Leprosy among Patient Contacts: A Multilevel Study of Risk Factors

Leprosy is an infectious disease that can lead to physical disabilities, social stigma, and great hardship. Transmitted from person to person, it is still endemic in developing countries, like Brazil and India. Effective treatment has been available since 1960, but early diagnosis of the disease remains the most effective way to stop the transmission chain and avoid late diagnoses and subsequent disabilities. Knowledge of the risk factors for leprosy can facilitate early detection; therefore, our study aimed to investigate the factors presented by leprosy patients and their contacts, who are considered at highest risk of contracting the disease. We studied 6,158 contacts of 1,201 patients under surveillance from 1987 to 2007 in a Public Health Care Center in the City of Rio de Janeiro, Brazil. We evaluated the ways patient and contact demographics and epidemiological characteristics were associated with the detection of leprosy. Statistical analyses took into account both individual and group characteristics and their interrelationships. The main characteristics facilitating the contraction of leprosy among contacts were shown to be consanguinity and household association. Conversely, the bacillary load index of leprosy patients was the principle factor leading to disease among their contacts

Polyploidization as a Retraction Force in Plant Genome Evolution: Sequence Rearrangements in Triticale

BACKGROUND: Polyploidization is a major evolutionary process in plants where hybridization and chromosome doubling induce enormous genomic stress and can generate genetic and epigenetic modifications. However, proper evaluation of DNA sequence restructuring events and the precise characterization of sequences involved are still sparse. METHODOLOGY/PRINCIPAL FINDINGS: Inter Retrotransposons Amplified Polymorphism (IRAP), Retrotransposons Microsatellite Amplified Polymorphism (REMAP) and Inter Simple Sequence Repeat (ISSR) largely confirmed the absence of any intraspecific variation in wheat, rye and triticale. The comparative analysis of banding profiles between wheat and rye inbred lines revealed 34% of monomorphic (common to both parental species) bands for the ten different primer combinations used. The analysis of triticale plants uncovered nearly 51% of rearranged bands in the polyploid, being the majority of these modifications, due to the loss of rye bands (83%). Sequence analysis of rye fragments absent in triticale revealed for instance homology with hydroxyproline-rich glycoproteins (HRGP), a protein that belongs to a major family of inducible defence response proteins. Conversely, a wheat-specific band absent in triticale comprises a nested structure of copia-like retrotransposons elements, namely Claudia and Barbara. Sequencing of a polyploid-specific band (absent in both parents) revealed a microsatellite related sequence. Cytological studies using Fluorescent In Situ Hybridization (FISH) with REMAP products revealed a widespread distribution of retrotransposon and/or microsatellite flanking sequences on rye chromosomes, with a preferential accumulation in heterochromatic sub-telomeric domains. CONCLUSIONS/SIGNIFICANCE: Here, we used PCR-based molecular marker techniques involving retrotransposons and microsatellites to uncover polyploidization induced genetic restructuring in triticale. Sequence analysis of rearranged genomic fragments either from rye or wheat origin showed these to be retrotransposon-related as well as coding sequences. Further FISH analysis revealed possible chromosome hotspots for sequence rearrangements. The role of chromatin condensation on the origin of genomic rearrangements mediated by polyploidization in triticale is also discussed

Community ecology of the Middle Miocene primates of La Venta, Colombia: the relationship between ecological diversity, divergence time, and phylogenetic richness

It has been suggested that the degree of ecological diversity that characterizes a primate community correlates positively with both its phylogenetic richness and the time since the members of that community diverged (Fleagle and Reed in Primate communities. Cambridge University Press, New York, pp 92–115, 1999). It is therefore questionable whether or not a community with a relatively recent divergence time but high phylogenetic richness would be as ecologically variable as a community with similar phylogenetic richness but a more distant divergence time. To address this question, the ecological diversity of a fossil primate community from La Venta, Colombia, a Middle Miocene platyrrhine community with phylogenetic diversity comparable with extant platyrrhine communities but a relatively short time since divergence, was compared with that of modern Neotropical primate communities. Shearing quotients and molar lengths, which together are reliable indicators of diet, for both fossil and extant species were plotted against each other to describe the dietary “ecospace” occupied by each community. Community diversity was calculated as the area of the minimum convex polygon encompassing all community members. The diversity of the fossil community was then compared with that of extant communities to test whether the fossil community was less diverse than extant communities while taking phylogenetic richness into account. Results indicate that the La Ventan community was not significantly less ecologically diverse than modern communities, supporting the idea that ecological diversification occurred along with phylogenetic diversification early in platyrrhine evolution

Angiotensin II Facilitates Breast Cancer Cell Migration and Metastasis

Breast cancer metastasis is a leading cause of death by malignancy in women worldwide. Efforts are being made to further characterize the rate-limiting steps of cancer metastasis, i.e. extravasation of circulating tumor cells and colonization of secondary organs. In this study, we investigated whether angiotensin II, a major vasoactive peptide both produced locally and released in the bloodstream, may trigger activating signals that contribute to cancer cell extravasation and metastasis. We used an experimental in vivo model of cancer metastasis in which bioluminescent breast tumor cells (D3H2LN) were injected intra-cardiacally into nude mice in order to recapitulate the late and essential steps of metastatic dissemination. Real-time intravital imaging studies revealed that angiotensin II accelerates the formation of metastatic foci at secondary sites. Pre-treatment of cancer cells with the peptide increases the number of mice with metastases, as well as the number and size of metastases per mouse. In vitro, angiotensin II contributes to each sequential step of cancer metastasis by promoting cancer cell adhesion to endothelial cells, trans-endothelial migration and tumor cell migration across extracellular matrix. At the molecular level, a total of 102 genes differentially expressed following angiotensin II pre-treatment were identified by comparative DNA microarray. Angiotensin II regulates two groups of connected genes related to its precursor angiotensinogen. Among those, up-regulated MMP2/MMP9 and ICAM1 stand at the crossroad of a network of genes involved in cell adhesion, migration and invasion. Our data suggest that targeting angiotensin II production or action may represent a valuable therapeutic option to prevent metastatic progression of invasive breast tumors

2D versus 3D human induced pluripotent stem cell-derived cultures for neurodegenerative disease modelling

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results. One possible avenue is the development of patient-derived models, e.g. by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), which can then be differentiated into any cell type for modelling. These systems contain key genetic information from the donors, and therefore have enormous potential as tools in the investigation of pathological mechanisms underlying disease phenotype, and progression, as well as in drug testing platforms. hiPSCs have been widely cultured in 2D systems, but in order to mimic human brain complexity, 3D models have been proposed as a more advanced alternative. This review will focus on the use of patient-derived hiPSCs to model AD, PD, HD and ALS. In brief, we will cover the available stem cells, types of 2D and 3D culture systems, existing models for neurodegenerative diseases, obstacles to model these diseases in vitro, and current perspectives in the field

Responsiveness of the Early Childhood Oral Health Impact Scale (ECOHIS) is related to dental treatment complexity

Abstract\ud \ud Background\ud The responsiveness of the Early Childhood Oral Health Impact Scale (ECOHIS) has varied greatly across studies; hence, we hypothesized that this discrepancy could be related to the complexity of dental treatment received. Thus, we aimed to evaluate the responsiveness of the ECOHIS to changes in oral health-related quality of life (OHRQoL) following dental treatments of varying complexity in preschool children.\ud \ud \ud Methods\ud Preschool children aged 3 to 6 years were selected; their parents responded to the ECOHIS at baseline. The parents responded to the ECOHIS again and a global transition question 30 days after the children were treated. The type of treatment received by the children was categorized according to complexity, as follows: 1) non-operative treatment only, 2) restorative treatment, and 3) endodontic treatment and/or tooth extraction. Change scores and effect sizes (ES) were calculated for total scores, as well as considering the different treatment types and global transition question responses.\ud \ud \ud Results\ud Of the 152 children who completed the study, the ECOHIS yielded large ES for total scores (0.89). The children showed increasing ES values associated with better perception of improvement, assessed by the global transition question. The magnitude of ES after treatment was related to treatment complexity (0.53, 0.92 and 1.43, for children who received non-operative treatment only, restorative treatment, and endodontic treatment and/or tooth extraction, respectively).\ud \ud \ud Conclusions\ud Parents whose children required more complex dental treatment are more likely to perceive treatment-related changes to OHRQoL assessed with the ECOHIS.The study was funded by Conselho Nacional de Desenvolvimento Científico\ud e Tecnológico – CNPq (Grants # 471817/2012–0 and 306,304/2015–5),\ud Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (Grant #\ud 2012/24243–7), and Coordenação de Aperfeiçoamento de Pessoal de Nível\ud Superior (CAPES)