An agent-based model of anoikis in the colon crypt displays novel emergent behaviour consistent with biological observations

Colorectal cancer (CRC) is a major cause of cancer mortality. Colon crypts are multi-cellular flask-shaped invaginations of the colonic epithelium, with stem cells at their base which support the continual turnover of the epithelium with loss of cells by anoikis from the flat mucosa. Mutations in these stem cells can become embedded in the crypts, a process that is strongly implicated in CRC initiation. We describe a computational model which includes novel features, including an accurate representation of the geometry of the crypt mouth. Model simulations yield previously unseen emergent phenomena, such as localization of cell death to a small region of the crypt mouth which corresponds with that observed in vivo. A mechanism emerges in the model for regulation of crypt cellularity in response to changes in either cell proliferation rates or membrane adhesion strengths. We show that cell shape assumptions influence this behaviour, with cylinders recapitulating biology better than spheres. Potential applications of the model include determination of roles of mutations in neoplasia and exploring factors for altered crypt morphodynamics

Does dental rehabilitation under general anaesthetic contribute to the development of temporomandibular disorders in children and adolescents? A scoping review

BACKGROUND: Temporomandibular disorders (TMDs) have multiple aetiological factors. Although some evidence suggests invasive and lengthy dental procedures may contribute toward TMD development, there is a relative paucity in the literature regarding an association between elements of paediatric dental general anaesthesia (pDGA) and TMDs. This review aims to consider the impact of dental rehabilitation (and its constituent elements) performed under general anaesthesia on the development of TMDs in childhood and adolescence and identify theories and/or gaps in knowledge which may benefit from future research. METHODS: Due to the need to preliminarily examine the nature and extent of the current evidence base, a scoping review approach was chosen. The review was conducted based on the framework provided by the methodological working group of the Joanna Briggs Institute (JBI) for conducting systematic scoping reviews. Electronic databases MEDLINE, Embase, Scopus, Web of Science and Cochrane Library were searched as well as the grey literature using OpenGrey, Nexis, Ethos, Google Scholar and ProQuest, with eligible studies uploaded onto Zotero (Mac Version 5.0.96.2). RESULTS: A total of 810 records were identified. After removing duplicates and those not available in English, 260 were identified for title and abstract screening. Seventy-six records underwent full text review of which only one met the broad inclusion criteria. The most common reasons for exclusion were no specific relation to general anaesthesia, not specifically relating to dental treatment and only being concerned with TMD management. The included study found that while development of TMDs following dental rehabilitation under GA did occur in children, whether the problems caused by treatment were exacerbated by other elements of the pDGA process remains unknown. CONCLUSION: This review has confirmed a distinct paucity of research in this field. While there is no current tangible scientific evidence that common and routine dental procedures lead to TMD, the literature shows that alterations to any one or a combination of critical factors can contribute to TMD development, which may be collectively exacerbated by iatrogenic macrotrauma during the pDGA process. We have highlighted elements of pre-, peri- and post-operative pDGA, alongside biopsychosocial factors, which may contribute to TMD development in childhood and adolescence and may benefit from future research

A cellular based model of the colon crypt suggests novel effects forApc phenotype in colorectal carcinogenesis

Colorectal cancer (CRC) is a major cause of cancer mortality; loss of the Apc gene is an early step in the formation of CRC. A new computational model of the colonic crypt has been developed to simulate the effects of Apc loss. The model includes a region of flat mucosa, which has not previously been considered in the context of Apc loss. The model suggests that Apc loss confers a survival advantage at the crypt mouth which may be a previously unknown method of mutation fixation

Blood feeding in juvenile Paragnathia formica (Isopoda: Gnathiidae): biochemical characterization of trypsin inhibitors, detection of anticoagulants, and molecular identification of fish hosts

SUMMARYThe 3 post-marsupial juvenile stages of the gnathiid isopod, Paragnathia formica, are haematophagous ectoparasites of fishes that may, in heavy infestations, cause host mortality. Protein digestion in fed stage 3 juveniles is accomplished by cysteine proteinases, but what bioactive compounds attenuate host haemostatic, inflammatory and immunological responses during feeding is unknown. Trypsin inhibitory activity and anticoagulant activity were detected in crude extracts of unfed P. formica stage 1 juveniles; fractionation of stage 1 crude extracts by ion exchange chromatography resulted in 3 preparations each displaying these bioactivities. Further characterization revealed anti-thrombin activity in 2 of these preparations, whilst the third displayed the strongest anticoagulant activity that targeted a factor of the intrinsic coagulation pathway. Three trypsin inhibitors (18 kDa, 21 kDa, and 22 kDa) were also detected using reverse zymography. In parallel, homogenates of fed stage 2 and 3 juveniles were used to identify their fish hosts by amplifying the 16S mitochondrial rDNA and 18S genomic rDNA vertebrate gene regions. Blood from at least 4 fish families had been ingested by separate individuals during feeding. This study demonstrates that trypsin inhibitors and anticoagulants are present in P. formica juveniles which could suppress host haemostatic, inflammatory and immunological responses during feeding, and that juveniles are not host specific

Shared Care, Elder and Family Member Skills Used to Manage Burden

Aim. The aim of this paper is to further develop the construct of Shared Care by comparing and contrasting it to related research, and to show how the construct can be used to guide research and practice. Background. While researchers have identified negative outcomes for family caregivers caused by providing care, less is known about positive aspects of family care for both members of a family dyad. Understanding family care relationships is important to nurses because family participation in the care of chronically ill elders is necessary to achieve optimal outcomes from nursing interventions. A previous naturalistic inquiry identified a new construct, Shared Care, which was used to describe a family care interaction that contributed to positive care outcomes. Methods. A literature review was carried out using the databases Medline, CINAHL, and Psych-info and the keywords home care, care receiver, disability, family, communication, decision-making and reciprocity. The results of the review were integrated to suggest how Shared Care could be used to study care difficulties and guide interventions. Results. The literature confirmed the importance of dyad relationships in family care. Shared Care extended previous conceptualizations of family care by capturing three critical components: communication, decision-making, and reciprocity. Shared Care provides a structure to expand the conceptualization of family care to include both members of a care dyad and account for positive and negative aspects of care. Conclusions. The extended view provided by the construct of Shared Care offers practitioners and scholars tools to use in the context of our ageing population to improve the effectiveness of family care relationships

From cell to multi-crypt: Agent-based models of the human colon suggests novel processes of field cancerisation

Colorectal cancer (CRC) is a major cause of cancer mortality. It is known that loss of APC gene function through mutation is followed by the expansion of a field of mutated tissue, but the mechanisms behind this expansion are poorly understood. This study aimed to examine the processes involved in field expansion using two agent-based computational models: a cell-scale model allowing mapping of Apc-mutated cell expansion in small multcrypt arrays, and a tissue-scale model allowing simulation of the entire colon over oncologically relevant timescales. The cell scale model predicts that mutated cells spread through the flat mucosa of the simulated tissue without invading neighbouring crypts - a process not previously hypothesised in the literature. The crypt-scale model’s predictions of field sizes correspond to those estimated in the literature from in vivo studies. Our dual-scale modelling approach renders the spatial and temporal scales at which field cancerisation processes occur in vivo accessible to exploration by simulation for the first time

Development of the NBS beryllium isotopic standard reference material

The National Bureau of Standards, in conjunction with the Oak Ridge National Laboratory and the Accelerator Mass Spectrometry community, is in the process of developing a beryllium isotopic solution Standard Reference Material. The master /sup 10/Be//sup 9/Be solution was characterized isotopically by resonance-ionization and secondary-ion mass-spectrometric-based techniques, and radioactivity measurements were by liquid scintillation counting. The master solution was gravimetrically diluted with /sup 9/Be to a final /sup 10/Be//sup 9/Be atomic ratio of 3 x 10/sup -11/. The preliminary data indicate a half life for /sup 10/Be of 1.3 million years, and AMS measurements are within 10% of the known beryllium isotopic ratio

Attitudes to a male contraceptive pill in a group of contraceptive users in the UK

BACKGROUND. Small scale trials of male hormonal contraception have produced encouraging results. Attitudes to and beliefs about a proposed male pill may affect uptake. METHODS. This paper examines attitudes towards a proposed ‘male contraceptive pill’ among a self selected sample of 54 men and 134 women, living in a non-metropolitan centre in the East of England, United Kingdom who were already users of contraception. Thirty four respondents were also interviewed and their views on the male pill were qualitatively analysed. RESULTS. The acceptability of a male pill was high with just under half (49.5%) of respondents indicating that they would use it. Gender, length of relationship, age and educational achievement did not affect the reported acceptability. 42% of respondents expressed concerns that men would forget to take a male pill. Women were significantly more likely to express this concern than men. 26% of respondents expressed health concerns. Willingness to take a male pill was associated with expressing the view that increased protection against pregnancy would be an advantage of such a method. Those unwilling or undecided were more likely to express concerns about the effect of a pill on future fertility. CONCLUSIONS. A male pill was accepted as a potential aid to increased fertility control by a large proportion of a convenience sample of contraceptive users in the East of England. If a male pill were to be marketed in the UK this study suggests that concerns about effects on future fertility and health risks may need to be addressed

Dietary trends inteh United States [1] (multiple letters)

The authors reply: To the Editor: Nusbaum and Eshleman suggest that dietary trends may reflect respondents’ adherence to the dietary guidelines of the time. From 1916 to 1976, nutritional recommendations relative to the basic food groups were fairly stable. The basic five food groups of 1916 were reduced to the basic four (two daily servings of milk and of meat, poultry, or eggs and four daily servings of fruits and vegetables and of breads and grains) in the 1960s. Not until the introduction of the U.S. Dietary Goals in 1977 did dietary guidelines explicitly recommend nutrient limitations for fats, sugars, and cholesterol. Neither our group nor others have attempted to quantify the dietary guidelines of the 1960s or to ascertain who followed the guidelines most closely