A Bayesian approach to fuzzy hypotheses testing for the estimation of optimal age for vaccination against measles

Fuzzy Bayesian tests were performed to evaluate whether the mother`s seroprevalence and children`s seroconversion to measles vaccine could be considered as ""high"" or ""low"". The results of the tests were aggregated into a fuzzy rule-based model structure, which would allow an expert to influence the model results. The linguistic model was developed considering four input variables. As the model output, we obtain the recommended age-specific vaccine coverage. The inputs of the fuzzy rules are fuzzy sets and the outputs are constant functions, performing the simplest Takagi-Sugeno-Kang model. This fuzzy approach is compared to a classical one, where the classical Bayes test was performed. Although the fuzzy and classical performances were similar, the fuzzy approach was more detailed and revealed important differences. In addition to taking into account subjective information in the form of fuzzy hypotheses it can be intuitively grasped by the decision maker. Finally, we show that the Bayesian test of fuzzy hypotheses is an interesting approach from the theoretical point of view, in the sense that it combines two complementary areas of investigation, normally seen as competitive. (C) 2007 IMACS. Published by Elsevier B.V. All rights reserved.

Bioinformatics construction of the human cell surfaceome

Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of polymorphisms, conservation among eukaryotic species, and patterns of gene expression. By integrating expression information from a variety of sources, we were able to identify surfaceome genes with a restricted expression in normal tissues and/or differential expression in tumors, important characteristics for putative tumor targets. A high-throughput and efficient quantitative real-time PCR approach was used to validate 593 surfaceome genes selected on the basis of their expression pattern in normal and tumor samples. A number of candidates were identified as potential diagnostic and therapeutic targets for colorectal tumors and glioblastoma. Several candidate genes were also identified as coding for cell surface cancer/testis antigens. The human cell surfaceome will serve as a reference for further studies aimed at characterizing tumor targets at the surface of human cells.

Therapeutic potential of interleukin-6 antagonism in bipolar disorder

Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder. Its underlying neurobiology remains largely unclear. A significant body of evidence indicates that inflammatory activation expressed by increased cytokines is relevant in its pathophysiology. IL-6 is one of the most important cytokines involved in the pathogenesis of immune and inflammatory disorders. Several studies recently showed increased levels of IL-6 in manic and depressive episodes and also during euthymia in subjects with BD. Tocilizumab is an IL-6 receptor antagonist being marketed for the treatment of rheumatoid arthritis and Castleman`s disease. In this article we discuss the possibility that tocilizumab may have a therapeutic role in treatment of BD through its anti-inflammatory action. (C) 2010 Elsevier Ltd. All rights reserved.

Hypotension caused by therapeutic doses of venlafaxine: case report and proposed pathophysiological mechanisms

Although venlafaxine is usually associated with modest increases in blood pressure and not so often clinical hypertension, there are a few reported cases of hypotension related to overdoses of this specific antidepressant. The case study of a young female patient with a history of Major Depressive Disorder who initiated treatment with venlafaxine 75 mg/day and developed hypotension when the dosage was titrated up to 225 mg/day is described. The patient did not present comorbid diseases nor use other medication. A temporal association and a dose-dependent relationship between the hypotension and the use of venlafaxine is shown. To the best of the knowledge of the authors, this is the first case report that specifically associates regular doses of venlafaxine with the presence of hypotension. A pathophysiological mechanism is proposed, involving the participation of presynaptic alpha2-adrenergic receptors and the presence of a possible genetic polymorphism of cytochrome P4502D6, which is associated with lower drug metabolization, to explain the relationship between venlafaxine in regular dosage and development of hypotension.

Therapeutic evaluation of free and liposome-loaded furazolidone in experimental visceral leishmaniasis

Drug delivery systems are promising pharmaceutical formulations used to improve the therapeutic index of drugs. In this study, we developed a liposomal formulation of furazolidone that targets Leishmania (Leishmania) chagasi amastigotes in a hamster model. Using laser scanning confocal microscopy, it was demonstrated that the liposomal drug co-localised with L. (L.) chagasi amastigotes within macrophages. Liposomal furazolidone administered intraperitoneally at 0.5 mg/kg for 12 consecutive days reduced spleen (74%) and liver (32%) parasite burden at a 100-fold lower dose than the free drug. Free furazolidone (50 mg/kg) also effectively reduced spleen (82.5%) and liver (85%) parasites; its in vitro activity against promastigotes and intracellular amastigotes demonstrated a high degree of parasite selectivity. Thus, furazolidone, both in the free and liposome-loaded formulation, is an effective inhibitor of L. (L.) chagasi, representing a possible cost-effective drug candidate for the treatment of visceral leishmaniasis. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Further evidences on a new diagnostic approach for monitoring human Leishmania (L.) infantum chagasi infection in Amazonian Brazil

This was a prospective study carried out during a period over 2 years (May/2006-September/2008) with a cohort of 1,099 individuals of both genders, aged 1 year old and older, from an endemic area of American visceral leishmaniasis (AVL) in Para state, Brazil. The object was to analyze the prevalence and incidence of human Leishmania (L.) infantum chagasi infection as well as the dynamics evolution of its clinical-immunological profiles prior identified: (1) asymptomatic infection (AI); (2) symptomatic infection (SI = AVL); (3) sub-clinical oligosymptomatic infection (SOI); (4) sub-clinical resistant infection (SRI) and; (5) indeterminate initial infection (III). The infection diagnosis was performed by using both the indirect fluorescent antibody test and leishmanin skin test with amastigotes and promastigotes antigens of L. (L.) i. chagasi, respectively. A total of 187 cases of infection were recorded in the prevalence (17%), 117 in the final incidence (6.9%), and 304 in the accumulated prevalence (26.7%), which provided the following distribution into the clinical-immunological profiles: AI, 51.6%; III, 22.4%; SRI, 20.1%; SOI, 4.3%; and SI (=AVL), 1.6%. The major finding regarding the dynamics evolution of infection was concerned to III profile, from which the cases of infection evolved to either the resistant profiles, SRI (21 cases, 30.8%) and AI (30 cases, 44.1%), or the susceptible SI (=AVL; 1 case, 1.5%); the latter 16 cases remained as III till the end of the study. These results provided the conclusion that this diagnostic approach may be useful for monitoring human L. (L.) i. chagasi infection in endemic area and preventing the high morbidity of severe AVL cases.

A practical approach to assess depression risk and to guide risk reduction strategies in later life

Background: Many factors have been associated with the onset and maintenance of depressive symptoms in later life, although this knowledge is yet to be translated into significant health gains for the population. This study gathered information about common modifiable and non-modifiable risk factors for depression with the aim of developing a practical probabilistic model of depression that can be used to guide risk reduction strategies. \Methods: A cross-sectional study was undertaken of 20,677 community-dwelling Australians aged 60 years or over in contact with their general practitioner during the preceding 12 months. Prevalent depression (minor or major) according to the Patient Health Questionnaire (PHQ-9) assessment was the main outcome of interest. Other measured exposures included self-reported age, gender, education, loss of mother or father before age 15 years, physical or sexual abuse before age 15 years, marital status, financial stress, social support, smoking and alcohol use, physical activity, obesity, diabetes, hypertension, and prevalent cardiovascular diseases, chronic respiratory diseases and cancer. Results: The mean age of participants was 71.7 +/- 7.6 years and 57.9% were women. Depression was present in 1665 (8.0%) of our subjects. Multivariate logistic regression showed depression was independently associated with age older than 75 years, childhood adverse experiences, adverse lifestyle practices (smoking, risk alcohol use, physical inactivity), intermediate health hazards (obesity, diabetes and hypertension), comorbid medical conditions (clinical history of coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease, emphysema or cancers), and social or financial strain. We stratified the exposures to build a matrix that showed that the probability of depression increased progressively with the accumulation of risk factors, from less than 3% for those with no adverse factors to more than 80% for people reporting the maximum number of risk factors. Conclusions: Our probabilistic matrix can be used to estimate depression risk and to guide the introduction of risk reduction strategies. Future studies should now aim to clarify whether interventions designed to mitigate the impact of risk factors can change the prevalence and incidence of depression in later life.

Negative Anti-C1q Antibody Titers May Influence Therapeutic Decisions and Reduce the Number of Renal Biopsies in Systemic Lupus Erythematosus

In a cross-sectional study involving 62 patients with systemic lupus erythematosus (SLE), we found that patients with biopsy-proven lupus nephritis (LN) had higher titers of anti-C1q antibodies than active SLE without nephritis patients. Anti-C1q was associated with a negative predictive value of 94.59%, a positive predictive value of 52%, a sensitivity of 86.66% and a specificity of 74.47% for the diagnosis of LN. We conclude that high titers of anti-C1q antibodies are strongly associated with the presence of active LN, and the negative predictive value of this test for diagnosing LN is very high; therefore, it can influence therapeutic decisions and reduce the number of renal biopsies in patients with SLE. Copyright (C) 2011 S. Karger AG, Basel

Laparoscopic resection of left liver segments using the intrahepatic Glissonian approach

Background Recent advances in laparoscopic techniques have resulted in growing indications for laparoscopic hepatectomy. However, this procedure has not been widely developed, and anatomic segmental liver resection is not Currently performed due to difficulty controlling the segmental Glissonian pedicles laparoscopically. This study aimed to report a novel technique for laparoscopic anatomic resection of left liver segments using the intrahepatic Glissonian approach based on small incisions according to anatomic landmarks such as Arantius` and round ligaments. Methods Nine consecutive patients underwent laparoscopic liver resection using the intrahepatic Glissonian technique from April 2007 to June 2008. Five patients underwent laparoscopic bisegmentectomy 2-3, one laparoscopic left hemihepatectomy, two resections of segment 3, and one resection of segment 4. Results One patient required a blood transfusion. The mean operation time was 180 min (range, 120-300 min), and the median hospital stay was 3 days (range, 1-5 days). No patient had postoperative signs of liver failure or bile leakage. No postoperative mortality was observed. Conclusion The main advantage of the intrahepatic Glissonian procedure over other techniques is the possibility of gaining a rapid and precise access to the left Glissonian sheaths facilitating left hemihepatectomy, bisegmentectomy 2-3, and individual resections of segments 2, 3, and 4. The authors believe that the intrahepatic Glissonian technique facilitates laparoscopic liver resection and may increase the development of segment-based laparoscopic liver resection.

An MRI-based approach for the measurement of the dorsolateral prefrontal cortex in humans

The dorsolateral prefrontal cortex (DLPFC) has been implicated in the pathophysiology of mental disorders. Previous region-of-interest MRI studies that attempted to delineate this region adopted various landmarks and measurement techniques, with inconsistent results. We developed a new region-of-interest measurement method to obtain morphometric data of this region from structural MRI scans, taking into account knowledge from cytoarchitectonic postmortem studies and the large inter-individual variability of this region. MRI scans of 10 subjects were obtained, and DLPFC tracing was performed in the coronal plane by two independent raters using the semi-automated software Brains2. The intra-class correlation coefficients between two independent raters were 0.94 for the left DLPFC and 0.93 for the right DLPFC. The mean +/- S.D. DLPFC volumes were 9.23 +/- 2.35 ml for the left hemisphere and 8.20 +/- 2.08 ml for the right hemisphere. Our proposed method has high inter-rater reliability and is easy to implement, permitting the standardized measurement of this region for clinical research applications. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Tentorial Posterior Fossa Meningioma Which Is the Ideal Surgical Approach: Supra/Infratentorial Combined or Retrosigmoid?

Tentorial meningiomas account for 2% to 3% of all intracranial meningiomas. The authors present their experience with posterior fossa tentorial meningiomas, and discuss the main features, which influence approaches and complications of the different surgical techniques. Twenty-four patients had meningiomas localized predominantly in posterior fossa. Their historical records and radiologic examinations were reviewed in accordance with Simpson`s classification. The extension of tumor removal was Simpson grade I in 12 patients (50%), grade II in 12 patients (50%), and grades III and IV in none of the patients. In 22 patients (91.66%), the meningioma was classified as grade I and in 2 cases (8.33%) classified as grade 11 (atypical meningioma). The combined supra/infiratentorial was employed in 12 cases, and complete resections were most common with this approach compared with retrosigmoid technique. Postoperative complications occurred in 10 patients (41.6%) with major deficits in 3 patients (12.5%). The authors believe that careful preoperative choice of the surgical approach should be based Oil tumor location and extension. It is then possible to achieve the best radical microsurgical tumor resection, avoiding additional injury to neurovascular structures.

Characterization of acid-base status in maintenance hemodialysis: physicochemical approach

Acidosis is a common and deleterious aspect of maintenance dialysis. Traditionally, it is considered to be an elevated anion gap acidosis caused by the inability to excrete nonvolatile anions. Stewart`s approach made it possible to identify real determinants of the acid-base status and allowed quantification of the components of these disturbances, especially the unmeasured anions. We performed a cross-sectional study to identify and quantify each component of acidosis in hemodialysis maintenance patients. Sixty-four maintenance hemodialysis patients and 14 controls were enrolled in this study. Gasometrical and biochemical analysis were performed before the midweek dialysis session. Quantitative physicochemical analysis was carried out using the Stewart methodology. Hemodialysis patients were found to have mild acidemia (mean pH: 7.33 +/- 0.06 versus 7.41 +/- 0.05) secondary to metabolic acidosis (serum bicarbonate: 18.8 +/- 0.26 versus 25.2 +/- 0.48 mEq/l). The metabolic acidosis was due to retention of unmeasured anions (6.5 +/- 0.29 versus 3.1 +/- 0.62 mEq/l), hyperchloremia (105.1 +/- 0.5 versus 101.8 +/- 0.7 mEq/l), and hyperphosphatemia (5.90 +/- 0.19 versus 3.66 +/- 0.14 mg/dl). Compared with control values, the unmeasured anions and hyperchloremia had a similar acidifying effect (3.4 and 3.3 mEq/l), corresponding to almost 90% of the metabolic acidosis. Unmeasured anions and hyperchloremia are important components of acidosis in maintenance hemodialysis, in addition to phosphorus. Future studies to determine the etiology and consequences of hyperchloremic acidosis are warranted.

Fusariosis in an immunocompromised patient: therapeutic success with voriconazole

Fusarium infection is known to be potentially severe in immunocompromised patients, especially those with hematologic malignancies. Mortality rates are high and there are few therapeutic options, due to the severe underlying condition of this group of patients and the relative resistance Of Fusarium to conventional antifungal therapy. Voriconazole has been shown to be an effective antifungal agent for neutropenic patients with fusariosis that are refractory or unresponsive to amphotericin B, We report the successful treatment of disseminated Fusarium infection in an immunocompromised host.

High frequency of submicroscopic chromosomal imbalances in patients with syndromic craniosynostosis detected by a combined approach of microsatellite segregation analysis, multiplex ligation-dependent probe amplification and array-based comparative genome hybridisation

We present the first comprehensive study, to our knowledge, on genomic chromosomal analysis in syndromic craniosynostosis. In total, 45 patients with craniosynostotic disorders were screened with a variety of methods including conventional karyotype, microsatellite segregation analysis, subtelomeric multiplex ligation-dependent probe amplification) and whole-genome array-based comparative genome hybridisation. Causative abnormalities were present in 42.2% (19/45) of the samples, and 27.8% (10/36) of the patients with normal conventional karyotype carried submicroscopic imbalances. Our results include a wide variety of imbalances and point to novel chromosomal regions associated with craniosynostosis. The high incidence of pure duplications or trisomies suggests that these are important mechanisms in craniosynostosis, particularly in cases involving the metopic suture.