Farming Sparus aurata (Teleostei: Sparidae) in marsh ponds: trophic characterization and trace metal accumulation.

Considering the overexploitation of fishing on most of the world coasts, the ingestion of fish and shellfish will depend mostly on aquaculture production. Since intensive mariculture usually involves environmental impact, developing sustainable cultures is a priority. In this sense, salt marshes can provide ecosystem services and incorporate both conservation and extensive aquaculture activities. In the present study we compared gilthead seabream Sparus aurata Linnaeus, 1758 cultured in extensive and semi-intensive marsh ponds with wild conspecifics from surrounding coastal areas, using trophic characterization (diet analysis and stable isotopes) and trace metal accumulation. Stomach content analysis revealed different feeding habits among gilthead seabream from different origin. Although wild specimens had the most diverse diet, results of stable isotopes showed that extensive diet had the wider isotopic niche and revealed the highest similarities between wild and extensively cultured gilthead seabream. A similar trace element signature was also measured in wild and extensive culture, whereas the semi-intensive culture showed different concentrations for several elements. Cr, Fe and Mn showed the highest concentrations in semi-intensive cultured fish, while As and Zn showed the lowest values in this group. In any case, average values measured in both extensive and semi-intensive culture were, in general terms, below the hazardous limits provided by the standards recommended for trace metals by national and international regulations. Therefore, marsh ponds provide a suitable environment where the cultured fish, especially extensive, should be promoted.

Bioaccessibility of glucosinolates, isothiocyanates and inorganic micronutrients in cruciferous vegetables through INFOGEST static in vitro digestion model.

Green tissues and seeds from cruciferous vegetables growing in conventional and ecological conditions (Brassica carinata; Brassica rapa; Eruca vesicaria and Sinapis alba) were analyzed to determine their contents of glucosinolates, isotihiocyanates (ITCs) and inorganic micronutrients (Ca, Cr, Cu, Fe, Mn, Ni, Se and Zn), and the bioaccessibility of these compounds. Regarding total contents and bioaccessibility values of these compounds, no clear difference was found between the organic and conventional systems. Glucosinolates bioaccessibility present in green tissues were high, with values around 60-78%. In additon, it was quantified in bioaccessible fraction ITCs concentrations such as Allyl - ITC; 3 - Buten - 1 - yl - ITC and 4 - Penten - 1 - yl - ITC. Trace elements bioaccessibility in green tissues was also high for Ca (2.26-7.66 mg/g), Cu (0.60-2.78 µg/g), Se (9.93-74.71 µg/Kg) and Zn (12.98-20.15 µg/g). By contrast, the bioaccessibility of glucosinolates and trace elements in cruciferous seeds was extremely low. With the exception of Cu, these bioaccessibility percentages did not exceed 1% in most cases.

Traceability and comparability through crosswalks with the NeuroMET Memory Metric.

Accurate assessment of memory ability for persons on the continuum of Alzheimer's disease (AD) is vital for early diagnosis, monitoring of disease progression and evaluation of new therapies. However, currently available neuropsychological tests suffer from a lack of standardization and metrological quality assurance. Improved metrics of memory can be created by carefully combining selected items from legacy short-term memory tests, whilst at the same time retaining validity, and reducing patient burden. In psychometrics, this is known as "crosswalks" to link items empirically. The aim of this paper is to link items from different types of memory tests. Memory test data were collected from the European EMPIR NeuroMET and the SmartAge studies recruited at Charité Hospital (Healthy controls n = 92; Subjective cognitive decline n = 160; Mild cognitive impairment n = 50; and AD n = 58; age range 55-87). A bank of items (n = 57) was developed based on legacy short-term memory items (i.e., Corsi Block Test, Digit Span Test, Rey's Auditory Verbal Learning Test, Word Learning Lists from the CERAD test battery and Mini Mental State Examination; MMSE). The NeuroMET Memory Metric (NMM) is a composite metric that comprises 57 dichotomous items (right/wrong). We previously reported on a preliminary item bank to assess memory based on immediate recall, and have now demonstrated direct comparability of measurements generated from the different legacy tests. We created crosswalks between the NMM and the legacy tests and between the NMM and the full MMSE using Rasch analysis (RUMM2030) and produced two conversion tables. Measurement uncertainties for estimates of person memory ability with the NMM across the full span were smaller than all individual legacy tests, which demonstrates the added value of the NMM. Comparisons with one (MMSE) of the legacy tests showed however higher measurement uncertainties of the NMM for people with a very low memory ability (raw score ≤ 19). The conversion tables developed through crosswalks in this paper provide clinicians and researchers with a practical tool to: (i) compensate for ordinality in raw scores, (ii) ensure traceability to make reliable and valid comparisons when measuring person ability, and (iii) enable comparability between test results from different legacy tests.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Servicios de Atención Farmacéutica en farmacias de comunidad privada de Costa Rica: percepción de usuarios / Pharmaceutical Care Services in private community pharmacies in Costa Rica: user perception

Introducción: Las farmacias de comunidad privada en Costa Rica tienen una amplia trayectoria. Sin embargo, los servicios de Atención Farmacéutica desarrollados en estos centros de salud son poco conocidos y documentados, lo que dificulta determinar la importancia de estos servicios para la sociedad.Método: Este es un estudio observacional, descriptivo realizado en los cinco cantones con mayor número de farmacias de comunidad privada de la provincia de San José (capital de Costa Rica). El estudio se realizó mediante la aplicación de un cuestionario a usuarios habituales de las farmacias seleccionadas durante el año 2018.Resultados: Se realizaron un total de 385 encuestas. El análisis de los cuestionarios indica que un 60,8% de los usuarios asisten por lo menos una vez al mes a la farmacia. El 93% considera que el farmacéutico es un profesional que trasmite confianza y seguridad y el 79% indica que su salud puede mejorar si recibe educación continua por parte del regente farmacéutico.Conclusiones: Los resultados evidencian la necesidad del desarrollo de un programa de Atención Farmacéutica en el ámbito privado. Ya que los usuarios consideran que, por ser las farmacias lugares de fácil acceso, su salud mejoraría de ser orientados sobre su tratamiento en una forma continua. (AU)

Introduction: Private community pharmacies in Costa Rica have a long history. However, developed Pharmaceutical Care services in these health centers are little known and documented, which makes it difficult to determine the importance of these services for society.Method: This is an observational, descriptive study carried out in the five cities in the province of San Jose (Costa Rica capital) with the highest number of pharmacies. The study was carried out by applying a questionnaire to regular users of the selected pharmacies during 2018.Results: A total of 385 surveys were conducted. The analysis of the questionnaires indicates that 60.8% of users attend the pharmacy at least once a month. 93% consider that the pharmacist is a professional who transmits confidence and security and 79% indicate that their health can improve if they receive continuous education from the pharmaceutical.Conclusions: The results show the need for the development of a Pharmaceutical Care program in the private sphere. Since users consider that, as pharmacies are easily accessible places, their health would improve if they were guided about their treatment on a continuous basis. (AU)

Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort.

Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

Histopathological features for coexistent invasive cancer in large colorectal adenomatous polyps.

BACKGROUND: Histopathological features associated with coexistent invasive adenocarcinoma in large colorectal adenomas have not been described. This study aimed to determine the association of histopathological features in areas of low-grade dysplasia with coexistent invasive adenocarcinoma. METHODS: High-grade lesions (containing high-grade dysplasia or adenocarcinoma) from a cohort of large (at least 20 mm) colorectal adenomas removed by endoscopic resection were subjected to detailed histopathological analysis. The histopathological features in low-grade areas with coexistent adenocarcinoma were reviewed and their diagnostic performance was evaluated. RESULTS: Seventy-four high-grade lesions from 401 endoscopic resections of large adenomas were included. In the low-grade dysplastic areas, a coexistent invasive adenocarcinoma was associated significantly with a cribriform or trabecular growth pattern (P < 0.001), high nuclear grade (P < 0.001), multifocal intraluminal necrosis (P < 0.001), atypical mitotic figures (P = 0.006), infiltrative lesion edges (P < 0.001), a broad fibrous band (P = 0.001), ulceration (P < 0.001), expansile nodules (P < 0.001) and an extensive tumour-infiltrating lymphocyte pattern (P = 0.04). Lesions with coexistent invasive adenocarcinoma harboured at least one of these features. The area under the receiver operating characteristic curve (AUROC) for coexistent invasive adenocarcinoma, using frequencies of adverse histopathological factors in low-grade areas, was 0.92. The presence of two or more of these adverse histopathological features in low-grade areas had a sensitivity of 86 per cent and a specificity of 84 per cent for coexistent invasive adenocarcinoma. CONCLUSION: Several histopathological features in low-grade dysplastic areas of adenomas could be predictive of coexistent adenocarcinoma.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study.

OBJECTIVE: The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. DESIGN: Prospective descriptive multicenter cohort study. SETTING: 26 Intensive care units (ICU) from Andalusian region in Spain. PATIENTS OR PARTICIPANTS: Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. INTERVENTIONS: None. VARIABLES: Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. RESULTS: 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%; 14 days mortality: 81/422 (19.2%); 28 days mortality: 121/422 (28.7%); 6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. CONCLUSION: Age, APACHE II, SOFA>value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Quantification and in vitro bioaccessibility of glucosinolates and trace elements in Brassicaceae leafy vegetables.

Leaf samples from five Brassicaceae species (Brassica carinata, Brassica oleracea, Brassica rapa, Eruca vesicaria and Sinapis alba) were analyzed to determine their contents of glucosinolates and trace elements, and the bioaccessibility of these compounds. Considerable variability in the total contents and glucosinolate profiles was observed in the Brassicaceae species, with the total amounts ranging from 8.5 µmol/g dw in Brassica oleracea to 32.9 µmol/g dw in Sinapis alba. Bioaccessibilities of the predominant glucosinolates were moderate, ranging from 13.1% for glucoraphanin to 43.2% for gluconapin, which is particularly relevant as they have been implicated in a variety of anti-carcinogenic mechanisms. Trace element concentrations were: Se (28-160 µg/Kg dw); Cr (0.31-4.03 µg/g dw); Ni (0.19-1.53 µg/g dw); Fe (8.6-18.8 µg/g dw); Zn (20.8-41.5 µg/g dw); Ca (6.2-15.2 mg/g dw). Brassicaceae leaves were also moderate dietary sources of Se, Ni, Zn and Ca.

[The development of an mHealth app with young people in mental health care using Agile; a practical experiment]. / Agile ontwikkelen van een m-healthapp met jongeren in de ggz: een praktijk-experiment.

BACKGROUND: In recent years, many mobile health (mHealth) apps have been developed to support diagnostics and treatment, among other purposes. It is likely that involving patients closely in the development process will lead to more relevant apps. In theory, the Agile style of software development can make this possible. However, whether this is feasible in mental healthcare practice has never been investigated.
AIM: To investigate whether it is possible in practice to develop an mHealth app together with young people in a highly specialized mental healthcare context, by using Agile.
METHOD: A proof-of-concept study that seeks to develop an mHealth app by implementing Agile together with clinically admitted, young psychiatric patients. Patients would directly influence the development goals and priorities.
RESULTS: In the period from May to July 2019 the app 'Constant Circles' has been developed using Agile together with patients. The main focus of this app is social support. The patients supplied 18 concrete user stories and also provided feedback with general principles for developing an mHealth app.
CONCLUSION: This study has demonstrated that it is possible to closely involve patients in highly specialized mental health care in the development process of an mHealth app by using Agile.

Proxy reporting of health-related quality of life for people with dementia: a psychometric solution.

BACKGROUND: The growing move towards personalised health and social care systems means that every effort needs to be made to generate patient-reported outcome data. However, the deteriorating nature of dementia can make it difficult for people with dementia to complete self-reported questionnaires and it is often necessary to rely on a family member (proxy) to report on their behalf. There is little evidence to guide how the difference between self- and proxy-reports of health reported quality of life (HRQL) in dementia can be interpreted. METHODS: We recruited people with dementia and their family carers from 78 memory Assessment Services in the UK. We used Rasch measurement methods to investigate whether a HRQL questionnaire known as DEMQOL (self-reported by the person with dementia) and DEMQOL-Proxy (proxy-reported by a family carer) can be placed on the same continuum and whether a revised scoring algorithm, based on this equated model, can be developed that takes account of the relationship between self- and proxy-reports. RESULTS: In a sample of 1434 patients and 1030 carers, our findings supported equating DEMQOL/DEMQOL-Proxy (overall fit to the model; no mis-fitting items) after addressing specific issues (eight disordered items requiring re-scoring, four pairs locally dependent items, and five items showing DIF). Cross walk tables have been produced. CONCLUSIONS: We have established for the first time that DEMQOL and DEMQOL-Proxy can be placed on the same continuum and that patients and carer proxies are reporting on the same construct when they complete these questionnaires. Where possible both DEMQOL and DEMQOL-Proxy should still be administered together, using the improved scoring algorithm reported here. Where only DEMQOL-Proxy is available, the cross walk tables provide an estimate of DEMQOL for a particular person from their DEMQOL-Proxy score.

¿Se debe restringir el ingreso en cuidados intensivos solo a los pacientes más graves? / Should intensive care admission be restricted to the most severely ill patients?

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Development of a new patient-reported outcome measure to evaluate treatments for acne and acne scarring: the ACNE-Q.

BACKGROUND: Psychosocial concerns represent important outcomes in studies of treatments for acne and acne scarring. Also important, but largely overlooked, is the concept of appearance. OBJECTIVES: To design an acne-specific patient-reported outcome measure for acne and acne scarring. METHODS: We used a mixed-methods approach. Phase I involved 21 patient interviews that were audio-recorded, transcribed and coded. Concepts were identified and developed into scales that were refined through 10 cognitive interviews and input from 16 clinical experts. Phase II involved data collection at hospital and community-based dermatology clinics in Canada and the U.S.A. Eligible participants were aged 12 years and older with acne and/or acne scars on the face, chest and/or back. Rasch Measurement Theory (RMT) analyses were performed to examine psychometric properties. RESULTS: Phase I led to the development of seven scales that measure appearance of facial skin, acne (face, chest and back) and acne scars, acne-specific symptoms and appearance-related distress. In phase II, 256 patients completed the ACNE-Q. RMT analysis provided evidence that the items of each scale worked together conceptually and statistically. Most participants scored within the range of measurement for each scale (81·9-93·1%). Reliability was high, with person separation index values and Cronbach alpha values > 0·90 for the appearance scales, ≥ 0·87 for appearance-related distress and ≥ 0·75 for symptoms. Worse scores on appearance scales correlated with worse symptom scores and more appearance-related distress. CONCLUSIONS: The ACNE-Q is a rigorously developed instrument that can be used to measure appearance and other patient-centred concerns. What's already known about this topic? Acne is a common dermatological condition that can have an important impact on psychosocial function. Current patient-reported outcome measures specific to acne focus mostly on measuring psychological and social impact. What does this study add? The ACNE-Q provides a set of independently functioning scales that measure appearance of facial, back and chest acne, acne scarring and facial skin. Additional scales measure appearance-related distress and acne symptoms. What are the clinical implications of this work? ACNE-Q provides the dermatology community with a rigorously developed patient-reported measure for acne that can be applied in clinical trials, research and patient care. The measurement of appearance by ACNE-Q scales is more comprehensive than in other instruments providing important information on appearance of their acne and/or acne scars from the patient perspective.

FACE-Q Skin Cancer Module for measuring patient-reported outcomes following facial skin cancer surgery.

BACKGROUND: The patient's perspective of their facial scar after skin cancer surgery influences perception of care and quality of life (QoL). Appearance satisfaction after surgery is also an important but often overlooked treatment outcome. OBJECTIVES: To report the psychometric validation of the FACE-Q Skin Cancer Module consisting of five scales, measuring appearance satisfaction (Satisfaction with Facial Appearance, Appraisal of Scars), QoL (Cancer Worry, Appearance-related Psychosocial Distress) and the patient experience (Satisfaction with Information: Appearance). METHODS: Participants underwent Mohs surgery for facial basal or squamous cell carcinoma or excision of early facial melanoma. Cohort 1 received a set of scales before and after surgery. Cohort 2 received the scales on two occasions in the postoperative period for test-retest reliability. Rasch measurement theory was used to select (item-reduce) the most clinically meaningful items for the scales. Reliability, validity, floor and ceiling effects and responsiveness were also analysed. RESULTS: Of 334 patients, 209 (response rate 62·6%) were included. Rasch analysis reduced the total scale items from 77 to 41. All items had ordered thresholds and good psychometric fit. Reliability was high (Person separation index and Cronbach's α ≥ 0·90) and scales measuring similar constructs were correlated. High floor and ceiling effects were seen for the scales. The Cancer Worry scale demonstrated responsiveness (P = 0·004). CONCLUSIONS: The FACE-Q Skin Cancer Module meet the requirements of the Rasch model providing linearized measurement. Discriminating between patients with minimal appearance or worry impairment may be a limitation. The scales can be used for larger validation studies, clinical practice and research.

Genetic immunization with mouse thyrotrophin hormone receptor plasmid breaks self-tolerance for a murine model of autoimmune thyroid disease and Graves' orbitopathy.

Experimental models of Graves' hyperthyroid disease accompanied by Graves' orbitopathy (GO) can be induced efficiently in susceptible inbred strains of mice by immunization by electroporation of heterologous human TSH receptor (TSHR) A-subunit plasmid. In this study, we report on the development of a bona fide murine model of autoimmune Graves' disease induced with homologous mouse TSHR A-subunit plasmid. Autoimmune thyroid disease in the self-antigen model was accompanied by GO and characterized by histopathology of hyperplastic glands with large thyroid follicular cells. Examination of orbital tissues showed significant inflammation in extra-ocular muscle with accumulation of T cells and macrophages together with substantial deposition of adipose tissue. Notably, increased levels of brown adipose tissue were present in the orbital tissue of animals undergoing experimental GO. Further analysis of inflammatory loci by 19 F-magnetic resonance imaging showed inflammation to be confined to orbital muscle and optic nerve, but orbital fat showed no difference in inflammatory signs in comparison to control ß-Gal-immunized animals. Pathogenic antibodies induced to mouse TSHR were specific for the self-antigen, with minimal cross-reactivity to human TSHR. Moreover, compared to other self-antigen models of murine Graves' disease induced in TSHR knock-out mice, the repertoire of autoantibodies to mouse TSHR generated following the breakdown of thymic self-tolerance is different to those that arise when tolerance is not breached immunologically, as in the knock-out models. Overall, we show that mouse TSHR A-subunit plasmid immunization by electroporation overcomes tolerance to self-antigen to provide a faithful model of Graves' disease and GO.