Microbial diversity has been pointed out as a major factor in the development and progression of colorectal cancer (CRC). We sought to explore the richness and abundance of the microbial community of a series of colorectal tumor samples treated at Barretos Cancer Hospital, Brazil, through 16S rRNA sequencing. The presence and the impact of Fusobacterium nucleatum ( Fn ) DNA in CRC prognosis was further evaluated by qPCR in a series of 152 CRC cases. An enrichment for potentially oncogenic bacteria in CRC was observed, with Fusobacterium being the most abundant genus in the tumor tissue. In the validation dataset, Fn was detected in 35/152 (23.0%) of fresh-frozen tumor samples and in 6/57 (10.5%) of paired normal adjacent tissue, with higher levels in the tumor ( p = 0.0033). Fn DNA in the tumor tissue was significantly associated with proximal tumors ( p = 0.001), higher depth of invasion ( p = 0.014), higher clinical stages ( p = 0.033), poor differentiation ( p = 0.011), MSI-positive status ( p < 0.0001), BRAF mutated tumors ( p < 0.0001), and the loss of expression of mismatch-repair proteins MLH1 ( p < 0.0001), MSH2 ( p = 0.003), and PMS2 ( p < 0.0001). Moreover, the presence of Fn DNA in CRC tissue was also associated with a worse patient cancer-specific survival (69.9 vs. 82.2% in 5 years; p = 0.028) and overall survival (63.5 vs. 76.5%; p = 0.037). Here we report, for the first time, the association of F. nucleatum presence with important clinical and molecular features in a Brazilian cohort of CRC patients. Tumor detection and classification based on the gut microbiome might provide a promising approach to improve the prediction of patient outcome.

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Gastric cancer is one of the most lethal types of cancer and its incidence varies worldwide, with the Andean region of South America showing high incidence rates. We evaluated the genetic structure of the population from Lima (Peru) and performed a case-control genetic association study to test the contribution of African, European, or Native American ancestry to risk for gastric cancer, controlling for the effect of non-genetic factors. A wide set of socioeconomic, dietary, and clinic information was collected for each participant in the study and ancestry was estimated based on 103 ancestry informative markers. Although the urban population from Lima is usually considered as mestizo (i.e., admixed from Africans, Europeans, and Native Americans), we observed a high fraction of Native American ancestry (78.4% for the cases and 74.6% for the controls) and a very low African ancestry (<5%). We determined that higher Native American individual ancestry is associated with gastric cancer, but socioeconomic factors associated both with gastric cancer and Native American ethnicity account for this association. Therefore, the high incidence of gastric cancer in Peru does not seem to be related to susceptibility alleles common in this population. Instead, our result suggests a predominant role for ethnic-associated socioeconomic factors and disparities in access to health services. Since Native Americans are a neglected group in genomic studies, we suggest that the population from Lima and other large cities from Western South America with high Native American ancestry background may be convenient targets for epidemiological studies focused on this ethnic group.

A survey for intestinal parasites was carried out in a homogenous rice cultivation area, in which people had equal opportunities of acquiring the local endemic helminthiases, including schistosomiasis mansoni. The numbers of Schistosoma mansoni eggs excreted in faeces were counted. Infections with S. mansoni, Ascaris lumbricoides, ancylostomes and Trichuris trichiura were not randomly distributed, but were correlated, depending on the species of worms present. The S. mansoni egg counts were positively correlated with ancylostome infection but inversely correlated with A. lumbricoides and T. trichiura. Patients with schistosomiasis associated with 2 other helminth infections excreted more S. mansoni eggs than the patients with S. mansoni plus only one other helminth infection.

Inherited mutations in components of desmosomes result in a spectrum of syndromes characterized by variable abnormalities in the skin and its appendages, including blisters and erosions, palmoplantar hyperkeratosis, woolly hair or hypotrichosis and, in some cases, extracutaneous features such as cardiomyopathy. We investigated the molecular basis of two Brazilian patients presenting with clinical features consistent with ectodermal dysplasia-skin fragility syndrome. In patient 1 we identified a homozygous nonsense mutation, p.R672X, in the PKP1 gene (encoding plakophilin 1). This particular mutation has not been reported previously but is similar to the molecular pathology underlying other cases of this syndrome. In patient 2 we found compound heterozygosity for two frameshift mutations, c.2516del4 and c.3971del4, in the DSP gene (encoding desmoplakin). Although there was considerable clinical overlap in the skin and hair abnormalities in these two cases, patient 2 also had early-onset cardiomyopathy. The mutation c.3971del4 occurs in the longer desmoplakin-I isoform (which is the major cardiac transcript) but not in the more ubiquitous desmoplakin-II. In contrast, PKP1 is not expressed in the heart, which accounts for the lack of cardiomyopathy in patient 1. Collectively, these cases represent the first desmosomal genodermatoses to be reported from Brazil and add to genotype-phenotype correlation in this group of inherited disorders. Loss-of-function mutations in the DSP gene can result in a phenotype similar to ectodermal dysplasia-skin fragility syndrome resulting from PKP1 mutations but only DSP pathology is associated with cardiac disease.

Melnick-Needles syndrome (MNS) (OMIM 309350) is a rare, X-linked dominant condition, caused by mutations in the filamin A gene (FLNA, on Xq28). In females, the syndrome presents with bone dysplasia and characteristic facial changes. Affected males may show two different phenotypes. One is similar to the female phenotype and is seen in children born to unaffected mothers and suggesting new mutations. Alternatively, males born to affected mothers have an embryonic or perinatally lethal disorder. It has been claimed that MNS constitutes part of a spectrum including frontometaphyseal dysplasia, otopalatodigital syndrome type 1 (OPD1) and otopalatodigital syndrome type 2 (OPD2). These conditions are produced by different mutations in the filamin A gene (FLNA). MNS is caused by three different mutations in FLNA exon 22, to date detected only in females. We describe the clinical manifestations and present the results of FLNA exon 22 mutations screening in two boys with the perinatally lethal form of MNS and their affected mothers. In order to obtain DNA amplification from paraffin-embedded tissues, we designed a new method based on hemi-nested PCR. One of the children (and his mother) had a previously undescribed mutation produced by a double SNP in the positions 3776 and 3777 of the gene and leading to an amino acid substitution (NP_001447:p.[Gly1176Asp]). The second child (and his mother) had an already known mutation (NP_001447.2:p[.Ser1199Leu]). This is the first report confirming the presence FLNA mutations in boys with the perinatally lethal phenotype of MNS. (

| Background: Frailty and sarcopenia are frequent conditions in the elderly and are related to inactivity and functionality. However, little is known about the influence of the sarcopenia indicators on the frailty profile or their functional implications. Objective: To evaluate whether the indirect indicators of sarcopenia and functionality influence the frailty profile in elderly subjects. Method: This was a cross-sectional study with 53 elderly subjects recruited by an active search in a secondary health care service. The indirect indicators of sarcopenia were body mass index (BMI), gait speed, Mini-Nutritional Assessment (MNA), Human Activity Profile (HAP), and handgrip strength. Frailty was characterized according to Fried's Frailty Phenotype. Functional capacity was assessed according to the Short Physical Performance Battery (SPPB). Physical activity level was assessed by HAP. Data were analyzed by analysis of variance (ANOVA) and multiple regression. Results: Overall, 75.5% of the subjects were women, with a mean age of 76.72 (±5.89) years; 15.1% were frail and 54.7% pre-frail; and the level of physical activity was the most prevalent indicator of sarcopenia. Significant differences (p<0.05) were observed in both the physical activity level and gait speed between the non-frail and pre-frail groups and between the non-frail and frail groups. In addition, some sarcopenia indicators were associated with functional capacity and geriatric depression score. Conclusion: The level of physical activity and gait speed appeared to be the most relevant factors in the development of frailty in the study sample, which may have functional implications. HOW TO CITE THIS ARTICLEViana JU, Silva SLA, Torres JL, Dias JMD, Pereira LSM, Dias RC. Influence of sarcopenia and functionality indicators on the frailty profile of community-dwelling elderly subjects: a cross-sectional study. Braz J Phys Ther. 2013 July-Aug; 17(4):373-381. http:// dx.

BackgroundArchaeology reports millenary cultural contacts between Peruvian Coast-Andes and the Amazon Yunga, a rainforest transitional region between Andes and Lower Amazonia. To clarify the relationships between cultural and biological evolution of these populations, in particular between Amazon Yungas and Andeans, we used DNA-sequence data, a model-based Bayesian approach and several statistical validations to infer a set of demographic parameters.ResultsWe found that the genetic diversity of the Shimaa (an Amazon Yunga population) is a subset of that of Quechuas from Central-Andes. Using the Isolation-with-Migration population genetics model, we inferred that the Shimaa ancestors were a small subgroup that split less than 5300 years ago (after the development of complex societies) from an ancestral Andean population. After the split, the most plausible scenario compatible with our results is that the ancestors of Shimaas moved toward the Peruvian Amazon Yunga and incorporated the culture and language of some of their neighbors, but not a substantial amount of their genes. We validated our results using Approximate Bayesian Computations, posterior predictive tests and the analysis of pseudo-observed datasets.ConclusionsWe presented a case study in which model-based Bayesian approaches, combined with necessary statistical validations, shed light into the prehistoric demographic relationship between Andeans and a population from the Amazon Yunga. Our results offer a testable model for the peopling of this large transitional environmental region between the Andes and the Lower Amazonia. However, studies on larger samples and involving more populations of these regions are necessary to confirm if the predominant Andean biological origin of the Shimaas is the rule, and not the exception.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-014-0174-3) contains supplementary material, which is available to authorized users.