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The use of 11C-acetate as a PET/CT tracer for atherosclerotic lesions preferentially labels anti-inflammatory/pro-resolution intra-plaque macrophages. An overview of the mechanisms involved in the selective uptake.

Objective To estimate the SARS-CoV-2 antibody seroprevalence in healthcare workers (HCWs) at a university hospital in Mallorca, Spain. Methods All HCWs received an e-mail inviting them to take part in the study. Participants had a nasopharyngeal swab test performed for reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and serological tests to detect SARS-CoV-2 antibodies (primary study). Additionally, they were invited to complete a questionnaire on their exposure to COVID-19 individuals and their COVID-19-related symptoms (secondary study). Prevalence of antibodies (IgG, IgM, or both) and 95% confidence intervals (CIs) were calculated. Results Seventy-nine percent of the hospitalʼs HCWs (N = 2210) took part in the primary study. Antibodies were detected in 61 participants, a prevalence of 2.8% (95% CI: 2.5–3.1). The prevalence was slightly higher in nurses (3.4%), registrars (3.9%), and wardens (3.4%). Thirty-nine percent of the primary study participants completed the secondary study questionnaire. Those with positive antibody test results had closer contact with COVID-19 individuals (60% vs. 92%; p Conclusion After the first wave of the COVID-19 pandemic in Spain, the seroprevalence of SARS-CoV-2 antibodies in our university hospital HCWs was around 2.8%, which is slightly higher than the seroprevalence in the general population in our region. We believe it would be advisable to perform additional seroprevalence studies during the second wave of the epidemic.

Background: Hypoxic-ischemic encephalopathy (HIE) is one of the main causes of neurodevelopmental disorders. We developed a model that has diagnostic and prognostic value in predicting the neurodevelopmental outcomes in newborns with HIE. HIE staging allows us to start therapeutic interventions early in newborns with suspected encephalopathy. Methods: This was a retrospective study in a cohort of 58 full-term neonates with clinical suspicion of HIE. We assessed electroclinical variables at birth [etiology of hypoxia, neonatal seizures, HIE stages based on Sarnat criteria, use of therapeutic hypothermia, neuroimaging tests and electroencephalography (EEG) findings] and two years of follow up (EEG findings, development of epilepsy, the presence of cognitive deficits, behavioral issues, language problems, visual or hearing disturbances, and cerebral palsy). Results: There was a high electro-clinical correlation to severe HIE (88.8%) and moderate HIE (50%). There was a considerable proportion of patients affected by mild HIE, based on clinical examination, who presented with an abnormal EEG (32.3%). There is a relationship between the onset of neonatal seizures, epilepsy, and severe HIE diagnosed with EEG (88.9%). A higher percentage of patients with moderate and severe HIE, based on EEG findings, present abnormal results in cranial ultrasound and cerebral magnetic resonance imaging (62.5%). At two years of age, functional neurodevelopment disturbances were observed most frequently in patients affected with severe and moderate HIE based on EEG. Conclusions: This study shows a model with diagnostic and prognostic value in predicting newborns' neurodevelopmental outcomes with suspected HIE. This knowledge allows us to assess the role of performing serial EEG in patients with suspected HIE and the relevance of EEG findings in the prognosis of neurodevelopmental disorders.

SUMMARY Motor-evoked potentials (MEPs) can be used to assess the integrity of the descending corticospinal tract in the laboratory. Evoked potentials (EPs) have been widely used in the past for the diagnosis of multiple sclerosis (MS), but they are now becoming more useful in assessing the prognosis of the disease. Motor-evoked potentials have been included in EP scales that have demonstrated good correlations with clinical disability. Soon after the onset of MS, it is possible to detect an ongoing process of neurodegeneration and axonal loss. Axonal loss is probably responsible for the disability and disease progression that occurs in MS. Given the good correlations of EPs in detecting disease progression in MS, they have been used to monitor the effects of drugs used to treat the disease. Several clinical trials used MEPs as part of their EP evaluation, but MEPs have never been used as a measure of efficacy in clinical trials testing neuroprotective agents, although MEPs could be a very promising tool to measure neuroprotection and remyelination resulting from these drugs. To be used in multicenter clinical trials, MEP readings should be comparable between centers. Standardized multicenter EP assessment with central reading has been demonstrated to be feasible and reliable. Although MEP measurements have been correlated with clinical scores and other measures of neurodegeneration, further validation of MEP amplitude measurements is needed regarding their validity, reliability, and sensitivity before they can be routinely used in clinical drug trials in MS.

The purpose of neurophysiological monitoring during surgery is to identify damage or functional neurological disturbances as soon as possible, ensuring spinal cord functionality and avoiding neurological complications. However, the lack of standardisation of the methodology, together with some inconsistencies in the studies on its usefulness, limit the establishment of universal recommendations for its use. The present paper intends to review neurophysiological monitoring procedures during surgery, including their strength and weaknesses, as well as to assess the convenience of their use during spinal surgery. It is concluded that, in general, the lack of its use in this surgery does not legally contravene the standard of care, as there is no evidence it could result in reverting neurological damage. Nevertheless, it can be used as evidence both in detecting the time and kind of neurological injury, and for increasing the defensibility. Protocols of use, provided either by scientific societies or hospitals themselves, are required.

© 2021 by the authors., Immunonutrition appears as a field with great potential in modern medicine. Since the immune system can trigger serious pathophysiological disorders, it is essential to study and implement a type of nutrition aimed at improving immune system functioning and reinforcing it individually for each patient. In this sense, the nucleotide-binding oligomerization domain-1 (NOD1), one of the members of the pattern recognition receptors (PRRs) family of innate immunity, has been related to numerous pathologies, such as cancer, diabetes, or cardiovascular diseases. NOD1, which is activated by bacterial-derived peptidoglycans, is known to be present in immune cells and to contribute to inflammation and other important pathways, such as fibrosis, upon recognition of its ligands. Since immunonutrition is a significant developing research area with much to discover, we propose NOD1 as a possible target to consider in this field. It is relevant to understand the cellular and molecular mechanisms that modulate the immune system and involve the activation of NOD1 in the context of immunonutrition and associated pathological conditions. Surgical or pharmacological treatments could clearly benefit from the synergy with specific and personalized nutrition that even considers the health status of each subject., This research was funded by Ministerio de Economía, Industria y Competitividad (RTI2018- 094727-B-100 and SAF2017-82436-R), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686, and Fondo Europeo de Desarrollo Regional.

Summary Background Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis. Methods We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 18–58 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov , number NCT01864148 . Findings Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0·89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment. Interpretation Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose. Funding Biogen.

© 2020 The Author(s)., [Objectives]: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters., [Methods]: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs)., [Results]: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22–0.47; p < 0.001) for tocilizumab, 0.82 (0.71–1.30; p 0.82) for IHDC, 0.61 (0.43–0.86; p 0.006) for PDC, and 1.17 (0.86–1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02–0.17; p < 0.001)., [Conclusions]: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situation., IJ has received honoraria for participating in an advisory board from Gilead Sciences, and for educational activities from ViiV. JB has received research grants from AbbVie, Gilead Sciences, Merck, and ViiV, and honoraria for being a speaker or advisory board participation from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV. JRA received fees for participating in an advisory board, being a speaker, and research grant support from Viiv, Janssen, Gilead, MSD, Teva, Alexa and Serono. PR is involved as speaker or advisory board participant for Gilead Sciences, AbbVie and ViiV. JR-B, JP, JC and MY have no conflicts of interest to declare. SAM-COVID was funded by Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (COV20/01031) co-funded by European Union (ERDF/ESF, “Investing in your future”) and Fundación SEIMC/GeSIDA. In addition, Juan Berenguer, Jesús Rodríguez-Baño, Inmaculada Jarrín, Jordi Carratalá, Jerónimo Pachón, and José R Arribas received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades – co- financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020 through the networks: Spanish AIDS Research Network (RIS) [RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16/0025/00XX (IJ)] and Spanish Network for Research in Infectious Diseases (REIPI)[RD16/0016/0001 (JRB), RD16/0016/0005 (JC), and RD16/0016/0009 (JP).

© 2022 The Authors., It has long been known that thyroid hormones have implications for multiple physiological processes and can lead to serious illness when there is an imbalance in its metabolism. The connections between thyroid hormone metabolism and the immune system have been extensively described, as they can participate in inflammation, autoimmunity, or cancer progression. In addition, changes in the normal intestinal microbiota involve the activation of the immune system while triggering different pathophysiological disorders. Recent studies have linked the microbiota and certain bacterial fragments or metabolites to the regulation of thyroid hormones and the general response in the endocrine system. Even if the biology and function of the thyroid gland has attracted more attention due to its pathophysiological importance, there are essential mechanisms and issues related to it that are related to the interplay between the intestinal microbiota and the immune system and must be further investigated. Here we summarize additional information to uncover these relationships, the knowledge of which would help establish new personalized medical strategies., The review was written by authors that work in a laboratory where projects are supported by: Ministerio de Economía, Industria y Competitividad (RTI2018-094727-B-100, SAF2017-82436-R, RYC-2015-18083, PID2019-107650RB-C22 and PID2019-108977RB-100), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional.

© 2020 Fernández-García, González-Ramos, Martín-Sanz, Castrillo and Boscá., Cardiovascular diseases (CVDs) incidence is becoming higher. This fact is promoted by metabolic disorders such as obesity, and aging. Atherosclerosis is the underlying cause of most of these pathologies. It is a chronic inflammatory disease that begins with the progressive accumulation of lipids and fibrotic materials in the blood-vessel wall, which leads to massive leukocyte recruitment. Rupture of the fibrous cap of the atherogenic cusps is responsible for tissue ischemic events, among them myocardial infarction. Extramedullary hematopoiesis (EMH), or blood cell production outside the bone marrow (BM), occurs when the normal production of these cells is impaired (chronic hematological and genetic disorders, leukemia, etc.) or is altered by metabolic disorders, such as hypercholesterolemia, or after myocardial infarction. Recent studies indicate that the main EMH tissues (spleen, liver, adipose and lymph nodes) complement the hematopoietic function of the BM, producing circulating inflammatory cells that infiltrate into the atheroma. Indeed, the spleen, which is a secondary lymphopoietic organ with high metabolic activity, contains a reservoir of myeloid progenitors and monocytes, constituting an important source of inflammatory cells to the atherosclerotic lesion. Furthermore, the spleen also plays an important role in lipid homeostasis and immune-cell selection. Interestingly, clinical evidence from splenectomized subjects shows that they are more susceptible to developing pathologies, such as dyslipidemia and atherosclerosis due to the loss of immune selection. Although CVDs represent the leading cause of death worldwide, the mechanisms involving the spleen-atherosclerosis-heart axis cross-talk remain poorly characterized., The review was written by authors that work in a laboratory where projects are supported by: Ministerio de Economía, Industria y Competitividad, Ministerio de Ciencia, Investigación y Universidades, and Agencia Estatal de Investigación (SAF2017-82436-R, RTC2017-6283-1, PID2019-104284RB-I00/AEI/10.13039/501100011033), Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CB16/11/00222), Fundación Ramón Areces (CIVP18A3864), Consorcio de Investigación en Red de la Comunidad de Madrid, S2017/BMD-3686 and Fondo Europeo de Desarrollo Regional.

Atherothrombosis, the main cause of acute coronary syndromes (ACS), is characterized by the rupture of the atherosclerotic plaque followed by the formation of thrombi. Fatal plaque rupture sites show large necrotic cores combined with high levels of inflammation and thin layers of collagen. Plaque necrosis due to the death of macrophages and smooth muscle cells (SMCs) remains critical in the process. To determine the contribution of the innate immunity receptor NOD1 to the stability of atherosclerotic plaque, Apoe&minus, /&minus, and Apoe&minus, Nod1&minus, atherosclerosis prone mice were placed on a high-fat diet for 16 weeks to assess post-mortem advanced atherosclerosis in the aortic sinus. The proliferation and apoptosis activity were analyzed, as well as the foam cell formation capacity in these lesions and in primary cultures of macrophages and vascular SMCs obtained from both groups of mice. Our results reinforce the preeminent role for NOD1 in human atherosclerosis. Advanced plaque analysis in the Apoe&minus, atherosclerosis model suggests that NOD1 deficiency may decrease the risk of atherothrombosis by decreasing leukocyte infiltration and reducing macrophage apoptosis. Furthermore, Nod1&minus, SMCs exhibit higher proliferation rates and decreased apoptotic activity, contributing to thicker fibrous caps with reduced content of pro-thrombotic collagen. These findings demonstrate a direct link between NOD1 and plaque vulnerability through effects on both macrophages and SMCs, suggesting promising insights for early detection of biomarkers for treating patients before ACS occurs.

Background Polyserositis (PS) is the inflammation, with effusion, of different serous membranes. It has been associated with different aetiologies, but the aetiology of PS remains unknown in a high percentage of patients. Aims The general objective of this retrospective study was to analyse the aetiology of PS cases seen at Son Llatzer Hospital in an 11-year period. Other objectives were to determine the epidemiological, clinical and analytical characteristics of these patients. Methods An observational, descriptive and retrospective study to analyse the aetiology of PS cases seen at Son Llatzer Hospital. The inflammation of two or more serous membranes confirmed by an imaging test was required and at least one of the serous fluid should be an exudate. Results A total of 92 patients was included in the study. The most common diagnosis was neoplasm (nearly one-third of cases) followed by infectious and autoimmune diseases. PS aetiology was unknown in more than one-third. Pleura and pericardium were the most common sites of serosal involvement (83%). Antinuclear antibodies' positivity in serum and increased levels of adenosine deaminase in pleural effusion were significantly associated with a final diagnosis of autoimmune disease. Increased pleural lactate dehydrogenase levels were significantly associated with a final diagnosis of neoplasm. In 9 of 14 patients with a previous cancer, PS represented a recurrence of their cancer. Cases of unknown aetiology presented most frequently as pleural and pericardial involvement, and the majority resolved. In very few patients, an infectious aetiology could be proven. Conclusion PS is a frequent clinical entity that is associated with different diseases and its diagnosis could be challenging, with a high rate of unknown aetiologies.

Diagnosis of latent tuberculosis infection in patients with immune-mediated inflammatory chronic diseases (IMIDs) can be challenged as diagnostic test reliability could be impaired by immunosuppression. We retrospectively analyzed the Quantiferon Gold-Test in-Tube (QFT-G-IT) results of all patients with IMIDs seen at the Department of Internal Medicine of Son Llatzer Hospital, Palma de Mallorca (Spain), looking for the factors related to QFT-G-IT indeterminate results. During the study period (2008–2015), 520 patients met the inclusion criteria. Factors associated with indeterminate QFT-G-IT results in a univariate analysis were inflammatory bowel disease, disease activity, lymphopenia, and medium-to-high doses of corticosteroids. In a subsequent multivariate analysis, only lymphopenia (defined as

Atherosclerosis is a chronic disease characterized by vascular lipid retention and inflammation, and pattern recognition receptors (PRRs) are important contributors in early stages of the disease. Given the implication of the intracellular PRR nucleotide-binding oligomerization domain 1 (NOD1) in cardiovascular diseases, we investigated its contribution to early atherosclerosis. We evidenced NOD1 induction in atherosclerotic human and mouse tissues, predominantly in vascular endothelial cells. Accordingly, NOD1 genetic inactivation in Apoe-/- mice reduced not only atherosclerosis burden, but also monocyte and neutrophil accumulation in atheromata. Of note, in the presence of either peptidoglycan or oxidized LDLs, endothelial NOD1 triggered VCAM-1 up-regulation through the RIP2-NF-¿B axis in an autocrine manner, enhancing firm adhesion of both sets of myeloid cells to the inflamed micro- and macrovasculature in vivo. Our data define a major proatherogenic role for endothelial NOD1 in early leukocyte recruitment to the athero-prone vasculature, thus introducing NOD1 as an innovative therapeutic target and potential prognostic molecule, This work was supported bythe the Ministry of Science, Innovation and Universities(Grants SAF2015-64767-R, SAF2016-79490-R, SAF2015-70747-R, SAF2016-75004-R, SAF2017-82436-R/RTC2017-6283-1), the Center for Biomedical Research Network Consortium in Cardiovascular Diseases (Grants CB16/11/00257, CB16/11/00405, CB/11/00222), Community of Madrid Grant BMD/3686, the German Research Foundation (Grants SFB914 TPA02/B08/B09/Z03, SFB1123 TP A06/B05/B08/Z01), and the Netherlands Organization for Scientific Research (VIDI proj-ect 91712303). This project was also financed, in part, by theEuropean Regional Development Fund. O.S. and L.B. con-tributed equally as senior authors.

The incorporation of People with Disability (PWD) in organizations is a subject taken up by international organizations, such as the European Union and the United Nations, which has had subsequent consequences in Spain with the development of legislation and specific initiatives. In this paper we have considered the concept of disability as part of diversity and, above all, as a fundamental subject of human rights and justice, which has allowed us to include the collective of PWD among the stakeholders of companies. The research on the incorporation of disability as an integral part of the policies of Corporate Social Responsibility (CSR) in companies is very recent, although the term Corporate Social Responsibility and Disability is already used. The main objective of this paper is to analyze the commitment with PWD of Spanish companies considered socially responsible by the sustainability indices used. We have included in four large dimensions (Stakeholders, Visibility, Human Resources and Accessibility) the indicators that have allowed us to analyze the information on PWD published by these companies in their sustainability reports or similar documents accessible through their websites. The results suggest that the companies are more concerned about improving their image towards the exterior than for the commitment with their own employees, which is consistent with the dimension Visibility being where the companies carry out more actions in favor of PWD.

Fruits may be exposed to several unfavorable mechanical, climatic, and biological factors during ripening. Harvest and storage also challenge fruit integrity before fruits reach the consumer. In order to preserve fruit properties/characteristics it is essential that the structural and chemical integrity of the cuticle is maintained throughout fruit development and expansion. In addition, cuticles serve as protection against multiple biotic and abiotic stress factors and primarily act as a barrier to prevent water loss. Despite the important functions attributed to the cuticle, little is known about fruit cuticle biosynthesis and assembly, which is highly relevant when coping with adverse conditions. Presently, drought and heat pose severe constraints to the fruit industry via penalties in yield and fruit quality. Available climate change models suggest a scenario in which the impact of these environmental factors will negatively affect the fruit industry. A comprehensive understanding of the physiological and biochemical effects of limited water availability on fruit traits is a prerequisite for implementing breeding and knowledge-based strategies that enhance fruit crop tolerance to limited water availability. To address some of these questions, this chapter aimed to revise the existing information on cuticle physiology, composition, structure, and properties, also considering its impact on fruit under abiotic stresses, with an emphasis on water deficit. We also address the recent molecular progress in cuticle biosynthesis pathways and highlight some of the major research questions that will have to be dealt with in the future.

[Background] Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures., [Patients and methods] In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded., [Results] Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy., [Conclusion] Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique., This work was supported by Instituto de Salud Carlos III, Ministry of Health – Spain – Grant number: EC08/00224-ISCIII; Grants from ISCIII cofunded by Fondos FEDER, FIS PI14/01015; RD/ oo19/0028 and RD16/0011/0034 to B Soria and PI16/00259 to A Hmadcha. The sponsor was the Andalusian Initiative for Advanced Therapies, supported by the Andalusian Health and Progress Foundation.

Introducción: en el contexto de la radioterapia, el control del dolor irruptivo oncológico (DIO) supone un reto especial. El DIO ha sido definido por la Sociedad Española del Dolor (SED), la Sociedad Española de Oncología Médica (SEOM) y la Sociedad Española de Cuidados Paliativos (SECPAL) como una exacerbación del dolor súbita y transitoria, de gran intensidad (EVA > 7) y de corta duración (inferior a 20-30 minutos), que aparece sobre la base de un dolor persistente estable cuando este se encuentra reducido a un nivel tolerable (EVA < 5) mediante el uso de opioides mayores. Objetivos: el objetivo principal de este estudio fue evaluar la intensidad del DIO inducido por tratamientos oncológicos que incluyeran radioterapia (RT), tanto exclusiva como asociada a quimioterapia (RT/QT). Secundariamente, se evaluó la eficacia del tratamiento con fentanilo sublingual pautado para el control del DIO. Material y métodos: estudio observacional retrospectivo realizado en 110 pacientes reclutados en 19 Servicios de Radioterapia españoles. Los pacientes debían presentar DIO inducido por RT o RT/QT, con o sin medicación pautada y cuya intensidad fuera de una EVA > 6 en las últimas 24-48 h. Se establecieron controles en el momento basal, y a los 3, 7, 15 y 30 días. Resultados: se apreció un descenso en la media de los valores en la escala EVA según avanzó el estudio (EVA = 6 en el control 0 a EVA = 3 en el control 3), y las diferencias fueron significativas (p < 0,0001). La satisfacción con el tratamiento fue calificada como buena o excelente por el 85,3% de los pacientes y por el 92,7% de los investigadores. Conclusiones: los resultados de este estudio demuestran la eficacia del tratamiento del DIO con fentanilo sublingual en el contexto del tratamiento oncológico radioterápico, con un descenso significativo en los valores EVA frente al valor basal. La elevada satisfacción de los médicos y pacientes con este tratamiento refleja la eficacia y la comodidad del fentanilo sublingual en el control del DIO.

Resumen Los avances en el conocimiento de la patogenia de la EM han permitido el desarrollo de terapias con base inmunologica y de farmacos efectivos capaces de reducir la actividad de la enfermedad (IFNB, acetato de glatiramero, inmunosupresores, natalizumab, fingolimod, alemtuzumab, rituximab, ocrelizumab, daclizumab, teriflunomida, BG-12 o dimetilfumarato, laquinimod). La estrategia de escalado terapeutico es la utilizada actualmente, pero en el futuro deberan evaluarse otras estrategias, como la terapia combinada, la terapia secuencial y la de induccion y mantenimiento. Mientras se investiga sobre la posibilidad de un tratamiento curativo efectivo para la EM, el medico debe tratar de aliviar los sintomas de la enfermedad con un enfoque multidisciplinar de cada sintoma, incluyendo farmacos, rehabilitacion, fisioterapia, terapia ocupacional, etc.

Resumen Las enfermedades de la mielina se dividen clasicamente en desmielinizantes o mielinoclasticas, en las que la mielina normal es destruida y enfermedades dismielinizantes o leucodistrofias, en las que una anomalia metabolica de origen genetico determina la formacion de mielina anormal o un fracaso completo de la mielinizacion. Las enfermedades desmielinizantes del SNC tienen en comun el ser enfermedades inflamatorias idiopaticas que destruyen selectivamente la mielina. Su curso puede ser cronico y con frecuencia recurrente (esclerosis multiple, etc.) o agudo y monofasico (encefalomielitis aguda diseminada, leucoencefalitis aguda hemorragica, etc.), pudiendo distribuirse en el SNC de forma difusa o localizada, lo que permite su clasificacion. La esclerosis multiples la mas caracteristica de las enfermedades desmielinizantes del SNC.

Interferon-γ release assays (IGRAs) are increasingly used for the diagnosis of latent tuberculosis infection (LTBI). Because of the lack of a gold standard for the diagnosis of LTBI, IGRAs are compared to the tuberculin skin test (TST) and yield conflicting results. We assessed the usefulness of an IGRA test, QuantiFERON(®)-TB Gold In-Tube (QFT-G-IT), for diagnosing LTBI compared with TST in the setting of a contact screening study.A prospective comparison between the QFT-G-IT and the TST in TB contact subjects in a low TB burden area was conducted sequentially between January 2006 and December 2012.A moderate concordance between the two tests (κ = 0.44 for TST cut-off of 5 mm and κ = 0.56 for TST cut-off of 15 mm) was found. A better agreement was shown in younger contacts and in non-vaccinated contacts when using a TST of 15 mm. Independent risk factors for a TST(+)/QFT-G-IT(-) discordance were history of BCG vaccination and age between 31 and 59 years. Discordance was also more frequent using a TST cut-off value of 5 mm. QFT-G-IT(+)/TST(-) was infrequent and was found in older contacts.Based on our data, we cannot recommend the use of QFT-G-IT as the only test to rule out LTBI, especially in older patients.

Social entrepreneurship has become an economic reality with great potential to provide a response to the existing social challenges. In this paper we identify two models of social enterprise, and we provide, for the first time, evidence from the human resource management of social enterprises in Spain. This allows us to analyse whether these social enterprises manage their human resources in an ethical way, and whether a different ethical human resource management exists in the two models. We have designed a questionnaire using the ethical practices of the ethical human resource management model as a basis. The results reveal that social enterprises in Spain manage their human resources ethically and a difference does not exist between the two models identified. We conclude by outlining the implications for a better understanding of ethical practices in human resource management in social enterprises.

Objective: To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. Method: We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. Results: MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Conclusions: Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Resumen: Objetivo: Establecer una guía clínica para la utilización clínica del estudio de potenciales evocados motores (PEM) en el diagnóstico y el seguimiento de la esclerosis múltiple (EM). Disponer de unas recomendaciones para la utilización clínica de los PEM contribuye a racionalizar y optimizar los recursos en el proceso diagnóstico y de seguimiento en los pacientes con EM. Método: Hemos llevado a cabo una extensa revisión de la literatura médica y puesto en común nuestros propios datos para consensuar recomendaciones para el uso clínico de los PEM en el estudio de la EM. Resultados: Los PEM contribuyen, junto con la resonancia magnética medular o cerebral, al diagnóstico y evaluación de los pacientes cuyo inicio clínico es un síndrome medular, que presentan hallazgos de neuroimagen poco específicos o que presentan criterios clínicos de EM con neuroimagen cerebral normal. Conclusiones: Es aconsejable realizar un estudio de potenciales evocados multimodales en pacientes con sospecha de EM para documentar la afectación de la vía motora como apoyo al diagnóstico de diseminación en espacio. Keywords: Multiple sclerosis, Motor evoked potentials, Clinical guidelines, Palabras clave: Esclerosis múltiple, Potenciales evocados motores, Guía clínica

Quantiferon-TB-Gold in Tube(®) test (QFT-G-IT) may have advantages if combined with TST when screening for Latent Tuberculosis Infection (LTBI) prior to initiating anti-TNF therapy in an area of intermediate tuberculosis incidence such as Spain. In a small-scale prospective study, we evaluate the use of QFT-G-IT in combination with the screening recommended in Spain (Tuberculin-Skin Test, TST retest, clinical data, and Chest X-Ray (CXR)) for LTBI in patients considered as candidates for anti-TNFα treatment.From June 2008 to October 2010, 123 patients from a 300-bed hospital in Palma de Mallorca (Spain) were included in the study. The majority of patients were under immunosuppressive therapy. A positive TST and TST booster were found in 22 and 17 patients, respectively. Thus 39 (31.7%) of the 123 patients had a positive TST. QFT-G-IT was positive in 16 patients (13.6%), indeterminate in 4 (3.2%), and negative in 103 (83.7%). One of the two tests was positive and LTBI was diagnosed in 34.1% of patients. The agreement between TST and QFT-G-IT among vaccinated patients was low and not statistically significant (Kappa=0.15) and was almost perfect among non-BCG vaccinated patients (K=0.81). TST positive responses were significantly related to BCG-vaccination (p0.05) and QFT-G-IT positive response rates were related to older age (p0.05).QFT-G-IT may have advantages when combined with TST in immunosuppressed patients especially in older patients with a negative TST; in BCG vaccinated patients with a positive TST, QFT-G-IT could avoid unnecessary treatments and toxicities related to a false-positive TST result.

Antecedentes. La distrofia muscular cintura-cadera tipo 1B es una enfermedad con herencia autosómica dominante y secundaria a una mutación en el gen LMNA. Esta enfermedad se caracteriza por su afectación a nivel neuromuscular y cardiaco.Objetivo. Realizar diagnóstico clínico y confirmatorio molecular en una paciente con debilidad muscular proximal y sintomatología cardíaca a través de secuenciación exómica.Materiales y métodos. Se presenta el caso de una paciente de 57 años de edad con cuadro de debilidad muscular proximal progresiva principalmente en extremidades y posterior afectación cardíaca; adicionalmente, la paciente tiene múltiples familiares con la misma sintomatología. Se realizó estudio de secuenciación exómica con confirmación, por método de Sanger, de la mutación hallada y posteriormente el análisis bioinformático de esta.Resultados. La detección de la mutación R377L en el gen LMNA por secuenciación exómica con confirmación por Sanger, junto con la sintomatología clínica de la paciente y el análisis bioinformático de la mutación hallada, permitió realizar diagnóstico confirmatorio de distrofia muscular cintura-cadera tipo 1B.Conclusión. Es difícil realizar un diagnóstico clínico debido a la heterogeneidad genética del fenotipo de distrofias musculares cintura-cadera. La aproximación diagnóstica es compleja y requiere clasificar las distrofias musculares según el patrón de afectación y el patrón de herencia de la enfermedad. Adicionalmente, debido a los múltiples genes que pueden generar clínica semejante a las diferentes distrofias musculares, se recomienda realizar secuenciación exómica solicitando especial énfasis en los genes candidatos de distrofias musculares cintura-cadera. Background. Limb-girdle muscular dystrophy type 1B has a dominant autosomal inheritance pattern and is caused by a mutation in the LMNA gene. This disease has a major neuromuscular and cardiac compromise; furthermore, it belongs to the limb-girdle muscular dystrophies.Objective. To make a clinical and molecular confirmatory diagnosis in a patient with proximal muscular weakness and cardiac symptoms using whole exome sequencing.Materials and Methods. This is the case of a 57 year old patient with a slowly progressive proximal muscular weakness and cardiac compromise; furthermore, the patient has many relatives with the same clinical history. Whole exome sequencing with Sanger confirmation and bioinformatics analysis was performed on the found mutation.Results. The detection of mutation R377L in the LMNA gen by whole exome sequencing with Sanger confirmation, the bioinformatic analysis of the mutation and the symptoms exhibited by the patient allowed the confirmatory diagnosis of limb-girdle muscular dystrophy type 1b.Conclusion. Due to genetic heterogeneity in the phenotype of limb-girdle muscular dystrophies it is difficult to make a clinical diagnosis. The diagnostic approach is complex and requires classification of the muscular dystrophies according to the pattern of muscular weakness and to identify the disease inheritance pattern. Additionally, due to the multiple genes that can generate similar symptoms in the different muscular dystrophies, the authors recommend the use of whole exome sequencing with a special emphasis on the candidate genes for limb-girdle muscular dystrophies.

A potentially fatal complication of influenza infection is the development of pneumonia, caused either directly by the influenza virus, or by secondary bacterial infection. Pneumonia related to the 2009 influenza A pandemic was found to be underestimated by commonly used pneumonia severity scores in many cases, and to be rapidly progressive, leading to respiratory failure. Confirmation of etiology by laboratory testing is warranted in such cases. Rapid antigen and immunofluorescence testing are useful screening tests, but have limited sensitivity. Confirmation of pandemic H1N1 influenza A infection can only be made by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR) or viral culture. The most effective preventive measure is annual influenza vaccination in selected individuals. Decisions to administer antiviral medications for influenza treatment or chemoprophylaxis should be based upon clinical and epidemiological factors, and should not be delayed by confirmatory laboratory testing results. Neuraminidase inhibitors (NI) are the agents of choice.

Aim: We examined ethnicity-related differences in the uptake of a temporary free-of-charge HPV vaccine (HPVV) catch-up programme offered in Denmark from August 2012 to December 2013 to women born from 1985–1992 and compared it with the previous self-payment system in place. Methods: We conducted a nationwide retrospective cohort study. We performed logistic regression analyses to examine the relationship between ethnic background and HPV vaccine (HPVV) programme initiation. Results: The free programme increased the vaccination uptake from 16% to 75%. Descendants (Denmark-born women with both parents of foreign origin) and immigrants in Denmark for more than 5 years were less likely to initiate the free HPVV programme than Denmark-born women ((aOR=0.56; 95% CI: 0.54–0.59) and (aOR=0.39; 95% CI: 0.38–0.40), respectively). The likelihood of HPVV programme initiation among immigrants increased with time in Denmark ((aOR=2.28; 95% CI: 2.11–2.48) for immigrants living in Denmark for 16–20 years compared to 6–10 years)). Conclusion: The initiation of the free-of-charge HPVV programme was satisfactory. However, large differences in uptake were demonstrated, indicating that some target groups are harder to reach than others. The integration process (as related to use of health services) occurs over many years where differences between the different population groups seem to vanish. Keywords: HPV, Human papillomavirus, Vaccine, Uptake, Ethnic background, Initiation

Natalizumab is a monoclonal antibody shown to be highly effective in the treatment of relapsing–remitting multiple sclerosis (RRMS). Patients treated with natalizumab can develop antibodies directed against this agent that may affect the efficacy and safety of the drug. In this observational study, the kinetics of the appearance and the incidence of anti-natalizumab antibodies were followed prospectively for 18 months in a cohort of 64 consecutive patients treated with natalizumab for relapsing MS. Blood samples were drawn immediately before starting natalizumab therapy and each month afterwards. The presence of antibodies against natalizumab was assessed by enzyme-linked immunosorbent assay (ELISA) in all patients. Anti-natalizumab antibodies were detected in nine (14.1%) natalizumab-treated patients, three (4.68%) of whom were transiently positive while six (9.37%) were persistently positive (these patients discontinued natalizumab). All positive titres were observed during the first 4 months of treatment. One patient with a hypersensitivity reaction also had persistent antibodies. We conclude that antibodies against natalizumab develop early, within the first 6 months of therapy with natalizumab. Although no antibodies were detected after 4 months of therapy in this particular study, this does not rule out their development later on in exceptional cases.

Resumen Introduccion Los test de deteccion in vitro de Interferon-γ frente a Mycobacterium tuberculosis (MTB) podrian ser una herramienta util en el diagnostico de enfermedad tuberculosa activa. Metodos Se realiza el test QuantiFERON-TB-Gold test in Tube (QFG-IT) en la sangre de 118 pacientes con tuberculosis pulmonar activa y se compara el resultado con la prueba de tuberculina. Resultados El estudio de QFG-IT fue positivo en 94 casos (79,7%), negativo en 17 (14,4%) e indeterminado en 7 (5,9%). QFG-IT negativo o indeterminado fue mas frecuente en pacientes mas ancianos (p=0,017) y en los casos de baciloscopia negativa (p=0,041). La concordancia kappa entre la prueba de la tuberculina y el QFG-IT fue de 74,5% con un valor kappa de 0,45 (SE:0,136). Trece de los enfermos estudiados estaban infectados por el VIH, la prueba de la tuebrculina fue positiva en 5 de los 12 casos (38,5%) en que se realizo,y el estudio de QFG-IT fue positivo en 9/13 (69,2%). Conclusiones QFG-IT puede ser una herramienta util complementaria a la prueba de la tuberculina en el diagnostico de enfermedad tuberculosa.

OBJETIVO: Caracterizar la antropometria y presion arterial de adultos del estado de Yucatan, Mexico. MATERIAL Y METODOS: Se evaluaron diferencias rural-urbanas por grupos sexo-edad en peso, talla, circunferencias de cintura y cadera, y presion arterial en 313 adultos de origen urbano y 271 del rural, de Yucatan. RESULTADOS: No hubo diferencias rural-urbanas en prevalencias de obesidad y sobrepeso, y en hipertension los urbanos tuvieron valores marginalmente mayores. Se encontro mayor prevalencia rural de cintura anormal solo en mujeres y hombres jovenes. La comparacion con dos encuestas nacionales y una regional (mixtecos rurales) mostro obesidad similar a la notificada en la Encuesta Nacional de Salud 2000 (ENSA) y mayor que mixtecos y la informada en la Encuesta Nacional de Enfermedades Cronicas 1993 (ENEC). La prevalencia de cintura anormal fue intermedia entre la indicada en la Encuesta Nacional de Salud y Nutricion 2006 (ENSANUT) y mixtecos, y la de hipertension intermedia entre la notificada en la ENEC y mixtecos. CONCLUSIONES: Las poblaciones maya y mestiza de Yucatan presentaron alta prevalencia de obesidad y cintura anormal que no se acompanaron de prevalencia mayor de hipertension. Esta observacion requiere confirmacion.

Inmunoterapia: La mejor comprension de los mecanismos inmunologicos en la patogenia de la esclerosis multiple (EM) ha permitido el desarrollo de terapias con base inmunologica. Los objetivos de estas inmunoterapias comprenden: el tratamiento del brote agudo y el tratamiento para modificar la historia natural de la enfermedad. Tratamiento de los brotes: Para el tratamiento de los brotes se considera de eleccion el tratamiento con altas dosis de metilprednisolona. Tratamiento de fondo: Los tratamientos para modificar la historia natural de la enfermedad mas estudiados en la EM son: inmunosupresores (azatioprina, ciclofosfamida, metotrexate, mitoxantrona); trasplante autologo de medula osea; inmunomoduladores (inmunoglobulinas intravenosas, plasmaferesis); estrategias basadas en el antigeno (acetato de glatiramero); aumento de citocinas antiinflamatorias (interferones); inhibicion de la migracion a traves de la barrera hematoencefalica mediante el bloqueo de las moleculas de adhesion con anticuerpos contra las moleculas de adhesion (natalizumab)

Concepto: La esclerosis multiple (EM) se caracteriza por su anatomia patologica, consistente en la aparicion de lesiones focales, multiples y distribuidas en la sustancia blanca de todo el sistema nervioso central, denominadas placas, en las que los mas llamativo es la perdida de mielina (desmielinizacion) con preservacion relativa de los axones. Etiopatogenia: La hipotesis patogenica mas aceptada es que la EM es fruto de la conjuncion de una determinada predisposicion genetica y un factor ambiental desconocido que, al aparecer en un mismo sujeto, originarian un amplio espectro de alteraciones en la respuesta inmunitaria, que a su vez serian las causantes de la inflamacion presente en las lesiones de la EM. Fisiopatologia: El proceso de desmielinizacion produce una alteracion en la conduccion saltatoria tipica de las vias mielinizadas normales, lentificandose la conduccion e incluso bloqueandose. Clinica: La caracteristica clinica mas llamativa de la EM es su gran variabilidad: los sintomas y signos determinados por la localizacion de las lesiones desmielinizantes que pueden ocurrir a todo lo largo del neuroeje. Curso clinico: El 90% de los pacientes con EM presentan un curso clinico caracterizado por la aparicion de episodios o brotes de disfuncion neurologica que, a medida que se repiten, van dejando secuelas funcionales neurologicas (forma en brotes o recidivante-remitente [RR o EMRR]). Tras 10 anos, un 50% de los pacientes pasan del curso en brotes a un curso progresivo (forma progresiva secundaria [EMPS]). Un 10% de los pacientes muestran un curso progresivo desde el comienzo (forma progresiva primaria [EMPP]). Diagnostico: El diagnostico clinico de la EM se realiza tomando en consideracion la existencia de criterios clinicos de diseminacion espacial y de dispersion temporal. La clinica se complementa con metodos de investigacion paraclinicos (liquido cefalorraquideo, potenciales evocados y resonancia magnetica)

Background Cervical cancer is the fourth most common cancer affecting women worldwide. Since 2006, two human papillomavirus vaccines (HPVV) have been licensed to protect women against the virus that causes cervical cancer. However, worldwide coverage remains unequal. Studies from the USA found strong evidence for differences in HPVV uptake by ethnicity and healthcare coverage. As the profile of ethnic groups and the healthcare system in the USA differ from countries in Europe where HPVV is free in most of the countries, we conducted a systematic review in order to analyze the determinants of HPVV uptake in Europe. Methods We performed a systematic Pubmed, Scopus, and Science Direct search to find articles published from HPVV availability in European countries until April 2014. No age restriction was applied. We included all studies assessing factors associated with HPVV uptake. Uptake refers to either initiation and/or completion of the three dose vaccination program. Results Out of the 23 eligible studies, 14 were retrospective reviews of data, six were cross-sectional surveys, and three were prospective cohort studies. Higher HPVV uptake was associated with ethnic majority populations, higher socio-economic status, regular cervical screening participation by the mother, and having received previous childhood vaccinations. Conclusion Since the vaccine is offered for free in most of the European countries, the findings suggest that ethno-cultural and educational factors play an important role when it comes to HPVV uptake. Girls who were undervaccinated had also a lower uptake of standard childhood vaccines and mothers who were less likely to attend cervical cancer screening. This may indicate that only few parents have specific concerns with HPVV, and that preventive health care should seek ways to target these vulnerable groups.

BACKGROUND The consumption of orange juice may lead to reduced oxidative stress and may enhance the antioxidant defense system. OBJECTIVE The aim was to evaluate the effects of the intake of orange juice containing either normal (NPJ) or high (HPJ) concentrations of polyphenols (299 and 745 mg/d, respectively) on the antioxidant defense system, oxidative stress biomarkers, and clinical signs of metabolic syndrome in 100 nonsmoking subjects who were either overweight or obese. METHODS A randomized, double-blind crossover study was conducted over two 12-wk periods with a 7-wk washout period. The effects on enzymatic and nonenzymatic blood antioxidant defense systems, urinary and plasma oxidative stress biomarkers, and clinical signs of metabolic syndrome were evaluated before and after an intervention with both of the orange juices. Paired t tests and linear mixed-effects models were used to evaluate the effects of juice, time, and interactions. RESULTS The intake of either NPJ or HPJ led to a decrease in urinary 8-hydroxy-2'-deoxyguanosine (NPJ: 935 ± 134 to 298 ± 19 ng/mg creatinine; HPJ: 749 ± 84 to 285 ± 17 ng/mg creatinine), 8-iso-prostaglandin F2α (NPJ: 437 ± 68 to 156 ± 14 ng/mg creatinine; HPJ: 347 ± 43 to 154 ± 13 ng/mg creatinine), erythrocyte catalase, and glutathione reductase activities. A decrease was also observed in body mass index, waist circumference, and leptin (all P < 0.05). The NPJ intervention decreased systolic and diastolic blood pressures (systolic blood pressure: 128 ± 1 to 124 ± 2 mm Hg; diastolic blood pressure: 79 ± 1 to 76 ± 1 mm Hg), whereas the HPJ intervention increased erythrocyte superoxide dismutase (SOD) activity (17.7 ± 1.5 to 23.1 ± 1.7 U/mg hemoglobin). CONCLUSIONS Our results show that the consumption of either NPJ or HPJ protected against DNA damage and lipid peroxidation, modified several antioxidant enzymes, and reduced body weight in overweight or obese nonsmoking adults. Only blood pressure and SOD activity were influenced differently by the different flavanone supplementations. This trial was registered at clinicaltrials.gov as NCT01290250.

[No abstract available]

Evidence for the effectiveness of immunosuppressive agents in MS is scanty. There are few good quality trials; most have methodological limitations, such as a small sample size and short duration. Moreover, there is no consistency in treatment regimes, patient groups or outcome measures and the clinical benefits remain unclear. Although azathioprine appears to reduce the relapse rate in MS patients, its effect on disability progression has not been demonstrated. Methotrexate may alter the course of disease favourably in patients with progressive MS, but the evidence is again sparse.

Choriocarcinoma is one of the most serious forms of gestational trophoblastic tumor. It is a malignant tumor from the epithelium of the chorionic villi. The most frequent location site is the uterus. Associated with ectopic pregnancy, it is extremely rare and in general, very aggressive. In 75% of the cases, it items from distant metastasis; therefore, a histological examination of the tubes must be performed in all ectopic pregnancies. Our patient was a 33-year-old woman who was admitted to emergency room (ER) with an intense pain in the right, iliac cavity, and limited genital bleeding. During the exploration, there was abdominal pain, with doubtful signs of peritoneal irritation. The vaginal ultrasound offered an image that was compatible with an extra uterine pregnancy in the left appendages. At emergency, right salpingectomy was performed via laparotomy. The patient was treated with polychemotherapy and contraceptives for a year, with no recurrence of the disease. Control follow-up was performed using beta-human chorionic gonadotropin (HCG) testing on a weekly basis during the first month and then bi-monthly during the first year of follow-up.

Combination therapy may benefit the subgroup of patients with secondary progressive multiple sclerosis (SPMS) who do not respond to interferon beta (IFNB). We performed a two-year study of azathioprine (AZA) combined with IFNB-1b in SPMS patients who had not responded well to IFNB-1b alone. Patients with SPMS were eligible for this non-controlled prospective study if they had two or more relapses requiring corticosteroid treatment or deteriorated by at least 0.5 points on the Expanded Disability Status Scale (EDSS) while on IFNB-1b in the year preceeding the study. Patients were to continue treatment with IFNB-1b (8 MIU qod, subcutaneous) and received AZA (50 mg tid, oral). Safety was assessed in terms of adverse reactions and laboratory measures graded according to the WHO toxicity scale. Efficacy was explored by changes in relapse rate, EDSS, 9-hole peg test (9-HPT), neuropsychological scores, and magnetic resonance imaging (MRI) results. Neutralizing antibodies (NAB) were measured. Ten SPMS patients (6 females) with a median EDSS score of 4.5 were enrolled. One patient withdrew because of gastrointestinal complaints, one was withdrawn owing to poor compliance, and 8 patients completed therapy. The only frequent side effect was lymphopenia, reported at least once in all patients. Annual relapse rate was reduced by approximately 50 % in the second year. There was a significant trend for EDSS increase. Total lesion load measured by MRI decreased at 12 and 24 months; only one patient had active lesions. No changes were seen in the 9-HPT. There was a significant improvement in neuropsychological tests after 24 months (p = 0.045). One patient tested positive for NAB throughout the study, and transient NAB were detected in 4 patients. In conclusion, combination therapy with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS. Strict clinical and laboratory monitoring is recommended during this combination therapy.

Little is known on the participation of immunoglobulin isotypes and subclasses in the pathogenesis of the severe disease caused by the pandemic influenza virus (influenza A(H1N1)pdm09).(1) To evaluate the association between plasma levels of IgG1, IgG2, IgG3, IgG4, IgA, IgM, IgE and outcome in patients with severe pandemic influenza. (2) To evaluate the association between immunoglobulin and cytokine levels in these patients.40 critically ill patients with community acquired pneumonia and influenza A(H1N1)pdm09 infection were recruited from November 2010 to February 2011. Plasma samples were collected during the first 24h following admission to the ICU. Immunoglobulins and 17 major cytokines were profiled in plasma.15 patients died (37.5%). When the association between clinical variables and prognosis was assessed, prior immunosuppression, APACHE II score, levels of IgG2 and levels of IgM were associated with outcome in a univariate Cox regression analysis. Kaplan Meier analysis showed that patients with levels of IgG2 and IgM59 and58 mg/dl respectively died earlier. Multivariate Cox regression analysis showed that APACHE II score and levels of IgM were the best predictors of outcome, being levels of IgM a protective factor against mortality. IgM was the immunoglobulin showing the largest number of negative correlations with cytokine levels.Our results support a central role of IgM in preventing uncontrolled inflammatory response and mortality in severe pandemic influenza. Early assessment of IgM could contribute to guide clinical decisions in these patients.

The application of agrochemical sprays to the aerial parts of crop plants is an important agricultural practice world-wide. While variable effectiveness is often seen in response to foliar treatments, there is abundant evidence showing the beneficial effect of foliar fertilizers in terms of improving the metabolism, quality, and yields of crops. This mini-review is focused on the major bottlenecks associated with the uptake and translocation of foliar-applied nutrient solutions. A better understanding of the complex scenario surrounding the ultimate delivery of foliar-applied nutrients to sink cells and organs is essential for improving the effectiveness and performance of foliar fertilizers.

Objective: To assess the association between previous term pregnancies and the prevalence of overweight in a group of urban women, controlling for the influence of age. Methods: One thousand twelve women, living in middle and low socioeconomic areas of Mexico City, were interviewed at home and their reproductive histories studied. Height and weight were measured in a clinical setting using controlled procedures. Overweight (BMI > 25) was the dependent variable used to calculate odds ratios and to perform a multiple logistic regression analysis. Results: Age and parity were significantly associated with the prevalence of overweight. Controlling for age, two or more previous pregnancies significantly increased the magnitude of the association. Conclusion: During the reproductive years parity seems to increase the risk of overweight in low and middle socioeconomic level urban women.