The role of the bone microenvironment in skeletal metastasis

AbstractThe bone microenvironment provides a fertile soil for cancer cells. It is therefore not surprising that the skeleton is a frequent site of cancer metastasis. It is believed that reciprocal interactions between tumour and bone cells, known as the “vicious cycle of bone metastasis” support the establishment and orchestrate the expansion of malignant cancers in bone. While the full range of molecular mechanisms of cancer metastasis to bone remain to be elucidated, recent research has deepened our understanding of the cell-mediated processes that may be involved in cancer cell survival and growth in bone. This review aims to address the importance of the bone microenvironment in skeletal cancer metastasis and discusses potential therapeutic implications of novel insights

Slow magnetisation relaxation in tetraoxolene-bridged rare earth complexes

Two tetraoxolene-bridged dinuclear Dy(iii) complexes exhibit slow relaxation in ac magnetic susceptibility studies with zero-field quantum tunnelling of the magnetisation that is suppressed by the application of a dc magnetic field

Bringing Upstairs Care Downstairs; Integration of Rehabilitation Medicine, Care Management, and the Hospital Elder Life Program (HELP) into an Emergency Department.

Introduction: Services such as physical therapy (PT), occupational therapy (OT), speech-language pathology (SLP), social work (SW), care management, and elder life specialists have long been an established part of care for patients admitted to Maine Medical Center (MMC) but not for patients in the Emergency Department (ED). Methods and Results: Driven in part by changes in Medicare reimbursement models, care management established a presence in the Emergency Department (ED) in 2003 with a focus on care planning and cost avoidance. In recent years PT, OT, SLP, SW, and the Hospital Elder Life Program (HELP) have increased their ED involvement substantially. These services not only support care management decisions but have become an invaluable part of the ED team. The timing, staffing models, and roles of these services in our emergency department are described. Discussion: There was strong leadership support to create these positions in the ED. Increased patient volume hospital wide has required staffing flexibility. Initial concerns for slowing the ED where anecdotally resolved. Other hospitals in our system are interested in this approach. Conclusions: While the value of this work feels self-evident and is already established for admitted patients, descriptive and outcome-oriented studies for ED patients would be enlightening

West Nile Virus and High Death Rate in American Crows

We document effects of West Nile virus (WNV) on American Crows. More than two thirds of our crows died of WNV infection, peaking when the proportion of infected mosquitoes at roosts was greatest. WNV antibody prevalence in crows was low. Local ecologic effects can be dramatic as WNV inhabits new areas

Assembly of the type II secretion system such as found in Vibrio cholerae depends on the novel Pilotin AspS

The Type II Secretion System (T2SS) is a molecular machine that drives the secretion of fully-folded protein substrates across the bacterial outer membrane. A key element in the machinery is the secretin: an integral, multimeric outer membrane protein that forms the secretion pore. We show that three distinct forms of T2SSs can be distinguished based on the sequence characteristics of their secretin pores. Detailed comparative analysis of two of these, the Klebsiella-type and Vibrio-type, showed them to be further distinguished by the pilotin that mediates their transport and assembly into the outer membrane. We have determined the crystal structure of the novel pilotin AspS from Vibrio cholerae, demonstrating convergent evolution wherein AspS is functionally equivalent and yet structurally unrelated to the pilotins found in Klebsiella and other bacteria. AspS binds to a specific targeting sequence in the Vibrio-type secretins, enhances the kinetics of secretin assembly, and homologs of AspS are found in all species of Vibrio as well those few strains of Escherichia and Shigella that have acquired a Vibrio-type T2SS

Effect of a Low–Resource-Intensive Lifestyle Modification Program Incorporating Gymnasium-Based and Home-Based Resistance Training on Type 2 Diabetes Risk in Australian Adults

OBJECTIVE—The purpose of this study was to assess the effectiveness of a low–resource-intensive lifestyle modification program incorporating resistance training and to compare a gymnasium-based with a home-based resistance training program on diabetes diagnosis status and risk

MBE grown GaAsBi/GaAs multiple quantum well structures: Structural and optical characterization

A series of GaAsBi/GaAs multiple quantum well p–i–n diodes were grown by molecular beam epitaxy. Nomarski images showed evidence of sub-surface damage in each diode, with an increase in the cross-hatching associated with strain relaxation for the diodes containing more than 40 quantum wells. X-ray diffraction ω–2θ scans of the (004) reflections showed that multiple quantum well regions with clearly defined well periodicities were grown. The superlattice peaks of the diodes containing more than 40 wells were much broader than those of the other diodes. The photoluminescence spectra showed a redshift of 56 meV and an attenuation of nearly two orders of magnitude for the 54 and 63 well diodes. Calculations of the quantum confinement and strain induced band gap modifications suggest that the wells in all diodes are thinner than their intended widths and that both loss of quantum confinement and strain probably contributed to the observed redshift and attenuation in the 54 and 63 well diodes. Comparison of this data with that gathered for InGaAs/GaAs multiple quantum wells, suggests that the onset of relaxation occurs at a similar average strain–thickness product for both systems. Given the rapid band gap reduction of GaAsBi with Bi incorporation, this data suggests that GaAsBi is a promising photovoltaic material candidate

SaferBirths bundle of care protocol: a stepped-wedge cluster implementation project in 30 public health-facilities in five regions, Tanzania

Background The burden of stillbirth, neonatal and maternal deaths are unacceptably high in low- and middle-income countries, especially around the time of birth. There are scarce resources and/or support implementation of evidence-based training programs. SaferBirths Bundle of Care is a well-proven package of innovative tools coupled with data-driven on-the-job training aimed at reducing perinatal and maternal deaths. The aim of this project is to determine the effect of scaling up the bundle on improving quality of intrapartum care and perinatal survival. Methods The project will follow a stepped-wedge cluster implementation design with well-established infrastructures for data collection, management, and analysis in 30 public health facilities in regions in Tanzania. Healthcare workers from selected health facilities will be trained in basic neonatal resuscitation, essential newborn care and essential maternal care. Foetal heart rate monitors (Moyo), neonatal heart rate monitors (NeoBeat) and skills trainers (NeoNatalie Live) will be introduced in the health facilities to facilitate timely identification of foetal distress during labour and improve neonatal resuscitation, respectively. Heart rate signal-data will be automatically collected by Moyo and NeoBeat, and newborn resuscitation training by NeoNatalie Live. Given an average of 4000 baby-mother pairs per year per health facility giving an estimate of 240,000 baby-mother pairs for a 2-years duration, 25% reduction in perinatal mortality at a two-sided significance level of 5%, intracluster correlation coefficient (ICC) to be 0.0013, the study power stands at 0.99. Discussion Previous reports from small-scale Safer Births Bundle implementation studies show satisfactory uptake of interventions with significant improvements in quality of care and lives saved. Better equipped and trained birth attendants are more confident and skilled in providing care. Additionally, local data-driven feedback has shown to drive continuous quality of care improvement initiatives, which is essential to increase perinatal and maternal survival. Strengths of this research project include integration of innovative tools with existing national guidelines, local data-driven decision-making and training. Limitations include the stepwise cluster implementation design that may lead to contamination of the intervention, and/or inability to address the shortage of healthcare workers and medical supplies beyond the project scope. Trial registration Name of Trial Registry: ISRCTN Registry. Trial registration number: ISRCTN30541755. Date of Registration: 12/10/2020. Type of registration: Prospectively Registered.publishedVersio

Population dynamics of species-rich ecosystems: the mixture of matrix population models approach

Matrix population models are widely used to predict population dynamics, but when applied to species-rich ecosystems with many rare species, the small population sample sizes hinder a good fit of species-specific models. This issue can be overcome by assigning species to groups to increase the size of the calibration data sets. However, the species classification is often disconnected from the matrix modelling and from the estimation of matrix parameters, thus bringing species groups that may not be optimal with respect to the predicted community dynamics. We proposed here a method that jointly classified species into groups and fit the matrix models in an integrated way. The model was a special case of mixture with unknown number of components and was cast in a Bayesian framework. An MCMC algorithm was developed to infer the unknown parameters: the number of groups, the group of each species and the dynamics parameters. We applied the method to simulated data and showed that the algorithm efficiently recovered the model parameters. We applied the method to a data set from a tropical rain forest in French Guiana. The mixture matrix model classified tree species into well-differentiated groups with clear ecological interpretations. It also accurately predicted the forest dynamics over the 16-year observation period. Our model and algorithm can straightforwardly be adapted to any type of matrix model, using the life cycle diagram. It can be used as an unsupervised classification technique to group species with similar population dynamics. (Résumé d'auteur

Structural insights into the function of aminoglycoside-resistance A1408 16S rRNA methyltransferases from antibiotic-producing and human pathogenic bacteria

X-ray crystal structures were determined of the broad-spectrum aminoglycoside-resistance A1408 16S rRNA methyltransferases KamB and NpmA, from the aminoglycoside-producer Streptoalloteichus tenebrarius and human pathogenic Escherichia coli, respectively. Consistent with their common function, both are Class I methyltransferases with additional highly conserved structural motifs that embellish the core SAM-binding fold. In overall structure, the A1408 rRNA methyltransferase were found to be most similar to a second family of Class I methyltransferases of distinct substrate specificity (m7G46 tRNA). Critical residues for A1408 rRNA methyltransferase activity were experimentally defined using protein mutagenesis and bacterial growth assays with kanamycin. Essential residues for SAM coenzyme binding and an extended protein surface that likely interacts with the 30S ribosomal subunit were thus revealed. The structures also suggest potential mechanisms of A1408 target nucleotide selection and positioning. We propose that a dynamic extended loop structure that is positioned adjacent to both the bound SAM and a functionally critical structural motif may mediate concerted conformational changes in rRNA and protein that underpin the specificity of target selection and activation of methyltransferase activity. These new structures provide important new insights that may provide a starting point for strategies to inhibit these emerging causes of pathogenic bacterial resistance to aminoglycosides