Comparative Disease Assessment: a multi-causal approach for estimating the burden of mortality

Journal of Public Health - The Comparative Risk Assessment (CRA) framework comprehensively evaluates the impact of exposure to risk factors on health populations using the counterfactual causal...     

In Silico identification of M. TB proteins with diagnostic potential

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.

     

Impairment of emotional expression recognition in schizophrenia: A Cuban familial association study

It is well established that schizophrenia is associated with difficulties in recognizing facial emotional expressions, but few studies have reported the presence of this deficit among their unaffected relatives. This study attempts to add new evidence of familial association on an emotional expression processing test. The study evaluated the performance of 93 paranoid schizophrenia patients, 110 first-degree relatives of probands from multiplex schizophrenia families, and 109 nonpsychiatric controls on a facial emotional recognition test using a computer morphing technique to present the dynamic expressions. The task entailed the recognition of a set of facial expressions depicting the six basic emotions presented in 21 successive frames of increasing intensity. The findings indicated that schizophrenia patients were consistently impaired for the recognition of the six basic facial expressions. In contrast, their unaffected relatives showed a selective impairment for the recognition of disgust and fearful expressions. Familial association of selective facial emotional expressions processing deficit may further implicate promising new endophenotypes that can advance the understanding of affective deficits in schizophrenia.     

Heritability of Trail Making Test performance in multiplex schizophrenia families: implications for the search for an endophenotype

The impairment of the Trail Making Test (TMT) performance as a measure of executive function deficits has been found both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that it might be considered as a familial vulnerability marker, but its heritability estimates are not well known. This study investigated the genetic heritability of impairments in TMT performance using a sample of 80 schizophrenia patients, 145 unaffected first-degree relatives and 127 healthy controls from families with multiple members with schizophrenia. Consistent with previous reports in the literature, relatives performed in between healthy controls and schizophrenia patients. Based on these results, a variance component-analysis provided small, but significant additive heritability estimates for performance indices relating performance in TMT-version A to TMT-version B. These results showed that this significant but small evidence of heritability on the one hand suggests an association with genetic predisposition to schizophrenia, but that TMT performance is also associated with epigenetic or environmental factors.     

In Silico identification of M. TB proteins with diagnostic potential

TB, caused by Mycobacterium tuberculosis (MTB), is one of the major global infectious diseases. For the pandemic control, early diagnosis with sensitive and specific methods is fundamental. With the advent of bioinformatics’ tools, the identification of several proteins involved in the pathogenesis of TB (TB) has been possible. In the present work, the MTB genome was explored to look for molecules with possible antigenic properties for their evaluation as part of new generation diagnostic kits based on the release of cytokines. Seven proteins from the MTB proteome and some of their combinations suited the computational test and the results suggested their potential use for the diagnosis of infection in the following population groups: Cuba, Mexico, Malaysia and sub-Saharan Africa. Our predictions were performed using public bioinformatics tools plus three computer programs, developed by our group, to facilitate information retrieval and processing.     

In silico identification of common epitopes from pathogenic mycobacteria

An in silico study was carried out to identify antigens for their possible collective use as vaccine candidates against diseases caused by different classes of pathogenic mycobacteria with significant clinical relevance. The genome sequences of the relevant causative agents were used in order to search for orthologous genes among them. Bioinformatics tools permitted us to identify several conserved sequences with 100% identity with no possibility of cross-reactivity to the normal flora and human proteins. Nine different proteins were characterized using the strain H37Rv as reference and taking into account their functional category, their in vivo expression and subcellular location. T and B cell epitopes were identified in the selected sequences. Theoretical prediction of population coverage was calculated for individual epitopes as well as their combinations. Several identical sequences, belonging to six proteins containing T and B cell epitopes which are not present in selected microorganisms of the normal microbial flora or in human proteins were obtained.