Bonding to sclerotic dentin using two conditioning methods

published_or_final_versio

Comparison of Anterior Segment Optical Tomography Parameters Measured Using a Semi-Automatic Software to Standard Clinical Instruments

10.1371/journal.pone.0065559PLoS ONE86

Impact of Rheumatic Musculoskeletal Disease on Psychological Development in Adolescents and Young Adults

Adolescents and young adults (AYAs) undergo significant physiological and psychological transformations. When developmental milestones are combined with additional challenges of growing up with a chronic rheumatic musculoskeletal disease (RMD), it can increase AYA's susceptibility to psychological problems. Emotional issues in adolescence can often persist into adulthood and negatively impact future health, social, and work outcomes. This chapter summarises psychological challenges for AYAs and recommends ways for healthcare professionals (HCPs) to promote mental wellbeing in AYAs with RMD

Calculating Ensemble Averaged Descriptions of Protein Rigidity without Sampling

Previous works have demonstrated that protein rigidity is related to thermodynamic stability, especially under conditions that favor formation of native structure. Mechanical network rigidity properties of a single conformation are efficiently calculated using the integer body-bar Pebble Game (PG) algorithm. However, thermodynamic properties require averaging over many samples from the ensemble of accessible conformations to accurately account for fluctuations in network topology. We have developed a mean field Virtual Pebble Game (VPG) that represents the ensemble of networks by a single effective network. That is, all possible number of distance constraints (or bars) that can form between a pair of rigid bodies is replaced by the average number. The resulting effective network is viewed as having weighted edges, where the weight of an edge quantifies its capacity to absorb degrees of freedom. The VPG is interpreted as a flow problem on this effective network, which eliminates the need to sample. Across a nonredundant dataset of 272 protein structures, we apply the VPG to proteins for the first time. Our results show numerically and visually that the rigidity characterizations of the VPG accurately reflect the ensemble averaged properties. This result positions the VPG as an efficient alternative to understand the mechanical role that chemical interactions play in maintaining protein stability

Communication about genetic testing with breast and ovarian cancer patients: a scoping review

© 2018, The Author(s). Genetic testing of patients with cancer is increasingly offered to guide management, resulting in a growing need for oncology health professionals to communicate genetics information and facilitate informed decision-making in a short time frame. This scoping review aimed to map and synthesise what is known about health professionals’ communication about genetic testing for hereditary breast and ovarian cancer with cancer patients. Four databases were systematically searched using a recognised scoping review method. Areas and types of research were mapped and a narrative synthesis of the findings was undertaken. Twenty-nine papers from 25 studies were included. Studies were identified about (i) information needs, (ii) process and content of genetic counselling, (iii) cognitive and emotional impact, including risk perception and recall, understanding and interpretation of genetic test results, and anxiety and distress, (iv) patients’ experiences, (v) communication shortly after diagnosis and (vi) alternatives to face-to-face genetic counselling. Patients’ need for cancer-focused, personalised information is not always met by genetic counselling. Genetic counselling tends to focus on biomedical information at the expense of psychological support. For most patients, knowledge is increased and anxiety is not raised by pre-test communication. However, some patients experience anxiety and distress when results are disclosed, particularly those tested shortly after diagnosis who are unprepared or unsupported. For many patients, pre-test communication by methods other than face-to-face genetic counselling is acceptable. Research is needed to identify patients who may benefit from genetic counselling and support and to investigate communication about hereditary breast and ovarian cancer by oncology health professionals

Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma

Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.United States. National Institutes of Health (R01GM107536)Alex's Lemonade Stand FoundationHoward Hughes Medical InstituteBoston Children's Hospital. Manton Center for Orphan Disease ResearchNational Institute of General Medical Sciences (U.S.) (T32GM007753

Deciphering the stem cell machinery as a basis for understanding the molecular mechanism underlying reprogramming

Stem cells provide fascinating prospects for biomedical applications by combining the ability to renew themselves and to differentiate into specialized cell types. Since the first isolation of embryonic stem (ES) cells about 30 years ago, there has been a series of groundbreaking discoveries that have the potential to revolutionize modern life science. For a long time, embryos or germ cell-derived cells were thought to be the only source of pluripotency—a dogma that has been challenged during the last decade. Several findings revealed that cell differentiation from (stem) cells to mature cells is not in fact an irreversible process. The molecular mechanism underlying cellular reprogramming is poorly understood thus far. Identifying how pluripotency maintenance takes place in ES cells can help us to understand how pluripotency induction is regulated. Here, we review recent advances in the field of stem cell regulation focusing on key transcription factors and their functional interplay with non-coding RNAs

Systems biology discoveries using non-human primate pluripotent stem and germ cells: novel gene and genomic imprinting interactions as well as unique expression patterns

The study of pluripotent stem cells has generated much interest in both biology and medicine. Understanding the fundamentals of biological decisions, including what permits a cell to maintain pluripotency, that is, its ability to self-renew and thereby remain immortal, or to differentiate into multiple types of cells, is of profound importance. For clinical applications, pluripotent cells, including both embryonic stem cells and adult stem cells, have been proposed for cell replacement therapy for a number of human diseases and disorders, including Alzheimer's, Parkinson's, spinal cord injury and diabetes. One challenge in their usage for such therapies is understanding the mechanisms that allow the maintenance of pluripotency and controlling the specific differentiation into required functional target cells. Because of regulatory restrictions and biological feasibilities, there are many crucial investigations that are just impossible to perform using pluripotent stem cells (PSCs) from humans (for example, direct comparisons among panels of inbred embryonic stem cells from prime embryos obtained from pedigreed and fertile donors; genomic analysis of parent versus progeny PSCs and their identical differentiated tissues; intraspecific chimera analyses for pluripotency testing; and so on). However, PSCs from nonhuman primates are being investigated to bridge these knowledge gaps between discoveries in mice and vital information necessary for appropriate clinical evaluations. In this review, we consider the mRNAs and novel genes with unique expression and imprinting patterns that were discovered using systems biology approaches with primate pluripotent stem and germ cells