1,074 research outputs found

    Differences in the Active Endometrial Microbiota across Body Weight and Cancer in Humans and Mice

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    Obesity is a risk factor for endometrial cancer. The aim of this study was to determine whether actively replicating microbiota in the endometrium differ between obese vs. lean and cancer vs. benign states. We performed 16S rRNA amplicon sequencing on endometrial tissues from lean and obese women with and without endometrial cancer, and lean and obese mice. Results displayed human endometrial microbiota clustered into three community types (R = 0.363, p = 0.001). Lactobacillus was dominant in community type 1 (C1) while community type 2 (C2) had high levels of Proteobacteria and more cancer samples when compared to C1 (p = 0.007) and C3 (p = 0.0002). A significant increase in the prevalence of the C2 community type was observed across body mass index and cancer (χ2 = 14.24, p = 0.0002). The relative abundance of Lactobacillus was lower in cancer samples (p = 0.0043), and an OTU with 100% similarity to Lactobacillus iners was enriched in control samples (p = 0.0029). Mouse endometrial microbiota also clustered into three community types (R = 0.419, p = 0.001) which were not influenced by obesity. In conclusion, obesity and cancer are associated with community type prevalence in the human endometrium, and Lactobacillus abundance is associated with normal uterine histologies in humans and mice

    Structure-function relationships in the feto-placental circulation from in silico interpretation of micro-CT vascular structures

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    A well-functioning placenta is critical for healthy fetal development, as the placenta brings fetal blood in close contact with nutrient rich maternal blood, enabling exchange of nutrients and waste between mother and fetus. The feto-placental circulation forms a complex branching structure, providing blood to fetal capillaries, which must receive sufficient blood flow to ensure effective exchange, but at a low enough pressure to prevent damage to placental circulatory structures. The branching structure of the feto-placental circulation is known to be altered in complications such as fetal growth restriction, and the presence of regions of vascular dysfunction (such as hypovascularity or thrombosis) are proposed to elevate risk of placental pathology. Here we present a methodology to combine micro-computed tomography and computational model-based analysis of the branching structure of the feto-placental circulation in ex vivo placentae from normal term pregnancies. We analyse how vascular structure relates to function in this key organ of pregnancy; demonstrating that there is a 'resilience' to placental vascular structure-function relationships. We find that placentae with variable chorionic vascular structures, both with and without a Hyrtl's anastomosis between the umbilical arteries, and those with multiple regions of poorly vascularised tissue are able to function with a normal vascular resistance. Our models also predict that by progressively introducing local heterogeneity in placental vascular structure, large increases in feto-placental vascular resistances are induced. This suggests that localised heterogeneities in placental structure could potentially provide an indicator of increased risk of placental dysfunction

    Everyday concept detection in visual lifelogs: validation, relationships and trends

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    The Microsoft SenseCam is a small lightweight wearable camera used to passively capture photos and other sensor readings from a user's day-to-day activities. It can capture up to 3,000 images per day, equating to almost 1 million images per year. It is used to aid memory by creating a personal multimedia lifelog, or visual recording of the wearer's life. However the sheer volume of image data captured within a visual lifelog creates a number of challenges, particularly for locating relevant content. Within this work, we explore the applicability of semantic concept detection, a method often used within video retrieval, on the novel domain of visual lifelogs. A concept detector models the correspondence between low-level visual features and high-level semantic concepts (such as indoors, outdoors, people, buildings, etc.) using supervised machine learning. By doing so it determines the probability of a concept's presence. We apply detection of 27 everyday semantic concepts on a lifelog collection composed of 257,518 SenseCam images from 5 users. The results were then evaluated on a subset of 95,907 images, to determine the precision for detection of each semantic concept. We conduct further analysis on the temporal consistency, co-occurance and trends within the detected concepts to more extensively investigate the robustness of the detectors within this novel domain. We additionally present future applications of concept detection within the domain of lifelogging

    Model for in vivo progression of tumors based on co-evolving cell population and vasculature

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    With countless biological details emerging from cancer experiments, there is a growing need for minimal mathematical models which simultaneously advance our understanding of single tumors and metastasis, provide patient-personalized predictions, whilst avoiding excessive hard-to-measure input parameters which complicate simulation, analysis and interpretation. Here we present a model built around a co-evolving resource network and cell population, yielding good agreement with primary tumors in a murine mammary cell line EMT6-HER2 model in BALB/c mice and with clinical metastasis data. Seeding data about the tumor and its vasculature from in vivo images, our model predicts corridors of future tumor growth behavior and intervention response. A scaling relation enables the estimation of a tumor's most likely evolution and pinpoints specific target sites to control growth. Our findings suggest that the clinically separate phenomena of individual tumor growth and metastasis can be viewed as mathematical copies of each other differentiated only by network structure

    GPs’ strategies in exploring the preschool child’s wellbeing in the paediatric consultation

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    Background: Although General Practitioners (GPs) are uniquely placed to identify children with emotional, social, and behavioural problems, they succeed in identifying only a small number of them. The aim of this article is to explore the strategies, methods, and tools employed by GPs in the assessment of the preschool child’s emotional, mental, social, and behavioural health. We look at how GPs address parental care of the child in general and in situations where GPs have a particular awareness of the child. Method: Twenty-eight Danish GPs were purposively selected to take part in a qualitative study which combined focus-group discussions, observation of child consultations, and individual interviews with GPs. Results: Analysis of the data suggests that GPs have developed a set of methods, and strategies to assess the preschool child and parental care of the child. They look beyond paying narrow attention to the physical health of the child and they have expanded their practice to include the relations and interactions in the consultation room. The physical examination of the child continues to play a central role in doctor-child communication. Conclusion: The participating GPs’ strategies helped them to assess the wellbeing of the preschool child but they often find it difficult to share their impressions with parents

    Protein disulfide-isomerase interacts with a substrate protein at all stages along its folding pathway

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    In contrast to molecular chaperones that couple protein folding to ATP hydrolysis, protein disulfide-isomerase (PDI) catalyzes protein folding coupled to formation of disulfide bonds (oxidative folding). However, we do not know how PDI distinguishes folded, partly-folded and unfolded protein substrates. As a model intermediate in an oxidative folding pathway, we prepared a two-disulfide mutant of basic pancreatic trypsin inhibitor (BPTI) and showed by NMR that it is partly-folded and highly dynamic. NMR studies show that it binds to PDI at the same site that binds peptide ligands, with rapid binding and dissociation kinetics; surface plasmon resonance shows its interaction with PDI has a Kd of ca. 10−5 M. For comparison, we characterized the interactions of PDI with native BPTI and fully-unfolded BPTI. Interestingly, PDI does bind native BPTI, but binding is quantitatively weaker than with partly-folded and unfolded BPTI. Hence PDI recognizes and binds substrates via permanently or transiently unfolded regions. This is the first study of PDI's interaction with a partly-folded protein, and the first to analyze this folding catalyst's changing interactions with substrates along an oxidative folding pathway. We have identified key features that make PDI an effective catalyst of oxidative protein folding – differential affinity, rapid ligand exchange and conformational flexibility

    Personality Traits in Miners with Past Occupational Elemental Mercury Exposure

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    In this study, we evaluated the impact of long-term occupational exposure to elemental mercury vapor (Hg(0)) on the personality traits of ex-mercury miners. Study groups included 53 ex-miners previously exposed to Hg(0) and 53 age-matched controls. Miners and controls completed the self-reporting Eysenck Personality Questionnaire and the Emotional States Questionnaire. The relationship between the indices of past occupational exposure and the observed personality traits was evaluated using Pearson’s correlation coefficient and on a subgroup level by machine learning methods (regression trees). The ex-mercury miners were intermittently exposed to Hg(0) for a period of 7–31 years. The means of exposure-cycle urine mercury (U-Hg) concentrations ranged from 20 to 120 μg/L. The results obtained indicate that ex-miners tend to be more introverted and sincere, more depressive, more rigid in expressing their emotions and are likely to have more negative self-concepts than controls, but no correlations were found with the indices of past occupational exposure. Despite certain limitations, results obtained by the regression tree suggest that higher alcohol consumption per se and long-term intermittent, moderate exposure to Hg(0) (exposure cycle mean U-Hg concentrations > 38.7 < 53.5 μg/L) in interaction with alcohol remain a plausible explanation for the depression associated with negative self-concept found in subgroups of ex-mercury miners. This could be one of the reason for the higher risk of suicide among miners of the Idrija Mercury Mine in the last 45 years

    Tulžies latakų akmenligė: ligos įtarimas, diagnozė, gydymas

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    Bile duct stones are a quite common (10–18%) complication of gallstone disease or an autonomous condition. New noninvasive diagnostic methods established in the last decades allow to confirm suspected choledocholithiasis with minimal risk of iatrogenic complications.In this literature review we discuss various scores for choledocholithiasis risk degree, different diagnostic investigations and management approaches including timing for invasive procedures.Tulžies latakų akmenys&nbsp;– gana dažna (10–18&nbsp;%) tulžies pūslės akmenligės komplikacija ar savarankiška patologija. Pastaraisiais dešimtmečiais atsiradę nauji neinvaziniai diagnostikos metodai&nbsp;leidžia patikslinti įtariamą tulžies latakų akmenligės diagnozę minimalizavus jatrogeninių komplikacijų riziką.Šioje literatūros apžvalgoje aptariamos rizikos vertinimo sistemos, leidžiančios apsispręsti dėl papildomų tyrimų tikslingumo, pristatomi&nbsp;įvairūs diagnostiniai metodai, skirtingos gydymo ir tyrimo taktikos, aptariamas gydymo laiko pasirinkimas

    An Ecological Momentary Assessment of Lapse Occurrences in Dieters

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    Purpose: The aim of this study is to investigate the factors related to dietary lapse occurrence in a community sample of dieters. Methods: An ecological momentary assessment (EMA) methodology, via mobile phone-based diaries, was employed to record dietary lapse occurrences in a group of dieters (N = 80; M age  = 41.21 ± 15.60 years; M BMI = 30.78 ± 7.26) over 7 days. Results: Analyses indicated that lapses were positively associated with the strength of dietary temptation, presence of others, coping responses, and the environment (exposure to food cues) in which the dieters were in; lapses were more likely to occur in the evening and were negatively associated with the use of coping mechanisms. Additionally, lapse occurrence was found to mediate the relationships among the above predictors of lapse and the self-efficacy to resist future dietary temptations. Conclusions: Results provide an insight into the occurrence of lapses in dieters and have implications for interventions focusing on weight loss maintenance and relapse prevention
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