Neuroimaging characterization of multiple sclerosis lesions in pediatric patients: an exploratory radiomics approach.

Introduction: Multiple sclerosis (MS), a chronic inflammatory immune-mediated disease of the central nervous system (CNS), is a common condition in young adults, but it can also affect children. The aim of this study was to construct radiomic models of lesions based on magnetic resonance imaging (MRI, T2-weighted-Fluid-Attenuated Inversion Recovery), to understand the correlation between extracted radiomic features, brain and lesion volumetry, demographic, clinical and laboratorial data. Methods: The neuroimaging data extracted from eleven scans of pediatric MS patients were analyzed. A total of 60 radiomic features based on MR T2-FLAIR images were extracted and used to calculate gray level co-occurrence matrix (GLCM). The principal component analysis and ROC analysis were performed to select the radiomic features, respectively. The realized classification task by the logistic regression models was performed according to these radiomic features. Results: Ten most relevant features were selected from data extracted. The logistic regression applied to T2-FLAIR radiomic features revealed significant predictor for multiple sclerosis (MS) lesion detection. Only the variable "contrast" was statistically significant, indicating that only this variable played a significant role in the model. This approach enhances the classification of lesions from normal tissue. Discussion and conclusion: Our exploratory results suggest that the radiomic models based on MR imaging (T2-FLAIR) may have a potential contribution to characterization of brain tissues and classification of lesions in pediatric MS.

Service user satisfaction with care in a specialist service for young people with attention deficit hyperactivity disorder.

OBJECTIVES: Consumer satisfaction is considered one of the most important measures of service quality in child mental health; however, there is limited understanding of factors that influence satisfaction. The objective of this study was to investigate key factors influencing satisfaction with care (SWC) in ADMiRE, a specialist service for young people (YP) with attention deficit hyperactivity disorder (ADHD). METHODS: Parents/carers (n = 67) and YP > 9 years (n = 44) attending ADMiRE completed an anonymous Experience of Service Questionnaire (ESQ), a quantitative/qualitative measure of service user satisfaction. Parents/carers also completed symptom severity rating scales. Data were analysed to determine (i) overall SWC, (ii) the relationship between parent- and youth-reported SWC and (iii) the impact of symptom severity on SWC. Thematic analysis of qualitative ESQ data was completed. RESULTS: Parents/carers were significantly more satisfied than YP (p = 0.028). Symptom severity did not impact significantly on parent/carer satisfaction. YP with severe hyperactive/impulsive and inattentive ADHD symptoms were significantly less satisfied with care than those with less severe ADHD symptoms (p = 0.022 and p = 0.017 respectively). Factors related to the therapeutic alliance were identified as being particularly important to both parents/carers and YP. CONCLUSIONS: This is the first Irish study that has investigated the impact of symptom severity on service user satisfaction in a child mental health service. The results highlight the different perspectives of YP and parents and provide novel insights into the impact of symptom severity on service user satisfaction. The importance of the therapeutic alliance should not be underestimated in future development of services.

Minding metabolism: targeted interventions to improve cardio-metabolic monitoring across early and chronic psychosis.

BACKGROUND: Antipsychotics (APs) increase weight, metabolic syndrome, diabetes and cardiovascular disease. Guidelines recommend cardio-metabolic monitoring at initial assessment, at 3 months and then annually in people prescribed APs. AIM: To determine the rates of cardio-metabolic monitoring in AP treated early and chronic psychosis and to assess the impact of targeted improvement strategies. METHODS: Medical records were reviewed in two cohorts of first-episode psychosis (FEP) patients before and after the implementation of a physical health parameter checklist and electronic laboratory order set. In a separate group of patients with chronic psychotic disorders, adherence to annual monitoring was assessed before and 3 months after an awareness-raising educational intervention. RESULTS: In FEP, fasting glucose (39% vs 67%, p=0.05), HbA1c (0% vs 24%, p=0.005) and prolactin (18% vs 67%, p=0.001) monitoring improved. There were no significant differences in weight (67% vs 67%, p=1.0), BMI (3% vs 10%, p=0.54), waist circumference (3% vs 0%, p=1.0), fasting lipids (61% vs 76% p=0.22) or ECG monitoring (67% vs 67%, p=1.0). Blood pressure (BP) (88% vs 57%, p=0.04) and heart rate (91% vs 65%, p=0.03) monitoring dis-improved. Diet (0%) and exercise (<15%) assessment was poor. In chronic psychotic disorders, BP monitoring improved (20% vs 41.4%, p=0.05), whereas weight (17.0% vs 34.1%, p=0.12), BMI (9.7% vs 12.1%, p=1.0), fasting glucose (17% vs 24.3%, p=0.58) and fasting lipids remained unchanged (17% vs 24.3%, p=0.58). CONCLUSIONS: Targeted improvement strategies resulted in a significant improvement in a limited number of parameters in early and chronic psychotic disorders. Overall, monitoring remained suboptimal.

Intervenções do enfermeiro de reabilitação que promovem a funcionalidade sexual da pessoa/família em situação de doença crónica / Interventions of the rehabilitation nurse that promote the sexual functionality of the person/family in a situation of chronic illness

No decorrer da nossa experiência em ensino clínico, verificámos que a intervenção dos enfermeiros de reabilitação perante pessoas com alterações à funcionalidade sexual é rara, destruturada e, cientificamente, pouco fundamentada. Daí emergiu a necessidade de aprofundar e obter evidência científica sobre a identificação e enquadramento teórico das competências e intervenções específicas do enfermeiro de reabilitação na promoção da funcionalidade sexual. Na procura e análise do conhecimento mais atual, recorremos à revisão sistemática da literatura e formulámos uma questão PICO. O processo de pesquisa foi realizado através da EBSCOhost Web nas bases de dados online - PubMed, B-on e Medline - tendo resultado um total de 161 artigos. Destes, foram selecionados três para análise completa. Os resultados encontrados, extraídos e categorizados à posteriori, relacionam-se com: estratégias de abordagem educacional; intervenientes no processo; contexto da intervenção e domínios da intervenção. Face aos resultados, que preconizam uma intervenção estruturada, sustentada na formação, treino e aperfeiçoamento de competências, apresentamos uma proposta de modelo de abordagem da reeducação funcional sexual que procura promover uma intervenção metodologicamente fundamentada e dar maior visibilidade à prática especializada em enfermagem de reabilitação

In the course of our experience in clinical teaching, we have noticed that the intervention of the rehabilitation nurses towards people with alterations to the sexual functionality is rare, unstructured and, scientifically, little substantiated. Hence emerged the need to deepen and obtain scientific evidence on the identification and theoretical framework of the competencies and specific interventions of the rehabilitation nurse in the promotion of sexual functionality. In the search and analysis of the most current knowledge, we resorted to the systematic review of the literature and formulated a PICO question The research process was carried out through EBSCOhost Web in the online databases - PubMed, B-on and Medline - resulting in a total of 161 articles. Of these, three were selected for complete analysis The results found, extracted and categorized à posteriori, are related to: strategies of educational approach; intervinients in the process; context of the intervention; and fields of intervention. Considering the results, which advocate a structured intervention, sustained in the formation, training and improvement of competences, we present a proposal of a model of approach to functional sexual reeducation that seeks to promote a methodologically based intervention and give greater visibility to the specialized practice in rehabilitation nursing

Iron gene expression profile in atherogenic Mox macrophages.

RATIONALE: The role of macrophage iron in the physiopathology of atherosclerosis is an open question that needs to be clarified. In atherosclerotic lesions, recruited macrophages are submitted to cytokines and oxidized lipids which influence their phenotype. An important phenotypic population driven by oxidized phospholipids is the Mox macrophages which present unique biological properties but their iron phenotype is not well described. OBJECTIVE: To investigate the effect of Mox polarization by oxidized LDL (oxLDL) on macrophage iron metabolism in the absence or presence of proinflammatory stimuli. METHODS: Bone marrow-derived macrophages were treated with different sources of LDL and/or LPS/IFNγ (M1 activator). Expression of ferroportin (Slc40a1, alias Fpn), heme oxygenase-1 (Hmox1), H- and L-ferritin (Fth1 and Ftl1), hepcidin (Hamp), ceruloplasmin (Cp) and interleukine-6 (Il6) was followed by quantitative PCR. FPN and HMOX1 protein expression was analyzed by immunofluorescence and in-cell-Western blotting. RESULTS: Mox macrophages expressed increased Hmox1 and Fth1 levels with basal FPN protein levels despite the significant increase of Fpn mRNA. Upregulation of Hmox1 and Fpn mRNA was specific to LDL oxidative modification and mediated by NRF2. The downregulation of both Cp isoforms and the upregulation of Hamp expression observed in Mox macrophages suggest that FPN mediated iron export could be compromised. Simultaneous exposure to oxLDL and LPS/IFNγ leads to a mixed Mox/M1 phenotype that is closer to M1. CONCLUSION: A microenvironment rich in oxLDL and proinflammatory cytokines could promote macrophage iron retention and lipid accumulation profiles, a specific cell phenotype that likely contributes to lesion development and plaque instability in atherosclerosis.

Dietary water affects human skin hydration and biomechanics.

It is generally assumed that dietary water might be beneficial for the health, especially in dermatological (age preventing) terms. The present study was designed to quantify the impact of dietary water on major indicators of skin physiology. A total of 49 healthy females (mean 24.5±4.3 years) were selected and characterized in terms of their dietary daily habits, especially focused in water consumption, by a Food Frequency Questionnaire. This allowed two groups to be set - Group 1 consuming less than 3,200 mL/day (n=38), and Group 2 consuming more than 3,200 mL/day (n=11). Approximately 2 L of water were added to the daily diet of Group 2 individuals for 1 month to quantify the impact of this surplus in their skin physiology. Measurements involving epidermal superficial and deep hydration, transepidermal water loss, and several biomechanical descriptors were taken at day 0 (T0), 15 (T1), and 30 (T2) in several anatomical sites (face, upper limb, and leg). This stress test (2 L/day for 30 days) significantly modified superficial and deep skin hydration, especially in Group 1. The same impact was registered with the most relevant biomechanical descriptors. Thus, in this study, it is clear that higher water inputs in regular diet might positively impact normal skin physiology, in particular in those individuals with lower daily water consumptions.

Decrease in APP and CP mRNA expression supports impairment of iron export in Alzheimer's disease patients.

Alzheimer's disease (AD) is a neurodegenerative disorder of still unknown etiology and the leading cause of dementia worldwide. Besides its main neuropathological hallmarks, a dysfunctional homeostasis of transition metals has been reported to play a pivotal role in the pathogenesis of this disease. Dysregulation of iron (Fe) metabolism in AD has been suggested, particularly at the level of cellular iron efflux. Herein, we intended to further clarify the molecular mechanisms underlying Fe homeostasis in AD. In order to achieve this goal, the expression of specific Fe metabolism-related genes directly involved in Fe regulation and export was assessed in peripheral blood mononuclear cells (PBMCs) from 73AD patients and 74 controls by quantitative PCR. The results obtained showed a significant decrease in the expression of aconitase 1 (ACO1; P=0.007); ceruloplasmin (CP; P<0.001) and amyloid-beta precursor protein (APP; P=0.006) genes in AD patients compared with healthy volunteers. These observations point out to a significant downregulation in the expression of genes associated with ferroportin-mediated cellular Fe export in PBMCs from AD patients, when compared to controls. Taken together, these findings support previous studies suggesting impairment of Fe homeostasis in AD, which may lead to cellular Fe retention and oxidative stress, a typical feature of this disease.

Indoor aerosol size distributions in a gymnasium.

In this study, an indoor/outdoor monitoring program was carried out in a gymnasium at the University of Leon, Spain. The main goal was a characterization of aerosol size distributions in a university gymnasium under different conditions and sports activities (with and without magnesia alba) and the study of the mass fraction deposited in each of the parts of the respiratory tract. The aerosol particles were measured in 31 discrete channels (size ranges) using a laser spectrometer probe. Aerosol size distributions were studied under different conditions: i) before sports activities, ii) activities without using magnesia alba, iii) activities using magnesia alba, iv) cleaning procedures, and v) outdoors. The aerosol refractive index and density indoors were estimated from the aerosol composition: 1.577-0.003i and 2.055 g cm(-3), respectively. Using the estimated density, the mass concentration was calculated, and the evolution of PM1, PM2.5 and PM10 for different activities was assessed. The quality of the air in the gymnasium was strongly influenced by the use of magnesia alba (MgCO3) and the number of gymnasts who were training. Due to the climbing chalk and the constant process of resuspension, average PM10 concentrations of over 440 µg m(-3) were reached. The maximum daily concentrations ranged from 500 to 900 µg m(-3). Particle size determines the place in the respiratory tract where the deposition occurs. For this reason, the inhalable, thoracic, tracheobronchial and respirable fractions were assessed for healthy adults and high risk people, according to international standards. The estimations show that, for healthy adults, up to 300 µg m(-3) can be retained by the trachea and bronchi, and 130 µg m(-3) may reach the alveolar region. The different physical activities and the attendance rates in the sports facility have a significant influence on the concentration and size distributions observed.

Particulate matter in the indoor and outdoor air of a gymnasium and a fronton.

An indoor/outdoor monitoring programme of PM10 was carried out in two sports venues (a fronton and a gymnasium). Levels always below 50 µg m(-3) were obtained in the fronton and outdoor air. Due to the climbing chalk and the constant process of resuspension, concentrations above 150 µg m(-3) were registered in the gymnasium. The chalk dust contributed to CO3 (2-) concentrations of 32 ± 9.4 µg m(-3) in this sports facility, which represented, on average, 18 % of the PM10 mass. Here, the carbonate levels were 128 times higher than those registered outdoors. Much lower concentrations, around 1 µg m(-3), were measured in the fronton. The chalk dust is also responsible for the high Mg(2+) concentrations in the gym (4.7 ± 0.89 µg m(-3)), unfolding a PM10 mass fraction of 2.7 %. Total carbon accounted for almost 30 % of PM10 in both indoor spaces. Aerosol size distributions were bimodal and revealed a clear dependence on physical activities and characteristics of the sports facilities. The use of climbing chalk in the gymnasium contributed significantly to the coarse mode. The average geometric mean diameter, geometric standard deviation and total number of coarse particles were 0.77 µm, 2.79 cm(-3) and 28 cm(-3), respectively.

Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulation.

Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.

Immune cells and hepatocytes express glycosylphosphatidylinositol-anchored ceruloplasmin at their cell surface.

BACKGROUND: Ceruloplasmin is a positive acute-phase protein with both anti- and pro-oxidant activities, thus having still unclear physiological functions in inflammatory processes. Importantly, ceruloplasmin has been implicated in iron metabolism due to its ferroxidase activity, assisting ferroportin on cellular iron efflux. Ceruloplasmin can be expressed as a secreted or as a membrane glycosylphosphatidylinositol-anchored protein (GPI-ceruloplasmin), this latter one being reported as expressed mostly in the brain. DESIGN AND METHODS: We studied the expression of both ceruloplasmin isoforms in human peripheral blood lymphocytes, monocytes, mouse macrophages and human hepatocarcinoma cell line HepG2, using immunofluorescence and immunoblotting techniques. Co-localization of ceruloplasmin and ferroportin was also investigated by immunofluorescence in mouse macrophages. RESULTS: Ceruloplasmin was detected by immunoblotting and immunofluorescence in membrane and cytosol of all cell types. The cell surface ceruloplasmin was identified as the GPI-isoform and localized in lipid rafts from monocytes, macrophages and HepG2 cells. In macrophages, increased expression levels and co-localization of ferroportin and GPI-ceruloplasmin in cell surface lipid rafts were observed after iron treatment. Such iron upregulation of ceruloplasmin was not observed in HepG2. CONCLUSIONS: Our results revealed an unexpected ubiquitous expression of the GPI-ceruloplasmin isoform in immune and hepatic cells. Different patterns of regulation of ceruloplasmin in these cells may reflect distinct physiologic functions of this oxidase. In macrophages, GPI-ceruloplasmin and ferroportin likely interact in lipid rafts to export iron from cells. Precise knowledge about ceruloplasmin isoforms expression and function in various cell types will help to clarify the role of ceruloplasmin in many diseases related to iron metabolism, inflammation and oxidative biology.

Ceruloplasmin expression by human peripheral blood lymphocytes: a new link between immunity and iron metabolism.

Ceruloplasmin (CP) is a multicopper oxidase involved in the acute phase reaction to stress. Although the physiological role of CP is uncertain, its role in iron (Fe) homeostasis and protection against free radical-initiated cell injury has been widely documented. Previous studies showed the existence of two molecular isoforms of CP: secreted CP (sCP) and a membrane glycosylphosphatidylinositol (GPI)-anchored form of CP (GPI-CP). sCP is produced mainly by the liver and is abundant in human serum whereas GPI-CP is expressed in mammalian astrocytes, rat leptomeningeal cells, and Sertolli cells. Herein, we show using RT-PCR that human peripheral blood lymphocytes (huPBL) constitutively express the transcripts for both CP molecular isoforms previously reported. Also, expression of CP in huPBL is demonstrated by immunofluorescence with confocal microscopy and flow cytometry analysis using cells isolated from healthy blood donors with normal Fe status. Importantly, the results obtained show that natural killer cells have a significantly higher CP expression compared to all other major lymphocyte subsets. In this context, the involvement of lymphocyte-derived CP on host defense processes via its anti/prooxidant properties is proposed, giving further support for a close functional interaction between the immune system and the Fe metabolism.