaucoma and their interplay with stress. Glucocorticoids have been shown to activate proinflammatory glial cells, contributing to the neuroinflammation in glaucoma. Glucocorticoids have also been shown to increase the IOP directly. Stress-associated autonomic dysfunction can affect the vascular homeostasis in the retina and create oxidative stress. Diabetes, hyperglycemic-mediated endothelial damage, and vascular inflammation also play important roles in the neuroinflammation in glaucoma and diabetic retinopathy. Psychosocial stress has been implicated in an increased IOP and glaucoma outcomes. People who experience maladaptive chronic stress suffer from a condition known as allostatic load, which describes pathologic neuroendocrine dysregulation. The effects of allostatic load and chronic stress have been studied in patients affected by a lower socioeconomic status (SES) and marginalized racial identities. A lower SES is associated with higher rates of glaucoma and also affects the access to care and screening. Additionally, people of African ancestry are disproportionately affected by glaucoma for reasons that are multifactorial. In conclusion, this review explores neuroinflammation in glaucoma, highlighting opportunities for future investigation.


Assuntos
Alostase , Glaucoma , Humanos , Alostase/fisiologia , Doenças Neuroinflamatórias , Estresse Psicológico/complicações , Classe Social , Desigualdades de Saúde
11.
Sci Rep ; 14(1): 4559, 2024 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402243

RESUMO

Simulating future land use changes can be an important tool to support decision-making, especially in areas that are experiencing rapid anthropogenic pressure, such as the Cerrado-Brazilian savanna. Here we used a spatially-explicit model to identify the main drivers of native vegetation loss in the Cerrado and then extrapolate this loss for 2050 and 2070. We also analyzed the role of property size in complex Brazilian environmental laws in determining different outcomes of these projections. Our results show that distance to rivers, roads, and cities, agricultural potential, permanent and annual crop agriculture, and cattle led to observed/historical loss of vegetation, while protected areas prevented such loss. Assuming full adoption of the current Forest Code, the Cerrado may lose 26.5 million ha (± 11.8 95% C.I.) of native vegetation by 2050 and 30.6 million ha (± 12.8 95% C.I.) by 2070, and this loss shall occur mainly within large properties. In terms of reconciling conservation and agricultural production, we recommend that public policies focus primarily on large farms, such as protecting 30% of the area of properties larger than 2500 ha, which would avoid a loss of more than 4.1 million hectares of native vegetation, corresponding to 13% of the predicted loss by 2070.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Animais , Bovinos , Brasil , Florestas , Agricultura , Ecossistema
14.
Actual. psicol. (Impr.) ; 37(135): 29-43, jul.-dic. 2023. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1556777

RESUMO

Resumen. Objetivo. Analizar el efecto de las expectativas y metas de progreso académicas en las dimensiones de la calidad de vida de estudiantes universitarios mexicanos. Método. El tipo de investigación es cuantitativa con un diseño transversal, abierto, observacional con alcances descriptivos y predictivos. Las técnicas estadísticas utilizadas fueron estadística descriptiva, coeficiente de correlación y análisis de senderos con el método GLS. El muestreo fue no probabilístico por conveniencia, con un total de 465 participantes. Resultados. Se demostró que, para el modelo explicativo resultante, la variable metas de progreso académicas es un predictor directo de la dimensión función física. Asimismo, las expectativas académicas de resultado son un predictor de las dimensiones rol emocional y la función física. Respecto a los componentes de la salud física y mental, este último presentó la puntuación más baja.


Abstract. Objective. To analyze the effect of expectations and goals of academic progress on the dimensions of the quality of life of Mexican university students. Method. The research was quantitative with a cross-sectional, open, observational design with descriptive and predictive scopes. The statistical techniques used were descriptive statistics, correlation coefficient and path analysis with the GLS method. Sampling was non-probabilistic for convenience, with a total of 465 participants. Results. For the resulting explanatory model the variable academic progress goals is a direct predictor of the physical function dimension. And academic expectations of outcome are a predictor of the emotional role and physical function dimensions.

15.
Heliyon ; 9(9): e20340, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37809541

RESUMO

COVID-19 is known to have deleterious effects on different systems such as the respiratory, cardiovascular, central nervous, and gastrointestinal. However, conflicting data about the possible implications for male reproductive health and fertility have been reported. In addition, the long-term consequences of SARS-CoV-2 infection remain unclear. Herein, we report a case of a 42-year-old man with no known co-morbidities and normal baseline semen quality, who subsequently suffered an asymptomatic SARS-CoV-2 infection. Shortly after, the patient developed sudden oligoasthenozoospermia, even reaching azoospermia, which gradually evolved into persistent severe oligonecrozoospermia, accompanied by semen inflammation and oxidative stress. Remarkably, the latter occurred in the absence of urogenital infections, hormonal imbalances, tissue/organ obstruction/damage, medication or drug treatment, smoking, or exposure to toxins/pollutants, radiation, or high temperature. This case constitutes valuable clinical evidence that adds to the current knowledge in the field and highlights the need for further and longer follow-up studies to better understand the putative long-term consequences of SARS-CoV-2 infection on male fertility.

16.
J Clin Med ; 12(20)2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37892675

RESUMO

INTRODUCTION: The objective of this study is to assess the failure of therapies with HFNO (high-flow nasal oxygen), CPAP, Bilevel, or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. METHODS: This was a retrospective and observational study of SARS-CoV-2-positive patients who required non-invasive respiratory support (NIRS) at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. RESULTS: Of 7355 patients, 197 (11.8%) were included; 95 of them failed this therapy (48.3%). We found that during hospitalization in the ward, the combined therapy of HFNO and CPAP had an overall lower failure rate and the highest treatment with Bilevel (p = 0.005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP, and combined therapy of HFNO with CPAP, (35.6% of patients) presented with 24.2% failure, compared to those who had two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64.4% of patients), with 75.8% associated failure (OR: 0, 374; CI 95%: 0.203-0.688. p = 0.001). CONCLUSIONS: The use of NIRS during conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy of Bilevel increases the probability of failure, with the combined therapy strategy of CPAP and HFNO being the most promising option.

17.
Genes (Basel) ; 14(9)2023 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-37761949

RESUMO

BACKGROUND/AIMS: Primary open-angle glaucoma (POAG) disproportionately affects individuals of African ancestry. In these patients' eyes, a large cup-to-disc ratio (LCDR > 0.90) suggests greater retinal ganglion cell loss, though these patients often display varied visual ability. This study investigated the prevalence and risk factors associated with LCDR in African ancestry individuals with POAG and explored the differences between blind (>20/200) and not blind (≤20/200) LCDR eyes. METHODS: A case-control methodology was used to investigate the demographic, optic disc, and genetic risk factors of subjects in the Primary Open-Angle African American Glaucoma Genetics Study. Risk factors were analyzed using univariable and multivariable logistic regression models with inter-eye correlation adjusted using generalized estimating equations. RESULTS: Out of 5605 eyes with POAG, 1440 eyes (25.7%) had LCDR. In the multivariable analysis, LCDR was associated with previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.04), decreased mean deviation (OR = 1.08), increased pattern standard deviation (OR = 1.06), thinner retinal nerve fiber layer (OR = 1.05), nasalization of vessels (OR = 2.67), bayonetting of vessels (OR = 1.98), visible pores in the lamina cribrosa (OR = 1.68), and a bean-shaped cup (OR = 2.11). Of LCDR eyes, 30.1% were classified as blind (≤20/200). In the multivariable analysis, the statistically significant risk factors of blindness in LCDR eyes were previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.05), decreased mean deviation (OR = 1.04), and decreased pattern standard deviation (OR = 0.90). CONCLUSIONS: These findings underscore the importance of close monitoring of intraocular pressure and visual function in African ancestry POAG patients, particularly those with LCDR, to preserve visual function.


Assuntos
Glaucoma de Ângulo Aberto , Disco Óptico , Humanos , Negro ou Afro-Americano/genética , Cegueira/genética , Glaucoma de Ângulo Aberto/genética
18.
Pathogens ; 12(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37764929

RESUMO

Consumer awareness of animal welfare and environmental health has led to a plateau level of global consumption putting serious pressure on the livestock industry [...].

19.
Front Physiol ; 14: 1220048, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497433

RESUMO

Introduction: COVID-19 exerts deleterious effects on the respiratory, cardiovascular, gastrointestinal, and central nervous systems, causing more severe disease in men than in women. However, cumulative reported data about the putative consequences on the male reproductive tract and fertility are controversial. Furthermore, the long-term effects of SARS-CoV-2 infection are still uncertain. Methods: In this study, we prospectively evaluated levels of inflammatory cytokines and leukocytes in semen and sperm quality parameters in a cohort of 231 reproductive-aged male patients, unvaccinated, who had recovered from mild or severe COVID-19 and in 62 healthy control individuals. Sperm quality was assessed early (less than 3 months) and long (more than 3 and up to 6 months) after having COVID-19. Interestingly, and unlike most reported studies, available extensive background and baseline data on patients' sperm quality allowed performing a more accurate analysis of COVID-19 effects on sperm quality. Results: Significantly higher levels of IL-1ß, TNF and IFNγ were detected in semen from patients recently recovered from mild and/or severe COVID-19 with respect to control individuals indicating semen inflammation. Moreover, patients recovered from mild and/or severe COVID-19 showed significantly reduced semen volume, lower total sperm counts, and impaired sperm motility and viability. Interestingly, all observed alterations returned to baseline values after 3 or more months after disease recovery. Discussion: These results indicate that COVID-19 associates with semen inflammation and impaired semen quality early after disease. However, long COVID-19 seems not to include long-term detrimental consequences on male fertility potential since the observed alterations were reversible after 1-2 spermatogenesis cycles. These data constitute compelling evidence allowing a better understanding of COVID-19 associated sequelae, fundamental for semen collection in assisted reproduction.

20.
BMJ Open Ophthalmol ; 8(1)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-37278425

RESUMO

BACKGROUND/AIMS: To investigate the rates of structural and functional progression of primary open-angle glaucoma in an African ancestry cohort and identify risk factors for progression. METHODS: This retrospective study included 1424 eyes from glaucoma cases in the Primary Open-Angle African American Glaucoma Genetics cohort, with ≥2 visits for retinal nerve fibre layer (RNFL) thickness and mean deviation (MD) measurements over ≥6-month follow-up. The rates of structural progression (change in RNFL thickness/year) and functional progression (change in MD/year) were calculated from linear mixed effects models, accounting for intereye correlation and longitudinal correlation. Eyes were categorised as slow, moderate or fast progressors. Risk factors for progression rates were assessed using univariable and multivariable regression models. RESULTS: The median (interquartile) rates of progression were -1.60 (-2.05 to -1.15) µm/year for RNFL thickness and -0.40 (-0.44 to -0.34) decibels/year for MD. Eyes were categorised as slow (structural: 19%, functional: 88%), moderate (structural: 54%, functional: 11%) and fast (structural: 27%, functional: 1%) progressors. In multivariable analysis, faster RNFL progression was independently associated with thicker baseline RNFL (p<0.0001), lower baseline MD (p=0.003) and beta peripapillary atrophy (p=0.03). Faster MD progression was independently associated with higher baseline MD (p<0.0001), larger cup-to-disc ratios (p=0.02) and lower body mass index (p=0.0004). CONCLUSION: The median rates of structural and functional progression in this African ancestry cohort were faster than the rates reported from previously published studies in other ethnic groups. Higher baseline RNFL thickness and MD values were associated with faster progression rates. Results highlight the importance of monitoring structural and functional glaucoma progression to provide timely treatment in early disease.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Disco Óptico , Humanos , Disco Óptico/diagnóstico por imagem , Glaucoma de Ângulo Aberto/genética , Estudos Retrospectivos , Pressão Intraocular , Testes de Campo Visual , Campos Visuais , Fibras Nervosas , Células Ganglionares da Retina , Fatores de Risco
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