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Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.
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BACKGROUND: Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity across multiple subtypes of relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma. PATIENTS AND METHODS: This phase II study (ELM-2; NCT03888105) evaluated odronextamab in patients with R/R follicular lymphoma (FL) after ≥2 lines of systemic therapy. Patients received intravenous odronextamab in 21-day cycles, with step-up dosing in Cycle 1 to help mitigate the risk of cytokine release syndrome (CRS), until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review. RESULTS: Among 128 patients evaluated, 95% completed Cycle 1, and 85% completed ≥4 cycles. At 20.1 months' efficacy follow-up, ORR was 80.0% and complete response rate was 73.4%. Median duration of complete response was 25.1 months. Median progression-free survival was 20.7 months, and median overall survival was not reached. Discontinuation of odronextamab due to adverse events (AEs) occurred in 16% of patients. The most common treatment-emergent AEs were CRS (56%; grade ≥3 1.7% [1/60] with 0.7/4/20 mg step-up), neutropenia (39%), and pyrexia (38%). CONCLUSIONS: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R FL.
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BACKGROUND: Adipose and muscle tissue wasting outlines the cachectic process during tumor progression. The sympathetic nervous system (SNS) is known to promote tumor progression and research suggests that it might also contribute to cancer-associated cachexia (CAC) energetic expenditure through fat wasting. METHODS: We sympathectomized L5178Y-R tumor-bearing male BALB/c mice by intraperitoneally administering 6-hydroxydopamine to evaluate morphometric, inflammatory, and molecular indicators of CAC and tumor progression. RESULTS: Tumor burden was associated with cachexia indicators, including a 10.5% body mass index (BMI) decrease, 40.19% interscapular, 54% inguinal, and 37.17% visceral adipose tissue loss, a 12% food intake decrease, and significant (p = 0.038 and p = 0.0037) increases in the plasmatic inflammatory cytokines IL-6 and IFN-γ respectively. Sympathectomy of tumor-bearing mice was associated with attenuated BMI and visceral adipose tissue loss, decreased interscapular Ucp-1 gene expression to basal levels, and 2.6-fold reduction in Mmp-9 relative gene expression, as compared with the unsympathectomized mice control group. CONCLUSION: The SNS contributes to CAC-associated morphometric and adipose tissue alterations and promotes tumor progression in a murine model.
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Caquexia , Progresión de la Enfermedad , Ratones Endogámicos BALB C , Sistema Nervioso Simpático , Animales , Caquexia/metabolismo , Caquexia/patología , Caquexia/etiología , Sistema Nervioso Simpático/metabolismo , Sistema Nervioso Simpático/fisiopatología , Masculino , Ratones , Proteína Desacopladora 1/metabolismo , Línea Celular Tumoral , Canales Iónicos/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Oxidopamina , Simpatectomía Química , Interleucina-6/metabolismo , Índice de Masa Corporal , Neoplasias/complicaciones , Neoplasias/patología , Neoplasias/metabolismoRESUMEN
INTRODUCTION: Data on positive rechallenge in idiosyncratic drug-induced liver injury (DILI) are scarce. We aim to analyse the clinical presentation, outcome and drugs associated with positive rechallenge in two DILI registries. METHODS: Cases from the Spanish and Latin American DILI registries were included. Demographics, clinical characteristics and outcome of cases with positive rechallenge according to CIOMS/RUCAM and current definitions were analysed. RESULTS: Of 1418 patients with idiosyncratic DILI, 58 cases had positive rechallenge (4.1%). Patients with positive rechallenge had shorter duration of therapy (p=0.001) and latency (p=0.003). In patients with rechallenge, aspartate transaminase levels were increased (p=0.026) and showed a prolonged time to recovery (p=0.020), albeit no differences were seen in terms of fatal outcomes. The main drug implicated in rechallenge was amoxicillin-clavulanate (17%). The majority of re-exposure events were unintentional (71%). Using both existing definitions of positive rechallenge, there were four cases which exclusively fulfilled the current criteria and five which only meet the historical definition. All cases of positive rechallenge, irrespective of the pattern of damage, fulfilled the criteria of either alanine transaminase (ALT) ≥3 times the upper limit of normal (ULN) and/or alkaline phosphatase (ALP) ≥2 times ULN. CONCLUSIONS: Episodes of rechallenge were characterised by shorter duration of therapy and latency, and longer time to resolution, but did not show an increased incidence of fatal outcome. Based on our findings, ALT ≥3 times ULN and/or ALP ≥2 times ULN, regardless of the pattern of damage, is proposed as a new definition of rechallenge in DILI.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Sistema de Registros , Humanos , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Estudios Prospectivos , España/epidemiología , Aspartato Aminotransferasas/sangre , Combinación Amoxicilina-Clavulanato de Potasio/efectos adversosRESUMEN
AIM: To review histologically confirmed diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) cases and carry out a detailed pathological-radiological correlation to see if computed tomography (CT) can be used to confidently identify DIPNECH. MATERIALS AND METHODS: Twenty-three histologically confirmed DIPNECH patients in the shared database of two NHS Trusts were reviewed. CT images were reviewed by two independent radiologists, each of them with >10 years of experience in thoracic imaging. All histological specimens were reviewed by a single pathologist with >25 years of experience. The diagnosis of DIPNECH was made according to the current World Health Organization (WHO) definition included in the WHO 2015 classification of pulmonary tumours. The results on histology were compared to the presence of nodules and air trapping on CT. Demographic information and, when available, molecular imaging studies and pulmonary function tests were also considered. RESULTS: There are prototypal clinical and radiological findings reflecting the presence of underlying histological DIPNECH: middle-aged women with multiple small and scattered nodules due to the clustering and proliferation of neuroendocrine cells. At least one larger, dominant, lung nodule reflecting a carcinoid tumour is very common and mosaic attenuation/air trapping is seen approximately in 50% of cases in inspiratory scans. Airflow obstruction is rarely associated with histological bronchial or peribronchial fibrosis, which suggests other mechanisms must be involved in its development. CONCLUSION: CT can be used to predict pathological DIPNECH in the appropriate clinical setting. It is important to consider DIPNECH to avoid overdiagnosis of more sinister conditions such as lung cancer or metastases.
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Enfermedades Pulmonares , Neoplasias Pulmonares , Células Neuroendocrinas , Persona de Mediana Edad , Humanos , Femenino , Hiperplasia/diagnóstico por imagen , Hiperplasia/patología , Células Neuroendocrinas/patología , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patologíaRESUMEN
Post-stroke dysphagia (PSD) is a severe and common complication after ischemic stroke. The role of silent aspiration as an important contributing factor in the development of a dysphagia-associated complications, in particular aspiration-associated pneumonia has been insufficiently understood. The aim of this study was to investigate the characteristics and risk factors of silent aspiration in patients with acute infratentorial stroke by FEES and to identify culprit lesions in stroke patient with a high risk of silent aspiration via voxel-based-symptom-lesion mapping (VBS/ML). This study is a retrospective observational study based on a prospectively collected FEES and stroke database. Consecutive patient cases with acute ischemic infratentorial stroke and FEES examination between 2017 and 2022 were identified. Group allocation was performed based on PAS scores. Imaging analysis was performed by manual assignment and by VBS/ML. Group comparisons were performed to assess silent aspiration characteristics. Binary logistic regression analysis was performed to determine if baseline clinical, demographic, and imaging parameters were helpful in predicting silent aspiration in patients. In this study 84 patient cases with acute infratentorial stroke who underwent FEES examination were included. Patients were moderately affected at admission (mean NIH-SS score at admission 5.7 SD ± 4.7). Most lesions were found pontine. Overall 40.5% of patients suffered from silent aspiration, most frequently in case of bilateral lesions. Patients with silent aspiration had higher NIH-SS scores at admission (p < 0.05), had a more severe swallowing disorder (p < 0.05) and were 4.7 times more likely to develop post-stroke pneumonia. Patients who underwent FEES examination later than 72 h after symptom onset were significantly more likely to suffer from silent aspiration and to develop pneumonia compared to patients who underwent FEES examination within the first 72 h (p < 0.05). A binary logistic regression model identified NIH-SS at admission as a weak predictor of silent aspiration. Neither in manual assignment of the lesions to brain regions nor in voxel-wise statistic regression any specific region was useful in prediction of silent aspiration. Silent aspiration is common in patients with infratentorial stroke and contributes to the risk for pneumonia. Patients with silent aspiration are more severely affected by stroke, but cannot reliably be identified by NIH-SS at admission or lesion location. Patients suffering from acute infratentorial stroke should been screened and examined for PSD and silent aspiration.
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Trastornos de Deglución , Neumonía por Aspiración , Neumonía , Accidente Cerebrovascular , Humanos , Trastornos de Deglución/diagnóstico por imagen , Trastornos de Deglución/etiología , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Neumonía por Aspiración/diagnóstico por imagen , Neumonía por Aspiración/etiología , Neumonía/complicaciones , Aspiración Respiratoria , DegluciónRESUMEN
PURPOSE: Detection of ischemic lesions in patients with transient neurovascular symptoms is relevant for the estimation of the risk of a subsequent stroke and etiological classification. To improve detection rates, different technical approaches have been used, such as diffusion-weighted imaging (DWI) with high b-values or higher magnetic field strength. Here, we sought to investigate the value of computed DWI (cDWI) with high b-values in these patients. METHODS: From an MRI report database we identified patients with transient neurovascular symptoms who underwent repeated MRI including DWI. cDWI was calculated with a monoexponential model with high b-values (2000, 3000, and 4000 s/mm2) and compared to the routinely used standard DWI with regard to presence of ischemic lesions and lesion detectability. RESULT: Overall 33 patients with transient neurovascular symptoms (71 [IQR 57-83.5] years; 21 [63.6%] male) were included. On DWI, acute ischemic lesions were observed in 22 (78.6%). Acute ischemic lesions were observed in 17 (51.5%) patients on initial DWI, and in 26 (78.8%) patients on follow-up DWI. Lesion detectability was rated significantly better on cDWI at 2000s/mm2 compared to standard DWI. In 2 (9.1%) patients, cDWI at 2000s/mm2 revealed an acute ischemic lesion proven on follow-up standard DWI which was not detected with certainty on the initial standard DWI. CONCLUSION: cDWI might be a valuable addition to routinely acquired standard DWI in patients with transient neurovascular symptoms since its use might result in improved ischemic lesion detection. A b-value of 2000s/mm2 seems most promising for clinical practice.
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Ataque Isquémico Transitorio , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Imagen de Difusión por Resonancia Magnética/métodos , Infarto , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/patologíaRESUMEN
BACKGROUND: This article aspires to show that pterygoid implants are a magnificent and viable alternative to other posterior implants of the maxilla, especially in cases of atrophy. MATERIAL AND METHODS: This study is based on a retrospective analysis of pterygoid implant data from 2003 to 2023, recollecting the following variables: year of placement, location, shape of the implant, diameter of the implant, length of the implant, torque of the implant, whether or not it was post-extraction, whether or not there was immediate loading, whether or not smoking was present (smoking habit), the brand of the implant and the success/survival or failure/non survival of the implant. RESULTS: The total of 178 pterygoid implants placed in the 113 patients eligible for the study was analysed by subgroups, with percentage of global success of 98.3% (3 failures). CONCLUSIONS: Pterygoid implants offer biomechanical and success/survival characteristics similar or superior to the so-called conventional implants and avoid a series of surgical and prosthodontic procedures more difficult than the ones required by other implants in many occasions.
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BACKGROUND: Functional impairment is the main consideration when it comes to choosing therapy for infantile hemangiomas (IH). However, since most hemangiomas are treated for cosmetic reasons, it is important to know the cosmetic outcome assessed by the parents. OBJECTIVE: To evaluate the aesthetic outcomes of IH, considering the characteristics of the lesions and the treatments used. PATIENTS AND METHODS: The Spanish Infantile Hemangioma Nationwide Prospective Cohort (2016-2022) recruited all consecutive patients diagnosed with IH in 12 Spanish hospitals. The children included had 2 photos of the IH lesion (at both baseline and at the end of the study). A panel of parents blindly assessed all available photos using a scale from 0 (worst cosmetic outcomes) to 10 (best cosmetic outcomes). The different scores -both before and after treatment-as well as the outcomes percent considered excellent (> 9) were described and compared. We analyzed the effect of receiving different therapies and performed causal model analyses estimating the mean treatment effect of parents' assessments. RESULTS: The median follow-up was 3.1 years. A total of 824 photos were evaluated. Baseline aesthetic impact was higher in the propranolol group vs the topical timolol and observation treatment groups (1.85 vs 3.14 vs 3.66 respectively; p < 0.001). After treatment, the aesthetic impact was similar between both treatment groups (7.59 vs 7.93 vs 7.90; p > 0.2). The causal model could only be applied to the comparison between topical timolol and observation, revealing no differences whatsoever. CONCLUSION: This is the first prospective cohort to analyze the aesthetic outcome of IH. The final aesthetic results of the 3 therapies were similar, with nearly 40% of patients achieving excellent aesthetic outcomes.
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This review analyzes the clinical associations between specific low genitourinary tract clinical circumstances in perimenopausal and postmenopausal women living with human immunodeficiency virus (WLHIV). Modern antiretroviral therapy (ART) improves survival and reduces opportunistic infections and HIV transmission. Despite appropriate ART, WLHIV may display menstrual dysfunction, risk of early menopause, vaginal microbiome alterations, vaginal dryness, dyspareunia, vasomotor symptoms and low sexual function as compared to women without the infection. They have increased risks of intraepithelial and invasive cervical, vaginal and vulvar cancers. The reduced immunity capacity may also increase the risk of urinary tract infections, side-effects or toxicity of ARTs, and opportunistic infections. Menstrual dysfunction and early menopause may contribute to the early onset of vascular atherosclerosis and plaque formation, and increased osteoporosis risks requiring specific early interventions. On the other hand, the association between being postmenopausal and having a low sexual function is significant and related to low adherence to ART. WLHIV deserve a specific approach to manage different low genitourinary risks and complications related to hormone dysfunction and early menopause.
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Dispareunia , Enfermedades Vaginales , Femenino , Humanos , Menopausia , VIH , Enfermedades Vaginales/tratamiento farmacológico , Vagina , Dispareunia/tratamiento farmacológicoRESUMEN
Globally, 2.5% of upper limb amputations are transhumeral, and both mechanical and electronic prosthetics are being developed for individuals with this condition. Mechanics often require compensatory movements that can lead to awkward gestures. Electronic types are mainly controlled by superficial electromyography (sEMG). However, in proximal amputations, the residual limb is utilized less frequently in daily activities. Muscle shortening increases with time and results in weakened sEMG readings. Therefore, sEMG-controlled models exhibit a low success rate in executing gestures. The LIBRA NeuroLimb prosthesis is introduced to address this problem. It features three active and four passive degrees of freedom (DOF), offers up to 8 h of operation, and employs a hybrid control system that combines sEMG and electroencephalography (EEG) signal classification. The sEMG and EEG classification models achieve up to 99% and 76% accuracy, respectively, enabling precise real-time control. The prosthesis can perform a grip within as little as 0.3 s, exerting up to 21.26 N of pinch force. Training and validation sessions were conducted with two volunteers. Assessed with the "AM-ULA" test, scores of 222 and 144 demonstrated the prosthesis's potential to improve the user's ability to perform daily activities. Future work will prioritize enhancing the mechanical strength, increasing active DOF, and refining real-world usability.
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Miembros Artificiales , Humanos , Implantación de Prótesis , Amputación Quirúrgica , Electroencefalografía , ElectromiografíaRESUMEN
An implementation proposal that seeks to globalize the scope of the sustainable technologies developed in the University laboratories is presented. This approach uses the generation of triple-impact projects placing people at the center of technological development to bring technical and scientific knowledge into a service design oriented to global sustainable solutions. This research is an approach to what a hub for scientific research, technological implementation, and human needs would look like by designing common environments in which to interact and expand knowledge in an iterated way through the experience of all the actors involved in technological implementation. As a control case, a new technology developed at the Universidad de Buenos Aires, consisting of using sustainable materials as tubular reactor fillers for water treatment was chosen. Based on data obtained within the framework of a University extension project, in which the water quality diagnosis for human consumption was carried out and cross-examined with the mathematical analysis of sorption, design parameters of the reactor, participatory design, and open source concepts application, different virtual environments were generated with distinct objectives: i) open design environment: publishing and mapping of installed sorption reactors, reactor model plans, and useful information related to drinking water quality (aimed at contributors of the open source design environment); ii) platform for academic actors linking: connecting data between prototyping lab for participatory design of sorption reactors (aimed at university research users); iii) information disclosure page: space where the implemented technology impact is displayed and shows options to contact researchers and request a reactor design diagnosis for another community (aimed at beneficiary users). A technological service designed to link the University with the community was proposed, by resolving one of the main gaps related to the possibility for communities to access public financing for self-managed improvement projects, increasing the appropriation of the adopted technology and democratizing public investment, making it sustainable over time.
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Calidad del AguaRESUMEN
Extracellular synthesis of functional cyclodextrins (CDs) as intermediates of starch assimilation is a convenient microbial adaptation to sequester substrates, increase the half-life of the carbon source, carry bioactive compounds, and alleviate chemical toxicity through the formation of CD-guest complexes. Bacteria encoding the four steps of the carbohydrate metabolism pathway via cyclodextrins (CM-CD) actively internalize CDs across the microbial membrane via a putative type I ATP-dependent ABC sugar importer system, MdxEFG-(X/MsmX). While the first step of the CM-CD pathway encompasses extracellular starch-active cyclomaltodextrin glucanotransferases (CGTases) to synthesize linear dextrins and CDs, it is the ABC importer system in the second step that is the critical factor in determining which molecules from the CGTase activity will be internalized by the cell. Here, structure-function relationship studies of the cyclo/maltodextrin-binding protein MdxE of the MdxEFG-MsmX importer system from Thermoanaerobacter mathranii subsp. mathranii A3 are presented. Calorimetric and fluorescence studies of recombinant MdxE using linear dextrins and CDs showed that although MdxE binds linear dextrins and CDs with high affinity, the open-to-closed conformational change is solely observed after α- and ß-CD binding, suggesting that the CM-CD pathway from Thermoanaerobacterales is exclusive for cellular internalization of these molecules. Structural analysis of MdxE coupled with docking simulations showed an overall architecture typically found in sugar-binding proteins (SBPs) that comprised two N- and C-domains linked by three small hinge regions, including the conserved aromatic triad Tyr193/Trp269/Trp378 in the C-domain and Phe87 in the N-domain involved in CD recognition and stabilization. Structural bioinformatic analysis of the entire MdxFG-MsmX importer system provided further insights into the binding, internalization, and delivery mechanisms of CDs. Hence, while the MdxE-CD complex couples to the permease subunits MdxFG to deliver the CD into the transmembrane channel, the dimerization of the cytoplasmatic promiscuous ATPase MsmX triggers active transport into the cytoplasm. This research provides the first results on a novel thermofunctional SBP and its role in the internalization of CDs in extremely thermophilic bacteria.
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Proteínas Portadoras , Dextrinas , Proteínas Portadoras/genética , Polisacáridos , Firmicutes , Bacterias Anaerobias , AlmidónRESUMEN
STUDY QUESTION: Is circulating cell-free DNA (cirDNA) from the endometrium elevated during menstruation and in endometriosis? SUMMARY ANSWER: Endometrial cirDNA does not increase during menstruation and is not elevated in endometriosis. WHAT IS KNOWN ALREADY: Changes in cirDNA associated with common benign conditions are a potential source of false positives in cancer diagnostic applications, but also present an opportunity for biomarker development for diseases such as endometriosis. Elevated cirDNA has been reported in endometriosis patients compared to healthy community controls, but no difference in total or endometrial cirDNA has been found between patients with endometriosis and patients with other gynaecological conditions. Likewise, menstruation is a potential driver of changes in cirDNA levels and tissue profile, but total and endothelial cirDNA do not increase during menstruation. STUDY DESIGN, SIZE, DURATION: For endometriosis comparisons, 59 participants with surgically confirmed endometriosis and 27 laparoscopic patients without endometriosis (hospital controls) were prospectively recruited, while 25 healthy community participants (healthy controls) were recruited in a university setting. Total and endometrial cirDNA and cirDNA fragmentation were measured across the three groups. For menstrual comparisons, 36 matched non-menstruating and menstruating samples were collected from healthy women recruited within a university setting, and the endometrial cirDNA was compared between the two groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: cirDNA was extracted from venous blood plasma then quantitated by quantitative PCR of ALU repetitive element (115 bp) and TP53 gene sequence (105 bp) for total concentration. cirDNA derived from the endometrium was quantitated by methylation-specific droplet digital PCR of a FAM101A region (69 bp) after bisulfite conversion of the DNA. A cirDNA size fragmentation ratio was obtained by quantifying a long segment of ALU repetitive element (247 bp) and expressing the amount relative to the 115 bp ALU target. MAIN RESULTS AND THE ROLE OF CHANCE: No differences in cirDNA level were found in any comparison populations in this study. Mean total cirDNA was unchanged between healthy controls (ALU-115-3.31 ng/ml; TP53-2.73 ng/ml), hospital controls (ALU-115-3.47 ng/ml; TP53-2.83 ng/ml) and endometriosis patients (ALU-115-3.35 ng/ml; TP53-2.66 ng/ml). Likewise, endometrial cirDNA was unchanged between healthy controls (18.3 copies/ml), hospital controls (20.6 copies/ml) and endometriosis patients (22 copies/ml). Endometrial cirDNA did not change during menstruation (non-menstruating: 38 copies/ml; menstruating: 33 copies/ml). Irrespective of endometriosis diagnosis, blood from patients undergoing laparoscopy (hospital controls: 0.77; endometriosis patients: 0.79), had a significantly higher cirDNA size ratio than community-recruited healthy controls (0.64), indicating increased abundance of long cirDNA fragments. LIMITATIONS, REASONS FOR CAUTION: It was not possible to completely match the age, BMI and parity between the three cohorts investigated, however of these, only age has been shown to influence circulating DNA levels and not within the age range of our cohort. Blood from community-recruited healthy women and women undergoing laparoscopy was collected via antecubital vein venepuncture (processed within 3 h) and with either peripheral cannula or venepuncture (processed within 6 h), respectively, which could potentially impact the size distribution of circulating DNA fragments. For the collection of non-menstruating phase blood samples, we did not differentiate between follicular phase, ovulation and luteal phase. Thus, only the mensturating samples were collected at a consistent phase, and any fluctuations in cirDNA that occur at the other phases may have obscured small changes during menstruation. WIDER IMPLICATIONS OF THE FINDINGS: There is no evidence that cirDNA has potential as a diagnostic biomarker for endometriosis. Endometriosis, representing a common benign gynaecological condition, and menstruation, representing a normal physiological occurrence in women, should not affect methylation-based diagnostics in other disease areas, including oncology. STUDY FUNDING/COMPETING INTEREST(S): N.L.Y.: Australian Government Research Training Program (RTP) Stipend through The University of New South Wales, Translational Cancer Research Network PhD Scholarship Top-Up Award via the Cancer Institute NSW, Beth Yarrow Memorial Award in Medical Science, UNSW Completion Scholarship; C.E.H.: Gynaecological Oncology Fund of the Royal Hospital for Women; K.W.: Ovarian Cancer Research Foundation and CAMILLA AND MARC. C.E.F.: UNSW Women's Wellbeing Academy and the Australian Human Rights Institute. We declare the following competing interest: K.W. holds stock in Guardant Health, Exact Sciences and Epigenomics AG. No other authors have competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Ácidos Nucleicos Libres de Células , Endometriosis , Humanos , Femenino , Endometriosis/genética , Menstruación , Australia , Endometrio , BiomarcadoresRESUMEN
BACKGROUND AND PURPOSE: Gadolinium leakage in ocular structures (GLOS) on fluid attenuated inversion recovery images (FLAIR) is a novel imaging marker in acute ischemic stroke and other neurological disorders. METHODS: In patients with transient neurovascular symptoms who underwent repeated MRI with intravenous contrast agent administration, the presence of acute ischemic lesions on diffusion-weighted images (DWI) as well as the frequency and pattern of blood-brain barrier and blood-retina barrier impairment as demonstrated by the hyperintense acute reperfusion marker (HARM) and GLOS respectively on postcontrast FLAIR were evaluated. RESULTS: Overall 28 patients with transient neurovascular symptoms (median age 70.5 years; 18 (64.3%) male) were included. Follow-up MRI was performed within 35 (IQR 21-47) hours after the initial MRI. On DWI, acute ischemic lesions were observed in 22 (78.6%). On contrast-enhanced FLAIR, GLOS was observed in 12 (42.9%) patients: in 1 (3.6%) only in the anterior chamber, and in 11 (39.3%) in the anterior chamber and vitreous body. HARM was observed in 3 (10.7%) patients. In one patient without ischemic lesion on DWI or HARM on FLAIR, GLOS was observed in the anterior chamber and vitreous body. Presence of GLOS was associated with higher age (pâ¯=â¯0.04) and detection of HARM (pâ¯=â¯0.03). CONCLUSIONS: In patients with transient neurovascular symptoms, GLOS is a frequent finding and associated with HARM on contrast-enhanced FLAIR. As GLOS was observed in one patient without an ischemic lesion or HARM, it might be useful as an additional imaging marker.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Anciano , Biomarcadores , Medios de Contraste , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Gadolinio , Humanos , Infarto , Masculino , Reperfusión , Accidente Cerebrovascular/patologíaRESUMEN
BACKGROUND: Acute respiratory failure (ARF) has become one of the most prevalent serious pathologies encountered in the emergency medical service (EMS). In hospital settings, noninvasive ventilation (NIV) therapy prevents complications from more aggressive treatments for that condition. However, the scarce evidence on the benefits of NIV in prehospital EMS (i.e., during transport to the hospital) is inconclusive. OBJECTIVES: To determine whether the administration of NIV during prehospital EMS in cases of ARF reduces in-hospital mortality compared with starting NIV on arrival to in-patient EMS. METHODS: This is a multicentre, observational, prospective cohort study. We recruited a total of 317 patients from the Madrid region (Spain) who were prescribed NIV for their ARF using a nonprobabilistic consecutive sampling method. Analyses of the main outcome (in-hospital mortality) and secondary outcomes (length of hospital stay, readmissions, percentage of intensive care unit admissions, and cost-effectiveness) will include descriptive analyses of patients' characteristics, as well as bivariate and multivariate analyses and cost-effectiveness analysis. DISCUSSION: This study will provide data on NIV management in prehospital and in-patient EMS in patients with ARF. Results will contribute to the existing evidence on the benefits of NIV in the context of prehospital EMS while underlining the importance of a standardized formal training for physicians and nurses working in prehospital and in-patient EMSs. CONCLUSION: The VentilaMadrid study will provide valuable data on the clinical factors of patients receiving NIV in prehospital EMS. Further, were our hypothesis to be confirmed, our results would strongly suggest that the administration of NIV in prehospital EMS by medical and nursing profesionals formally trained in the technique reduces mortality and improves prognoses.
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Servicios Médicos de Urgencia , Ventilación no Invasiva , Síndrome de Dificultad Respiratoria , Estudios de Cohortes , Servicios Médicos de Urgencia/métodos , Humanos , Estudios Multicéntricos como Asunto , Ventilación no Invasiva/métodos , Estudios Observacionales como Asunto , Estudios Prospectivos , EspañaRESUMEN
Pulmonary cysts are thin-walled radiolucent lesions that may appear in a variety of uncommon disorders known as diffuse cystic lung diseases (DCLD) that essentially includes lymphangioleiomyomatosis (LAM), Langerhans cell histiocytosis (LCH), lymphocytic interstitial pneumonia (LIP), Pneumocystis jiroveci pneumonia (PJP), and Birt-Hogg-Dubé syndrome (BHDS). Moreover, they have been reported in several cases of coronavirus disease 2019 (COVID-19). The purpose of this review is to provide a practical approach for evaluating lung cysts when encountered on CT. We describe the imaging findings of DLCD emphasising their differences in terms of shape and distribution of the cysts, as well as their association with other findings such as nodules or ground-glass opacities, which may help in making a confident diagnosis. We also discuss the link between pulmonary cysts and COVID-19.
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Quistes/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Humanos , Pulmón/diagnóstico por imagenRESUMEN
Routine determination of troponin levels is recommended for all patients with acute ischemic stroke. In 20-55% of these patients the troponin levels are elevated, which may be caused by ischemic as well as non-ischemic myocardial damage and particularly neurocardiogenic myocardial damage. In patients with acute ischemic stroke, the prevalence of previously unknown coronary heart disease is reported to be up to 27% and is prognostically relevant for these patients; however, relevant coronary stenoses are less frequently detected in stroke patients with troponin elevation compared to patients with non-ST elevation myocardial infarction. The risk of secondary intracerebral hemorrhage due to the necessity for dual platelet aggregation inhibition illustrates the challenging indication for invasive coronary diagnostics and revascularization. Therefore, a diagnostic work-up and interdisciplinary risk evaluation appropriate to the urgency are necessary in order to be able to determine a reasonable treatment approach with timing of the intervention, type and duration of blood thinning. In addition to conventional examination methods, multimodal cardiac imaging is increasingly used for this purpose. This review article aims to provide a pragmatic and clinically oriented approach to diagnostic and therapeutic procedures, taking into account the available evidence.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico , TroponinaRESUMEN
The results reported by different studies on telemonitoring in patients with chronic obstructive pulmonary disease (COPD) have been contradictory, without showing clear benefits to date. The objective of this study was to ascertain whether an early discharge and home hospitalization telehealth program for patients with COPD exacerbation is as effective as and more efficient than a traditional early discharge and home hospitalization program. A prospective experimental non-inferiority study, randomized into two groups (telemedicine/control) was conducted. The telemedicine group underwent monitoring and was required to transmit data on vital constants and ECGs twice per day, with a subsequent telephone call and 2 home visits by healthcare staff (intermediate and at discharge). The control group received daily visits. The main variable was time until first exacerbation. The secondary variables were: number of exacerbations; use of healthcare resources; satisfaction; quality of life; anxiety-depression; and therapeutic adherence, measured at one and 6 months of hospital discharge. A total of 116 patients were randomized (58 to each group) without significant differences in baseline characteristics or time until first exacerbation, i.e. median 48 days (pp. 25-75:23-120) in the control group, and 47 days (pp. 25-75:19-102) in the intervention group; p = 0.52). A significant decrease in the number of visits was observed in the intervention versus the control group, 3.8 ± 1 vs 5.1 ± 2(p = 0.001), without significant differences in the number of exacerbations. In conclusion follow-up via a telemedicine program in early discharge after hospitalization is as effective as conventional home follow up, being the cost of either strategy not significantly different.