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Background: The effect that cytokines can exert on the progression from mild cognitive impairment (MCI) to ongoing dementia is a matter of debate and the results obtained so far are controversial. Objective: The aim of the study is to analyze the influence of markers of subclinical inflammation on the progression of MCI to dementia. Methods: A prospective study involving a cohort of patients ≥ 65 years of age diagnosed with MCI and followed for 3 years was conducted. 105 patients were enrolled, and serum concentrations of several subclinical inflammatory markers were determined. Results: After 3.09 (2 - 3.79) years of follow-up, 47 (44.76%) patients progressed to dementia. Alpha 1-antichymotrypsin (ACT) was found to be significantly higher in patients who progressed to dementia (486.45 ± 169.18 vs. 400.91 ± 163.03; p = 0.012), and observed to significantly increase the risk of developing dementia in patients with mild cognitive impairment (1.004, 1.001-1.007; p= 0.007). IL-10 levels were significantly higher in those who remained stable (6.69 ± 18.1 vs. 32.54 ± 89.6; p = 0.04). Regarding the type of dementia to which our patients progressed, we found that patients who developed mixed dementia had higher IL-4 levels than those who converted to AD (31.54 ± 63.6 vs. 4.43 ± 12.9; p = 0.03). No significant differences were observed between the groups with regard to the ESR and LPa, CRP, IL-1 and TNF-α levels. Conclusion: ACT levels have a significant predictive value in the conversion of MCI to dementia. IL-10 levels could be a protective factor. It is necessary to conduct studies with serial determinations of these and other inflammatory markers in order to determine their effect on the progression of MCI to dementia.

IL-1 axis activation during placental malaria induces poor pregnancy outcomes that are obliterated after treatment with Anakinra., Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic dissection, we reveal that inflammasome activation pathways are involved in the production and detrimental action of interleukin-1β (IL-1β) in the infected placenta. The IL-1R pharmacological antagonist Anakinra improved pregnancy outcomes by restoring fetal growth and reducing resorption in an experimental model. These findings unveil that IL-1β–mediated signaling is a determinant of PM pathogenesis, suggesting that IL-1R antagonists can improve clinical outcomes of malaria infection in pregnancy.

Background: Evidence of the effect of vascular risk factors and white matter lesions on the progression of mild cognitive impairment (MCI) to dementia is not conclusive. Objective: The study aimed to analyze the impact of these factors on MCI progression to dementia from a global perspective. Methods: Our study included a population of 105 patients with MCI. Results: After a mean follow-up period of 3.09 years (range, 2-3.79), 47 patients (44.76%) progressed to dementia: 32 (30.8%) to mixed dementia, 13 (12.5%) to probable AD, and 2 (1.9%) to vascular dementia. Total cholesterol levels (OR: 1.015 [1.003-1.028]) and LDL cholesterol levels (OR: 1.018 [1.004-1.032]) increased the risk of progression to dementia. Cystatin C was a protective factor against progression to dementia (OR: 0.119 [0.015-0.944], p = 0.044). During the second year of follow-up, the presence of subcortical white matter hyperintensities increased the risk of progression to dementia (OR: 5.854 [1.008- 33.846]). Subcortical and periventricular white matter hyperintensities were also associated with an increased risk of progression to dementia during the second year of follow-up (OR: 3.130 [1.098-8.922] and OR: 3.561 [1.227-10.334], respectively). The same was true for silent infarcts (OR: 4.308 [1.480- 12.500]). Conclusion: A high percentage of patients progressed to dementia. Total cholesterol, LDL cholesterol, and white matter hyperintensities were found to be associated with MCI progression to dementia. In contrast, cystatin C was shown to be a protective factor against progression to dementia.

Las inmunoglobulinas son proteínas heterodiméricas compuestas de 2 cadenas pesadas y 2 cadenas ligeras. La inmunoglobulina G humana es un derivado del plasma y contiene más de 95 % de IgG. La composición de las subclases de IgG es similar a la del plasma humano normal. El tratamiento con inmunoglobulina comenzó hace más de 50 años y su uso se ha descrito en numerosas enfermedades. En Colombia, la importancia de este recurso inmunomodulador condujo a la necesidad de contar con una guía de práctica clínica para su uso, para lo cual se reunió un grupo multidisciplinario de expertos, quienes se distribuyeron en mesas de trabajo, por especialidad, para redactar un texto base. Se llevaron a cabo búsquedas bibliográficas sistemáticas; las evidencias identificadas se valoraron y clasificaron para sustentar un texto preliminar que fue discutido, analizado y corregido. Se emitieron recomendaciones de uso de la inmunoglobulina intravenosa en patologías que abarcan inmunodeficiencias primarias y secundarias, enfermedades autoinmunes, alteraciones neurológicas, infecciones, trasplantes y enfermedades misceláneas; se asignaron calificaciones según el sistema GRADE para cada una. El resultado final se tradujo en las recomendaciones que se presentan con la finalidad de informar, orientar y apoyar en el uso óptimo de dicho recurso inmunomodulador.

The surf gene family of the human malaria parasite Plasmodium falciparum encodes for antigens with largely unknown functions. Three of the ten surf genes found in the P. falciparum 3D7 genome are annotated as pseudogenes, and one of these – surf4.1 (PF3D7_0402200) - was continuously transcribed in P. falciparum 3D7 blood stage forms. GFP-tagging revealed that despite several stop codons a full-length protein was expressed, which localized to developing merozoites. Analysis of cDNAs showed that no specific editing occurred pointing to readthrough of stop codons during translation. Intriguingly, attempts to generate parasite lines containing an additional artificial stop codon failed. Transcript knockdown revealed that surf4.1 is essential for merozoite formation in late trophozoite/schizont stages while DNA replication seemed not to be influenced. SURFIN4.1 is the first example of a plasmodial multigene family member of which a knockout is deleterious and may pose as a novel target for anti-malarial therapy.

O processo de congelação é uma tecnologia fundamental que constitui uma das formas mais frequentes de conservação de produtos a longo prazo. Este processo é um dos mais frequentemente aplicado, quando se pretende conservar um alimento por um período de tempo mais extenso. Aplicar a congelação a produtos requer cuidados que deverão ser seguidos de forma rigorosa para que os produtos mantenham as suas características originais num prazo de vida útil elevado. Desta forma, é responsabilidade das empresas de comércio de alimentos garantir que se estabelecem condições de operacionalidade que permitam efetuar o processo de congelação de modo a manter as características dos produtos, e garantam que estes são seguros do ponto de vista alimentar. O trabalho desenvolvido numa empresa do ramo alimentar consistiu no acompanhamento de uma larga gama de produtos congelados por dois processos distintos: congelação em túnel de ar forçado e congelação em túnel espiral. Para ambos os métodos, a temperatura dos produtos e os tempos de congelação foram acompanhados, de forma a parametrizar os valores obtidos, estabelecendo margens de segurança que permitam assegurar a conclusão do processo de congelação e a qualidade e a segurança alimentar dos produtos congelados. O procedimento consistiu na medição de temperaturas através da utilização de um termómetro (com sonda de perfuração) por infravermelhos, para os artigos congelados em túnel em espiral, e por uma sonda de perfuração, em contacto com o centro térmico do produto, para a congelação em túnel de ar forçado. O estudo englobou o acompanhamento de artigos de várias dimensões/calibres, de forma a compreender o comportamento de um elevado número de gramagens congeladas na empresa. O estudo efetuado identificou o tempo necessário à permanência dos produtos em túnel de forma a garantir a congelação dos produtos. Os resultados demonstraram que é possível uma redução do tempo de permanência dos artigos em túnel de congelação em espiral, permitindo uma maior poupança de energia e rentabilização do equipamento. A análise dos resultados identificou também tempos de congelação para artigos que não possuíam uma parametrização deste tempo em túnel de ar forçado, tendo-se identificado medidas que podem conduzir a uma maior redução do tempo de passagem no túnel. Os tempos de permanência dos produtos nos túneis foram alterados na instrução da empresa, após validação por confrontação de dados e literatura. Foram elaboradas sugestões que podem conduzir à diminuição de tempo no processo de congelação por ar forçado.

Made available in DSpace on 2018-11-26T17:52:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-06-19 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) All Plasmodium species express variant antigens which may mediate immune escape in the vertebrate host. In Plasmodium falciparum, the rif gene family encodes variant antigens which are partly exposed on the infected red blood cell surface and may function as virulence factors. Not all rif genes are expressed at the same time and it is unclear what controls rif gene expression. In this work, we addressed global rif transcription using plasmid vectors with two drug resistance markers, one controlled by a rif 5' upstream region and the second by a constitutively active promoter. After spontaneous integration into the genome of one construct, we observed that the resistance marker controlled by the rif 5' upstream region was expressed dependent on the applied drug pressure. Then, the global transcription of rif genes in these transfectants was compared in the presence or absence of drugs. The relative transcript quantities of all rif loci did not change profoundly between strains grown with or without drug. We conclude that either there is no crosstalk between rif loci or that the elusive system of allelic exclusion of rif gene transcription is not controlled by their 5' upstream region alone. Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo, SP, Brazil Westfalische Wilhelms Univ, Inst Anim Physiol, Schlosspl 8, Munster, Germany State Univ Sao Paulo, IBB IBTEC, Dept Parasitol, Botucatu, SP, Brazil State Univ Sao Paulo, IBB IBTEC, Dept Parasitol, Botucatu, SP, Brazil FAPESP: 2012/23306-5 FAPESP: 2015/17174-7

Chagas disease, is caused by the protozoan Trypanosoma cruzi. The available chemotherapy is restricted to two compounds: Nifurtimox and Benzonidazol. The T. cruzi life cycle occurs among invertebrate and vertebrate hosts and its survival strongly depends on its ability to catabolise both, carbohydrates and amino acids to obtain energy. The amino acids have an important role in several biological processes in this parasite. In this context, we studied the L-asparagine (Asn) relevance in the metabolism, differentiation and stress resistance of the T cruzi. Our results have shown that epimastigotes use Asn as carbon source, and contributes with the resistance to nutritional and oxidative stress. The Asn also showed a positive influence in metacyclogenesis and supported the ATP synthesis. Finally, the absence of Asn interfered with the proliferation of the replicative forms of T. cruzi. Taken together, our results suggest the involvement of the Asn metabolism in the protection of T. cruzi when submitted to different stress conditions. Chagas disease, is caused by the protozoan Trypanosoma cruzi. The available chemotherapy is restricted to two compounds: Nifurtimox and Benzonidazol. The T. cruzi life cycle occurs among invertebrate and vertebrate hosts and its survival strongly depends on its ability to catabolise both, carbohydrates and amino acids to obtain energy. The amino acids have an important role in several biological processes in this parasite. In this context, we studied the L-asparagine (Asn) relevance in the metabolism, differentiation and stress resistance of the T cruzi. Our results have shown that epimastigotes use Asn as carbon source, and contributes with the resistance to nutritional and oxidative stress. The Asn also showed a positive influence in metacyclogenesis and supported the ATP synthesis. Finally, the absence of Asn interfered with the proliferation of the replicative forms of T. cruzi. Taken together, our results suggest the involvement of the Asn metabolism in the protection of T. cruzi when submitted to different stress conditions.

The aim of the study was to analyze lexical access strategies in patients with multiple sclerosis (MS) and their changes over time. We studied lexical access strategies during semantic and phonemic verbal fluency tests and also confrontation naming in a 2-year prospective cohort of 45 MS patients and 20 healthy controls. At baseline, switching lexical access strategy (both in semantic and in phonemic verbal fluency tests) and confrontation naming were significantly impaired in MS patients compared with controls. After 2 years follow-up, switching score decreased, and cluster size increased over time in semantic verbal fluency tasks, suggesting a failure in the retrieval of lexical information rather than an impairment of the lexical pool. In conclusion, these findings underline the significant presence of lexical access problems in patients with MS and could point out their key role in the alterations of high-level communications abilities in MS.

Background and objective Current evidence shows that numerous classic vascular risk factors (VRF) contribute to mild cognitive impairment (MCI), but the effects of emerging VRFs are less well-known. Using a comprehensive approach, we assessed the frequency and strength of association between MCI and classic VRFs, subclinical markers of atherosclerosis (cystatin C, lipoprotein(a), high-sensitivity C-reactive protein, and intima-media thickness) and white matter hyperintensities (WMH). Methods In this case-control study of consecutive MCI patients and cognitively normal controls, subjects underwent clinical and neuropsychological examinations, laboratory analyses, a carotid duplex scan, and a brain magnetic resonance imaging scan. Results The study included 105 patients with amnestic MCI (aMCI): 24 with single domain amnestic MCI, 81 with multiple domain amnestic MCI, and 76 controls. Compared to controls, patients with aMCI were significantly older and had higher rates of arterial hypertension, atrial fibrillation, and depression. They also had a larger intima-media thickness and higher load of WMHs, both periventricular (WMHpv) and subcortical (WMHsc). In the adjusted analysis, all variables except WMHsc displayed a significant association with aMCI. Body mass index exerted a protective effect. Conclusions Our findings suggest a direct association between aMCI and age, hypertension, atrial fibrillation depression, intima-media thickness, and WMHpv. Body mass index has a protective effect on this MCI subtype.

Introduccion Se ha realizado un estudio prospectivo para evaluar la calidad del intercambio de informacion y la satisfaccion en una consulta de teledermatologia entre un hospital comarcal en la isla de El Hierro y un hospital de referencia en la isla de Tenerife. Material y metodos Se realizaron consultas mediante teledermatologia en tiempo real con pacientes que estaban en lista de espera para la consulta convencional. Los pacientes, familiares, tecnicos y dermatologos respondian a un cuestionario con preguntas que intentaban valorar la calidad tecnica de la teleconsulta, la calidad en el intercambio de informacion a traves de la teleconsulta, la interaccion entre el especialista y paciente, preferencias entre telemedicina y el modelo convencional de consulta y la satisfaccion global con el proceso de teleconsulta. Resultados Casi todos los pacientes (95 %) declararon estar dispuestos a repetir la experiencia y a recomendar la telemedicina a otros posibles pacientes. Cuando la alternativa a la teleconsulta era «esperar para ver a un especialista en persona », el 65 % de los pacientes prefirieron «usar telemedicina», el 15 % manifesto preferir «tener una consulta por telemedicina » a «ver al especialista en persona», mientras que el 55% eran indiferentes ante ambas opciones. En el 48 % de las consultas, el medico considero que no habia obtenido la misma calidad de informacion que hubiera podido obtener en una consulta «cara a cara». Discusion Los resultados del estudio muestran que los pacientes no constituyen una barrera a la difusion de la actividad asistencial en dermatologia a traves de telemedicina.

The natural history of cognitive impairment in multiple sclerosis (MS) and its relationship with disease activity is not well known. In this study, we evaluate a prospective cohort of 44 MS patients who were followed every 3 months for 2 years. Cognitive evaluation was done at baseline and by the end of the study using the Brief Repeatable Battery-Neuropsychology. Clinical evaluation included assessment of new relapses and changes in disability (Extended Disability Status Scale (EDSS)) confirmed at 6 months. RESULTS: We found that verbal memory performance deteriorates after 2 years in patients with MS. These changes were observed in stable and active patients both in terms of relapses and disability progression, even at the beginning of the disease, and in patients with or without cognitive impairment at study entry. Attention and executive functions measured with the symbol digit modality test (SDMT) declined after 2 years in patients with confirmed disability progression. Furthermore, SDMT performance correlated with the EDSS change. CONCLUSIONS: Our findings indicate that verbal memory steadily declines in patients with MS from the beginning of the disease and independently of other parameters of disease activity.

Mental illness affects a large number of people in the world, seriously impairing their quality of life and resulting in high socioeconomic costs for health care systems and society. Our aim is to estimate the socioeconomic impact of mental illness in Spain for the year 2002, including health care resources, informal care and loss of labour productivity. A prevalence-based approach was used to estimate direct medical costs, direct non-medical costs, and loss of labour productivity. The total costs of mental illness have been estimated at 7,019 million euros. Direct medical costs represented 39.6% of the total costs and 7.3% of total public healthcare expenditure in Spain. Informal care costs represented 17.7% of the total costs. Loss of labour productivity accounted for 42.7% of total costs. In conclusion, the costs of mental illness in Spain make a considerable economic impact from a societal perspective.

Understanding the contribution of the brain white matter pathways to declarative verbal memory processes has been hindered by the lack of an adequate model in humans. An attractive and underexplored approach to study white matter region functionality in the living human brain is through the use of non-aprioristic models which specifically search disrupted white matter pathways. For this purpose, we employed voxel-based lesion–function mapping to correlate white matter lesions on the magnetic resonance images of 46 multiple sclerosis patients with their performance on declarative verbal memory storage and retrieval . White matter correlating with storage was in the temporal lobe–particularly lateral to the hippocampus and in the anterior temporal stem–, in the thalamic region and in the anterior limb of the internal capsule, all on the left hemisphere, and also in the right anterior temporal stem. The same volumes were relevant for retrieval, but to them were added temporo-parieto-frontal paramedian bundles, particularly the cingulum and the fronto-occipital fasciculus. These 3D maps indicate the white matter regions most critically involved in declarative verbal memory in humans.

This study estimated the economic impact of schizophrenia-related direct costs (medical and nonmedical costs) in Spain. Direct medical costs (hospitalizations, outpatient consultations, drug costs) and direct nonmedical costs (costs of informal care) were estimated based on prevalence costs for 2002. The total costs of schizophrenia were estimated at euro 1,970.8 million; direct medical costs accounted for 53% and informal care costs 47%. Despite having implemented a conservative approach, the health care costs associated with schizophrenia account for 2.7% of total public health care expenditure in Spain. The sum of medical and nonmedical costs give us a better definition of the magnitude of the problem in Spain as well as contributing to helping make the debate on this issue more transparent.