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Background Neurofilament light (NfL) is a promising biomarker of early neurodegeneration in Alzheimer's disease (AD). We examined whether plasma NfL was associated with in vivo amyloid beta and tau, and cognitive performance in non-demented presenilin-1 (PSEN1) E280A mutation carriers. Methods Twenty-five mutation carriers and 19 non-carriers (age range: 28 to 49 years) were included in this study. Participants underwent 11C Pittsburgh compound B (PiB)-PET (positron emission tomography), flortaucipir-PET, blood sampling, and cognitive testing. Results Mutation carriers exhibited higher plasma NfL levels than non-carriers. In carriers, higher NfL levels were related to greater regional tau burden and worse cognition, but not amyloid beta load. When we adjusted for age, a proxy of disease progression, elevated plasma NfL levels were only correlated with worse memory recall. Conclusions Findings support an association between plasma NfL, cognition, and tau pathology in non-demented individuals at genetic risk for developing AD dementia. Plasma NfL may be useful for selecting individuals at increased risk and tracking disease progression in AD.

Background Inactivated poliovirus vaccine (IPV) alone does not induce mucosal immunity. However, it was hypothesized that administration of IPV together with bivalent (types 1+3) oral poliovirus vaccine (bOPV) may stimulate mucosal cross-immunity to poliovirus type 2 (PV2). Methods Cuban infants were randomized to receive either one dose of IPV (Arm A); one dose of IPV with bOPV (Arm B) at about 6 months of age or no vaccine (Arm C). Subjects were challenged with one dose of trivalent OPV (tOPV); they were about 7 months old in arms A and B, and about 3 months old in arm C at a time of the tOPV challenge. Sera were collected before vaccination and 30 days after tOPV challenge and tested for presence of poliovirus neutralizing antibodies; stool samples were collected at days 0, 7, 14, 21 and 49 post-challenge and tested for presence of poliovirus. Results We enrolled 333 children. Excretion of PV2 following tOPV challenge was highest on day 7 (75 [CI 95% = 65-82%], 68 [CI 95% = 58-75%] and 73 [CI 95% = 63-80%] for study arms A, B, and C respectively); excretion decreased with every subsequent stool sampling; no significant differences either in proportion of PV2 excretion or in its duration were observed between study arms. Conclusions There was no reduction in excretion of PV2 after tOPV challenge in children who had received IPV with bOPV when compared to those who had received IPV alone or no vaccine. Polio eradication program cannot assume any PV2 mucosal response with the current polio immunization schedule. Clinical Trials Registration The trial was registered with the Australian New Zealand Clinical Trials Registry and allocated trial number ACTRN12616000169448.

Background: Analysis of the claims made by patients could be an indicator of quality and show strengths and aspects of improvement in the organization of a rheumatology department Objectives: The aims of the present study are to evaluate these claims, describe the sociodemographic and clinical characteristics of claiming patients and to determine the association between medical history and types of complaints. Methods: cross-sectional study. Claims made by patients treated by a Rheumatology department between 04/2016 and 12/2017 were analyzed. A descriptive analysis of these claims was carried out followed by a multivariate logistic regression model to determine the effect of the diagnosis of Fibromyalgia (FM)/Chronic Widespread Pain (CWP) on the type of claim and its association with clinical variables. A p Results: One hundred and nine patients (mean age 54.7 ± 18.5 years, 78% women and 50.5% residents in rural areas) made 113 claims. The main reasons for claiming were: “advance medical evaluation and/or tests” (45.1%), ”request for evaluation by a specific physician” (24.8%) and ”rejection of evaluation by specific physician” (13, 3%). 67% of the claims were satisfied. The least satisfied claims were “request for evaluation by specific doctor” (39.3%) while claims for “cancellation of evaluation” were satisfied in 88% of the cases. Median time between claim and previous medical visit was 99 [34-203] days and between claim and the subsequent medical consultation was 44 [28-82] days. Patients whose claims were due to ”unpleasant attendance” were the first to complaint (median 28 [2-72] days) but waited for the longest time to be attended (median 103 [46-147] days). “Cancellation of evaluation” was attended after a median of 31.5 [28-33] days. The main reasons for medical evaluation were: inflammatory/systemic disease in 25 patients (22.15%), neck and low back pain in 23 patients (20.35%) and FM/CWP also in 20.35% of patients. As personal medical history, Psychiatric Disorders were present in 20.5% of patients and multiple comorbidities in 19.6% of patients. Twenty patients had no medical history of interest. Regarding the type of claims, differences were observed related to the diagnosis and the patient‘s medical history. The logistic regression model (FM as dependent variable) adjusted for sex, age, rural area, time to/after the claim and medical history showed that patients with FM/CWP requested more frequently to “be evaluated by other physician” (OR of 23.92 ( 95% CI, 1.4-409.06) and “reject to be evaluated by a specific physician” (OR of 8.48 (95% CI, 1.2-60.09) than rest of the patients and also presented more frequently with psychiatric history (OR of 22.39 (95% CI, 1.15-437.23) Conclusion: the present study reflects main reasons for claiming of patients treated in a rheumatology department. Reasons of claiming and comorbidities of patients with FM/CWP differ from those of the rest of patients. These findings may be of interest for the organization of resources in rheumatology departments. Disclosure of Interests: Enrique Judez Navarro Consultant for: Roche, Carlos Sanchez-Piedra: None declared, Gines Sanchez Nievas: None declared, Isabel Labiano: None declared, Manuela Sianes: None declared, Gloria Garcia Consuegra: None declared, Sandra Soro: None declared, M Angeles Garcia Morales: None declared

Background Shortcomings of inhaled antibiotic treatments for Pseudomonas aeruginosa infection in patients with cystic fibrosis (CF) include poor drug penetration, inactivation by sputum, poor efficiency due to protective biofilm, and short residence in the lung. Methods Eligible patients with forced expiratory volume in 1 s (FEV1) ≥25% of predicted value at screening and CF with chronic P. aeruginosa infection were randomly assigned to receive 3 treatment cycles (28 days on, 28 days off) of amikacin liposome inhalation suspension (ALIS, 590 mg QD) or tobramycin inhalation solution (TIS, 300 mg BID). The primary endpoint was noninferiority of ALIS vs TIS in change from baseline to day 168 in FEV1 (per-protocol population). Secondary endpoints included change in respiratory symptoms by Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results The study was conducted February 2012 to September 2013. ALIS was noninferior to TIS (95% CI, −4.95 to 2.34) for relative change in FEV1 (L) from baseline. The mean increases in CFQ-R score from baseline on the Respiratory Symptoms scale suggested clinically meaningful improvement in both arms at the end of treatment in cycle 1 and in the ALIS arm at the end of treatment in cycles 2 and 3; however, the changes were not statistically significant between the 2 treatment arms. Treatment-emergent adverse events (TEAEs) were reported in most patients (ALIS, 84.5%; TIS, 78.8%). Serious TEAEs occurred in 17.6% and 19.9% of patients, respectively; most were hospitalisations for infective pulmonary exacerbation of CF. Conclusions Cyclical dosing of once-daily ALIS was noninferior to cyclical twice-daily TIS in improving lung function. ClinicalTrials.gov Identifier: NCT01315678

Background Pregnancy and the postpartum period are times of great change for women and their partners, often bringing substantial challenges and stress. Approximately 10%–20% of women suffer from mood disorders such as depression in the perinatal period. There are risks involved in using psychopharmacological interventions to treat perinatal depression. Mindfulness and compassion-based educational programs could be efficacious and cost-effective options for the prevention and treatment of perinatal mood disorders. The aim of this study is to assess the efficacy of an adapted Mindfulness-Based Childbirth and Parenting (MBCP) program that includes compassion training for pregnant women in primary care (PC) settings in the Spanish National Health System to decrease perinatal depression. Methods A multicenter randomized controlled trial (RCT) will be conducted. Participants will be pregnant women (n = 122) and their partners who wish to participate. They will be enrolled and assessed in PC settings and randomly assigned to either: (1) an adapted MBCP educational program tailored to the Spanish National Health System + treatment as usual (TAU); or (2) TAU only. The main outcome to be assessed will be depression, evaluated with the Edinburgh Postnatal Depression Scale (EPDS). Secondary outcomes will include self-reported measures of perceived stress, affects, mindfulness, self-compassion, maternal self-efficacy, and use of health and social services. Patients will be assessed at four timepoints: baseline; post-treatment; and at three and six months after childbirth. Intention-to-treat and per-protocol analyses will be carried out using linear regression mixed models. Effect sizes will be estimated using Cohen’s d. Discussion Perinatal depression is a significant health problem. An effective and low-cost childbirth education program that incorporates mindfulness and compassion practices may be a beneficial preventive complementary healthcare modality for expectant women and their partners. This study will be the first multicenter RCT in Spanish PC settings using adapted MBCP and compassion practices to reduce symptoms of depression during pregnancy and the postpartum period. Trial registration ClinicalTrials.gov, NCT03247491. Registered on 31 July 2017.

In this targeted review, we summarize current knowledge on substance-use disorder (SUD)-related cognitive deficits, the link between these deficits and clinical outcomes, and the cognitive training, remediation, and pharmacological approaches that have the potential to rescue cognition. We conclude that: (i) people with SUDs have moderate deficits in memory, attention, executive functions, and decision-making (including reward expectancy, valuation, and learning); (ii) deficits in higher-order executive functions and decision-making are significant predictors of relapse; (iii) cognitive training programs targeting reward-related appetitive biases, cognitive remediation strategies targeting goal-based decision-making, and pharmacotherapies targeting memory, attention, and impulsivity have potential to rescue SUD-related cognitive deficits. We suggest avenues for future research, including developing brief, clinically oriented harmonized cognitive testing suites to improve individualized prediction of treatment outcomes; computational modeling that can achieve deep phenotyping of cognitive subtypes likely to respond to different interventions; and phenotype-targeted cognitive, pharmacological, and combined interventions. We conclude with a tentative model of neuroscience-informed precision medicine. .En este artículo de revisión, se resume el conocimiento actual acerca de los déficits cognitivos relacionados con el trastorno por uso de sustancias (TUS), el vínculo entre estos déficits y los resultados clínicos, y el entrenamiento cognitivo, la remediación y los enfoques farmacológicos potencialmente útiles para la recuperación cognitiva. Se concluye que: 1) las personas con TUS tienen déficits moderados en memoria, atención, funciones ejecutivas y en la toma de decisiones (incluidas la expectativa de recompensa, la valoración y el aprendizaje), 2) los déficits en las funciones ejecutivas superiores y en la toma de decisiones son importantes predictores de recaída, 3) los programas de entrenamiento cognitivo orientados a los sesgos en las apetencias relacionadas con la recompensa, las estrategias de remediación cognitiva dirigidas a la toma de decisiones basadas en objetivos y las farmacoterapias focalizadas en memoria, atención e impulsividad tienen el potencial de recuperar los déficits cognitivos relacionados con el TUS. Se sugieren alternativas para futuras investigaciones, incluyendo el desarrollo de secuencias de pruebas cognitivas breves, armónicas y con una orientación clínica para mejorar la predicción individual de los resultados del tratamiento; los modelos computacionales que pueden conseguir un fenotipado profundo de los subtipos cognitivos que respondan probablemente a diferentes intervenciones; y las intervenciones cognitivas y/o farmacológicas para un fenotipo específico. Se concluye con un modelo tentativo de medicina de precisión basada en la neurociencia.Nous résumons dans cet article ciblé les connaissances actuelles sur les troubles cognitifs liés à l’utilisation d’une substance (TUS), sur le lien entre ces troubles et les résultats cliniques, sur l’entraînement cognitif, la remédiation cognitive et les traitements pharmacologiques qui peuvent aider la cognition. Nos conclusions sont les suivantes : 1) les troubles des personnes souffrant de TUS sont modérés pour la mémoire, l’attention, les fonctions exécutives et la prise de décision (y compris l’attente de récompense, l’évaluation et l’apprentissage) ; 2) les troubles des fonctions exécutives et de prise de décision d’ordre supérieur sont des prédicteurs significatifs de rechute ; 3) les programmes d’entraînement cognitif ciblant les biais appétitifs liés à la récompense, les stratégies de remédiation cognitive ciblant la prise de décision basée sur objectif et les traitements médicamenteux ciblant la mémoire, l’attention et l’impulsivité peuvent aider les troubles cognitifs liés aux TLS. Nos propositions de recherche future sont : des séquences de tests cognitifs brèves, harmonisées et cliniquement orientées pour améliorer une prédiction individualisée des résultats thérapeutiques ; un modelage numérique pour un phénotypage profond des sous-types cognitifs susceptibles de répondre aux différentes interventions ; et des interventions cognitives ciblées sur le phénotype, pharmacologiques et associées. Nous proposons en conclusion un modèle de médecine de précision éclairé par les neurosciences.

When an astronaut transitions from a low to high gravitational environment, fluid shifts from the head towards the feet resulting in orthostatic intolerance and syncope. Ground based experiments have shown that by stimulating the cardiovascular system via simple mental stressors, syncope can be delayed, potentially enabling astronauts to reach assistance before loss of consciousness. However, the effect of mental stressors on the stimulation of the cardiovascular system in gravitational environments different than that of Earth’s is unknown. As such, this paper investigates the effects that mental stressors under various gravitational environments. To do this, a pilot study was performed in which two participants were flown on two separate parabolic flights that simulated hyper and hypogravity conditions. The plane used was an Aerobatic Single-Engine Cap-10B plane (twin seater), and each participant executed 11 parabolas. The participants were the winners of the Barcelona Zero-G Challenge 2011 organized by UPC Universitat Politecnica de Catalunya-BarcelonaTech and Aeroclub Barcelona-Sabadell. Measurements were made of the participants’ hemodynamic and autonomic response throughout the parabolas, using a Chronocord: high precision HRV monitor. Comparisons of the baseline response without mental stressors, and the response with mental stressors during different gravitational loading conditions were made. It was observed that there is an increase in cardiovascular activity during hypo- and hyper-gravity when performing mental arithmetic. Our results show that the twin seater aerobatic single engine CAP-10B aicraft can provide changing gravitational loading conditions for enough periods to study changes in physiological systems.

Allergy to house dust mite is one of the most common causes of allergic rhinitis. A novel tyrosine-adsorbed, modified allergen product, Acarovac Plus, developed for the treatment of perennial mite allergy seeks to address the underlying cause of allergic rhinitis in this instance. One of two dosing regimens may be used, either the Conventional Regimen or the Cluster Regimen. We sought to compare the efficacy and safety of a specific immunotherapy, developed for the treatment of perennial mite allergy, administered under a Conventional and Clustered dosing schedule in patients with persistent allergic rhinitis. Thirty adult patients, between 18 and 65 years old, with allergic rhinitis and/or asthma secondary to hypersensitivity to Dermatophagoides pteronyssinus were administered with either conventional or cluster initial regime, with a final visit one week after the last dose administration. The efficacy to the Conventional and Cluster regimens was measured using a Nasal Challenge Test monitoring clinical symptoms and peak nasal inspiratory flow. Total IgE, serum-specific inmunoglobulins (IgE and IgG4) to Dermatophagoides pteronyssinus and relevant cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13) were assessed. A Satisfaction Questionnaire (TSQM) was completed after each patient's final visit. The tolerability of the vaccine was assessed monitoring adverse reactions. No adverse events were recorded in either conventional or cluster regime. The specific Nasal Challenge Test led to a decrease in symptom scores and a significant decrease in mean nasal peak inspiratory flow drop was recorded in both dosing regimen groups. A significant increase in IgG4-specific antibody titres was assessed. No significant changes were observed in concentrations of total IgE, specific IgE or cytokines (IFN-γ, IL-4, IL-5, IL-10 and IL-13). Patients declared themselves most satisfied in relation to “Secondary effects”, with high overall satisfaction in both groups. Cluster and conventional specific immunotherapy resulted in no adverse reaction(s) and led to similar improvements in immunological parameters, clinical efficacy (Nasal Challenge Test) and high overall satisfaction.

Background Fractional-dose administration of inactivated poliovirus vaccine (fIPV) could increase IPV affordability and stretch limited supplies. We assessed immune responses following fIPV administered intradermally, compared with full-dose IPV administered intramuscularly, among adults with a history of oral poliovirus vaccine (OPV) receipt. Methods We conducted a randomized, controlled noninferiority trial in Cuba. fIPV or IPV were administered on days 0 and 28; serum was collected on days 0, 7, 28, and 56 for analysis by a neutralization assay. The primary end point was seroconversion or a ≥4-fold rise in antibody titer. The noninferiority limit was 10%. The secondary end point was safety, assessed by the number and intensity of adverse reactions. Results A total of 503 of 534 enrolled participants (94.2%) completed all study requirements. Twenty-eight days after the first dose, 94.8%, 98.0%, and 98.0% of fIPV recipients had an immune response to poliovirus types 1, 2, and 3, respectively, compared with 98.1% (P = .06), 98.0% (P = 1.00), and 99.2% (P = .45) in the IPV arm. Noninferiority was achieved on days 7, 28, and 56 for all serotypes. No serious adverse events were reported. Conclusion fIPV induced similar boosting immune responses, compared with full-dose IPV. This suggests that fIPV would be an effective strategy to boost population immunity in an outbreak situation. Clinical Trials Registration ACTRN12615000305527.

Aim: A 1-year follow-up study comparing the safety and tolerability of the dosing schedules, satisfaction and effectiveness of a novel microcrystalline tyrosine-adsorbed mite (Dermatophagoides pteronyssinus)-allergoid subcutaneous immunotherapy (Acarovac Plus™) in 30 adult patients (18–65 years) with allergic rhinitis and/or asthma. Materials & methods: The effectiveness of the product was assessed by nasal provocation test measuring peak nasal inspiratory flow/symptoms, in vitro immunologic changes (IgE, IgG4 and IL-10) and Treatment Satisfaction Questionnaire for Medication. Results: No adverse events were reported during dosing schedules. Significant decreases in symptom scores and drop of peak nasal inspiratory flow in follow-up visits (4 weeks and 1 year) were recorded. Significant increases in IgG4-specific antibody titers and IL-10 were exhibited. Conclusion: Significant decreases in clinical symptoms and immunological parameters were observed, accompanying a high level of patient satisfaction and tolerance.

AIM To evaluate the real-world effectiveness of golimumab in ulcerative colitis (UC) and to identify predictors of response. METHODS We conducted an observational, prospective and multi-center study in UC patients treated with golimumab, from September 2014 to September 2015. Clinical activity was assessed at wk 0 and 14 with the physician' s global clinical assessment (PGA) and the partial Mayo score. Colonoscopies and blood tests were performed, following daily-practice clinical criteria, and the results were recorded in an SPSS database. RESULTS Thirty-three consecutive patients with moderately to severely active UC were included. Among them, 54.5% were female and 42 years was the average age. Thirty percent had left-sided UC (E2) and 70% had extensive UC (E3). All patients had an endoscopic Mayo score of 2 or 3 at baseline. Twenty-seven point three percent were anti-tumor necrosis factor (TNF) treatment naive, whereas 72.7% had previously received infliximab and/or adalimumab. Sixty-nine point seven percent showed clinical response and were steroid-free at wk 14 (a decrease from baseline in the partial Mayo score of at least 3 points). Based on PGA, the clinical remission and clinical response rates were 24% and 55% respectively. Withdrawal of corticosteroids was observed in 70.8% of steroid-dependent patients at the end of the study. Three out of 10 clinical non-responders needed a colectomy. Mean fecal calprotectin value at baseline was 300 mu g/g, and 170.5 mu g/g at wk 14. Being anti-TNF treatment naive was a protection factor, which was related to better chances of reaching clinical remission. Twenty-seven point three percent of the patients required treatment intensification at 14 wk of followup. Only three adverse effects (AEs) were observed during the study; all were mild and golimumab was not interrupted. CONCLUSION This real-life practice study endorses golimumab's promising results, demonstrating its short-term effectiveness and confirming it as a safe drug during the induction phase.

The World Health Organization recommends that as part of the polio end-game strategy a dose of inactivated poliovirus vaccine (IPV) be introduced by the end of 2015 in all countries currently using only oral poliovirus vaccine (OPV). Administration of fractional dose (1/5 of full dose) IPV (fIPV) by intradermal (ID) injection may reduce costs, but its conventional administration is with Bacillus Calmette-Guerin (BCG) needle and syringe (NS), which is time consuming and technically challenging. We compared injection quality achieved with BCG NS and three needle-free jet injectors and assessed ergonomic features of the injectors.Children between 12 and 20 months of age who had previously received OPV were enrolled in the Camaguey, Cuba study. Subjects received a single fIPV dose administered intradermally with BCG NS or one of three needle-free injector devices: Bioject Biojector 2000® (B2000), Bioject ID Pen® (ID Pen), or PharmaJet Tropis® (Tropis). We measured bleb diameter and vaccine loss as indicators of ID injection quality, with desirable injection quality defined as bleb diameter ≥5mm and vaccine loss10%. We surveyed vaccinators to evaluate ergonomic features of the injectors. We further assessed the injection quality indicators as predictors of immune response, measured by increase in poliovirus neutralizing antibodies in blood between day 0 (pre-IPV) and 21 (post-vaccination).Delivery by BCG NS and Tropis resulted in the highest proportion of subjects with desirable injection quality; health workers ranked Biojector2000 and Tropis highest for ergonomic features. We observed that vaccine loss and desirable injection quality were associated with an immune response for poliovirus type 2 (P=0.02, P=0.01, respectively).Our study demonstrated the feasibility of fIPV delivery using needle-free injector devices with high acceptability among health workers. We did not observe the indicators of injection quality to be uniformly associated with immune response.

To compare a mixing vs. a cycling strategy of use of anti-Pseudomonas antibiotics on the acquisition of resistant Gram-negative bacilli in the critical care setting.Prospective, open, comparative study of two strategies of antibiotic use.Two medical intensive care units of a university hospital.A total of 346 patients admitted foror=48 hrs to two separate medical intensive care units during an 8-month period.Patients, who according to the attending physician's judgment required an anti-Pseudomonas regimen, were assigned to receive cefepime/ceftazidime, ciprofloxacin, a carbapemen, or piperacillin-tazobactam in this order. "Cycling" was accomplished by prescribing one of these antibiotics during 1 month each. "Mixing" was accomplished by using the same order of antibiotic administration on consecutive patients. Interventions were carried out during two successive 4-month periods, starting with mixing in one unit and cycling in the other.Swabbing of nares, pharynx, and rectum and culture of respiratory secretions were obtained thrice weekly. The main outcome variable was the proportion of patients acquiring enteric or nonfermentative Gram-negative bacilli resistant to the antibiotics under intervention. The scheduled cycling of antibiotics was only partially successful. Although the expected antibiotic was the most prevalent anti-Pseudomonas agent used within the corresponding period, it never accounted for45% of all anti-Pseudomonas antimicrobials administered. During mixing, a significantly higher proportion of patients acquired a strain of Pseudomonas aeruginosa resistant to cefepime (9% vs. 3%, p = .01), and there was a trend toward a more frequent acquisition of resistance to ceftazidime (p = .06), imipenem (p = .06), and meropenem (p = .07). No differences in the rate of acquisition of potentially resistant Gram-negative bacilli or incidence of intensive care unit-acquired infections and infections due to particular organisms were observed.In critically ill medical patients, a strategy of monthly rotation of anti-Pseudomonas beta-lactams and ciprofloxacin may perform better than a strategy of mixing in the acquisition of P. aeruginosa resistant to selected beta-lactams.

Summary Background Artemisia vulgaris is a widespread weed in the Mediterranean area and several allergens have been detected in its pollen. One of them, Art v 3, belongs to the lipid-transfer protein (LTP) family and its prevalence in Artemisia-sensitized patients or its relationship with other LTP allergens is not clear. Objective To assess the pattern of sensitization to an array of mugwort allergens in a Mediterranean population, and to study the cross-reactivity of Art v 3 with Pru p 3 and Par j 1, relevant LTP allergens in the area. Methods Skin prick test was performed with whole extracts (A. vulgaris, Parietaria judaica and peach) and pure natural allergens Art v 1, Art v 3, Art v 60 kDa and Par j 1 in 24 mugwort-allergic patients from a Mediterranean area. In vitro assays included measurement of specific IgE and ELISA inhibition among LTP allergens. Results The three Artemisia allergens elicited a positive skin response in 70–80% of the patients. Seven patients were clearly sensitized to Par j 1 and 11 to Pru p 3. There was no correlation between Par j 1 and Pru p 3 sensitization, but a highly significant correlation was found between peach extract and Art v 3 as regards the skin response. No IgE cross-reactivity was observed between Art v 3/Par j 1 or Pru p 3/Par j 1. In contrast, Art v 3 significantly inhibited the binding to Pru p 3 of IgE from three patients' sera out of six studied, but Pru p 3 was not able to inhibit the IgE binding to Art v 3. Conclusion Art v 3 is a major mugwort allergen and in some patients with IgE to both Art v 3 and Pru p 3, Art v 3 behaves as the primary sensitizing agent.

Several members of the plant non-specific lipid transfer protein (LTP) family have been identified as relevant allergens in foods and pollens. These allergens are highly resistant to both heat treatment and proteolytic digestion. These characteristics have been related with the induction of severe systemic reactions in many patients, and with the possibility of being primary sensitizers by the oral route. A specific geographical distribution pattern of sensitization to LTP allergens has been uncovered. This allergen family is particularly important in the Mediterranean area, but shows a very limited incidence in Central and Northern Europe. The potential role in the plant, as well as the biochemical and allergenic properties of the LTP family, are reviewed here.

Mutations in parkin are implicated in the pathogenesis of autosomal recessive juvenile parkinsonism (AR-JP) disease. We show that homozygote Cys212Tyr parkin mutation in AR-JP patients renders lymphocytes sensitive to dopamine, iron and hydrogen peroxide stimuli. Indeed, dopamine-induced apoptosis by four alternative mechanisms converging on caspase-3 activation and apoptotic morphology: (1) NF-kappaB-dependent pathway; mitochondrial dysfunction either by (2) H(2)O(2) or (3) hydroxyl exposure and (4) increase of unfolded-protein stress. We also demonstrate that 17beta-estradiol and testosterone prevent homozygote lymphocytes from oxidative stressors-evoked apoptosis. These results may contribute to understanding the relationship between genetic and environmental factors and iron in AR-JP.

Background Lipid transfer proteins (LTPs) are clinically relevant plant food panallergens and have been proposed as ideal tools to study true food allergy. Pru p 3, the major peach allergen in the Mediterranean area, is among the best-characterized allergenic members of the LTP family. Its diagnostic value for Rosaceae fruit allergy has been demonstrated both in vivo and in vitro. Objective We sought to locate major IgE-binding epitopes of Pru p 3. Methods A serum pool and individual sera from patients with peach allergy and positive skin prick test results to Pru p 3 were used. Three-dimensional modeling was achieved by using experimentally available structures of Pru p 3 homologues as templates. Theoretical prediction of potential IgE-binding regions was performed by selecting specific residues on the molecular surface displaying prominent electrostatic potential features. Point mutants of Pru p 3 were constructed by standard polymerase chain reaction procedures with the appropriate primers. Mutants were expressed in P pastoris by means of the pPIC 9 vector and purified from the corresponding supernatants by gel-filtration chromatography followed by RP-HPLC. IgE binding by Pru p 3 mutants was tested by immu-nodetection and quantified by ELISA and ELISA inhibition assays. Synthetic peptides (10 mer; 5 amino acids overlapping) covering the full Pru p 3 sequence were used to detect IgE epitopes by 125 I–anti-IgE immunodetection. Results Pru p 3 showed a 3-dimensional structure comprising 4 α-helixes and a nonstructured C-terminal coil (residues 73 to 91). Regions around amino acids in positions 23 to 36, 39 to 44, and 80 to 91, particularly residues R39, T40, and R44, K80 and K91, were predicted as potential antibody recognition sites according to their relevant surface and electrostatic properties. Point mutants K80A and K91A were found to have an IgE-binding capacity similar to that of recombinant Pru p 3, but the triple mutant R39A/T40A/R44A showed a substantial decrease (approximately 5 times) of IgE binding. IgE immu-nodetection of synthetic peptides led to the identification of Pru p 3 sequence regions 11 to 25, 31 to 45, and 71 to 80 as major IgE epitopes. Conclusions Main IgE-binding regions of the Pru p 3 amino acid sequence were identified. The three major ones comprised the end of an α-helix and some residues of the following interhelix loop. These data can help to search for Pru p 3 hypoallergenic forms.

The low rate of organ donation among Hispanics is of increasing concern to the transplant community at a time when the Hispanic population is growing rapidly, especially in Southern California. OneLegacy, the nation's largest organ procurement organization, commissioned a series of in-depth individual interviews with Spanish-language-dominant Hispanics to identify barriers and motivators to organ and tissue donation. Participants included 5 families who had consented to the donation of a loved one's organs within the past year and 7 families from the general Hispanic public who were either opposed to or ambivalent about organ donation. Individuals from both groups indicated a common reticence to speak of or make plans for either their own or a family member's death and lacked knowledge of procedures surrounding donation (whether consenting or being a donor themselves). Some respondents from the opposing group did not understand that organ donation takes place after death, expressing fears that declaring themselves donors would put them at risk of being allowed to die so that their organs could be recovered. Other attitudinal barriers included the wish to die with all body parts intact and reluctance to have another person's organ in their bodies. Consenting respondents found comfort in having helped another person to live. They wished for a personal expression of thanks from the recipients and an opportunity to learn more about and meet them. Interview findings suggest a great need to further educate the Hispanic community about organ donation, especially concerning brain death, the process for organ donation, and the protections afforded to donors and their families in the United States. Overcoming the taboos surrounding discussion of death and planning for death is an essential first step.

Background To ensure that developing countries have the option to produce inactivated poliovirus vaccine (IPV), the Global Polio Eradication Initiative has promoted the development of an IPV using Sabin poliovirus strains (Sabin IPV). This trial assessed the reactogenicity and immunogenicity of Sabin IPV and adjuvanted Sabin IPV in healthy adults in Cuba. Methods This is a randomized, controlled phase I trial, enrolling 60 healthy (previously vaccinated) male human volunteers, aged 19–23 years to receive one dose of either Sabin IPV (20:32:64 DU/dose), adjuvanted Sabin IPV (10:16:32 DU/dose), or conventional Salk IPV (40:8:32 DU/dose). The primary endpoint for reactogenicity relied on monitoring of adverse events. The secondary endpoint measured boosting immune responses (i.e. seroconversion or 4-fold rise) of poliovirus antibody, assessed by neutralization assays. Results Sixty subjects fulfilled the study requirements. No serious adverse events reported were attributed to trial interventions during the 6-month follow-up period. Twenty-eight days after vaccination, boosting immune responses against poliovirus types 1–3 were between 90% and 100% in all vaccination groups. There was a more than 6-fold increase in median antibody titers between pre- and post-vaccination titers in all vaccination groups. Discussion Both Sabin IPV and adjuvanted Sabin IPV were well tolerated and immunogenic against all poliovirus serotypes. This result suggests that the aluminum adjuvant may allow a 50% (or higher) dose reduction.

The aim of the present study was to explore cross-cultural differences in emotion control, using the Emotion Control Questionnaire [ECQ — Roger, D., & Najarian, B. (1989). The construction and validation of a new scale for measuring emotional control. Personality and Individual Differences, 10 , 845–853]. The ECQ has been extensively validated on English samples, but rather than using the original published factor structure to derive mean scores, the study was based on comparisons between new factor analyses of ECQ data obtained from comparable samples of English, Spanish and Korean subjects. Consistent differences emerged, suggesting that the Korean subjects in particular differed in the way they construed emotional behaviour. Subsequent confirmatory factor analyses suggested that a two-factor model comprising emotional inhibition and emotional rumination offered the best fit for the data across all three samples, and new scales based on these findings are proposed.

Despite the intensive research on plant chitinases, largely bolstered by their antifungal properties, little is known at present about the structure-activity relationships of these enzymes. Here we report the identification of essential active site residues in endochitinase Ch3, a class I enzyme abundant in chestnut seeds. Knowledge-based protein modeling as well as structural and sequence comparisons were performed to identify potential catalytic residues. Different mutated proteins were then generated by site-directed mutagenesis, expressed in Escherichia coli , and characterized for their chitinolytic activity. Glu124 and Glu146, the only carboxylic residues properly located into the active site cleft to participate in catalysis, were both mutated to Gln and Asp. Our results suggest that Glu124 functions as the general acid catalyst whereas Glu146 is likely to act as a general base. Other mutations involving three highly conserved active site residues, Gln173, Thr175, and Asn254, also impaired the chitinolytic activity of Ch3. The effects of these variants on the fungus Trichoderma viride revealed that catalysis is not necessary for antifungal activity. Similarly to its homologous nonenzymatic polypeptides hevein and stinging nettle lectin, the N-terminal chitin-binding domain of Ch3 appears to interfere itself with hyphal growth.

Summary Background Putative wheat allergens with molecular sizes around 35kDa have been repeatedly detected in immunoblots using sera from patients with baker's asthma. However, none of these allergens had been previously isolated. Objective To purify and characterize a major component of the 35 kDa aliergenic band which seems to be present in flour from diploid. tetraploid (pasta) and hexaploid (bread) wheats. Methods Gel-filtration chromatography followed by RP-HPLC have allowed the purification of a new wheat allergen. Immunodetection with sera from allergic patients and with a specific serum for asparagine-linked complex glycans, as well as amino acid sequencing, were used to identify the isolated protein. Results A 36 kDa allergen has been purified from wheat flour. Its N-terminal and internal sequences, N-linked glycans, and enzymatic activity indicated that this allergen is a seed-specific peroxidase. Sera from six out of 10 patients hypersensitive to wheat flour displayed positive reactions when assayed against the purified dot-blotted allergen. Conclusion Seed-specific peroxidases from cereals (flours) seem to be important allergens in hypersensitive diseases associated with the manipulation of these plant materials. A new enzyme has thus been involved in IgE-mediated diseases.

The α-amylase activity was determined throughout the larval development of Spodoptera frugiperda. Maximal activities with optimal pH in the range 8.5–9.5 were found in last instars. Protein preparations enriched in heterotetrameric inhibitors from wheat flour were active towards gut amylases from last instars, while those corresponding to homodimeric and monomeric inhibitors showed low inhibition levels. These results were further supported by testing purified members of each inhibitor type and by analyzing the effects of the inhibitors on the amylase isoenzyme pattern from native PAGE. High levels of trypsin-like activity were also found in gut extracts from last instars. Different genetic variants of the major barley trypsin inhibitor were active against this gut enzyme. None of the other larval digestive protease activities (chymotrypsin-like, elastase-like, leucine aminopeptidase-like, and carboxypeptidase A and B-like) were inhibited, indicating that the barley inhibitor is specific towards trypsin-like enzymes.

To reduce the costs of maintaining a poliovirus immunization base in low-income areas, we assessed the extent of priming immune responses after the administration of inactivated poliovirus vaccine (IPV).We compared the immunogenicity and reactogenicity of a fractional dose of IPV (one fifth of a full dose) administered intradermally with a full dose administered intramuscularly in Cuban infants at the ages of 4 and 8 months. Blood was collected from infants at the ages of 4 months, 8 months, 8 months 7 days, and 8 months 30 days to assess single-dose seroconversion, single-dose priming of immune responses, and two-dose seroconversion. Specimens were tested with a neutralization assay.A total of 320 infants underwent randomization, and 310 infants (96.9%) fulfilled the study requirements. In the group receiving the first fractional dose of IPV, seroconversion to poliovirus types 1, 2, and 3 occurred in 16.6%, 47.1%, and 14.7% of participants, respectively, as compared with 46.6%, 62.8%, and 32.0% in the group receiving the first full dose of IPV (P0.008 for all comparisons). A priming immune response to poliovirus types 1, 2, and 3 occurred in 90.8%, 94.0%, and 89.6% of participants, respectively, in the group receiving the fractional dose as compared with 97.6%, 98.3%, and 98.1% in the group receiving the full dose (P=0.01 for the comparison with type 3). After the administration of the second dose of IPV in the group receiving fractional doses, cumulative two-dose seroconversion to poliovirus types 1, 2, and 3 occurred in 93.6%, 98.1%, and 93.0% of participants, respectively, as compared with 100.0%, 100.0%, and 99.4% in the group receiving the full dose (P0.006 for the comparisons of types 1 and 3). The group receiving intradermal injections had the greatest number of adverse events, most of which were minor in intensity and none of which had serious consequences.This evaluation shows that vaccinating infants with a single fractional dose of IPV can induce priming and seroconversion in more than 90% of immunized infants. (Funded by the World Health Organization and the Pan American Health Organization; Australian New Zealand Clinical Trials Registry number, ACTRN12610001046099.).

Major wheat and rye allergens associated with baker's asthma have been identified as specific inhibitors of Dermatophagoides pteronyssinus alpha-amylase (Der p 4). the most active inhibitors were the wheat tetrameric one and the rye dimeric RDAI-1. these data suggest that interaction between mite and cereal allergens (alpha-amylase/inhibitor complexes) might occur in house-dust-mite-infected flours. In contrast to the strong inhibition of the d. pteronyssinus enzyme by the wheat and rye inhibitors, the amylases from D. farinae, Lepidoglyphus destructor, and Tyrophagus putrescentiae were much less affected. Moreover, the D. pteronyssinus amylase showed higher pH optimum (6.5 versus 5.0) and activity level (2-6 times/mg of protein in whole-mite extracts) than those from the three other mite species.

A food-frequency questionnaire (FFQ) for low-income Mexican-Americans in Starr County, Texas, was developed as part of an epidemiologic study of gallbladder disease during 1985 and 1986. The FFQ was developed from 7-day food records collected from the first sample. In the validity study, using the second sample, correlations between nutrients calculated from 3-day food records and the FFQ were 0.77, 0.76, and 0.61 for energy, total fat, and saturated fat, respectively. In the reliability study, using the third sample, for the 1-month interval between baseline and a repeat FFQ measurement correlations ranged from 0.90 for energy to 0.85 for total fat and for the 2-month interval they were 0.84 for energy and 0.70 for total fat. The high correlations are largely explained by the lack of diversity in the diets of Starr County individuals which facilitated the high agreement between the FFQ and the food records for estimates of energy, fats, and cholesterol.

A rye flour protein of about 13.5 kDa, as well as its barley homologue, have been isolated. The rye component was recognized in vitro by IgE of allergic patients and provoked positive responses in 15 out of 21 baker's asthma patients (71%) when skin prick tests were performed. Its barley homologue showed no detectable in vitro reactivity and caused positive responses in only one-third of patients. Although no inhibitory activity against different α-amylases or trypsin was found for these two proteins, their N-terminal sequencing revealed considerable similarity to several members of the cereal α-amylase/trypsin inhibitor family.

The prevalence of obesity among Hispanic American populations is generally greater than among white populations in the United States. Among Mexican Americans, the prevalence of obesity was higher than among either Cuban Americans or Puerto Ricans. It is well known that the prevalence of diabetes increases with increasing levels of obesity or body mass index. However, it does not appear that the high prevalence of obesity in Mexican Americans completely accounts for the higher prevalence of diabetes seen in this ethnic group. Among Mexican Americans, the association of selected cardiovascular disease risk factors, high-density lipoprotein cholesterol subfractions and systolic blood pressure, was similar to that seen among other U.S. populations. Individuals with diabetes had higher values than seen among those without diabetes. In a comparison of nutrient intake in two Mexican-American populations, one rural and one urban, there were no major differences other than higher calorie intakes in the rural population compared with the urban population. In addition, the diet in the rural population, based on higher levels of the Keys score, was more atherogenic than that of the urban population.

This study assesses the impact of a paid media advertising campaign employing Spanish language, culturally sensitive television and radio spots airing on major Hispanic stations in southern California. An advertising tracking study with a baseline and three postintervention telephone surveys was conducted from 2001 through 2003 among 500 randomly selected self-identified, primarily Spanish language dominant adult Hispanics. Measures of organ donation attitudes and behaviors (decision and declared intent to donate organs) improved significantly (P.05) in 2001 and 2002, then leveled off or declined in 2003. Among the reasons given for not making a decision to donate was fear that medical personnel might withhold care from identified organ donors, suggesting lack of knowledge and distrust of the health care system. Few respondents talked to health care professionals or contacted the organ procurement agency for information either before or after the campaign. Findings from this study indicate a need for ongoing public education in the Hispanic community about organ transplantation and donation. Health professionals need to become more engaged in encouraging Hispanic patients to learn about organ transplantation and donation, and to inform their families that they have made the personal decision to donate.

To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the development of organ failure and outcome in critically ill patients with septic syndromes.Prospective, observational study in a medical intensive care unit of a university hospital.224 consecutively admitted patients.Epidemiological data, severity scores, and the primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-beta, and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were carried out.The primary outcome variables were organ dysfunction and mortality.Eighty-eight subjects had septic shock at ICU entry or within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G, mainly due to multiorgan failure. After adjusting for SAPS II at admission the genotypes independently associated with ICU mortality in septic shock were TNF-B2/B2 (OR 2.83, 1.04-7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02-4.85). The PAI-1 genotype did not determine susceptibility to infection or the outcome in nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and nosocomial septic shock.Homozygosity for 4G of the PAI-1 gene confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure.

Household water treatment is increasingly recognized as an effective means of reducing the burden of diarrheal disease among low-income populations without access to safe water. Oxfam GB undertook a pilot project to explore the use of household-based ceramic water filters in three remote communities in Colombia. In a randomized, controlled trial over a period of six months, the filters were associated with a 75.3% reduction in arithmetic mean thermotolerant coliforms (TTCs) (P < 0.0001). A total of 47.7% and 24.2% of the samples from the intervention group had no detectible TTCs/100 mL or conformed to World Health Organization limits for low risk (1-10 TTCs/100 mL), respectively, compared with 0.9% and 7.3% for control group samples. Overall, prevalence of diarrhea was 60% less among households using filters than among control households (odds ratio = 0.40, 95% confidence interval = 0.25, 0.63, P < 0.0001). However, the microbiologic performance and protective effect of the filters was not uniform throughout the study communities, suggesting the need to consider the circumstances of the particular setting before implementing this intervention.

Background: The peach lipid transfer protein Pru p 3 has been identified as a major allergen from this fruit. Homologous cross-reactive allergens have been found in several plant foods and pollens. Recombinant Pru p 3 has been recently produced in the yeast Pichia pastoris . Objective: We sought to evaluate the potential role of recombinant Pru p 3 as a novel tool for the diagnosis of fruit allergy. Methods: Circular dichroism analysis was used to compare the protein folding of natural Pru p 3 and recombinant Pru p 3. IgE binding by both molecular forms was quantified by means of ELISA and ELISA inhibition assays, and their biologic activity was estimated by using basophil activation, histamine release, and sulphidoleukotriene production tests. Individual sera or blood samples from patients with peach allergy (up to 17) were used in the assays. Results: A nearly identical circular dichroism spectra was shown by using natural Pru p 3 and recombinant Pru p 3, indicating that both protein forms are similarly folded. No difference was detected in the IgE-binding capacity of the 2 mo-lecular versions. Basophil activation and induction of sulphidoleukotriene production were positive in 9 of 10 patients, and histamine release was induced in at least half of the patients, with similar effects of the natural and recombinant forms in the 3 assays. Conclusion: Recombinant Pru p 3 shows a strong immunologic activity equivalent to that of its natural counterpart, and therefore it can be a useful tool for diagnosis (and future immunotherapy) of fruit allergy. (J Allergy Clin Immunol 2003;111:628-33.)

Pru p 3 is a lipid transfer protein (LTP) that has been identified as the major peach (Prunus persica) allergen. However, little is known about the amount present in both raw and processed foodstuffs. Moreover, the in vivo release upon consumption of peach-containing foods remains unclear. We have developed a sensitive monoclonal antibody-based ELISA for Pru p 3. The method has been applied to measure the allergen levels in foodstuffs and the allergen release under different physiological conditions. A significant variability in all raw peaches and peach-containing foods tested has been detected. The allergen was extracted more efficiently at a low pH, and it was highly resistant to pepsin. This ELISA will be very useful in controlling the allergen concentration in diagnostics, in evaluating threshold levels in provocation tests, and in detecting hidden allergens in processed foods and cosmetics.

Beer has recently been implicated as the causative agent of contact urticaria and severe IgE-mediated anaphylaxis. However, no allergen from beer has as yet been isolated and characterized. Two major components of 45 kd and 9 kd were detected in crude protein preparations from beer. Both components were purified; they were identified as barley protein Z 4 (45 kd) and lipid transfer protein 1 (LTP1; 9 kd). Protein Z 4 was recognized by the 4 individual sera tested but provoked weak positive responses to skin testing in 2 of 4 beer-allergic patients. Purified LTP1 showed reactivity with 3 of 4 individual sera and induced strong positive skin prick responses in all 4 patients tested. Barley LTP1 and protein Z 4 have been identified as the main beer allergens. (J Allergy Clin Immunol 2001;108:647-9.)

Summary Background A number of wheat and barley flour proteins that belong to the cereal α-amylase/trypsin inhibitor family have been identified as major allergens associated with baker's asthma. However, the allergenic role of this protein family had not been investigated in rye. Objective To study the allergenicity of flve purified proteins from rye flour which belong to the same inhibitor family, as well as to compare their properties with those of their wheat and barley homologues. Methods In vivo skin-prick tests were carried out in 21 patients with radioallergo-sorbent test (RAST) 2–3 to rye and allergic sensitization mainly to this cereal flour. In addition, sera from all these patients were used to assay the IgE binding capacity of dot blotted purified proteins. Results Three of the rye proteins tested, namely Sec c 1, RDAI-1 and RDAI-3, provoked positive skin-prick tests in more than 50% of patients, although their in vitro reactivity was lower. Different reactivities were found for the rye components compared with their wheat and barley homologues. Statistical analyses showed a significant correlation between the results of in vivo and in vitro tests for seven out of the nine purified proteins considered in this study. Conclusion Members of the rye α-amylase inhibitor family are main allergens involved in allergic reactions to cereal flours. However, different allergenic behaviours were found between homologous allergens from rye, barley, and wheat.

Abstract 5028 Introduction There are few studies that evaluate the difference in incidence and survival of primary extranodal lymphomas (PEL) as compared to nodal lymphomas. In the Population Based Cancer Registry of Zaragoza (PCRZ) working since 1960, all incident cases of hematologic and non hematologic cancer are including. PCRZ is a data source for epidemiological studies. Objectives 1. Review and reclassify cases of NHL diagnosed during the period 1992-2004. 2. Define the incidence of PEL in PCRZ during this period. 3. Analyze the survival of the PEL and compare it with that of nodal NHL. Materials and methods Based on the data PCRZ, we have reviewed and reclassified the patients with NHL according to REAL classification and the new WHO classification (2008), diagnosed during the period 1992-2004, to determine location and histology. The follow-up period of cases was completed by December 31, 2007 Data sources: medical records, histological reports and discharged hospital reports. Population at risk: 9,255,818 person-years. We have calculated crude incidence rates (IR) and standardized by age (SIR), using the European population as standard. For the calculation of survival and confidence intervals (95%) had used the Kaplan-Meier method and the log-rank test was used to compare survival curves. Results During the period of study a total of 4,570 primary hematological disorders were included in the PCRZ; 1,987 (43.4%) were NHL (IR: 19×105 person-years), 331 (16.6%) of them were classified as PEL, which represented a 2.7 SIR x105 person-years (male: 183 cases (55.2%), mean age 59.2 years, SIR: 3.1 ×105 person-years and women 148 cases (44.7%), mean age 66.8 years, SIR: 2,4 ×105 person-years. Only 10% of cases will be reclassified related to histology or location. The most common site was gastrointestinal tract (50.4%), skin (19.8%), glands (10.0%), oral cavity and pharynx (7.9%), lung (2.9%), CNS (2.4%), orbit (2.1%) and other locations (4.5%). Histological types: MALT 60.2%, BDLCNHL: 18.3%, FNHL: 4.7%, MCNHL: 3.2%, MZNHL: 6.5%, T-NHL: 7.1%. Median survival for PEL was 6.61 years (95% CI: 3.7-9.5) and 5.01 years for nodal lymphomas (95% CI: 4.1-5.9). The survival at 5 years was 53.5% and 50% respectively. There were no statistically significant differences between PEL group and the nodal NHL, according to the location or by gender. The differences in survival were associated with histological subtype of lymphoma. These results were similar to those in the data EUROCARE. Conclusions No differences in incidence in PEL and nodal NHL were observed according to gender and age. There were no statistically significant differences between the survival of the PEL and nodal NHL, survival is more influenced by histology than by location. This work partially funded by the project HAEMACARE Disclosures No relevant conflicts of interest to declare.

Introduccion. Los signos clinicos de la arteriopatia cerebral autosomica dominante con infartos subcorticales y leucoencefalopatia (CADASIL) se expresan principalmente en el sistema nervioso y recientemente se han descrito en la retina. Objetivo. Establecer la prevalencia y el riesgo de enfermedad periodontal en sujetos de familias con historia de presencia de mutacion CADASIL del departamento de Antioquia, Colombia. Sujetos y metodos. Se realizo un estudio transversal (cross-sectional), con asignacion al grupo CADASIL y grupo control segun genotipificacion de cada sujeto para la mutacion R1031C y C455R en Notch3. Cada participante firmo voluntariamente el consentimiento informado y recibio evaluacion clinica neurologica, neuropsicologica y periodontal. Resultados. No existieron diferencias significativas entre los dos grupos segun edad, sexo, escolaridad, tabaquismo, estado cognitivo, estado funcional y presencia de dientes naturales. La frecuencia de placa blanda, gingivitis y enfermedad periodontal fue significativamente mayor en el grupo de portadores de mutacion CADASIL que en el grupo control. El grupo CADASIL presento seis veces mas riesgo de tener placa blanda mayor o igual al 20% que el grupo control. La prevalencia de gingivitis mayor o igual al 10% se presento en el total de los integrantes del grupo CADASIL. Las personas que conformaron el grupo CADASIL presentaron cinco veces mas riesgo de tener enfermedad periodontal que el grupo control. Conclusion. Las personas portadoras de mutacion CADASIL presentan mayor prevalencia y riesgo de enfermedad periodontal.

Background. Leukaemia and non-Hodgkin’s lymphomas (NHL) are the commonest haematological malignancies (HMs), accounting for about 10% of incident cases and 6% of all cancer deaths in the European Union (EU). There are few studies in order to estimate the differences in incidence and survival of primary extranodal Lymphoma (PEL). In Zaragoza (Spain) there is a population-based Cancer Registry (ZPCR), that includes all non-haematological and haematological (HMs) incident cases, conducted since 1960. The main aims of this study are: To review all cases with PEL diagnosis. To estimate the incidence of PEL in the ZPCR registered cases during the period 1992–2002. 2. To calculate the survival of PEL Methods. All PEL occurred in patients residing in Zaragoza during the period 1992–2002 were selected from ZPCR. All cases were reviewed in order to confirm the primary location and the morphology classification according to REAL. The population at risk was 9.266.609 person-years. The crude (CIR) and age standardized incidence rate (ASR) were calculated, using the European population as standard. Kaplan-Maier method was applied to calculate median survival time and their 95% confidence intervals, as well as 5-year survival. The end of follow-up was 31 December 2007 and Log-Rank was used to compare survival curves. Results. Among all 4,340 HMs, a total of 1,757 (40.0%) were NHL (CIR: 19×105 person-year), 252 (14.0%) of them were classified as PEL, yielding an ASR of 2.1×105 person-year (males: 140 cases (53.0%), mean age: 59.2 years, ASR: 2.7×105 person-year and females 112 cases (47.0%), mean age: 66.8 years ASR: 1.6×105 person-year. According to topography the most frequent sites were digestive tract (50.4%), skin (19.8%), gland tissue (10.0%), oral cavity-pharynx (7.9%), lung (2.9%), CNS (2.4%), orbit (2.1%) and others (4.5%). The median survival for PEL was 6.61 years (95%CI: 3.7–9.5) and for nodal Lymphomas 5.01 years (95%CI: 4.1–5.9). The 5-year relative survival was 53.5% and 50.0% respectively. There are not significant differences between both groups. Moreover, non significant differences in survival were observed between males and females. Theses results are similar to those found in the EU. Conclusions. The occurrence of PEL according to gender and mean age is similar to nodal NHL. No significant differences in survival were observed between nodal and extranodal NHL, probably the survival is more conditioned by the histology than topography.

Rationale The aim of this work was to assess in vivo the pattern of sensitization to an array of Artemisia vulgaris pollen allergens in a Mediterranean population, and to study the possible association of sensitization to Art v 3 and other relevant LTP allergens: Par j 1 and Pru p 3. Methods 24 mugwort pollen-allergic patients were selected on the basis of positive SPT, specific IgE and positive nasal provocation tests. SPT was performed with pure natural pollen allergens Art v 1, Art v 3, Art v 60-kDa –no systematic name yet- and Par j 1, and with a peach extract with known Pru p 3 concentration. In vitro assays included measurement of specific IgE to pure allergens and ELISA-inhibition among LTP allergens. Results The three mugwort allergens elicited a positive SPT in 70–80% of patients. A significant correlation, both in wheal areas and IgE levels, was observed between the mugwort extract and each of the mugwort allergens. Fourteen patients had a positive SPT to peach extract, and a highly significant correlation between the skin responses to peach extract and Art v 3 was found. Art v 3 significantly inhibited the binding of IgE from three patients' sera to Pru p 3. Pru p 3 and Par j 1 could not inhibit the IgE-binding to the other allergens. Conclusions It has been shown that Art v 1, Art v 3 and Art v 60-kDa are major mugwort pollen allergens. Besides, Art v 3 seems to be the primary sensitizing agent in some peach-allergic patients.

AIM: To investigate the responses of TT virus (TTV) and hepatitis B virus (HBV) to a long-term lamivudine therapy. METHODS: Sixteen patients infected with both TTV and HBV were treated with lamivudine 100 mg daily for 30 mo. Blood samples were drawn at the beginning of the therapy and subsequently at month 3, 6, 9, 12 and 30. Serum TTV was quantified by real time PCR and serum HBV was detected by hybridization assay and nested polymerase chain reaction. RESULTS: TTV infection was detected in 100% of HBV-infected patients. Loss of serum TTV DNA after one year of treatment occurred in 1/16 (6%) patients. At the end of therapy, TTV DNA was positive in 94% of them. The decline of HBV viremia was evident at 3 mo after therapy and the response rate was 31%, 44%, 63%, 50% and 50% at month 3, 6, 9, 12 and 30, respectively. CONCLUSION: TTV replication is not sensitive to lamivudine and is highly prevalent in HBV-infected patients.

A rapid, precise, sensitive, and specific radioreceptorassay (RRA) for serum luteinizing hormone (LH), using a 15,000 X g pellet from bovine corpora lutea, was developed. A comparative study of the serum LH levels in human subjects as measured by this RRA and by radioimmunoassay (RIA) using the same standard preparation was then conducted. The serum LH profile throughout the entire menstrual cycle and the pituitary responsiveness to LH-releasing hormone (LH-RH) stimulation during the two phases of the cycle were studied in two normal women. In addition, LH levels in two normal postpubertal men were measured in blood samples obtained before and after LH-RH administration. Similar, although not identical, LH profiles were found in all cases by both hormone assay methods. Higher RRA-assayable LH values were obtained throughout the menstrual cycle as compared with those obtained by RIA. A significant LH-RH pituitary response in terms of LH in both RRA and RIA during the luteal phase was observed as compared with that observed during the early follicular phase. In the two normal men, the LH values obtained with RRA were higher than those obtained with RIA. It is concluded that the LH RRA is a practical and efficient tool for clinical research.