Risk factors for suicide in multiple sclerosis: a case-control study

ABSTRACT Objective To evaluated the prevalence and the suicide risk in a Brazilian sample of patients with multiple sclerosis (MS) and to identify potential factors associated with the risk of suicide. A study was performed with outpatient with MS. The risk of suicide and the presence of psychiatric disorders were assessed by version 5.0 of the Mini-International Neuropsychiatric Interview (MINI). The sample of patients at risk for suicide was matched by sex and age to a control group of patients with MS. Results Eight point three percent of the patients had a past history of attempted suicide, and 8.3% had a current suicide risk, totaling 16.6%. The results of this study suggest that the risk factors associated with suicide in this population are depression, marital status single, widowed or divorced, and lower education level.

Multiple arterial anomalies in the newborn infant. Echocardiographic and angiographic diagnosis

Multiple arterial anomalies characterized by tortuosity and rolling of the pulmonary arteries and aorta were diagnosed on echocardiography in an asymptomatic newborn infant with a phenotype suggesting Ehlers-Danlos syndrome. These changes were later confirmed on angiography, which also showed peripheral vascular abnormalities. The electrocardiogram showed a probable hemiblock of the left anterosuperior branch, and the chest x-ray showed an excavated pulmonary trunk with normal pulmonary flow.

Multiple recurrences of cardiac myxomas with acute tumoral pulmonary embolism

We report the case of a 42-year-old female with a second recurrence of cardiac myxoma. Her first diagnosis was at the age of 24 years, when cardiac tumors were withdrawn from her right ventricle and left atrium. Her first recurrence was at the age of 36 years, when tumors were removed from the left and right atria, and the right ventricle. Six years later, the patient was admitted to the Hospital das Clínicas de Porto Alegre complaining of sudden dyspnea, dry cough, and pain in the right hypochondrium, which bore no relation to breathing. The transesophageal echocardiography showed a small tumor in the interatrial septum, close to the superior vena cava, and 2 larger tumors in the right ventricle, 1 close to the outflow tract and the other almost completely obstructing the right branch of the pulmonary artery. The patient was referred to surgery, in which myxomas were removed from the right atrium and ventricle with extension to the right pulmonary artery. The postoperative period was uneventful.

Multiple Embolism in a Female Patient with Infective Endocarditis: Low Back Pain and Hematuria as the Initial Clinical Manifestations

A 59-year-old female patient with mitral valve prolapse and a previous history of lumbosacral spondyloarthrosis and lumbar disk hernia had an episode of infective endocarditis due to Streptococcus viridans, which evolved with peripheral embolism to the left kidney, spleen, and left iliac artery, and intraventricular cerebral hemorrhage. Her clinical manifestations were low back pain and hematuria, which were initially attributed to an osteoarticular condition. Infective endocarditis is a severe polymorphic disease with multiple clinical manifestations and it should always be included in the differential diagnosis by clinicians.

Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part I: experimental factorial design

Lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water enclose, at least in theory, a biomimetic aqueous-core suitable for housing hydrophilic biomolecules such as proteins, peptides and bacteriophage particles. The research effort entertained in this paper reports a full statistical 23x31 factorial design study (three variables at two levels and one variable at three levels) to optimize biomimetic aqueous-core lipid nanoballoons for housing hydrophilic protein entities. The concentrations of protein, lipophilic and hydrophilic emulsifiers, and homogenization speed were set as the four independent variables, whereas the mean particle hydrodynamic size (HS), zeta potential (ZP) and polydispersity index (PI) were set as the dependent variables. The V23x31 factorial design constructed led to optimization of the higher (+1) and lower (-1) levels, with triplicate testing for the central (0) level, thus producing thirty three experiments and leading to selection of the optimized processing parameters as 0.015% (w/w) protein entity, 0.75% (w/w) lipophilic emulsifier (soybean lecithin) and 0.50% (w/w) hydrophilic emulsifier (poloxamer 188). In the present research effort, statistical optimization and production of protein derivatives encompassing full stabilization of their three-dimensional structure, has been attempted via housing said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion.

Epidemiology of multiple congenital anomalies in Europe: a EUROCAT population-based registry study.

BACKGROUND: This study describes the prevalence, associated anomalies, and demographic characteristics of cases of multiple congenital anomalies (MCA) in 19 population-based European registries (EUROCAT) covering 959,446 births in 2004 and 2010. METHODS: EUROCAT implemented a computer algorithm for classification of congenital anomaly cases followed by manual review of potential MCA cases by geneticists. MCA cases are defined as cases with two or more major anomalies of different organ systems, excluding sequences, chromosomal and monogenic syndromes. RESULTS: The combination of an epidemiological and clinical approach for classification of cases has improved the quality and accuracy of the MCA data. Total prevalence of MCA cases was 15.8 per 10,000 births. Fetal deaths and termination of pregnancy were significantly more frequent in MCA cases compared with isolated cases (p < 0.001) and MCA cases were more frequently prenatally diagnosed (p < 0.001). Live born infants with MCA were more often born preterm (p < 0.01) and with birth weight < 2500 grams (p < 0.01). Respiratory and ear, face, and neck anomalies were the most likely to occur with other anomalies (34% and 32%) and congenital heart defects and limb anomalies were the least likely to occur with other anomalies (13%) (p < 0.01). However, due to their high prevalence, congenital heart defects were present in half of all MCA cases. Among males with MCA, the frequency of genital anomalies was significantly greater than the frequency of genital anomalies among females with MCA (p < 0.001). CONCLUSION: Although rare, MCA cases are an important public health issue, because of their severity. The EUROCAT database of MCA cases will allow future investigation on the epidemiology of these conditions and related clinical and diagnostic problems.

Attaques cérébrovasculaires ischémiques multiples dues à une méningovasculite à Borrelia garinii. [Multiple ischemic strokes due to Borrelia garinii meningovasculitis].

The most frequent clinical manifestation of borreliosis in Switzerland is erythema migrans, with about 2500 patients each year. Neurological manifestations are rare, mostly hyperalgesic radiculitis (Bannwarth syndrome), aseptic meningitis or cranial nerve involvement. We report the first Swiss patient with meningovasculitis due to neuroborreliosis, with recurrent multiple ischemic strokes in multiple vascular territories. The treatment with ceftriaxone stopped the progression, but the patient is still suffering from severe invalidating cognitive disorders. We also comment on the pathophysiology and review the literature of other clinical cases.

Multiple paternity and its consequences in the white campion " Silene latifolia "

Summary Several studies have demonstrated that the number of pollen donors siring seeds of individual fruits is frequently greater than one and, consequently, that plants have multiple mates. Multiple paternity can have important consequences at the population level. It influences the genetic variability of a population, the reproductive success of males and the fitness of females and future generations. It also influences male-male interactions for fertilization and it is fundamental in providing opportunity of female choice. I investigated the occurrence and the importance of multiple paternity within fruits in natural populations of the dioecious Silene latifolia using microsatellite DNA markers, especially developed for this study. I found that multiple paternity occurs in all populations investigated in the European range of the species, varying from one to nine sires per fruit with a mean of three, suggesting that multiple paternity is highly prevalent in natural populations. In the presence of multiple paternity I investigated if there was a female genotype influence on siring success of the males. I used the same pollen mixture from two males and applied it to three replicate females of different relatedness (two full sisters and one unrelated). I found female genotype influence in one of the two populations investigated, which might reflect different population history. Since these results suggested some degree of female choice, we investigated whether the occurrence of multiple paternity and post-pollination selection could provide opportunity for inbreeding avoidance. First, I measured inbreeding depression at different life-cycle stages for offspring obtained by single-donor crosses with brothers or unrelated males replicated on distinct flowers on the same female plant. To address inbreeding avoidance, I determined paternity in crosses using mixed pollen loads of the two males. I found significant inbreeding depression in the studied population, even under benign experimental conditions, and although the unrelated male did not sire significantly more offspring, there was an effect of genetic dissimilarity on paternity. This suggests that paternity is affected by relatedness among mates, but maybe additionally affected by other factors such as pollen competitive ability or male-female interactions. Using inbred and outbred crosses, I further investigated sex ratio bias inheritance in this species, and found that sex ratio bias of the parental generation was significantly correlated to pollen germination success of the F2 generation, which suggests that sex ratio bias in this species results from the specific X/Y combination and not only on Y performance. An effect of X and Y is consistent with sex chromosome meiotic drive. In conclusion, I found multiple paternity to be widespread in the study species and that females of similar genotype produce similar paternity shares. I found that inbreeding depression is substantial, therefore receiving pollen from several donors might lead to fewer inbred offspring, I also found an effect of genetic dissimilarity on paternity shares, which indicates that there is some ability to discriminate against related pollen, although this seems not to be the only determinant of paternity outcome. Finally I found sex ratio bias to be dependent on both X and Y chromosomes as predicted by sex chromosome meiotic drive. Résumé Plusieurs études ont démontré qu'il n'était pas rare que les graines contenues dans un même fruit soient issues de la fécondation par plusieurs pollens provenant de mâles différents, ce qui sous-entend que les plantes peuvent avoir plusieurs partenaires sexuels. La paternité multiple peut avoir d'importantes conséquences au niveau populationnel dans la mesure où elle peut influencer le degré de variabilité génétique de la population, le succès reproducteur des mâles, la fitness des femelles et des futures générations. La paternité multiple peut également avoir un impact sur les interactions mâle-mâle lors de la fertilisation et peut être considérée comme fondamentale vis-à-vis de la femelle, qui y trouve alors une opportunité de choisir son ou ses partenaires. Dans le cadre de ce travail de thèse j'ai cherché à déterminer si la paternité multiple était un phénomène observable et important dans les populations naturelles de l'espèce dioïque, Silene latifolia. Pour ce faire, j'ai utilisé des marqueurs microsatellites, spécialement développés pour cette étude. J'ai observé des phénomènes de paternité multiple dans toutes les populations de l'étude, réparties dans l'aire de distribution européenne de l'espèce. Le nombre de pères par fruit varie de un à neuf, avec un nombre moyen de trois, ce qui signifie que la paternité multiple est très répandue dans les populations naturelles. En raison de ces résultats, je me suis demandée si le génotype de la femelle influence le succès de paternité des mâles. J'ai alors réalisé des pollinisations manuelles sur la base d'un mélange de pollens issus de deux mâles, que j'ai appliqué sur trois femelles (réplicats) présentant différents degrés d'apparentement (deux soeurs. et une femelle étrangère). Il ressort de cette expérience que le génotype de la femelle peut influencer la paternité dans l'une des deux populations étudiées, ce qui pourrait refléter des différences en terme d'histoire des populations. Dans la mesure où ces résultats suggèrent un certain degré de choix chez la femelle, j'ai cherché à savoir si la paternité multiple et la sélection post-pollinisation pouvaient être des moyens d'éviter les croisements consanguins. Dans un premier temps, j'ai évalué la dépression de consanguinité à différentes étapes du cycle de vie chez des descendants issus de croisements à un seul donneur, celui-ci étant alternativement un frère ou un étranger, répliqués sur plusieurs fleurs d'une même plante femelle. Afin d'estimer l'évitement de croisements consanguins, j'ai effectué des croisements dont le pollen était un mélange des deux mâles (frère et étranger), puis j'ai déterminé la paternité dans les fruits obtenus. J'ai pu mettre en évidence un effet de dépression de consanguinité- significatif dans les populations étudiées, même dans des conditions expérimentales moins rudes qu'à l'extérieur. Bien que le mâle étranger n'ait pas engendré un nombre significativement plus important de graines, il y avait un effet de dissimilarité génétique sur la paternité. Ceci suggère que la paternité est affectée par le degré d'apparentement entre les partenaires, mais qu'elle peut aussi être affectée par d'autres facteurs tels que la compétitivité du pollen ou encore par les interactions mâles-femelles. L'utilisation de croisements consanguins et hybrides m'a également permis d'étudier l'héritabilité du biais de sex ratio chez cette espèce. Il s'est avéré que le biais de sex ratio de la génération parentale était significativement corrélé au succès de germination du pollen de la génération F2, ce qui signifie que, chez cette espèce, le biais de sex ratio résulte d'une combinaison spécifique de X/Y et non uniquement de la performance de Y. Un effet de X et Y est compatible avec l'hypothèse de distorsion de ségrégation méiotique des chromosomes sexuels. En conclusion, il ressort de mes résultats que la paternité multiple est un phénomène largement répandu chez S. latifolia et la paternité accomplie par un mâle est plus similaire entre soeurs qu'avec une femelle étrangère J'ai également mis en évidence que la dépression de consanguinité a un impact considérable; aussi, recevoir du pollen de plusieurs donneurs différents pourrait permettre à la femelle de produire moins de descendants consanguins. J'ai aussi trouvé un effet de la dissimilarité génétique sur le partage de paternité, ce qui indique que la discrimination contre le pollen d'apparentés est possible, bien que cela ne semble pas être le seul facteur déterminant dans le résultat de la paternité. Enfin, j'ai trouvé que le biais de sex ratio est dépendant des deux chromosomes X et Y, conformément à la théorie de distorsion de ségrégation méiotique des chromosomes sexuels.

Peroxisomal beta-oxidation--a metabolic pathway with multiple functions.

Fatty acid degradation in most organisms occurs primarily via the beta-oxidation cycle. In mammals, beta-oxidation occurs in both mitochondria and peroxisomes, whereas plants and most fungi harbor the beta-oxidation cycle only in the peroxisomes. Although several of the enzymes participating in this pathway in both organelles are similar, some distinct physiological roles have been uncovered. Recent advances in the structural elucidation of numerous mammalian and yeast enzymes involved in beta-oxidation have shed light on the basis of the substrate specificity for several of them. Of particular interest is the structural organization and function of the type 1 and 2 multifunctional enzyme (MFE-1 and MFE-2), two enzymes evolutionarily distant yet catalyzing the same overall enzymatic reactions but via opposite stereochemistry. New data on the physiological roles of the various enzymes participating in beta-oxidation have been gathered through the analysis of knockout mutants in plants, yeast and animals, as well as by the use of polyhydroxyalkanoate synthesis from beta-oxidation intermediates as a tool to study carbon flux through the pathway. In plants, both forward and reverse genetics performed on the model plant Arabidopsis thaliana have revealed novel roles for beta-oxidation in the germination process that is independent of the generation of carbohydrates for growth, as well as in embryo and flower development, and the generation of the phytohormone indole-3-acetic acid and the signal molecule jasmonic acid.

Simultaneous CD8+ T cell responses to multiple tumor antigen epitopes in a multipeptide melanoma vaccine.

The recent identification and molecular characterization of tumor-associated antigens recognized by tumor-reactive CD8+ T lymphocytes has led to the development of antigen-specific immunotherapy of cancer. Among other approaches, clinical studies have been initiated to assess the in vivo immunogenicity of tumor antigen-derived peptides in cancer patients. In this study, we have analyzed the CD8+ T cell response of an ocular melanoma patient to a vaccine composed of four different tumor antigen-derived peptides administered simultaneously in incomplete Freund's adjuvant (IFA). Peptide NY-ESO-1(157-165) was remarkably immunogenic and induced a CD8+ T cell response detectable ex vivo at an early time point of the vaccination protocol. A CD8+ T cell response to the peptide analog Melan-A(26-35 A27L) was also detectable ex vivo at a later time point, whereas CD8+ T cells specific for peptide tyrosinase(368-376) were detected only after in vitro peptide stimulation. No detectable CD8+ T cell response to peptide gp100(457-466) was observed. Vaccine-induced CD8+ T cell responses declined rapidly after the initial response but increased again after further peptide injections. In addition, tumor antigen-specific CD8+ T cells were isolated from a vaccine injection site biopsy sample. Importantly, vaccine-induced CD8+ T cells specifically lysed tumor cells expressing the corresponding antigen. Together, these data demonstrate that simultaneous immunization with multiple tumor antigen-derived peptides can result in the elicitation of multiepitope-directed CD8+ T cell responses that are reactive against antigen-expressing tumors and able to infiltrate antigen-containing peripheral sites.