Assessment of obesity stigma and discrimination among Spanish subjects with a wide weight range: the OBESTIGMA study.

Introduction: This study aims to assess the extent of rejection and instances of stigmatization linked to obesity within the Spanish population, encompassing a diverse spectrum of weights ranging from normal weight to morbid obesity. Additionally, the study seeks to identify the primary factors influencing these experiences and further examines the impact of bariatric surgery on such dynamics. Materials and methods: Multicenter observational study with involving a total of 1,018 participants who were recruited from various Obesity Units. Negatives attitudes towards people with obesity were assessed through three questionnaires: (i) Antifat Attitudes Scale (AFA), (ii) Stigmatizing Situations Inventory (SSI) and (iii) Weight Bias Internalization Scale (WBIS). Subjects were categorized into four groups based on their BMI and history of prior bariatric surgery. Results: The cumulative score across all questionnaires (AFA, SSI and WBIS) exhibited a progressive increase, from participants with normal weight to those with obesity (p < 0.001 for all). Within the AFA questionnaire, males showed more rejection towards people with obesity than women, also perceiving obesity as a disease linked to a lack of willpower (p = 0.004 and p = 0.030, respectively). The overall SSI score was negatively associated with age (r = -0.080, p = 0.011), with young participants encountering more stigmatizing experiences than their adult counterparts. Neither employment status nor educational demonstrated a significant association with any of the questionnaires. Interestingly, patients who underwent lost weight following bariatric surgery did not exhibit improved outcomes. Conclusion: Individuals with obesity demonstrate a heightened level of aversion towards the disease compared to those with normal weight. Concurrently, the incidence of stigmatizing encounters displays a concerning escalation among younger individuals.

Dermatitis por Paederus. Acerca de tres casos / Paederus dermatitis. About three cases

Resumen La "dermatitis por Paederus", es una dermatitis vesicante secundaria al contacto con coleópteros de este género. Se describen más de 600 especies de Paederus, con predominio en áreas tropicales y subtropicales, varias de ellas se asocian a dermatitis. Al ser apretado o aplastado contra la piel, la hemolinfa que contiene paederina, lesiona la epidermis, por medio del bloqueo de la mitosis de células epiteliales basales y células suprabasales. Se exponen tres casos clínicos dermatológicos con lesiones características compatibles con "dermatitis por Paederus". Se realiza además una revisión bibliográfica sobre el tema, a fin de exponer los puntos más importantes de esta patología de gran interés médico y que representa en muchas ocasiones desafíos diagnósticos.

Summary "Paederus dermatitis" is a vesicant dermatitis secondary to contact with this beetle. There are more than 600 species of Paederus described, with a predominance in tropical and subtropical areas, some of these are associated with dermatitis. When they are pressed or crushed against the skin, releases secretions with pederin, that causes an injury in the epidermis, by mitosis blocking of basal and suprabasal epithelial cells. This article describes three dermatological clinical cases with charac-teristic lesions compatible with "Paederus dermatitis". In addition a bibliographic review is presented in order to expose the most important points of this medical interest pathology, that frequently represents diagnostic challenges.

Intoxicación severa por Nicotiana glauca (Palán Palán) con miocardio atontado / Severe poisoning by Nicotiana glauca (Palán Palán) with stunned myocardium

Resumen Nicotiana glauca también llamada Palán Palán, es un arbusto con hojas verdes azuladas y despulidas y una flor amarilla tubular pendulante que presenta alcaloides piridínicos, como nicotina, nornicotina, anatabina y anabastina (análogo estructural de la Nicotina). Se presenta el caso clínico de una paciente de 50 años con cuadro agudo de debilidad muscular generalizada que evoluciona con paro respiratorio, tras la ingesta accidental de una cantidad desconocida de hojas de Nicotiana glauca, cultivadas en una huerta hogareña mediante técnica de hidroponía y confundidas por su conviviente con espinaca. Presentó aumento de lactato y Troponina Ultra Sensible e Hipoquinesia Global de Ventrículo Izquierdo en el ecocardiograma, compatible con Aton tamiento Miocárdico (AM), que evolucionó favorablemente. Si bien hay pocos reportes, se han informado muertes de animales y humanos, tras la ingesta accidental de Nicotiana glauca. El inicio del cuadro es rápido, con patrón bifásico, con vómitos y estímulo simpático, seguido por bloqueo ganglionar y neuromuscular, pudiendo presentar paro respiratorio, shock, convulsiones y coma. El AM es una disfunción miocárdica prolongada con retorno gradual de la actividad contráctil, posterior a un episodio breve de isquemia grave, puede ser asintomático, pudiendo presentar alteraciones en el electrocardiograma, enzimas cardíacas o ecocardiograma. Generalmente presenta pronóstico favorable, pudiendo presentar insuficiencia cardíaca ante patologías concurrentes o aumento de requerimientos de oxígeno.

Abstract Nicotiana glauca is a shrub with bluish green leaves and a pendulous tubular yellow flower. It has pyridine alkaloids, such as nicotine, nornicotine, anatabine and anabastine (structural analog of Nicotine). We present the case of a 50 years old pa- tient with acute generalized muscle weakness that evolves to respiratory arrest, after accidentally ingesting an unknown quantity of Nicotiana glauca leaves, grown in a home vegetable garden, using a hydroponic technique and confused by her cohabiting with spinach. She presented increased lactate and Ultra Sensitive Troponin and Left Ventricular Global Hypokinesia in the echo- cardiogram, compatible with Myocardial Stunned, that it evolved favorably. There are few reports, animal and human deaths have been reported following accidental ingestion of Nicotiana glauca. The onset of the symptoms is early, with a biphasic pattern, with vomiting and sympathetic stimulation, followed by ganglionic and neuromuscular blockage and may present respiratory arrest, shock, seizures and coma. Myocardial Stunned is a prolonged myocardial dysfunction with gradual return of contractile activity after a brief episode of severe ischemia, it can be asymptomatic, and it can present alterations in the electrocardiogram, cardiac enzymes or echocardiogram. Generally presents a benign prognosis, being able to present heart failure with concurrent patholo- gies or increased requirements.

DAPA-RWE: a retrospective multicenter study comparing dapagliflozin and sitagliptin in patients with Type 2 diabetes treated under routine clinical practice in Spain.

Background: Weight reduction and glycemic control are key goals during Type 2 diabetes management. However, there are few country-specific, real-world data on cotransporter 2 inhibitors. Materials & methods: DAPA-RWE was a retrospective, multicenter study comparing the efficacy of dapagliflozin versus sitagliptin in Type 2 diabetes patients in Spain. Results: The study population comprised 1046 patients (594 with dapagliflozin, 452 with sitagliptin). Age was 61.8 ± 10.0 and 66.2 ± 11.4 years and glycosylated hemoglobin (HbA1c) 8.9 and 8.8%, respectively. The main end point (reduction in weight and HbA1c) was reached by 24.4 and 56.1% of patients, respectively; p < 0.05. This was confirmed with a propensity score matching analysis balanced for obesity-related variables at baseline. Conclusion: DAPA-RWE confirmed dapagliflozin to be more effective than sitagliptin in reducing HbA1c and weight.

Variaciones de caracteres morfológicos dentro de la especie Bothrops alternatus / Morphological characters variations within the Bothrops alternatus species

Resumen El género Bothrops (yarará) es responsable de más del 95% de los accidentes por ofidios venenosos en Argentina. La mayoría de éstos son notificados en provincias del Nordeste y Noroeste. Bothrops alternatus, es la especie más frecuentementehallada, siendo el vipérido de gran talla más meridional del mundo y una de las especies de mayor importancia sanitaria en Argentina, pudiendo hallarse en relación a núcleos urbanos. Presentan en el dorso figuras arriñonadas características, que remedan atubos de teléfono o porotos unidos, completos o incompletos, hasta la forma fusionada. Presenta foseta loreal, órgano termore-ceptor ubicado entre el ojo y la fosa nasal. Su dentición es solenoglifa, dientes inoculadores huecos, con conducto cerrado, fijosa un hueso maxilar móvil. Si bien se describen variaciones entre animales, se considera una especie monotípica. Su identificaciónes importante dada la abundancia de especímenes y de hallazgos en regiones periurbanas.

Abstract The Bothrops genus is responsible for more than 95% of ophidian accidents in Argentina, most of these are reported in the Northeast and Northwest provinces. Bothrops alternatus, is the most frequent species of the genus Bothrops (yarará), themost southern large-scale viperid in the world and one of the most important species in Argentina, being able to be found in rela-tion to urban nucleus. Their characteristic features are kidney-like figures in the skin, that mimic phone tubes or beans, completeor incomplete, until the merged form. It presents a loreal pit, thermoreceptor organ located between the eye and the nostril. Itsdentition is solenoglyphous, hollow inoculating teeth, with closed duct, fixed to a mobile maxillary bone. Although variationsbetween animals are described, it is considered a monotypic species. The identification of this snake is important due their abun-dance in around urban regions and its frequency of finding.

Control y prevención de los accidentes causados por Tityus trivittatus (Scorpiones: Buthidae) / Control and prevention of accidents caused by Tityus trivittatus (Scorpiones: Buthidae)

Resumen Las picaduras por alacranes pueden producir cuadros de intoxicación aguda y conducir a la muerte por falla cardíaca y distrés respiratorio, siendo la población pediátrica la de mayor riesgo, tanto en Argentina como en el resto del mundo. Muchasde las especies de escorpiones en el mundo son sinantrópicas, y en Argentina, las que se han relacionado con muertes, comoTityus trivittatus y Tityus confluens, poseen esas características. La sinantropía, aumenta la posibilidad de contacto humano -escorpión y por lo tanto la ocurrencia de accidentes, por lo que las medidas de prevención en este caso, deben tomarse no soloconductualmente sino ambientalmente para evitar ese contacto. Las características biológicas de los escorpiones del géneroTityus dificultan las labores de prevención. Muchas son las herramientas para disminuir el contacto con los escorpiones y de esamanera prevenir los accidentes como los controles químicos, biológicos y ambientales, así como la búsqueda y eliminación deescorpiones. Sin embargo, no todas son efectivas si no son aplicadas racionalmente y si no son combinadas. En ocasiones lamala planificación o uso de las diferentes medidas para el combate de escorpiones pueden ser contraproducentes y no solo serinefectivas sino aumentar la probabilidad de ocurrencia de accidentes. En esta revisión se exponen los diferentes métodos deprevención del escorpionismo, con especial referencia a las especies de Tityus de Argentina.

Abstract Scorpion stings may produce acute envenoming and lead to death from heart failure and respiratory distress, being the pediatric population that with the highest risk of severe envenomation and death, in Argentina as in the rest of the world. Manyof the scorpion species in the world are synanthropic, including Tityus trivittatus and Tityus confluens, which are responsible forhuman deaths in Argentina. Synanthropy increases the possibility of human-scorpion contact and therefore the occurrence ofaccidents, so preventive measures to avoid the contact must be taken not only behaviorally but environmentally. The biologi-cal characteristics of scorpions of the genus Tityus make prevention of the contact with humans rather difficult. There are manychemical, biological and environmental tools to reduce the possibility of contact between humans and scorpions. However, notall these measures are effective if they are not rationally applied and if these are not combined. Sometimes the poor planningor use of different measures to control scorpions' population can be counterproductive and not only ineffective, increasing theprobability of accidents. In this review, we discuss the different methods of prevention and combat of scorpionism, with specialreference to the prevention of accidents with Tityus species from Argentina.

Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort.

OBJECTIVE: Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality. METHODS: A nested ALS case-control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma-mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models. RESULTS: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1-15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08-3.87) and lead (OR = 1.89, 95% CI = 0.97-3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27-0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers. INTERPRETATION: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a-n/a.

Toxicological study of bee venom (Apis mellifera mellifera) from different regions of the province of Buenos Aires, Argentina.

Samples of Apis mellifera mellifera venom from different hives in two regions of the Buenos Aires province and its pool were analyzed for their lethal potency, myotoxic, defibrinogenating, hemolytic and inflammatory-edematizing activity and for the histological alterations they produce in the heart, lungs, kidneys, skeletal muscle and liver of mice. In vitro studies focused on the venom's hemolytic activity in different systems and species (horse, man, sheep and rabbit), the cytotoxicity in cellular lines, and on the proteolytic and coagulant activity in plasma and fibrinogen. Hemolytic activity, either observed in vitro or in vivo, showed similar toxicity levels for all samples. Erythrocytes of different species varied in their sensitivity to the venom pool, equines being the most sensitive and sheep the most resistant to direct hemolytic action. Local and systemic myotoxicity was evidenced by either the elevation of serum creatine kinase and/or histopathological lesions, observed in different muscles. All samples caused significant pathological alterations; pulmonary, cardiac, renal and skeletal muscle lesions were substantive and can be related to the pathophysiological mechanisms of envenomation. The venoms from different apiaries and regions of the Buenos Aires province showed very similar toxicological characteristics. These results suggest that severity of envenomation in case of a swarming could therefore be more related to the number of bees than to the differential toxicity of the venom from different regions of the province. This is the first study on the toxicity and toxicological characteristics of Apis mellifera venom in Argentina.

New Metrics to Assess Type 2 Diabetes After Bariatric Surgery: The "Time-Within-Remission Range".

Almost one third of patients do not achieve type 2 diabetes remission after bariatric surgery or are unable to sustain this effect long term. Our objective was to delve further into the dynamic responses of diabetes after bariatric surgery and to evaluate the "time-within-remission range" as a variable of metabolic control. A descriptive cohort study was done using a computerised multicentre and multidisciplinary registry. All data were adjusted by propensity score. A total of 1186 subjects with a follow-up of 4.5 ± 2.5 years were included. Type of surgery, diabetes remission, recurrence of diabetes, "time-within-remission range" and key predictors of diabetes outcomes were assessed. All patients (70% women, 51.4 ± 9.2 years old, body mass index (BMI) 46.3 ± 6.9 kg/m2) underwent primary bariatric procedures. "Time-within-remission range" were 83.3% (33.3-91.6) after gastric bypass, 68.7% (7.1-87.5) after sleeve gastrectomy and 90% (83.3-92.8) after malabsorptive techniques (p < 0.001 for all). Duration of diabetes, baseline HbA1c and insulin treatment were significantly negatively correlated with the "time-within-remission range". The association of bariatric techniques with "time-within-remission range", using gastric bypass as a reference, were: odds ratio (OR) 3.70 (2.34-5.84), p < 0.001 for malabsorptive techniques and OR 0.55 (0.40-0.75), p < 0.001 for sleeve gastrectomy. Characteristics of type 2 diabetes powerfully influence the outcomes of bariatric surgery. The "time-within-remission range" unveils a superiority of gastric bypass compared to sleeve gastrectomy.

Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort.

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB. CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.

Vaccination strategies.

Currently all prion diseases are without effective treatment and are universally fatal. It is increasingly being recognized that the pathogenesis of many neurodegenerative diseases, such as Alzheimer disease (AD), includes "prion-like" properties. Hence, any effective therapeutic intervention for prion disease could have significant implications for other neurodegenerative diseases. Conversely, therapies that are effective in AD might also be therapeutically beneficial for prion disease. AD-like prion disease has no effective therapy. However, various vaccine and immunomodulatory approaches have shown great success in animal models of AD, with numerous ongoing clinical trials of these potential immunotherapies. More limited evidence suggests that immunotherapies may be effective in prion models and in naturally occurring prion disease. In particular, experimental data suggest that mucosal vaccination against prions can be effective for protection against orally acquired prion infection. Many prion diseases, including natural sheep scrapie, bovine spongiform encephalopathy, chronic wasting disease, and variant Creutzfeldt-Jakob disease, are thought to be acquired peripherally, mainly by oral exposure. Mucosal vaccination would be most applicable to this form of transmission. In this chapter we review various immunologically based strategies which are under development for prion infection.

Immunotherapy to improve cognition and reduce pathological species in an Alzheimer's disease mouse model.

BACKGROUND: Alzheimer's disease (AD) is characterized by physiologically endogenous proteins amyloid beta (Aß) and tau undergoing a conformational change and accumulating as soluble oligomers and insoluble aggregates. Tau and Aß soluble oligomers, which contain extensive ß-sheet secondary structure, are thought to be the most toxic forms. The objective of this study was to determine the ability of TWF9, an anti-ß-sheet conformation antibody (aßComAb), to selectively recognize pathological Aß and phosphorylated tau in AD human tissue compared with cognitively normal age-matched controls and to improve the performance of old 3xTg-AD mice with advanced pathology in behavioral testing after acute treatment with TWF9. METHODS: In this study, we used immunohistochemistry, immunoprecipitation, and enzyme-linked immunosorbent assay (ELISA) to characterize TWF9 specificity. We further assessed cognitive performance in old (18-22 months) 3xTg-AD mice using both a Barnes maze and novel object recognition after intraperitoneal administration of TWF9 (4 mg/kg) biweekly for 2 weeks before the start of behavioral testing. Injections continued for the duration of the behavioral testing, which lasted 2 weeks. RESULTS: Histological analysis of TWF9 in formalin-fixed paraffin-embedded human control and AD (ABC score: A3B3C3) brain tissue revealed preferential cytoplasmic immunoreactivity in neurons in the AD tissue compared with controls (p < 0.05). Furthermore, ELISA using oligomeric and monomeric Aß showed a preferential affinity for oligomeric Aß. Immunoprecipitation studies showed that TWF9 extracted both phosphorylated tau (p < 0.01) and Aß (p < 0.01) from fresh frozen brain tissues. Results show that treated old 3xTg-AD mice have an enhanced novel object recognition memory (p < 0.01) and Barnes maze performance (p = 0.05) compared with control animals. Overall plaque burden, neurofibrillary tangles, microgliosis, and astrocytosis remained unchanged. Soluble phosphorylated tau was significantly reduced in TWF9-treated mice (p < 0.05), and there was a trend for a reduction in soluble Aß levels in the brain homogenates of female 3xTg-AD mice (p = 0.06). CONCLUSIONS: This study shows that acute treatment with an aßComAb can effectively improve performance in behavioral testing without reduction of amyloid plaque burden, and that peripherally administered IgG can affect levels of pathological species in the brain.

Potential Novel Approaches to Understand the Pathogenesis and Treat Alzheimer's Disease.

There is growing genetic and proteomic data highlighting the complexity of Alzheimer's disease (AD) pathogenesis. Greater use of unbiased "omics" approaches is being increasingly recognized as essential for the future development of effective AD research, that need to better reflect the multiple distinct pathway abnormalities that can drive AD pathology. The track record of success in AD clinical trials thus far has been very poor. In part, this high failure rate has been related to the premature translation of highly successful results in animal models that mirror only limited aspects of AD pathology to humans. We highlight our recent efforts to increase use of human tissue to gain a better understanding of the AD pathogenesis subtype variety and to develop several distinct therapeutic approaches tailored to address this diversity. These therapeutic approaches include the blocking of the Aß/apoE interaction, stimulation of innate immunity, and the simultaneous blocking of Aß/tau oligomer toxicity. We believe that future successful therapeutic approaches will need to be combined to better reflect the complexity of the abnormal pathways triggered in AD pathogenesis.

Anti-ß-sheet conformation monoclonal antibody reduces tau and Aß oligomer pathology in an Alzheimer's disease model.

BACKGROUND: Oligomeric forms of amyloid-ß (Aß) and tau are increasing being recognized as key toxins in the pathogenesis of Alzheimer's disease (AD). METHODS: We developed a novel monoclonal antibody (mAb), GW-23B7, that recognizes ß-sheet secondary structure on pathological oligomers of neurodegenerative diseases. RESULTS: The pentameric immunoglobulin M kappa chain (IgMκp) we developed specifically distinguishes intra- and extracellular pathology in human AD brains. Purified GW-23B7 showed a dissociation constant in the nanomolar range for oligomeric Aß and did not bind monomeric Aß. In enzyme-linked immunosorbent assays, it recognized oligomeric forms of both Aß and hyperphosphorylated tau. Aged triple-transgenic AD mice with both Aß and tau pathology infused intraperitoneally for 2 months showed IgMκp in the soluble brain homogenate, peaking at 24 h postinoculation. Treated mice exhibited significant cognitive rescue on radial arm maze testing compared with vehicle control-infused mice. Immunohistochemically, treatment resulted in a significant decrease of extracellular pathology. Biochemically, treatment resulted in significant reductions of oligomeric forms of Aß and tau. CONCLUSIONS: These results suggest that GW-23B7, an anti-ß-sheet conformational mAb humanized for clinical trials, may be an effective therapeutic agent for human AD.

Production of Monoclonal Antibodies to Pathologic ß-sheet Oligomeric Conformers in Neurodegenerative Diseases.

We describe a novel approach to produce conformational monoclonal antibodies selected to specifically react with the ß-sheet secondary structure of pathological oligomeric conformers, characteristic of many neurodegenerative diseases. Contrary to past and current efforts, we utilize a mammalian non-self-antigen as an immunogen. The small, non-self peptide selected was covalently polymerized with glutaraldehyde until it reached a high ß-sheet secondary structure content, and species between 10-100kDa that are immunogenic, stable and soluble (p13Bri). Inoculation of p13Bri in mice elicited antibodies to the peptide and the ß-sheet secondary structure conformation. Hybridomas were produced and clones selected for their reactivity with at least two different oligomeric conformers from Alzheimer's, Parkinson and/or Prion diseases. The resulting conformational monoclonals are able to detect pathological oligomeric forms in different human neurodegenerative diseases by ELISA, immunohistochemistry and immunoblots. This technological approach may be useful to develop tools for detection, monitoring and treatment of multiple misfolding disorders.

Immunotherapeutic approaches for Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent form of dementia worldwide and is an emerging global epidemic. It is characterized by an imbalance between production and clearance of amyloid ß (Aß) and tau proteins. Oligomeric forms of Aß and tau are believed to be the most toxic. Dramatic results from AD animal models showed great promise for active and passive immune therapies targeting Aß. However, there is very limited evidence in human studies of the clinical benefits from these approaches. Immunotherapies targeting only tau pathology have had some success but are limited so far to mouse models. The majority of current methods is based on immunological targeting of a self-protein; hence, benefits need to be balanced against risks of stimulating excessive autoimmune toxic inflammation. For greater efficacy the next generation of vaccines needs to focus more on concurrently targeting all the intermediate toxic conformers of oligomeric Aß and tau species.

Time trends in serum organochlorine pesticides and polychlorinated biphenyls in the general population of Biscay, Spain.

Despite the measures adopted, levels of organochlorine compounds (OCs) are still being detected in the human body. This study aimed to explore factors related to changes in the concentrations of polychlorinated biphenyls (PCBs) and pesticide OCs in blood samples obtained from a general population cohort. Two cross-sectional samples were taken from 162 adults (2-75 years of age), with a gap of 2 years, from four areas in Biscay (Spain). More than 75 % had quantifiable levels of hexachlorobenzene (HCB), beta-hexachlorocyclohexane (ß-HCH), dichlorodiphenyldichloroethylene, and PCBs 138 153 and 180. During this time, significant changes were observed: PCB 180 and HCB levels increased, and PCB 138 and ß-HCH levels decreased. Regarding age, this study shows a decrease suggesting a cohort effect. The period was not related to the decrease of levels in all age intervals, but a statistically significant increase of PCBs in older people was found. High body mass index was associated with lower PCB 180 levels and greater HCH levels. Inversely, greater levels of HCB and ß-HCH were in those who had lost weight before the study. Levels of HCB and ß-HCH were also greater in women who had had children, although they were lower in those who breastfed. Levels of these same OCs were greater in fish consumers, whereas those of PCBs 138 and 153 were greater in those who consumed local produce; all of these trends were close to significance. Efforts should continue to decrease exposure to these pollutants and to assess their influence on general population.

Mucosal immunization with an attenuated Salmonella vaccine partially protects white-tailed deer from chronic wasting disease.

Prion disease is a unique category of illness, affecting both animals and humans, in which the underlying pathogenesis is related to a conformational change of a normal, self-protein called PrP(C) (C for cellular) to a pathological and infectious conformer known as PrP(Sc) (Sc for scrapie). Bovine spongiform encephalopathy (BSE), a prion disease believed to have arisen from feeding cattle with prion contaminated meat and bone meal products, crossed the species barrier to infect humans. Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. In the current study, white-tailed deer were orally inoculated with attenuated Salmonella expressing PrP, while control deer were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals were boosted orally and locally by application of polymerized recombinant PrP onto the tonsils and rectal mucosa. The vaccinated and control animals were then challenged orally with CWD-infected brain homogenate. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a significant prolongation of the incubation period (median survival 909 days; p=0.012 by Weibull regression analysis) and one deer has remained CWD free both clinically and by RAMALT and tonsil biopsies. This negative vaccinate has the highest titers of IgA in saliva and systemic IgG against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrP(CWD). We document the first partially successful vaccination for a prion disease in a species naturally at risk.

Use of urinary trichloroacetic acid as an exposure biomarker of disinfection by-products in cancer studies.

Urinary trichloroacetic acid (TCAA) has been proposed as a valid exposure biomarker for ingested disinfection by-products (DBP) for reproductive studies. However, it has never been used in epidemiologic studies on cancer. We investigate the performance of urinary TCAA as a biomarker of DBP exposure in the framework of an epidemiologic study on cancer. We conducted home visits to collect tap water, first morning void urine, and a 48h fluid intake diary among 120 controls from a case-control study of colorectal cancer in Barcelona, Spain. We measured urine TCAA and creatinine, and 9 haloacetic acids and 4 trihalomethanes (THM) in tap water. Lifetime THM exposure was estimated based on residential history since age 18 plus routine monitoring data. Robust linear regressions were used to estimate mean change in urinary TCAA adjusted by covariates. Among the studied group, mean age was 74 years (range 63-85) and 41 (34%) were females. Mean total tap water consumption was 2.2l/48h (standard error, 0.1l/48h). Geometric mean urine TCAA excretion rate was 17.3pmol/min [95%CI: 14.0-21.3], which increased 2% for a 10% increase in TCAA ingestion and decreased with total tap water consumption (-17%/l), water intake outside home (-32%), plasmatic volume (-64%/l), in smokers (-79%), and in users of non-steroidal anti-inflammatory drugs (-50%). Urinary TCAA levels were not associated with lifetime THM exposure. In conclusion, our findings support that urine TCAA is not a valid biomarker in case-control studies of adult cancer given that advanced age, comorbidites and medication use are prevalent and are determinants of urine TCAA levels, apart from ingested TCAA levels. In addition, low TCAA concentrations in drinking water limit the validity of urine TCAA as an exposure biomarker.

Adenopatía cervical como presentación de ampuloma neuroendocrino / Cervical adenopathy as first symptom of a neuroendocrine ampullary tumor

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