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1.
Biology (Basel) ; 13(8)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39194516

RESUMO

The nutritional composition of food for animal production can be enhanced using olive tree and plant by-products due to their high content of bioactive compounds such as pentacyclic triterpenes. Here, we present a novel application of near-infrared spectroscopy (NIRS) for the prediction of the total or individual [maslinic acid (MA), oleanolic acid (OA), and uvaol (UO)] pentacyclic triterpene concentrations in a feed additive obtained from a plant mixture. The oxygen radical absorbance capacity of these types of samples demonstrated the existence of a high antioxidant capacity. The conventional determination methods of pentacyclic triterpene concentration are costly, labor-intensive, and not practical for analyzing several lines within a limited timeframe at the factory level. The optimal regression model developed in our work demonstrated high correlation values for the calibration and validation sets, along with a high residual prediction deviation value. We used 63 samples for the development of the model. The NIRS method can be applied directly to dried powder and makes extraction and high-performance liquid chromatography (HPLC) analysis unnecessary. Our results also demonstrate that NIRS can accurately quantify pentacyclic triterpenes even at low concentrations in food additives. It can be used at the factory level to directly determine the pentacyclic triterpene concentrations in the additive powder at the same time that the powder is produced.

2.
Dose Response ; 22(3): 15593258241266469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39132282

RESUMO

Background: Buprenorphine (BPN) is a widely used analgesic in the pediatric population, although there are few studies on the pharmacokinetics and pharmacodynamics of this drug. Objective: The objective was to characterize the pharmacokinetics of BPN after intravenous administration and analyze the effect of age, gender, weight, height, body mass index (BMI), and drug-drug interactions as covariates. Methods: Ninety-nine children (2-10 years), who underwent orthopedic surgery under regional, general, or combined anesthesia were included. Patients evaluated according to the American Society of Anesthesiologists Physical Status Classification, who received intravenous BPN 2 µg/kg were enrolled. Blood was collected from 1-240 min. Drug plasma concentrations were determined by LC-MS/MS. Population pharmacokinetic parameters were obtained with Monolix 2021R1 software. Pearson's correlation and/or ANOVA were used for statistical analysis. Results: Age was associated with changes in clearance and central compartment volume and the female gender was associated with lower intercompartmental clearance, while BMI modified clearance, central and peripheral compartment volume. Concomitant administration of BPN with fentanyl and dexamethasone produced decreases in clearance. Conclusions: The covariates of sex, age, and BMI are directly related to the increase or decrease in BPN pharmacokinetic parameters.

4.
Eur Heart J Open ; 4(4): oeae065, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39175848

RESUMO

Aims: Catheter ablation, consisting of pulmonary vein isolation (PVI), is the most effective treatment modality for the management of symptomatic patients with atrial fibrillation (AF). Unfortunately, this procedure has a considerable relapse rate, ranging from 15 to 50% depending on AF type and other patient factors. Hypertension (HTN) is associated with a higher risk of developing AF and can also be managed with a catheter-based procedure-renal denervation (RDN). This meta-analysis aimed to compare the effect of PVI with and without RDN in hypertensive patients with AF. Methods and results: OVID MEDLINE and Embase were searched on 1 February 2023 and trials that reported the effects of RDN on AF recurrence in hypertensive patients were included. A total of 637 patients across 8 randomised controlled trials were included. The results from the pooled analysis showed that when compared with PVI alone, RDN added to PVI: (1) Lowered AF recurrence [RR 0.67 (0.53, 0.85), P = 0.001, I 2 = 23%, NNT = 5.9 patients]; (2) Reduced both systolic blood pressure and diastolic blood pressure, with medium effect size, as reflected by standardised mean differences of 0.5 (P = 0.02, I 2 = 80%) and 0.43 (P = 0.006, I 2 = 60%), respectively; and (3) was not associated with a decrease in estimated glomerular filtration rate (+7.19 mL/min/1.73 m2, P = 0.15, I 2 = 89%). Conclusion: Adding RDN to PVI in patients with AF and resistant HTN was associated with a reduction of blood pressure levels and AF recurrence. Consideration to RDN should be given as an adjunctive treatment for patients with AF and resistant HTN.

5.
Ann Surg Oncol ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060691

RESUMO

BACKGROUND: Some procedures performed during cytoreductive surgery (CRS) and hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) are based on empirical data. One of these procedures is systematic cholecystectomy. This study aimed to perform a critical analysis of the need for systematic cholecystectomy during CRS+HIPEC of patients with peritoneal carcinomatosis using long-term follow-up data. METHODS: Patients with peritoneal surface malignancies who were candidates for CRS+HIPEC and underwent surgery between January 2008 and December 2022 were analyzed. For patients with gallbladder involvement due to the disease or for patients whose preoperative study showed the presence of cholelithiasis, cholecystectomy was performed as part of the surgery, which was avoided for the remaining patients. All postoperative adverse events that occurred in the first 90 days were recorded, and clinical records focused on the development of biliary pathology during the follow-up period were studied. RESULTS: The results from a consecutive series of 443 patients with peritoneal surface malignancies who underwent surgery between January 2008 and December 2022 were analyzed. The average age of the cohort was 50 years. The median follow-up period for the cohort was 41 months (range, 12-180 months), with a disease-free survival of 17 months. For 373 of the patients, CRS+HIPEC was completed without an associated cholecystectomy, and in 16 of them, the appearance of cholelithiasis was detected during the follow-up period. Only two patients in the series showed complications derived from gallstones and required a delayed cholecystectomy. CONCLUSIONS: Although cholecystectomy is a safe procedure in the context of CRS+HIPEC, it is not risk free, and its routine performance may be unnecessary.

6.
Data Brief ; 55: 110585, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38974004

RESUMO

Wheat (Triticum aestivum) is a major cereal crop planted in the Southern Great Plains. This crop faces diverse pests that can affect their development and reduce yield productivity. For example, aphids are a significant pest in wheat, and their management relies on pesticides, which affect the sustainability and biodiversity of natural predators that prey on aphids. Coccinellids, commonly named lady beetles, are the most abundant natural predators of wheat. These natural enemies contribute to the natural predation of aphids, which can reduce the use of excessive pesticides for aphid management. Usually, visual observations of these natural enemies are performed during pest sampling; however, it is time-consuming and requires manual labor, which can be expensive. An automation system or detection models based on machine learning approaches that can detect these insects is needed to reduce unnecessary pesticide applications and manual labor costs. However, developing an automation system or computer vision models that automatically detect these natural enemies requires imagery to train and validate this cutting-edge technology. To solve this research problem, we collected this dataset, which includes images and label annotations to help researchers and students develop this technology that can benefit wheat growers and science to understand the capabilities of automation in Entomology. We collected a dataset using mobile devices, which included a diverse range of coccinellids on wheat images. The dataset consists of 2,133 images with a standard size of 640 × 640 pixels, which can be used to train and develop detection models for machine learning purposes. In addition, the dataset includes annotated labels that can be used for training models within the YOLO family or others, which have been proven to detect small insects in crops. Our dataset will increase the understanding of machine learning capabilities in entomology, precision agriculture, education, and crop pest management decisions.

7.
An Pediatr (Engl Ed) ; 101(2): 84-94, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39068038

RESUMO

INTRODUCTION: Asthma is a common chronic disease in the paediatric age group that requires close follow-up. Clinical practice guidelines offer evidence-based recommendations to achieve adequate control of the disease. OBJECTIVE: To assess the management of childhood asthma in the primary care setting in the Community of Madrid, and the adherence of health care professionals to guideline recommendations. To analyse the association of asthma management with age, the socioeconomic level of the catchment population and the workload of primary care centres. METHODS: retrospective longitudinal study in patients aged 6-14 years newly diagnosed with asthma in primary care centres of the Community of Madrid in 2021. We analysed sociodemographic and clinical variables and the compliance with recommendations at the time of diagnosis and over 1 year of follow-up. The source of data was the electronic health record database of the primary care system. RESULTS: We found a proportion of compliance with the recommendations upon diagnosis of the disease of 5.84%, with differences associated to the socioeconomic level of the catchment population (P = .033), and the pressure of care (P = .006). The proportion of compliance with recommendations during follow-up was 12.73%, with differences based on age (P = .01), socioeconomic level (P = 0.006) and centre workloads (P = .002). CONCLUSIONS: Compliance with the recommendations of the main childhood asthma management guidelines in the primary care setting was low in the Community of Madrid. Strategies need to be implemented to improve the management of this disease and the adherence of professionals to the protocols developed for this purpose.


Assuntos
Asma , Fidelidade a Diretrizes , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde , Humanos , Asma/terapia , Asma/diagnóstico , Criança , Atenção Primária à Saúde/normas , Atenção Primária à Saúde/estatística & dados numéricos , Espanha , Fidelidade a Diretrizes/estatística & dados numéricos , Estudos Retrospectivos , Adolescente , Masculino , Feminino , Estudos Longitudinais , Fatores Socioeconômicos
8.
Pract Radiat Oncol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38729261

RESUMO

PURPOSE: With transition from supine to prone position, tenting of the pectoralis major occurs, displacing the muscle from the chest wall and shifting the level I and II axillary spaces. For patients for whom we aim to treat the level I and II axillae using the prone technique, accurate delineation of these nodal regions is necessary. Although different consensus guidelines exist for delineation of nodal anatomy in supine position, to our knowledge, there are no contouring guidelines in the prone position that account for this change in nodal anatomy. METHODS AND MATERIALS: The level I and II nodal contours from the Radiation Therapy Oncology Group (RTOG) breast cancer supine atlas were adapted for prone position by 2 radiation oncologists and a breast radiologist based on anatomic changes observed from supine to prone positioning on preoperative diagnostic imaging. Forty-three patients from a single institution treated with prone high tangents from 2012 to 2018 were identified as representative cases to delineate the revised level I and II axillae on noncontrast computed tomography (CT) scans obtained during radiation simulation. The revised nodal contours were reviewed by an expanded expert multidisciplinary panel including breast radiologists, radiation oncologists, and surgical oncologists for consistency and reproducibility. RESULTS: Consensus was achieved among the panel in order to create modifications from the RTOG breast atlas for CT-based contouring of the level I and II axillae in prone position using bone, muscle, and skin as landmarks. This atlas provides representative examples and accompanying descriptions for the changes described to the caudal and anterior borders of level II and the anterior, posterior, medial, and lateral borders of level I. A step-by-step guide is provided for properly identifying the revised anterior border of the level I axilla. CONCLUSIONS: The adaptations to the RTOG breast cancer atlas for prone positioning will enable radiation oncologists to more accurately target the level I and II axillae when the axillae are targets in addition to the breast.

9.
Resusc Plus ; 18: 100635, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38646093

RESUMO

Introduction: Recent data are not available on ongoing CPR for emergency services with an onboard physician. The aim of the present study was to identify factors associated with the decision to transport patients to hospital with ongoing CPR and examine their survival to hospital discharge with good neurological status. Methods: An observational study based on a registry of out-of-hospital cardiac arrests attended to by emergency services with an onboard physician. All OHCA cases occurring between the 1st of January and the 31st of December 2022 were included. Patients receiving ongoing CPR during transport to the hospital were compared with patients pronounced dead at the scene following arrival of the care team. The dependent variable was ongoing CPR during transport to the hospital. The main characteristics and the neurological status of patients surviving to discharge were described. Results: A total of 9321 cases were included, of which 350 (3.7%) were transported to hospital with ongoing CPR. Such patients were young (59.9 ± 20.1 years vs 64.6 ± 16.9 years; p < 0.001; 95%CI: 0.98 [0.98; 0.99]) with arrest taking place outside of the home (151 [44.5%] vs 4045 [68.01%]; p < 0.001; 95%CI: 0.41 [0.31; 0.54]) and being witnessed by EMS (126 [36.0%] vs 667 [11.0%]; p < 0.001; 95%CI: 4.31 [3.19; 5.80]), whilst initial rhythm differed from asystole (164 [47.6%] vs 4325 [73.0%]; p < 0.01; 95%CI: 0.44 [0.33; 0.60]) and a mechanical device was more often employed during resuscitation and transport to hospital (199 [56.9%] vs 2050 [33.8%]; p < 0.001; 95%CI: 2.75 [2.10; 3.59]). Seven patients (2%) were discharged alive from hospital, five with ad integrum neurological recovery (CPC1) and two with minimally impaired neurological function (CPC2). Conclusions: The strategy of ongoing CPR is uncommon in EMS with an onboard physician. Despite their limited efficacy, the availability of mechanical chest compression devices, together with the possibility of specific hospital treatments, mainly ICP and ECMO, opens up the possibility of this approach with determined patients.

10.
Plants (Basel) ; 13(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674567

RESUMO

This paper evaluates an experimental wetland as part of a pilot soil reclamation project in a mining area. The wetland was constructed using materials of mining origin from the area; most reactive materials of acid pH were stabilised using limestone filler. The study selected macrophytes that are tolerant to potentially toxic elements (PTEs) and resistant to salinity, namely Phragmites australis, Juncus effusus, and Iris pseudacorus. These macrophytes were then placed in pots containing substrates composed of different mixtures of topsoil, peat, and mining waste (black or yellow sand). A thorough analysis of the physicochemical and mineralogical characteristics of the materials included studies of PTE mobilisation. This study emphasises the significance of the rhizosphere in directing the transfer of PTEs to the plant and the correlation between the substrate and the development of plant defence mechanisms, such as the formation of Fe-plates. Scanning electron microscopy was used to highlight these aspects and validate the results of the analytical determinations. These wetlands can be proposed as a phytoremediation strategy for areas affected by mining and maritime influence. They are easy to construct and remain stable, providing important ecosystem services such as the natural attenuation of acid mine drainage, support for vegetation development and fauna, and a clean ecosystem.

12.
J Clin Med ; 13(7)2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38610620

RESUMO

Background: The objectives were as follows: (a) to identify, among patients with axial spondyloarthritis (axSpA), "clusters" of patients based on the presence of peripheral and extra-musculoskeletal manifestations (EMMs) and (b) to compare the effectiveness of the first anti-TNF drugs across the different clusters after 6 months of follow-up. Methods: An observational and retrospective study of 90 axSpA patients naïve to bDMARDs was conducted. An unsupervised cluster analysis using the "k-means" technique was performed using variables of peripheral and EMMs. Baseline clinical and sociodemographic characteristics were evaluated, and the response to anti-TNF treatment (considering responders as those with an improvement ≥1.1 for the Ankylosing Spondylitis Disease Activity Score (ASDAS) or ≥2.0 for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) was compared across the clusters after 6 months of follow-up. Results: Two clusters were identified: cluster 1 (n = 14), with a higher prevalence of peripheral manifestations, inflammatory bowel disease (IBD), and HLA-B27-positive status, and a lower prevalence of uveitis in comparison with cluster 2 (n = 76). Patients from cluster 1 experienced a more pronounced absolute improvement in ASDAS and BASDAI indices after 6 months. The percentage of responders after 6 months of follow-up was superior in cluster 1 compared to cluster 2 (85.7% vs. 48.7%, p = 0.011). Conclusion: This study suggests the existence of two clinical profiles in axSpA patients according to the peripheral and EMMs, with higher rates of anti-TNF effectiveness after 6 months in those with a greater presence of peripheral features.

13.
Emergencias ; 36(2): 131-139, 2024 Apr.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-38597620

RESUMO

SUMMARY: Out-of-hospital cardiac arrest is a serious public health problem worldwide. The annual incidence is estimated at around 400 000 cases in Europe and the United States, and survival rates scarcely reach 10%. However, there is considerable variation between countries and even between regions that share a similar health care system within a single country. Information recorded by the Out-of-Hospital Spanish Cardiac Arrest Registry (OHSCAR) provides information on care provided by emergency ambulance services, final health outcomes after cardiac arrest cases (including variations), the possibility of organ donation, and the impact of the COVID-19 pandemic. This paper presents the OHSCAR report for Spanish emergency services for the year 2022.


RESUMEN: La parada cardiorrespiratoria extrahospitalaria (PCREH) es un grave problema de salud pública mundial, con una incidencia anual estimada entorno a entorno a los 350.000 y 400.000 casos de PCERH en Europa y Estados Unidos, respectivamente. La supervivencia final se sitúa en porcentajes que apenas alcanzan el 10%, aunque existe una importante variabilidad entre países e incluso entre regiones del mismo país con modelos de atención similares. En España, el Registro Español de Parada Cardiaca Extrahospitalaria (acrónimo OHSCAR) ha ofrecido información sobre la asistencia a la PCRE prestada por los servicios de emergencias (SEM) y sus resultados finales en salud, así como sobre variabilidad, posibilidades de programas de donación o impacto de la pandemia COVID-19. A continuación se presenta el informe OHSCAR correspondiente a la asistencia a la PCRE por los SEM españoles durante el año 2022.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Humanos , Estados Unidos , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/terapia , Incidência , Pandemias , Sistema de Registros , Hospitais
14.
Anal Chim Acta ; 1302: 342487, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38580405

RESUMO

BACKGROUND: Many of the chemicals frequently used as additives have been recognised as hazardous substances, and therefore their analysis is necessary to evaluate plastic contamination risk. Additives analysis in plastic samples is usually performed by methods involving high volumes of toxic solvents or having high detection limits. In this work, a novel, fast, solventless and reliable green method was developed for the automated analysis of plastic additives from plastic samples. The proposed method consists of in-tube extraction dynamic headspace sampling (ITEX-DHS) combined with gas chromatography (GC) and mass spectrometry (MS/MS) determination. RESULTS: Several parameters affecting the ITEX-DHS extraction of 47 additives in plastic samples (including phthalates, bisphenols, adipates, citrates, benzophenones, organophosphorus compounds, among others) were optimised. The use of matrix-matched calibration, together with labelled surrogate standards, minimises matrix effects, resulting in recoveries between 70 and 128%, with good quantitation limits (below 0.1 µg g-1 for most compounds) and precision (<20%). The method proposed can be applied to any type of polymer, but due to the existence of the matrix effect, calibrates with the adequate matrix should be performed for each polymer. SIGNIFICANCE: This method represents an effective improvement compared to previous methods because it is fast, solvent-free, fully automated, and provides reliable quantification of additives in plastic samples.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38490245

RESUMO

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

16.
Environ Pollut ; 348: 123808, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38521396

RESUMO

The term "Plastisphere" refers to the biofilm layer naturally formed by microorganisms attaching to plastic surfaces. This layer possesses the capability to adsorb persistent organic and inorganic pollutants, particularly trace metals, which are the focus of this research study. Immersion experiments were concurrently conducted in five locations spanning four European countries (France, Ireland, Spain, and Italy) utilising eight distinct polymers. These immersions, repeated every three months over a one-year period, aimed to evaluate the baseline bioaccumulation of 12 trace metals. The study underscores the intricate nature of metal bioaccumulation, influenced by both micro-scale factors (such as polymer composition) and macro-scale factors (including geographical site and seasonal variations). Villefranche Bay in France exhibited the lowest metals bioaccumulation, whereas Naples in Italy emerged as the site where bioaccumulation was often the highest for the considered metals. Environmental risk assessment was also conducted in the study. The lightweight nature of certain plastics allows them to be transported across significant distances in the ocean. Consequently, evaluating trace metal concentrations in the plastisphere is imperative for assessing potential environmental repercussions that plastics, along with their associated biota, may exert even in locations distant from their point of emission.


Assuntos
Poluentes Ambientais , Metais Pesados , Oligoelementos , Poluentes Químicos da Água , Bioacumulação , Poluentes Químicos da Água/análise , Metais , França , Polímeros , Monitoramento Ambiental , Metais Pesados/análise , Plásticos
17.
Healthcare (Basel) ; 12(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38470671

RESUMO

The experience of menstruation is often associated with negative connotations and gender stereotypes, which results in making it invisible. This research aimed to explore the perceptions, beliefs, and knowledge of young Spanish women regarding the menstrual cycle and menstruation and their impact on their lives. The study delves into their understanding, menstrual management practices, the types of menstrual products employed, and their experiences related to menstrual health. Qualitative methodology was used with discussion groups as a data collection technique. The participants comprised 45 young Spanish women, aged between 18 and 23, hailing from both rural and urban areas. The majority were university students, with some engaged in part-time work, and one participant working full-time. While many experienced menstrual pain ranging from mild to debilitating, a normalization of this pain often led them to forego seeking specialist assistance. Disposable menstrual products (DMPs) are the most used by participants, despite limited awareness of their absorption capacity. Regarding reusable menstrual products (RMPs), menstrual cup users emphasized comfort but expressed a need for proper training. Negative menstruation experiences could evoke fear and difficulties, underscoring the importance of providing comprehensive menstrual health education encompassing both theoretical and practical components.

18.
Nature ; 626(8001): 1108-1115, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326622

RESUMO

Psychosocial stress has profound effects on the body, including the immune system and the brain1,2. Although a large number of pre-clinical and clinical studies have linked peripheral immune system alterations to stress-related disorders such as major depressive disorder (MDD)3, the underlying mechanisms are not well understood. Here we show that expression of a circulating myeloid cell-specific proteinase, matrix metalloproteinase 8 (MMP8), is increased in the serum of humans with MDD as well as in stress-susceptible mice following chronic social defeat stress (CSDS). In mice, we show that this increase leads to alterations in extracellular space and neurophysiological changes in the nucleus accumbens (NAc), as well as altered social behaviour. Using a combination of mass cytometry and single-cell RNA sequencing, we performed high-dimensional phenotyping of immune cells in circulation and in the brain and demonstrate that peripheral monocytes are strongly affected by stress. In stress-susceptible mice, both circulating monocytes and monocytes that traffic to the brain showed increased Mmp8 expression following chronic social defeat stress. We further demonstrate that circulating MMP8 directly infiltrates the NAc parenchyma and controls the ultrastructure of the extracellular space. Depleting MMP8 prevented stress-induced social avoidance behaviour and alterations in NAc neurophysiology and extracellular space. Collectively, these data establish a mechanism by which peripheral immune factors can affect central nervous system function and behaviour in the context of stress. Targeting specific peripheral immune cell-derived matrix metalloproteinases could constitute novel therapeutic targets for stress-related neuropsychiatric disorders.


Assuntos
Transtorno Depressivo Maior , Metaloproteinase 8 da Matriz , Monócitos , Estresse Psicológico , Animais , Humanos , Camundongos , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/enzimologia , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/metabolismo , Espaço Extracelular/metabolismo , Metaloproteinase 8 da Matriz/sangue , Metaloproteinase 8 da Matriz/deficiência , Metaloproteinase 8 da Matriz/genética , Metaloproteinase 8 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Monócitos/química , Monócitos/imunologia , Monócitos/metabolismo , Núcleo Accumbens/metabolismo , Núcleo Accumbens/patologia , Tecido Parenquimatoso/metabolismo , Análise da Expressão Gênica de Célula Única , Comportamento Social , Isolamento Social , Estresse Psicológico/sangue , Estresse Psicológico/genética , Estresse Psicológico/imunologia , Estresse Psicológico/metabolismo
19.
EMBO Rep ; 25(3): 1541-1569, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38263330

RESUMO

To globally profile circRNAs, we employ RNA-Sequencing paired with chimeric junction analysis for alpha-, beta-, and gamma-herpesvirus infection. We find circRNAs are, as a population, resistant to host shutoff. We validate this observation using ectopic expression assays of human and murine herpesvirus endoribonucleases. During lytic infection, four circRNAs are commonly induced across all subfamilies of human herpesviruses, suggesting a shared mechanism of regulation. We test one such mechanism, namely how interferon-stimulation influences circRNA expression. 67 circRNAs are upregulated by either interferon-ß or -γ treatment, with half of these also upregulated during lytic infection. Using gain and loss of function studies we find an interferon-stimulated circRNA, circRELL1, inhibits lytic Herpes Simplex Virus-1 infection. We previously reported circRELL1 inhibits lytic Kaposi sarcoma-associated herpesvirus infection, suggesting a pan-herpesvirus antiviral activity. We propose a two-pronged model in which interferon-stimulated genes may encode both mRNA and circRNA with antiviral activity. This is critical in cases of host shutoff, such as alpha- and gamma-herpesvirus infection, where the mRNA products are degraded but circRNAs escape.


Assuntos
Herpes Simples , Herpesviridae , Humanos , Camundongos , Animais , RNA Circular , Interferons , RNA Mensageiro , Simplexvirus , Antivirais
20.
Breast Cancer Res Treat ; 204(3): 485-495, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38183516

RESUMO

PURPOSE: Our institution was an early adopter of 5-fraction accelerated partial breast irradiation (ABPI) to treat women with early-stage breast cancer. This study reports long-term oncologic and cosmetic outcomes. METHODS: We included patients receiving APBI 600 cGy × 5 fx delivered every other day or every day between 2010 and 2022. Logistic regression models were used to identify factors associated with development of late toxicities, clinician, and patient-rated cosmesis. Kaplan-Meier methodology was used to calculate overall survival (OS), disease-free survival (DFS), and locoregional recurrence-free survival (LR-RFS). RESULTS: 442 patients received APBI either daily (56%) or every other day (44%) in the prone position (92%). At a median follow-up of 48 months (range: 5.96-155 months), 12 (2.7%) patients developed a local recurrence (LR). Out of 258 patients with > 3-month toxicity data available, the most common late grade ≥ 2 adverse event was breast fibrosis (6.2%). On multivariate analysis, daily APBI treatment (vs every other day) did not correlate with an increased risk of any late grade ≥ 2 toxicity though it did correlate with a lower risk of any late grade ≥ 2 fibrosis. Overall, at a median follow-up of 80 months, the rates of good-excellent physician and patient-rated cosmesis were 95% and 85%, respectively, with no difference between patients treated on consecutive vs. every other day. On multivariate analysis, patients who did not receive any adjuvant therapy were at increased risk of developing a LR. Five-year OS, LRFS, and DFS were 97.2%, 97.7%, and 89.5%, respectively. CONCLUSIONS: Five-fraction APBI delivered primarily in the prone position either daily or every other day was effective with low rates of local recurrence, minimal toxicity, and excellent cosmesis at long-term follow-up.


Assuntos
Braquiterapia , Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/etiologia , Braquiterapia/efeitos adversos , Mastectomia Segmentar , Mama/cirurgia , Fibrose , Resultado do Tratamento
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