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1.
Eur Radiol ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38780764

RESUMEN

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians. KEY POINTS: Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents  the standardized tool for this purpose. Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations. The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively.

2.
Insights Imaging ; 14(1): 143, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37667135

RESUMEN

OBJECTIVES: Imaging guidelines could play an important role in the training of radiologists, but the extent of their adoption in residency programs is unclear. With this survey, the European Society of Urogenital Radiology (ESUR) Junior Network aimed to assess the dissemination of the ESUR guidelines on endometrial cancer MRI staging (EC-ESUR guidelines) among young radiologists. METHODS: An online questionnaire targeted to last year radiology residents and radiologists in the first year of their career was designed. It included 24 questions, structured in 4 sections (i.e., background, general, acquisition protocol, interpretation, and reporting). The survey was active between April and May 2022, accepting answers worldwide. Answers were solicited with a social media campaign and with the support of national scientific societies. Subgroup analysis was performed based on variables such as subspecialty of interest and number of EC-ESUR guidelines consultations using the Wilcoxon rank sum test. RESULTS: In total, 118 participants completed the questionnaire, of which 94 (80%) were from Europe and 46 (39%) with a special interest in urogenital radiology. Overall, 68 (58%) stated that the guidelines were not part of their residency teaching programs while 32 (27%) had never even consulted the guidelines. Interest in urogenital radiology as a subspecialty and EC-ESUR guidelines consultations were associated with greater confidence in supervising scan acquisition, interpreting, and reporting EC MRI staging exams. CONCLUSION: Four years after publication, the adoption of EC-ESUR guidelines in residency programs is heterogeneously low. Despite a possible selection bias, our findings indicate that active promotion of EC-ESUR guidelines is required. KEY POINTS: • The adoption of ESUR guidelines on endometrial cancer in radiology residency programs is heterogeneous. • Almost one third of respondents stated they had never even consulted the guidelines. • Confidence toward guidelines was higher in those who were exposed to more endometrial cancer MRI staging scans. • Reading the guidelines was associated with a greater confidence in protocol acquisition, interpretation, and reporting. • Active efforts to promote their dissemination are required.

3.
J Pers Med ; 13(5)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37240898

RESUMEN

PURPOSE: To assess the ability of apparent diffusion coefficient (ADC) measurements in predicting the histological grade of endometrial cancer. A secondary goal was to assess the agreement between MRI and surgical staging as an accurate measurement. METHODS: Patients with endometrial cancers diagnosed between 2018-2020 and having received both MRI and surgical staging were retrospectively enrolled. Patients were characterized according to histology, tumor size, FIGO stage (MRI and surgical stage), and functional MRI parameters (DCE and DWI/ADC). Statistical analysis was performed to determine if an association could be identified between ADC variables and histology grade. Secondarily, we assessed the degree of agreement between the MRI and surgical stages according to the FIGO classification. RESULTS: The cohort included 45 women with endometrial cancer. Quantitative analysis of ADC variables did not find a statistically significant association with histological tumor grades. DCE showed higher sensitivity than DWI/ADC in the assessment of myometrial invasion (85.00% versus 65.00%) with the same specificity (80.00%). A good agreement between MRI and histopathology for the FIGO stage was found (kappa of 0.72, p < 0.01). Differences in staging between MRI and surgery were detected in eight cases, which could not be justified by the interval between MRI and surgery. CONCLUSIONS: ADC values were not useful for predicting endometrial cancer grade, despite the good agreement between MRI interpretation and histopathology of endometrial cancer staging at our center.

4.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-36834764

RESUMEN

The use of viral vectors as therapeutic products for multiple applications such as vaccines, cancer treatment, or gene therapies, has been growing exponentially. Therefore, improved manufacturing processes are needed to cope with the high number of functional particles required for clinical trials and, eventually, commercialization. Affinity chromatography (AC) can be used to simplify purification processes and generate clinical-grade products with high titer and purity. However, one of the major challenges in the purification of Lentiviral vectors (LVs) using AC is to combine a highly specific ligand with a gentle elution condition assuring the preservation of vector biological activity. In this work, we report for the first time the implementation of an AC resin to specifically purify VSV-G pseudotyped LVs. After ligand screening, different critical process parameters were assessed and optimized. A dynamic capacity of 1 × 1011 total particles per mL of resin was determined and an average recovery yield of 45% was found for the small-scale purification process. The established AC robustness was confirmed by the performance of an intermediate scale providing an infectious particles yield of 54%, which demonstrates the scalability and reproducibility of the AC matrix. Overall, this work contributes to increasing downstream process efficiency by delivering a purification technology that enables high purity, scalability, and process intensification in a single step, contributing to time-to-market reduction.


Asunto(s)
Vectores Genéticos , Lentivirus , Lentivirus/genética , Ligandos , Reproducibilidad de los Resultados , Terapia Genética/métodos
5.
Arq. Asma, Alerg. Imunol ; 6(1): 4-48, jan.mar.2022. ilus
Artículo en Inglés, Portugués | LILACS | ID: biblio-1400091

RESUMEN

A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.


Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.


Asunto(s)
Humanos , Terapéutica , Conjuntivitis Alérgica , Diagnóstico , Queratoconjuntivitis , Pacientes , Plantas Medicinales , Prurito , Psicoterapia , Asma , Signos y Síntomas , Sociedades Médicas , Visión Ocular , Cambio Climático , Conjuntivitis Alérgica/complicaciones , Conjuntivitis Alérgica/epidemiología , Terapias Complementarias , Inmunoglobulina E , Pruebas Serológicas , Pruebas Cutáneas , Alérgenos , Rinitis , Rinitis Alérgica Estacional , Probióticos , Acupuntura , Pyroglyphidae , Dermatitis Atópica , Contaminación Ambiental , Alergia e Inmunología , Anticuerpos Monoclonales Humanizados , Omalizumab , Estabilizadores de Mastocitos , Antagonistas de los Receptores Histamínicos , Hipersensibilidad , Inmunosupresores , Inmunoterapia , Medicina Ayurvédica , Ácaros
6.
J Med Internet Res ; 23(9): e25472, 2021 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-34550077

RESUMEN

BACKGROUND: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients' daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities. OBJECTIVE: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage. METHODS: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R. RESULTS: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were ≤40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83). CONCLUSIONS: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users' general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use.


Asunto(s)
Asma , Aplicaciones Móviles , Adulto , Asma/epidemiología , Asma/terapia , Ejercicio Físico , Conductas Relacionadas con la Salud , Humanos
7.
JMIR Mhealth Uhealth ; 9(5): e26442, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-34032576

RESUMEN

BACKGROUND: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). METHODS: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. RESULTS: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). CONCLUSIONS: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.


Asunto(s)
Asma , Aplicaciones Móviles , Adolescente , Adulto , Asma/tratamiento farmacológico , Estudios de Factibilidad , Humanos , Cumplimiento de la Medicación , España
8.
Artículo en Inglés | MEDLINE | ID: mdl-33498858

RESUMEN

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.


Asunto(s)
Asma , Adolescente , Asma/diagnóstico , Asma/epidemiología , Femenino , Humanos , Masculino , Fenotipo , Portugal/epidemiología , Estudios Prospectivos , España/epidemiología
9.
Front Med Technol ; 3: 649506, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35047915

RESUMEN

Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support. Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use. Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app ≥30 days was used as the cut-off for higher app use. Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25-P75) 16-36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3-45] days, translated on a median use rate of 15 [3-38]%. Median inhaler adherence assessed through the app was 34 [4-73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6-83]% and 43 [3-73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen. Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.

10.
Biotechnol J ; 16(1): e2000019, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33089626

RESUMEN

Lentiviral vectors (LVs) have been increasingly used as a tool for gene and cell therapies since they can stably integrate the genome in dividing and nondividing cells. LV production and purification processes have evolved substantially over the last decades. However, the increasing demands for higher quantities with more restrictive purity requirements are stimulating the development of novel materials and strategies to supply the market with LV in a cost-effective manner. A detailed review of each downstream process unit operation is performed, limitations, strengths, and potential outcomes being covered. Currently, the majority of large-scale LV manufacturing processes are still based on adherent cell culture, although it is known that the industry is migrating fast to suspension cultures. Regarding the purification strategy, it consists of batch chromatography and membrane technology. Nevertheless, new solutions are being created to improve the current production schemes and expand its clinical use.


Asunto(s)
Vectores Genéticos , Lentivirus , Técnicas de Cultivo de Célula , Cromatografía por Intercambio Iónico , Vectores Genéticos/genética , Vectores Genéticos/aislamiento & purificación , Células HEK293 , Humanos , Lentivirus/genética , Lentivirus/aislamiento & purificación
11.
Acta Radiol ; 62(6): 839-847, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32702998

RESUMEN

BACKGROUND: PI-RADS classification has recently been updated, with the magnitude of changes implemented currently unknown. PURPOSE: To quantify the categorization shifts between PI-RADS v2.0 and v2.1. MATERIAL AND METHODS: Retrospective review of 535 consecutive diagnostic magnetic resonance imaging (MRI) studies performed over 18 months, assigning to each case a PI-RADS category in the peripheral zone (PZ), the transition zone (TZ), and the whole gland using both PI-RADS v2.0 and v2.1. Significance of changes in category assignments and of differences in the number of positive or negative MRIs were evaluated using the McNemar test. RESULTS: Comparing v2.0 to v2.1 for the whole gland, 11.2% of PI-RADS 2 categories shifted to PI-RADS 1 (6.9% in the PZ, 56.8% in the TZ), 16.1% of PI-RADS 3 categories shifted to PI-RADS 2 (15.0% in the PZ, 20.0% in the TZ), and 2.1% of PI-RADS 2 categories shifted to PI-RADS 3 (0.3% in the PZ, 1.9% in the TZ). The proportion of PI-RADS 1 significantly increased from 0.6% to 7.3%, PI-RADS 2 significantly decreased from 60.0% to 53.8%, and PI-RADS 3 non-significantly decreased from 11.6% to 11.0%. The total number of positive exams (PI-RADS 3-5) did not change significantly (39.4% versus 38.8%). CONCLUSION: The most prominent change between v2.0 and v2.1 was observed in the TZ with the downgrading of typical benign prostatic hyperplasia nodules from category 2 into category 1. Overall, there were no significant changes in the number of positive and negative MRI results, with an expected low influence in clinical management.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Neoplasias de la Próstata/diagnóstico por imagen , Sistemas de Información Radiológica/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/clasificación , Estudios Retrospectivos , Sensibilidad y Especificidad
12.
Diagn Interv Radiol ; 26(5): 403-410, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32815522

RESUMEN

PURPOSE: We aimed to identify if there is an association between the severity of cervical cancer at diagnosis and the pattern of recurrence. METHODS: We conducted a retrospective study of recurrent cervical cancers diagnosed between 2016 and 2018. We characterized the cases according to histology, size, FIGO stage (according to 2009 and 2018 FIGO classifications) and nodal involvement at diagnosis, symptoms at the time of recurrence, interval between the end of treatment and recurrence, imaging methods used, and location of the recurrence. Statistical analysis was performed between histology, size, FIGO stage and nodal involvement at diagnosis and time to recurrence and type of recurrence (locoregional versus lymph node, distant or multiple site involvement). RESULTS: We included 48 patients with recurrent cervical cancer. At diagnosis, mean tumor size was 5 cm and 83% of the patients had squamous cell carcinoma. The FIGO stage changed in 43.8% of patients between the 2009 and the 2018 classifications. A mean of 26 months elapsed between the end of treatment and recurrence. Recurrence was symptomatic in 64.6% of patients. Imaging identified recurrence in 97.9% of patients. The most frequent recurrence sites were locoregional and lymph node metastases. We found a statistically significant association between 2009 FIGO stage and time to recurrence (P = 0.030) and lymph node involvement at diagnosis and type of recurrence (P = 0.022). As expected patients with more advanced disease recurred sooner, though this was only observed for the 2009 FIGO classification. Absence of lymph nodes at initial diagnosis was associated with locoregional recurrence, while presence of lymph node involvement was associated with lymph node, distant or multiple site involvement of recurrence. No other significant associations were found. CONCLUSION: In our cohort of recurrent cervical cancer, we found an association between patients without lymph node metastases at initial diagnosis and locoregional recurrence. Further studies are needed in order to evaluate whether this association has predictive value.


Asunto(s)
Neoplasias del Cuello Uterino , Femenino , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Recurrencia Local de Neoplasia/diagnóstico por imagen , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología
13.
Biotechnol J ; 15(4): e1900411, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31950598

RESUMEN

Recent clinical trials have shown the potential of oncolytic adenoviruses as a cancer immunotherapy. A successful transition of oncolytic adenovirus to clinical applications requires efficient and good manufacturing practice compatible production and purification bioprocesses. Suspension cultures are preferable for virus production as they can reduce process costs and increase product quality and consistency. This work describes the adaptation of the A549 cell line to suspension culture in serum-reduced medium validated by oncolytic adenovirus production in stirred tank bioreactor. Cell concentrations up to 3 × 106 cells mL-1 are obtained during the production process. At harvest 1.4 × 1010 infectious particles mL-1 and 6.9 ± 1.1 × 1010 viral genome mL-1 are obtained corresponding to a viral genome: infectious particles ratio of 5.2 (± 1.9): 1 confirming the virus quality. Overall, the suspension characteristics of these A549 cells support an easily scalable, less time-consuming, and more cost-effective process for expanded success in the use of oncolytic viruses for cancer therapy.


Asunto(s)
Adenoviridae/crecimiento & desarrollo , Técnicas de Cultivo de Célula/métodos , Virus Oncolíticos/crecimiento & desarrollo , Células A549 , Adenoviridae/genética , Reactores Biológicos , Medios de Cultivo , Genoma Viral , Humanos , Microscopía Electrónica de Transmisión , Virus Oncolíticos/genética , Suspensiones , Cultivo de Virus
14.
BMJ Open ; 9(11): e031732, 2019 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-31699737

RESUMEN

OBJECTIVE: We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance. DESIGN: Baseline data from two prospective multicentre observational studies. SETTING: 29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal. PARTICIPANTS: 395 patients (≥13 years old) with persistent asthma. MEASURES: Data on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV1) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0-50; medium 51-80; high 81-100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients' and physicians' VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation. RESULTS: High inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65-95) mm; 53% VAS>80) and by physicians (84 (68-95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (rs=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R2=44%). CONCLUSION: Although both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.


Asunto(s)
Asma/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Relaciones Médico-Paciente , Administración por Inhalación , Adolescente , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
15.
J Vet Intern Med ; 33(5): 2280-2285, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31441559

RESUMEN

BACKGROUND: Wei Le San (WLS) is a Chinese herbal formula comprised of 9 herbs selected for their putative anti-inflammatory effects. OBJECTIVES: To evaluate the effects of WLS administration in horses with nonglandular gastric ulcers. ANIMALS: Ten mixed breed mares (aged 7-21 years, 401-567 kg body weight). METHODS: Experimental design was a blinded, prospective, 2-period crossover study. All horses received a placebo (25 mL dextrose-based syrup; n = 10) and the treatment (WLS, 5 g in 25 mL dextrose-based syrup; n = 10), administered twice daily. Horses underwent a 1-week, alternating feed-deprivation period to induce or worsen existing ulcers; treatment began on day 7. Gastroscopic examination was performed on d0, d6, and d35, with gastric fluid pH obtained on d6 and d35. Gastric ulcer scores assigned by 3 masked observers were averaged for each examination. RESULTS: Ulcer number scores for horses treated with WLS (median = 0; range, 0-4) was not different from the untreated controls (median = 0.5; range, 0-4; P = .81) by the end of the treatment period. Ulcer severity score for treated horses (median = 0; range, 0-1) was also unchanged compared to the control group (median = 0.5; range, 0-1; P = .85). Gastric pH was not altered by either treatment, with a median of 2.1 (range, 1.9-4.1) for the horses treated with WLS and 2.8 (range, 1.6-7.2) in the untreated controls (P = .46). CONCLUSIONS AND CLINICAL IMPORTANCE: The experimental model used to induce gastric ulceration was unable to discern a difference between the herbal supplement and the placebo in normal horses.


Asunto(s)
Medicamentos Herbarios Chinos/farmacología , Contenido Digestivo/química , Enfermedades de los Caballos/tratamiento farmacológico , Úlcera Gástrica/veterinaria , Administración Oral , Animales , Estudios Cruzados , Medicamentos Herbarios Chinos/administración & dosificación , Femenino , Privación de Alimentos , Gastroscopía/veterinaria , Caballos , Concentración de Iones de Hidrógeno , Estudios Prospectivos , Úlcera Gástrica/tratamiento farmacológico
16.
PLoS One ; 13(1): e0190974, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29315346

RESUMEN

Mucins are high-molecular weight glycoproteins (0.25-20 MDa) containing one or more domains that are heavily O-glycosylated. Their implications as targets for cancer treatment have increased the interest in these glycoproteins, mainly in the fields of vaccines and antibodies. However, mucins present high heterogeneity, posing challenges that affect purification processes and quality control analysis. In that sense, it is necessary to develop and improve downstream processes and analytical methods to characterize these products. Here a tool based on biolayer interferometry analysis to improve mucin's detection and quantification in a fast, simple and label free-way is presented. Taking advantage of lectin recognition of mucins' carbohydrate structures, several lectins were evaluated and immobilized on streptavidin biosensors. Different assay conditions were optimized and the most suitable lectin, Aleuria aurantia lectin (AAL), was selected. Bovine Submaxillary Gland and human MUC5B mucins were used as proof of concept and were successfully detected and quantified at different stages of purification. High sensitivity levels were achieved with LOD and LOQ of 3.8 µg mL-1 and 11.7 µg mL-1 for BSM, and 0.2 µg mL-1 and 0.6 µg mL-1 for MUC5B. AAL binding specificity was also confirmed with fucose competition assays. Our method represents an advance on mucins detection and quantification since the existing methods present several disadvantages for process development. Hereafter, it can be applied to the optimization of new or already established downstream processes for mucins' purification.


Asunto(s)
Modelos Moleculares , Mucinas/metabolismo , Cromatografía en Gel , Electroforesis en Gel de Poliacrilamida , Glicosilación
17.
Rev Bras Ter Intensiva ; 28(3): 330-334, 2016 Sep.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-27737432

RESUMEN

OBJECTIVE: To identify and evaluate the correct positioning of the most commonly used medical devices as visualized in thoracic radiograms of patients in the intensive care unit of our center. METHODS: A literature search was conducted for the criteria used to evaluate the correct positioning of medical devices on thoracic radiograms. All the thoracic radiograms performed in the intensive care unit of our center over an 18-month period were analyzed. All admissions in which at least one thoracic radiogram was performed in the intensive care unit and in which at least one medical device was identifiable in the thoracic radiogram were included. One radiogram per admission was selected for analysis. The radiograms were evaluated by an independent observer. RESULTS: Out of the 2,312 thoracic radiograms analyzed, 568 were included in this study. Several medical devices were identified, including monitoring leads, endotracheal and tracheostomy tubes, central venous catheters, pacemakers and prosthetic cardiac valves. Of the central venous catheters that were identified, 33.6% of the subclavian and 23.8% of the jugular were malpositioned. Of the endotracheal tubes, 19.9% were malpositioned, while all the tracheostomy tubes were correctly positioned. CONCLUSION: Malpositioning of central venous catheters and endotracheal tubes is frequently identified in radiograms of patients in an intensive care unit. This is relevant because malpositioned devices may be related to adverse events. In future studies, an association between malpositioning and adverse events should be investigated.


Asunto(s)
Equipos y Suministros , Unidades de Cuidados Intensivos , Radiografía Torácica/métodos , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Equipos y Suministros/efectos adversos , Femenino , Humanos , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/instrumentación , Masculino , Estudios Retrospectivos
18.
Rev. bras. ter. intensiva ; 28(3): 330-334, jul.-set. 2016. tab, graf
Artículo en Portugués | LILACS | ID: lil-796169

RESUMEN

RESUMO Objetivo: Identificar e avaliar o posicionamento correto dos dispositivos médicos mais comumente utilizados, observados nas radiografias de tórax de pacientes durante a permanência em unidade de terapia intensiva de nosso centro. Métodos: Foi realizada uma pesquisa bibliográfica quanto aos critérios utilizados para avaliar o posicionamento correto dos dispositivos médicos nas radiografias de tórax. Avaliamos todas as radiografias de tórax realizadas na unidade de terapia intensiva de nosso centro durante um período de 18 meses. Incluíram-se todas as admissões nas quais foi realizada uma radiografia do tórax na unidade de terapia intensiva, nas quais fosse identificável a presença de pelo menos um dispositivo médico. Para análise, selecionou-se uma radiografia por admissão. As radiografias foram avaliadas por um observador independente. Resultados: De um total de 2.312 radiografias analisadas, 568 foram incluídas neste estudo. Identificaram-se diversos dispositivos médicos, incluindo eletrodos de monitoramento, tubos endotraqueais, cânulas de traqueostomia, cateteres venosos centrais, marca-passos e próteses valvares cardíacas. Dentre os cateteres venosos centrais identificados, 33,6% dos subclávios e 23,8% dos jugulares estavam mal posicionados. Dentre os tubos endotraqueais, 19,9% estavam mal posicionados, enquanto todas as cânulas de traqueostomia tinham posicionamento correto. Conclusão: Frequentemente se identificam, na radiografia de tórax realizada em pacientes na unidade de terapia intensiva, cateteres venosos e tubos endotraqueais mal posicionados. Isso é importante, pois dispositivos mal posicionados podem se relacionar a eventos adversos. Estudos futuros devem investigar possíveis associações entre o mau posicionamento dos dispositivos e eventos adversos.


ABSTRACT Objective: To identify and evaluate the correct positioning of the most commonly used medical devices as visualized in thoracic radiograms of patients in the intensive care unit of our center. Methods: A literature search was conducted for the criteria used to evaluate the correct positioning of medical devices on thoracic radiograms. All the thoracic radiograms performed in the intensive care unit of our center over an 18-month period were analyzed. All admissions in which at least one thoracic radiogram was performed in the intensive care unit and in which at least one medical device was identifiable in the thoracic radiogram were included. One radiogram per admission was selected for analysis. The radiograms were evaluated by an independent observer. Results: Out of the 2,312 thoracic radiograms analyzed, 568 were included in this study. Several medical devices were identified, including monitoring leads, endotracheal and tracheostomy tubes, central venous catheters, pacemakers and prosthetic cardiac valves. Of the central venous catheters that were identified, 33.6% of the subclavian and 23.8% of the jugular were malpositioned. Of the endotracheal tubes, 19.9% were malpositioned, while all the tracheostomy tubes were correctly positioned. Conclusion: Malpositioning of central venous catheters and endotracheal tubes is frequently identified in radiograms of patients in an intensive care unit. This is relevant because malpositioned devices may be related to adverse events. In future studies, an association between malpositioning and adverse events should be investigated.


Asunto(s)
Humanos , Masculino , Femenino , Radiografía Torácica/métodos , Unidades de Cuidados Intensivos , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Estudios Retrospectivos , Equipos y Suministros/efectos adversos , Intubación Intratraqueal/efectos adversos , Intubación Intratraqueal/instrumentación
19.
Rev. psicol. organ. trab ; 15(2): 146-156, jun. 2015. tab
Artículo en Portugués | LILACS-Express | LILACS | ID: lil-747921

RESUMEN

Esta investigação pretende relacionar dois conceitos de natureza psicológica integrados no sistema do self a autoestima e a satisfação com a vida de adultos portugueses em situação de desemprego. Face à atual conjuntura socioeconômica, as taxas de desemprego têm disparado para valores históricos, havendo necessidade de conhecer de que forma esse fenômeno se relaciona com a percepção dos sujeitos na avaliação de si próprios e de satisfação com suas vidas. O estudo de natureza correlacional é constituído por 80 sujeitos em situação de desemprego, inscritos em um centro de emprego e que recebem proteção social por meio da atribuição do Rendimento Social de Inserção (RSI). Os resultados apontam para correlações positivas significativas entre a autoestima e a satisfação com a vida, a idade e a duração da situação de desemprego, a idade e a duração do período de atribuição do RSI e, ainda, esse período e a duração da situação de desemprego. Foi registrada uma correlação negativa e significativa entre a autoestima e a duração da situação de desemprego. Conclui-se globalmente que a duração da situação de desemprego do sujeito afeta sua autoestima e que a proteção social, como garantia de subsistência primária, não se relaciona com as variáveis do sistema do self em estudo, mais sofisticadas e com outras necessidades implícitas. O estudo aponta para a atenção que deverá ser dirigida aos desempregados de longa duração, mais velhos e, portanto, que recebem proteção social há mais tempo.


This research aims to relate two psychological concepts integrated in the self system, namely, self-esteem and life satisfaction of unemployed Portuguese adults. Given the current socio-economic situation, unemployment rates have been increasing to historical levels, raising the need to know how this phenomenon relates to the perception of self-evaluation and of the evaluation of life satisfaction. This is a correlational study based on a sample of 80 unemployed subjects registered in a job center and who receive social protection through the Social Inclusion Income (SII). The results show significant positive correlations between self-esteem and life satisfaction, between the subjects' age and the duration of the unemployment situation, between the subjects' age and the duration of the period during which they receive the SII, and even between this period and the duration of unemployment. There was only one significant negative correlation between self-esteem and the duration of unemployment. We conclude that the overall duration of the unemployment situation affects the self-esteem and that social protection, as a primary means of subsistence, is not related to the variables of the self system under study, which are more sophisticated and with other implied needs. The study suggests that attention should be directed to the long-term unemployed subjects, who are older and therefore have been receiving social protection for a longer period of time.


Esta investigación pretende comparar dos conceptos de naturaleza psicológica, integrados en el sistema del self, a saber, la autoestima y la satisfacción con la vida de adultos portugueses que se encuentran desempleados. Dado el actual contexto socio-económico, las tasas de desempleo se han disparado a niveles históricos, haciendo necesario conocer cómo este fenómeno se relaciona con la percepción de los sujetos en la evaluación de sí mismos y en la evaluación que hacen de la satisfacción con su vida. El estudio, de naturaleza correlacional, comprendió 80 sujetos que estaban desempleados, registrados en un centro de empleo y que recibían protección social por medio de la concesión del Rendimiento Social de Inserción (RSI). Los resultados muestran correlaciones significativas positivas entre la autoestima y la satisfacción con la vida, entre la edad y la duración del desempleo, entre la edad y la duración del período de recibimiento del RSI y entre este período y la duración de la situación de desempleo. Se registró una correlación negativa y significativa entre la autoestima y la duración de la situación de desempleo. Se concluyó que, globalmente, la duración de la situación de desempleo del sujeto afecta su autoestima y que la protección social, como garantía de subsistencia primaria no se relaciona con las variables del sistema del self en este estudio, más sofisticadas y otras necesidades implícitas. El estudio señala que se deberá prestar atención a las personas que están desempleadas por largos periodos, que son mayores y que, por lo tanto, reciben la protección social por más tiempo.

20.
Anal Chim Acta ; 764: 24-31, 2013 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-23374211

RESUMEN

This work describes a mid-infrared (MIR) metabolic profiling study of 2nd trimester amniotic fluid in relation to selected prenatal disorders, with results focusing on fetal malformations (FM), preterm delivery (PTD) and premature rupture of membranes (PROM), the latter two conditions occurring later in pregnancy. Partial least squares-discriminant analysis (PLS-DA) models were obtained for FM and pre-PTD subject groups, supported by Monte Carlo Cross Validation (MCCV), and identified specific MIR profile changes. For pre-PROM subjects, minor changes were noted. MIR interpretation was assisted by intra- (MIR/MIR) and inter- (MIR/NMR) domain statistical correlation analysis, the results unveiling possible biomarker MIR signatures for FM and pre-PTD subjects. Biofluid MIR metabolic profiling holds enticing possibilities as a low cost, easy to use, rapid method and the results presented have shown its sensitivity to clinically diagnosed conditions such as FM, and to the pre-clinical stages of PTD. Specific improvement needs are discussed, namely regarding sample numbers and experimental reproducibility.


Asunto(s)
Líquido Amniótico/metabolismo , Rotura Prematura de Membranas Fetales/diagnóstico , Nacimiento Prematuro/diagnóstico , Espectrofotometría Infrarroja , Líquido Amniótico/química , Anomalías Congénitas , Análisis Discriminante , Diagnóstico Precoz , Femenino , Rotura Prematura de Membranas Fetales/metabolismo , Edad Gestacional , Humanos , Análisis de los Mínimos Cuadrados , Método de Montecarlo , Embarazo , Segundo Trimestre del Embarazo , Nacimiento Prematuro/metabolismo , Diagnóstico Prenatal
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