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1.
J Chem Phys ; 161(13)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39351936

RESUMO

We present a comprehensive, combined experimental and theoretical study of the core-level photoelectron and near-edge x-ray absorption fine structure (NEXAFS) spectra of 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil at the oxygen 1s, nitrogen 1s, carbon 1s, and the sulfur 2s and 2p edges. X-ray photoelectron spectra were calculated using equation-of-motion coupled-cluster theory (EOM-CCSD), and NEXAFS spectra were calculated using algebraic diagrammatic construction and EOM-CCSD. For the main peaks at O and N 1s as well as the S 2s edge, we find a single photoline. The S 2p spectra show a spin-orbit splitting of 1.2 eV with an asymmetric vibrational line shape. We also resolve the correlation satellites of these photolines. For the carbon 1s photoelectrons, we observe a splitting on the eV scale, which we can unanimously attribute to specific sites. In the NEXAFS spectra, we see very isolated pre-edge features at the oxygen 1s edge; the nitrogen edge, however, is very complex, in contrast to the XPS findings. The C 1s edge NEXAFS spectrum shows site-specific splitting. The sulfur 2s and 2p spectra are dominated by two strong pre-edge transitions. The S 2p spectra show again the spin-orbit splitting of 1.2 eV.

2.
Rev Sci Instrum ; 95(10)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39373612

RESUMO

In this paper, the design and implementation of a temperature-controlled recirculating flat jet system for liquid crystals (LCs)-based experiments are presented. In these experiments, the target liquid is usually exposed to medium to high laser fluences, possibly resonant with specific excitation, thus resulting in a change of local temperature and sudden degradation. To overcome this problem, each laser pulse must interact with a new volume of liquid, preferably with flat surfaces, while avoiding the use of substrates. A well-established solution consists of impinging two identical laminar jets that force the liquid into a radial expansion perpendicular to the plane formed by the jets, resulting in a consecutive chain of flat sheets bound by thick rims. In this context, LCs pose several challenges considering their viscosity, non-Newtonian behavior, and mesophase nature. Here, a precise control of temperature, thus mesophase, and pressure is demonstrated enabling the use of LCs in an impinging jet system. In particular, the system presented here delivers stable fluid chains of different sizes and thicknesses. The viscosity and non-Newtonian behavior of the LCs have a significant impact on the thickness of the chains as a function of the nozzle inner diameter, impinging angle, and radial distance from the impinging point. The flow rate, on the other hand, primarily affects the width and length of the liquid sheet.

3.
Exp Appl Acarol ; 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271544

RESUMO

Hyalomma anatolicum is a tick of significant one-health importance due to its role as a vector for various pathogens affecting humans, animals and the environment, such as Theileria annulata, which causes tropical theileriosis in cattle, leading to severe economic losses. When infected with pathogens like T. annulata, the salivary glands of H. anatolicum undergo gene expression changes, secrete modified proteins and activate immune responses, all of which facilitate pathogen survival and transmission by modulating the host immune response and optimizing conditions for pathogen development. Understanding these responses is crucial for developing control strategies for tick-borne diseases. To understand the interaction between H. anatolicum and T. annulata, we performed a differential gene expression analysis of H. anatolicum salivary glands. An average of approximately 25 million raw sequencing reads were generated in each replicate using Illumina Sequencing. The sequenced reads were de novo assembled and the assembled transcriptome yielded approximately 50,231 non-redundant transcripts after clustering with CD-HIT using a sequence identity of 95% and alignment coverage of 90%. The assembly quality was evaluated with BUSCO analysis and found to be 86% complete using the Arachnida dataset and then blasted against non-redundant protein sequence database from NCBI followed by counting of reads and differential expression analysis. Overall, around 2400 and 400 genes were found differentially expressed with logFC > 1 and logFC > 2 respectively at FDR < 0.05. Top up-regulated genes included Calpain, Papilin, Neprilysin, and Ankyrin repeat-containing protein. Top down-regulated genes included Scoloptoxin, and Selenoprotein S and other uncharacterized proteins. Many other up-regulated proteins with high significance were uncharacterized suggesting room for further H. anatolicum functional and structural characterization studies. To our best knowledge, this is the first study of H. anatolicum sialotranscriptome which greatly contributes to sialotranscriptome information not only as sequence database but also indicates the potential targets for development of vaccine against ticks and transmission-blocking vaccines against T. annulata.

4.
Brain Behav ; 14(9): e70044, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39295105

RESUMO

BACKGROUND: Respiratory health problems are one of the main causes of morbidity and mortality in adult people with cerebral palsy (CP). The influence of respiratory muscle training has not yet been studied in this population group. The objective of the study was to evaluate and compare the efficacy of two protocols with inspiratory muscle training (IMT), low intensity and high intensity, to improve respiratory strength and pulmonary function in adults with CP. METHODS: The study was a controlled, randomized, double-blind trial with allocation concealment. Twenty-seven institutionalized CP patients were recruited and randomly distributed in the high-intensity training group (HIT) or low-intensity training group (LIT). Over 8 weeks, an IMT protocol was followed 5 days/week, 10 series of 1 min with 1 min rest between them. HIT trained with a load of 40% of the maximum inspiratory pressure (MIP) and LIT with 20%. Respiratory strength and pulmonary function were evaluated. RESULTS: After IMT intervention, MIP, maximum expiratory pressure, forced expiratory volume in 1 s (FEV1) and peak expiratory flow increased in both groups; in HIT 29%, 19%, 13%, and 8%, respectively (p = 0.000, p = 0.000, p = 0.002, p = 0.001) and in LIT 17%, 7%, 3%, and 4%, respectively (p = 0.000, p = 0.000, p = 0.049, p = 0.113). All the improvements were significantly higher in HIT than in LIT. CONCLUSION: Inspiratory muscle training improved respiratory muscle strength and pulmonary function in adults with CP. Training with a 40% MIP load improved all the evaluated parameters and was the most effective treatment for adults with CP.


Assuntos
Exercícios Respiratórios , Paralisia Cerebral , Força Muscular , Músculos Respiratórios , Humanos , Método Duplo-Cego , Masculino , Adulto , Feminino , Exercícios Respiratórios/métodos , Paralisia Cerebral/reabilitação , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/terapia , Músculos Respiratórios/fisiopatologia , Músculos Respiratórios/fisiologia , Adulto Jovem , Força Muscular/fisiologia , Inalação/fisiologia , Pessoa de Meia-Idade , Resultado do Tratamento , Testes de Função Respiratória
5.
Nat Commun ; 15(1): 7730, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231983

RESUMO

Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key nuclear receptor mediating CBD's beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.


Assuntos
Canabidiol , Doenças Mitocondriais , PPAR gama , Animais , Feminino , Humanos , Masculino , Camundongos , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Doença de Leigh/tratamento farmacológico , Doença de Leigh/metabolismo , Doença de Leigh/genética , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Doenças Mitocondriais/tratamento farmacológico , Doenças Mitocondriais/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , PPAR gama/metabolismo , PPAR gama/genética
6.
NPJ Vaccines ; 9(1): 174, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294184

RESUMO

Vaccines are the most effective and sustainable intervention to control ticks and tick-borne diseases (TBD). Using a personalized vaccine design based on regional tick genotypes, a Rhipicephalus appendiculatus Subolesin protective antigen was used in a field trial evaluating tick vaccine efficacy, effectiveness, and safety in cattle infested with multiple tick species in different Ugandan agro-ecological zones. Vaccination with SUB was safe with a protective capacity against anemia and infection, and reduced the number of infested cattle, tick fitness (feeding and reproduction) with vaccine effectiveness against multiple tick species between 93.2% at 167-196 days post-vaccination (dpv) and 61.4% at 251-327 dpv. Total integrated vaccine efficacy/effectiveness was estimated as 98.8%. The Subolesin-based vaccine is protective against multiple cattle tick infestations under field conditions in Uganda. These results support registration and commercialization of the vaccine to reduce tick populations and associated risks for human and animal TBD and chemical acaracides in Uganda.

7.
Emerg Infect Dis ; 30(10): 2169-2173, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39320330

RESUMO

Clinical infection and death caused by bluetongue virus infection has been reported in the Eurasian lynx. Bluetongue virus surveillance in the Iberian lynx revealed widespread and repeated exposure to serotypes 1 and 4 in wild and captive populations of this species. This exposure is possibly from a spillover event from sympatric ruminants.


Assuntos
Vírus Bluetongue , Bluetongue , Lynx , Animais , Vírus Bluetongue/classificação , Bluetongue/virologia , Bluetongue/epidemiologia , Lynx/virologia , Espanha/epidemiologia , História do Século XXI
8.
Nutrients ; 16(18)2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39339706

RESUMO

(1) The main aim of this study was to analyze the relationship of the Mediterranean diet (MD) with vascular function in participants with and without increased insulin resistance (IR) in the Spanish population. A secondary aim was to study differences by gender. (2) Methods: Data were analyzed from 3401 subjects in the EVA, MARK, and EVIDENT studies (mean age = 60 years and 57% men). IR was evaluated with the triglyceride and glucose index (TyG index). TyG index = Ln [(fasting triglyceride mg/dL × fasting glucose mg/dL)/2]. The MD was measured against the MEDAS questionnaire, with the 14 items used in the PREDIMED study. Vascular stiffness was estimated with the brachial-ankle pulse wave velocity (baPWV) and the cardio ankle vascular index (CAVI) using the Vasera VS-1500®. (3) Results: The mean MEDAS value was 5.82 ± 2.03; (men: 5.66 ± 2.06; women: 6.04 ± 1.99; p < 0.001). MD adherence was 36.8% (men: 34.2%; women: 40.3%; p < 0.001). The mean baPWV value was 14.39 ± 2.78; (men: 14.50 ± 2.65; women: 14.25 ± 2.93; p = 0.005). A baPWV value ≥ 14.5 m/s was found in 43.4% (men: 43.6%; women: 40.0%; p = 0.727). The mean CAVI value was 8.59 ± 1.28; (men: 8.75 ± 1.28; women: 8.37 ± 1.26; p < 0.001). CAVI values ≥ 9 were present in 39.0% (men: 44.4%; women: 31.7%; p < 0.001). The mean value of the TGC/G index was 10.93 ± 1.39; (men: 11.08 ± 1.33; women: 10.73 ± 1.43; p < 0.001). IR was found in 49.9%. The average value of the MD score value was negatively associated with baPWV and CAVI in all groups analyzed (<0.05), except in the group of women with insulin resistance. (4) Conclusions: The results suggest that MD adherence is negatively associated with the vascular stiffness parameters analyzed in all the groups studied except the group of women with insulin resistance.


Assuntos
Dieta Mediterrânea , Resistência à Insulina , Análise de Onda de Pulso , Rigidez Vascular , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Rigidez Vascular/fisiologia , Idoso , Glicemia/metabolismo , Triglicerídeos/sangue , Índice Tornozelo-Braço , Espanha , Estudos Transversais , Índice Vascular Coração-Tornozelo
9.
Am J Hypertens ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292514

RESUMO

BACKGROUND: The progression of Central Blood Pressure (CBP) values and central hemodynamic parameters and its relationship with cardiovascular risk factors is quite unknown. We sought to investigate this association in a Spanish adult population without cardiovascular diseases. METHODS: Prospective observational research with a five-year follow-up. Randomly sampled 501 individuals (mean age 56±14 years, 50.3% women). After five years, 480 individuals had a follow-up. Measurements taken using the SphygmoCor® (AtCor Medical Pty Ltd., Head Office,West Ryde, Australia), following all the recommendations established in the "International task force"1, giving an estimate of central blood pressure relative to measured brachial blood pressure (type 1 device). RESULTS: Progressions during follow-up: central systolic blood pressure (cSBP): 4.16±13.71 mmHg; central diastolic blood pressure (cDBP): 2.45±11.37 mmHg; central pulse pressure (cPP): 1.72±12.43 mmHg; pulse pressure amplification (PPA): 2.85±12.20 mmHg; ejection duration (ED): 7.00±47.87 ms; subendocardial viability ratio (SEVR): -8.04±36.24%. In multiple regression analysis: cSBP positively associated with: BMI (ß=0.476); waist size (ß=0.159); number of cigarettes per day (ß=0.192). Inversely associated with peripheral systolic blood pressure (ß=-0.282). cDBP increase positively associated with number of cigarettes per day (ß=0.174). Inversely associated with peripheral diastolic blood pressure (ß=-0.292). cPP increase positively associated with BMI (ß=0.330). Inversely associated with peripheral pulse pressure (ß=-0.262). PPA increase positively associated with: BMI (ß=0.276); number of cigarettes per day (ß=0.281). ED progress inversely associated with basal plasma glucose (ß=-0.286). CONCLUSIONS: All measures increased except for SEVR. Progressions in CBP and PPA were positively associated with anthropometric parameters and number of cigarettes and CBP inversely associated with peripheral blood pressure, although this association was different according to sex.

10.
Obes Facts ; : 1-11, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39116845

RESUMO

INTRODUCTION: This study explores the under-investigated area of obesity-related discrimination and stigmatization across different countries, specifically comparing Spain (Europe) and Egypt (Middle East). METHODS: We conducted a cross-sectional observational study involving 2,090 participants from both countries. Participants completed three well-validated questionnaires to assess their attitudes toward obesity, experiences of weight-related stigma, and internalization of weight bias: Antifat Attitudes Scale (AFA), Stigmatizing Situations Inventory (SSI), and Weight Bias Internalization Scale (WBIS). Participants were categorized into four groups based on body mass index (BMI) and history bariatric surgery. RESULTS: Egyptian participants (BMI = 30.2 ± 6.7 kg/m2 [range: 18.5-69.0 kg/m2]) showed significantly higher aversion toward obesity, as indicated by higher AFA score, compared to their Spanish counterparts (BMI = 35.4 ± 10.1 kg/m2 [18.5-71.9 kg/m2]). In contrast, Spanish participants reported higher levels of weight bias internalization with increasing BMI, while in Egypt, this association was negative. The association of bariatric surgery on stigma reduction also differed between the countries. Multivariate analysis revealed that residing in Egypt was an independent risk factor for higher scores in AFA and WBIS (odds ratio 8.20 [95% confidence interval: 6.78-9.62], p < 0.001 and odds ratio (OR) 6.28 [95% CI: 4.78-7.78], p < 0.001, respectively). In contrast, Spaniards experienced more stigmatizing situations than Egyptians (OR -2.54 [95% CI: 6.78-9.62], p < 0.001). CONCLUSION: Our study underscores the complex and diverse nature of obesity-related attitudes across cultures. Understanding these cultural differences is crucial for developing effective, culturally sensitive strategies to tackle weight stigma. This research opens avenues for further studies and interventions tailored to cultural contexts.

11.
Nutrients ; 16(15)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39125444

RESUMO

The aim of this study was to analyze the relationship between healthy vascular aging (HVA) and the Mediterranean diet alongside other lifestyles in a Spanish population aged 35 to 75 years without previous cardiovascular diseases. METHODS: In this cross-sectional descriptive study, 501 individuals aged 35 to 75 years were recruited from five health centers by random sampling stratified by age and sex (55.90 ± 14.24 years, 49.70% men). HVA was determined in two steps. Step 1: Subjects with vascular damage to the carotid arteries or peripheral arterial disease were classified as non-HVA. Step 2: The study population was classified by age and sex using the percentiles of the vascular aging index (VAI), with VAI ≤p25 considered HVA and >p25 considered non-HVA. The VAI was estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76. Carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor® device, and carotid intima-media thickness using Sonosite Micromax® ultrasound. Mediterranean diet (MD) adherence, alcohol and tobacco use were recorded through validated questionnaires. Physical activity was assessed with the ActiGraph-GT3X® accelerometer. RESULTS: The mean VAI value was 61.23 ± 12.86 (men-63.47 ± 13.75 and women-59.04 ± 11.54; p < 0.001). HVA was found in 18.9% (men-19.9% and women-17.8%). In the multiple regression analysis after adjusting for possible confounding factors, the mean VAI value showed a positive association with alcohol use (ß = 0.020) and sedentary hours per week (ß = 0.109) and a negative association with hours of activity per week (ß = -0.102) and with the number of healthy lifestyles (ß = -0.640). In the logistic regression analysis, after adjusting for possible confounding factors and compared to those classified as non-HVA, subjects classified as HVA were more likely to show MD adherence (OR = 0.571), do more than 26 h per week of physical activity (OR = 1.735), spend under 142 h per week being sedentary (OR = 1.696), and have more than two healthy lifestyles (OR = 1.877). CONCLUSION: The results of this study suggest that the more time spent doing physical activity and the less time spent in a sedentary state, the lower the vascular aging index and the greater the likelihood of being classified in the group of subjects with HVA.


Assuntos
Dieta Mediterrânea , Estilo de Vida , Humanos , Dieta Mediterrânea/estatística & dados numéricos , Pessoa de Meia-Idade , Masculino , Feminino , Espanha , Idoso , Adulto , Estudos Transversais , Exercício Físico , Espessura Intima-Media Carotídea , Envelhecimento Saudável , Análise de Onda de Pulso
12.
Prev Vet Med ; 232: 106330, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39216329

RESUMO

Coxiella burnetii is a multi-host bacterium of major public and animal health concern. This pathogen circulates among several wild species in the Iberian Peninsula, however, the role of the Iberian lynx (Lynx pardinus) in the epidemiology of this emerging pathogen is still unknown. The objective of this work was to assess the circulation of C. burnetii in Iberian lynx populations from the Iberian Peninsula and to study the molecular characterisation of this pathogen in lynxes and their feeding ticks. A total of 922 lynxes, including free-ranging and captive individuals, were sampled between 2010 and 2022 for the collection of sera (n = 543), spleen samples (n = 390) and ticks (n = 357 from 61 lynxes). The overall seroprevalence was 7.7 % (42/543; 95 %CI: 5.5-10.0 %), with age being significantly associated with the C. burnetii exposure in free-ranging lynxes. A longitudinal study was also carried out to assess the dynamics of the circulation of C. burnetii in this wild host, revealing that 7 of the 37 longitudinally surveyed individuals seroconverted during the study period. The PCR prevalence was 4.4 % (17/390, 95 %CI: 2.3-6.4 %) for spleen samples and 1.1 % (4/357; 95 % CI: 0.0-2.2) in ticks. This is the first study to evaluate the circulation of C. burnetii in the Iberian lynx and to confirm the infection in this felid. The results obtained show a moderate, wide, homogeneous, and endemic circulation of this bacterium in the Iberian lynx populations.


Assuntos
Coxiella burnetii , Lynx , Febre Q , Animais , Lynx/microbiologia , Coxiella burnetii/isolamento & purificação , Febre Q/veterinária , Febre Q/epidemiologia , Febre Q/microbiologia , Espanha/epidemiologia , Feminino , Masculino , Estudos Soroepidemiológicos , Prevalência , Estudos Longitudinais
13.
Environ Pollut ; 359: 124563, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019307

RESUMO

Gulls commonly rely on human-generated waste as their primary food source, contributing to the spread of antibiotic-resistant bacteria and their resistance genes, both locally and globally. Our understanding of this process remains incomplete, particularly in relation to its potential interaction with surrounding soil and water. We studied the lesser black-backed gull, Larus fuscus, as a model to examine the spatial variation of faecal bacterial communities, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) and its relationship with the surrounding water and soil. We conducted sampling campaigns within a connectivity network of different flocks of gulls moving across functional units (FUs), each of which represents a module of highly interconnected patches of habitats used for roosting and feeding. The FUs vary in habitat use, with some gulls using more polluted sites (notably landfills), while others prefer more natural environments (e.g., wetlands or beaches). Faecal bacterial communities in gulls from flocks that visit and spend more time in landfills exhibited higher richness and diversity. The faecal microbiota showed a high compositional overlap with bacterial communities in soil. The overlap was greater when compared to landfill (11%) than to wetland soils (6%), and much lower when compared to bacterial communities in surrounding water (2% and 1% for landfill and wetland water, respectively). The relative abundance of ARGs and MGEs were similar between FUs, with variations observed only for specific families of ARGs and MGEs. When exploring the faecal carriage of ARGs and MGEs in bird faeces relative to soil and water compartments, gull faeces were enriched in ARGs classified as High-Risk. Our results shed light on the complex dynamics of antibiotic resistance spread in wild bird populations, providing insights into the interactions among gull movement and feeding behavior, habitat characteristics, and the dissemination of antibiotic resistance determinants across environmental reservoirs.


Assuntos
Charadriiformes , Fezes , Charadriiformes/microbiologia , Animais , Fezes/microbiologia , Resistência Microbiana a Medicamentos/genética , Ecossistema , Microbiota/genética , Microbiota/efeitos dos fármacos , Monitoramento Ambiental , Bactérias/genética , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia , Microbiologia do Solo
14.
Reprod Biomed Online ; 49(4): 104107, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39067212

RESUMO

RESEARCH QUESTION: Does the application of a micro-dose of copper chloride gel increase endometrial production of vascular endothelial growth factor (VEGF) without compromising endometrial function or producing embryo toxicity? DESIGN: An estimate of optimal dose was made based on cell culture studies. Ten healthy participants received an initial uterine application of placebo gel, followed by copper chloride gel (37.5 µM, 75 µM, or 150 µM dose) in a later hormone replacement cycle. Endometrial biopsies (day 5.5 luteal) and pelvic ultrasound were carried out during each cycle to evaluate endometrial function and growth. Uterine fluid was assessed for residual copper levels on the day of biopsy, and copper chloride gel underwent mouse embryos assay assessment for potential embryo toxicity. RESULTS: The copper gel significantly increased endometrial VEGF expression (quantitative polymerase chain reaction), and also increasing endometrial thickness by an average of 2.2 mm compared with matched control cycles. The copper gel did not adversely affect endometrial morphology or maturation (histological dating and molecular receptivity testing), and mouse embryos assay studies showed no evidence of embryo toxicity. Furthermore, uterine cavity flush samples mostly lacked copper, with only negligible amounts present in one sample. CONCLUSION: Applying copper chloride gel to the uterine cavity upregulated endometrial VEGF and significantly increased endometrial thickness and volume. No adverse effects on the endometrium or embryos were observed. Copper chloride gels show promise for treating suboptimal endometrial thickness if the results of this study are confirmed by larger randomized controlled trials.


Assuntos
Cobre , Endométrio , Géis , Fator A de Crescimento do Endotélio Vascular , Feminino , Endométrio/efeitos dos fármacos , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cobre/toxicidade , Cobre/farmacologia , Animais , Camundongos , Adulto , Voluntários Saudáveis
16.
J Leukoc Biol ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041661

RESUMO

Tumor-derived prostaglandin E2 (PGE2) impairs anti-tumor immunity by priming suppressive functions on various immune cell types, including dendritic cells (DCs). In this way, tumors mediate DC dysfunction and hamper their anti-tumoral activity. PGE2 is known to modulate DC function via signaling through the E-prostanoid receptor type (EP) 2 and EP4. Preclinical studies have demonstrated the therapeutic value of targeting EP2/4 receptor signaling in DCs. Ongoing phase I clinical trials with EP antagonists have shown immunomodulation in cancer patients. However, the systemic drug administration leads to off-target events and subsequent side-effects. To limit the off-target effects of EP targeting, EP2 and EP4 antagonists were encapsulated in polymeric nanoparticles (NPs). In this study we evaluated the efficacy of EP2/4 specific antagonists encapsulated in NPs to protect cDC2s from suppressive effects of tumor-derived PGE2 in different tumor models. We show that tumor-derived PGE2 signals via EP2/4 to mediate the acquisition of a suppressive phenotype of cDC2s. EP2/4 antagonists encapsulated NPs impaired the conversion of cDC2s towards a suppressive state and inhibited the occurrence of suppressive features such as IL-10 production or the ability to expand Tregs. Importantly, the NPs abolished the transition towards this suppressive state in different tumor models: Melanoma-conditioned media, ascites fluid derived from ovarian cancer patients (2D), and upon coculture with colorectal cancer patient-derived organoids (3D). We propose that targeting the PGE2-EP2/4 axis using NPs can achieve immunomodulation in the immune system of cancer patients, alleviate tumor-derived suppression, and thus facilitate the development of potent anti-tumor immunity in cancer patients.

17.
Sex Transm Infect ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38964839

RESUMO

BACKGROUND: Condyloma acuminatum is caused by human papillomavirus (HPV), which typically presents as excrescent, pedunculated, papillomatous lesions which may be of a pale colour. On rare occasions, we have observed pigmented genital lesions that are similar to seborrhoeic keratoses, but with histological findings of condyloma acuminatum and positive genotyping for HPV. We have termed these 'seborrhoeic keratosis-like' type condylomas. METHODS: This is an observational retrospective study. The following clinical data were collected: age, sex, time of evolution, location, isolated or multiple lesions, monomorphous or polymorphous/mixed lesions. HPV genotyping was performed in all cases, and excision for histological study in eight cases. RESULTS: A total of 31 patients were diagnosed with this type of pigmented condylomata acuminata. Of these, 16 had isolated lesions (less than five lesions) and 15 had multiple lesions. 67% of the lesions exhibited slow growth, with an evolution period of greater than 1 year. The most frequent location was the base of the penis and pubis. HPV genotyping of the lesions was positive in all cases, with the HPV-6 genotype predominating (28 cases, 90.3%). The lesions exhibited dermoscopic differences from other pigmented lesions and histological findings attributable to HPV infection (pseudoparakeratosis, koilocytosis, etc) and others similar to those observed in seborrhoeic keratoses. CONCLUSIONS: A total of 31 patients were diagnosed with pigmented verrucous lesions, excrescents, isolated or multiple, in the genital region. These lesions exhibited clinical characteristics similar to seborrhoeic keratoses, with positive genotyping for HPV. In the majority of cases, the genotype was HPV-6. These lesions have been named 'pigmented condylomata acuminata seborrhoeic keratosis-like'. Only 10 cases of these lesions have been described in the literature.

18.
Nutrients ; 16(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931300

RESUMO

The main objective of this work is to investigate the relationship between the Mediterranean diet (MD) and metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary objective is to analyze sex differences. METHODS: A cross-sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, and a total of 3417 subjects with a mean age ± SD of 60.14 ± 9.14 years (57% men) were included. We followed the five criteria established in the National Cholesterol Education Program III to define MetS. The MD was assessed with the 14-item Mediterranean diet adherence screener (MEDAS) used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. RESULTS: The mean ± SD value of the MEDAS questionnaire was 5.83 ± 2.04 (men 5.66 ± 2.06 and women 6.04 ± 1.99; p < 0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p < 0.001). MetS was observed in 41.6% (39.0% men and 45.2% women; p < 0.001). In the multiple regression analysis, after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (ß = -0.336), and with the different components of MetS: systolic blood pressure (ß = -0.011), diastolic blood pressure (ß = -0.029), glycemia (ß = -0.009), triglycerides (ß = -0.004), and waist circumference (ß = -0.026), except with the HDL-cholesterol value which showed a positive association (ß = 0.021); p < 0.001 in all cases. In the logistic regression analysis performed, we found that an increase in MD adherence was associated with a decrease in the probability of MetS (OR = 0.56) and its components: blood pressure levels ≥ 130/85 mmHg (OR = 0.63), fasting plasma glucose ≥ 100 mg/dL (OR = 0.62), triglyceride levels ≥ 150 mg/dL (OR = 0.65), waist circumference levels ≥ 88 cm in women and ≥102 cm in men (OR = 0.74), and increased high-density lipoprotein cholesterol < 40 mg/dL in men and <50 mg/dL in women (OR = 1.70); p < 0.001 in all cases. The results by sex were similar, both in multiple regression and logistic regression. CONCLUSIONS: The results found in our work indicate that the greater the adherence to the MD, the lower the probability of presenting MetS. This result is repeated in the study by sex. More studies are needed to clarify that these results can be extended to the rest of the Mediterranean countries, and to other countries outside the Mediterranean basin.


Assuntos
Dieta Mediterrânea , Síndrome Metabólica , População Branca , Humanos , Dieta Mediterrânea/estatística & dados numéricos , Síndrome Metabólica/epidemiologia , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Idoso , Adulto , Fatores Sexuais , Circunferência da Cintura , Inquéritos e Questionários , Pressão Sanguínea , Triglicerídeos/sangue , Glicemia/metabolismo
19.
Res Vet Sci ; 176: 105316, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38875889

RESUMO

To improve the knowledge on the role of bats in the maintenance and transmission of tick-borne pathogens, a molecular approach was used to characterize Anaplasma spp., Rickettsia spp., Coxiella burnetii, Borrelia burgdorferi s.l., piroplasmids, Hepatozoon spp., flaviviruses and nairoviruses in ticks collected from Iberian bats. A total of 732 bats from 25 species were captured at 38 sampling sites distributed in seven provinces of Spain between 2018 and 2022. Seventy-nine Ixodes simplex ticks were collected from 31 bats (Eptesicus isabellinus, Hypsugo savii, Myotis capaccini, Myotis emarginatus, Myotis myotis, Miniopterus schreibersii, Pipistrellus pipistrellus and Rhinolophus ferrumequinum). Sixty of 79 I. simplex were positive for at least one pathogen tested and were collected from 23 bats captured in southeast Spain. We detected the presence of Rickettsia slovaca in 12 ticks collected from M. emarginatus, H. savii, M. schreibersii and E. isabellinus; Rickettsia aeschlimannii in 1 tick from M. schreibersii; Anaplasma ovis in 3 ticks from H. savii and M. schreibersii; C. burnetii in 2 ticks from H. savii; Occidentia massiliensis in 1 tick from H. savii; piroplasmids in 12 ticks from H. savii, M. schreibersii and E. isabellinus; and a novel nairovirus in 1 tick from M. schreibersii. Furthermore, blood samples obtained from 14 of the 31 tick-infested bats were negative in all PCR analyses. This study describes new host and pathogen associations for the bat-specialist I. simplex, highlights the risk of spread of these pathogens, and encourages further research to understand the role of Iberian bats in the epidemiology of tick-borne pathogens.


Assuntos
Quirópteros , Ixodes , Animais , Quirópteros/microbiologia , Quirópteros/virologia , Ixodes/microbiologia , Ixodes/virologia , Espanha/epidemiologia , Rickettsia/isolamento & purificação , Rickettsia/genética , Anaplasma/isolamento & purificação , Anaplasma/genética , Borrelia burgdorferi/isolamento & purificação , Infestações por Carrapato/veterinária , Infestações por Carrapato/epidemiologia , Coxiella burnetii/isolamento & purificação , Coxiella burnetii/genética
20.
BMC Prim Care ; 25(1): 227, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914974

RESUMO

INTRODUCTION: Teledermatology is the practice of dermatology through communication technologies. The aim of this study is to analyze its implementation in a Spanish health area during its first two years. METHODS: Cross-sectional descriptive study. It included interconsultations between dermatologists and family physicians in the Salamanca Health Area (Spain) after the implementation of the non-face-to-face modality over a period of two consecutive years. A total of 25,424 consultations were performed (20,912 face-to-face and 4,512 non-face-to-face); 1000 were selected by random sampling, half of each modality. MAIN MEASURES: referral rate, response time and resolution time, type of pathology, diagnostic concordance, and quality of consultation. RESULTS: The annual referral rate was 42.9/1000 inhabitants (35.3 face-to-face and 7.6 non-face- to-face). The rate of face-to-face referrals was higher in urban areas (37.1) and the rate of non- face-to-face referrals in rural areas (10.4). The response time for non-face-to-face consultations was 2.4 ± 12.7 days and 56 ± 34.8 days for face-to-face consultations (p < 0.001). The resolution rate for non-face-to-face consultations was 44%. Diagnostic concordance, assessed by the kappa index, was 0.527 for face-to-face consultations and 0.564 for non-face-to-face consultations. Greater compliance with the quality criteria in the non-attendance consultations. CONCLUSIONS: Teledermatology appears to be an efficient tool in the resolution of dermatological problems, with a rapid, effective, and higher quality response for attention to skin pathologies. REGISTRY: ClinicalTrials.gov Identifier: NCT05625295. Registered on 21 November 2022 ( https://clinicaltrials.gov/ct2/show/ NCT05625295).


Assuntos
Dermatologia , Encaminhamento e Consulta , Dermatopatias , Telemedicina , Humanos , Espanha , Dermatologia/métodos , Estudos Transversais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Dermatopatias/diagnóstico , Dermatopatias/terapia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Consulta Remota/estatística & dados numéricos , Idoso , Adolescente , Adulto Jovem , Criança
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