Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a globally prevalent cause of diarrhea. Though usually self-limited, it can be severe and debilitating. Little is known about the host transcriptional response to infection. We report the first gene expression analysis of the human host response to experimental challenge with ETEC. METHODS: We challenged 30 healthy adults with an unattenuated ETEC strain, and collected serial blood samples shortly after inoculation and daily for 8 days. We performed gene expression analysis on whole peripheral blood RNA samples from subjects in whom severe symptoms developed (n = 6) and a subset of those who remained asymptomatic (n = 6) despite shedding. RESULTS: Compared with baseline, symptomatic subjects demonstrated significantly different expression of 406 genes highlighting increased immune response and decreased protein synthesis. Compared with asymptomatic subjects, symptomatic subjects differentially expressed 254 genes primarily associated with immune response. This comparison also revealed 29 genes differentially expressed between groups at baseline, suggesting innate resilience to infection. Drug repositioning analysis identified several drug classes with potential utility in augmenting immune response or mitigating symptoms. CONCLUSIONS: There are statistically significant and biologically plausible differences in host gene expression induced by ETEC infection. Differential baseline expression of some genes may indicate resilience to infection.

Multiplex real-time PCR monitoring of intestinal helminths in humans reveals widespread polyparasitism in Northern Samar, the Philippines

The global socioeconomic importance of helminth parasitic disease is underpinned by the considerable clinical impact on millions of people. While helminth polyparasitism is considered common in the Philippines, little has been done to survey its extent in endemic communities. High morphological similarity of eggs between related species complicates conventional microscopic diagnostic methods which are known to lack sensitivity, particularly in low intensity infections. Multiplex quantitative PCR diagnostic methods can provide rapid, simultaneous identification of multiple helminth species from a single stool sample. We describe a multiplex assay for the differentiation of Ascaris lumbricoides, Necator americanus, Ancylostoma, Taenia saginata and Taenia solium, building on our previously published findings for Schistosoma japonicum. Of 545 human faecal samples examined, 46.6% were positive for at least three different parasite species. High prevalences of S. japonicum (90.64%), A. lumbricoides (58.17%), T. saginata (42.57%) and A. duodenale (48.07%) were recorded. Neither T. solium nor N. americanus were found to be present. The utility of molecular diagnostic methods for monitoring helminth parasite prevalence provides new information on the extent of polyparasitism in the Philippines municipality of Palapag. These methods and findings have potential global implications for the monitoring of neglected tropical diseases and control measures.

Determination of a Total Body Model of Efficiency Applied to a Rowing Movement in Humans

Efficiency represents the ratio of work done to energy expended. In human movement, it is desirable to maximise the work done or minimise the energy expenditure. Whilst research has examined the efficiency of human movement for the lower and upper body, there is a paucity of research which considers the efficiency of a total body movement. Rowing is a movement which encompasses all parts of the body to generate locomotion and is a useful modality to measure total body efficiency. It was the aim of this research to develop a total body model of efficiency and explore how skill level of participants and assumptions of the modelling process affected the efficiency estimates Three studies were used to develop and evaluate the efficiency model. Firstly, the efficiency of ten healthy males was established using rowing, cycling and arm cranking. The model included internal work from motion capture and efficiency estimates were comparable to published literature, indicating the suitability of the model to estimate efficiency. Secondly, the model was developed to include a multi-segmented trunk and twelve novice and twelve skilled participants were assessed for efficiency. Whilst the efficiency estimates were similar to published results, novice participants were assessed as more efficient. Issues such as the unique physiology of trained rowers and a lack of energy transfers in the model were considered contributing factors. Finally the model was redeveloped to account for energy transfers, where skilled participants had higher efficiency at large workloads. This work presents a novel model for estimating efficiency during a rowing motion. The specific inclusion of energy transfers expands previous knowledge of internal work and efficiency, demonstrating a need to include energy transfers in the assessment of efficiency of a total body action.

Reply to Bonten and Mevius : Less Evidence for an Important Role of Food-Producing Animals as Source of Antibiotic Resistance in Humans

To the Editor—We thank Bonten and Mevius for their interest in our systematic review [1]. In their letter, they disagree with our finding that whole-bacterium transmission (WBT) of expanded-spectrum cephalosporin-resistant (ESCR) Escherichia coli between food-producing animals and humans likely contributes to the burden of human extraintestinal infections. We respectfully argue against 2 assumptions that underlie their assertion.

Factors affecting gut metabolism and bioavailabilty of orange juice flavanones in humans

Several studies have supported a beneficial role of dietary flavonoids in reducing the risk/progression of chronic diseases (including hypertension, cardiovascular disease, certain cancers, type-2-diabetes, cognitive dysfunction, age-related bone disease). Their beneficial properties are likely to be affected by their structure, distribution in foods, food matrix, life habits (physical activity). Most dietary polyphenols reach the colon where they are metabolized to phenolic acids by gut bacteria. Lack of knowledge of the factors affecting flavonoid metabolism and bioavailability hinders understanding of their health effects. Therefore, this thesis aimed to investigate the effect of factors on bioavailability and metabolism of dietary polyphenols from orange juices (OJ) in in vitro and in vivo studies. In chapter 3, the variability of orange juice polyphenolic content was assessed using in vitro models of the human gastrointestinal tract. Chapter 4 investigated the reduced urinary phenolic acids after OJ and yoghurt (Y) in humans compared to OJ alone using in vitro models of the human gut. In chapter 5, raftiline and glucose were tested for effects on metabolism of hesperidin (flavanone not OJ). In chapter 6, an intervention study of 4 weeks moderate intensity exercise determined whether exercise affected bioavailability and metabolism of OJ flavanones in healthy sedentary females. The studies in this thesis showed that food sources, food matrix and physical exercise may determine the significant variations in bioavailability and metabolism of flavonoids, seen in a number of studies. These factors could result in differences in bioactivity and bioefficacy of polyphenols, and need to be taken into account in further studies of the effects of flavanones on disease risk.

Effects of physical exercise training in DNA damage and repair activity in humans with different genetic polymorphisms ofhOGG1(Ser326Cys)

The main purpose of this pilot study was to investigate the possible influence of genetic polymorphisms of the hOGG1 (Ser326Cys) gene in DNA damage and repair activity by 8-oxoguanine DNA glycosylase 1 (OGG1 enzyme) in response to 16 weeks of combined physical exercise training. Thirty-two healthy Caucasian men (40-74 years old) were enrolled in this study. All the subjects were submitted to a training of 16 weeks of combined physical exercise. The subjects with Ser/Ser genotype were considered as wild-type group (WTG), and Ser/Cys and Cys/Cys genotype were analysed together as mutant group (MG). We used comet assay in conjunction with formamidopyrimidine DNA glycoslyase (FPG) to analyse both strand breaks and FPG-sensitive sites. DNA repair activity were also analysed with the comet assay technique. Our results showed no differences between DNA damage (both strand breaks and FPG-sensitive sites) and repair activity (OGG1) between genotype groups (in the pre-training condition). Regarding the possible influence of genotype in the response to 16 weeks of physical exercise training, the results revealed a decrease in DNA strand breaks in both groups, a decrease in FPG-sensitive sites and an increase in total antioxidant capacity in the WTG, but no changes were found in MG. No significant changes in DNA repair activity was observed in both genotype groups with physical exercise training. This preliminary study suggests the possibility of different responses in DNA damage to the physical exercise training, considering the hOGG1 Ser326Cys polymorphism.

A single theoretical framework for circular features processing in humans: orientation and direction of motion compared

Common computational principles underlie processing of various visual features in the cortex. They are considered to create similar patterns of contextual modulations in behavioral studies for different features as orientation and direction of motion. Here, I studied the possibility that a single theoretical framework, implemented in different visual areas, of circular feature coding and processing could explain these similarities in observations. Stimuli were created that allowed direct comparison of the contextual effects on orientation and motion direction with two different psychophysical probes: changes in weak and strong signal perception. One unique simplified theoretical model of circular feature coding including only inhibitory interactions, and decoding through standard vector average, successfully predicted the similarities in the two domains, while different feature population characteristics explained well the differences in modulation on both experimental probes. These results demonstrate how a single computational principle underlies processing of various features across the cortices.

Erratum: A single theoretical framework for circular features processing in humans: orientation and direction of motion compared (vol 6, pg 28, 2012)

Erratum to: A single theoretical framework for circular features processing in humans: orientation and direction of motion compared. In: Frontiers in computational neuroscience 6 (2012), 28

Dietary nitrate modulates cerebral blood flow parameters and cognitive performance in humans : a double-blind, placebo-controlled, crossover investigation

Clostridium difficile ribotypes in humans and animals in Brazil

Clostridium difficile is an emerging enteropathogen responsible for pseudomembranous colitis in humans and diarrhoea in several domestic and wild animal species. Despite its known importance, there are few studies about C. difficile polymerase chain reaction (PCR) ribotypes in Brazil and the actual knowledge is restricted to studies on human isolates. The aim of the study was therefore to compare C. difficile ribotypes isolated from humans and animals in Brazil. Seventysix C. difficile strains isolated from humans (n = 25), dogs (n = 23), piglets (n = 12), foals (n = 7), calves (n = 7), one cat, and one manned wolf were distributed into 24 different PCR ribotypes. Among toxigenic strains, PCR ribotypes 014/020 and 106 were the most common, accounting for 14 (18.4%) and eight (10.5%) samples, respectively. Fourteen different PCR ribotypes were detected among human isolates, nine of them have also been identified in at least one animal species. PCR ribotype 027 was not detected, whereas 078 were found only in foals. This data suggests a high diversity of PCR ribotypes in humans and animals in Brazil and support the discussion of C. difficile as a zoonotic pathogen.

Characterization of bone pathologies in the ins2+/akita mouse, a new model for diabetes insulindependent: contribution for a better understanding of the disease in humans

Tese de Doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Bite by moray eel

Injuries caused by moray eels are not a common problem, but are distributed throughout the globe, affecting mainly fishermen while manipulating hooked or netted fish. on a lesser scale, scuba divers and snorkelers, practicing or not spear fishing, are occasional victims of bites. With more than 185 species distributed among 15 genera, mostly in tropical to temperate shallow water, moray eels easily come into contact with humans and occasional injuries are not uncommon. The current study reports one case of moray eel bite and discusses the circumstances in which the accident happened, as well as wound evolution and therapy.