The relationship between adiposity, bone density and microarchitecture is maintained in young women irrespective of diabetes status

Background: The relationship between bone health and adiposity and how it may be affected in people with chronic metabolic conditions is complex. Methods: 17 women with Type 1 diabetes mellitus (T1DM) and 9 age-matched healthy women with a median age of 22.6 yrs (range, 17.4, 23.8) were studied by 3T-MRI and MR spectroscopy to assess abdominal adiposity, tibial bone microarchitecture and vertebral bone marrow adiposity. Additional measures included DXA-based assessments of total body (TB), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and fat mass (FM). Results: Although women with T1DM had similar BMI and bone marrow adiposity to the controls, they had higher visceral and subcutaneous adiposity on MRI (p<0.05) and total body FM by DXA (p=0.03). Overall, in the whole cohort, a clear inverse association was evident between bone marrow adiposity and BMD at all sites (p<0.05). These associations remained significant after adjusting for age, BMI, FM, and abdominal adiposity. In addition, visceral adiposity, but not subcutaneous adiposity, showed a positive association with bone marrow adiposity (r,0.4, p=0.03), and a negative association with total body BMD (r,0.5, p=0.02). Apparent trabecular separation as assessed by MRI showed an inverse association to total body BMD by DXA (r,–0.4, p=0.04). Conclusion: Irrespective of the presence of an underlying metabolic condition, young women display a negative relationship between MRI-measured bone marrow adiposity and DXA-based assessment of bone mineral density. Furthermore, an association between bone marrow adiposity and visceral adiposity supports the notion of a common origin of these two fat depots

Education and training methods for healthcare professionals to lead conversations concerning deceased organ donation: An integrative review

Objectives: To determine which training methods positively influenced healthcare professionals’ communication skills and families’ deceased organ donation decision-making. Methods: An integrative review using systematic methods and narrative synthesis for data analysis. Electronic databases of PubMed, Cumulative Index to Nursing and Allied Health Literature (EBSCO), Embase (OVID) and ProQuest Dissertations & Theses Global, were searched between August 1997 and March 2020, retrieving 1019 papers. Included papers (n = 14) were appraised using the Medical Education Research Study Quality Instrument. Results: Training programmes offered theory, experiential learning, feedback and debriefing including self-reflection, the opportunity to role-play and interact with simulated participants within realistic case scenarios. Programmes reported observed and self-rated improvements in communication learning and confidence. The methodological quality score averaged 13, (72% of maximum); few studies used an experimental design, examined behavioural change or families’ perspectives. Weak evidence suggested training could increase organ donation authorisation/consent rates. Conclusions: Multiple training strategies are effective in improving interprofessional healthcare professionals’ confidence and learning of specialised communication. Methodological limitations restricted the ability to present definitive recommendations and further research is warranted, inclusive of family decision-making experiences. Practice implications: Learning of specialised communication skills is enhanced by using multiple training strategies, including role-play and debriefing

Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP

Elevation of intracellular calcium levels in the presence of normal androgen levels has been implicated in apoptotic prostate cell death. Since the androgen receptor (AR) plays a critical role in the regulation of growth and differentiation of the prostate, it was of interest to determine whether Ca2+ would affect the expression of androgen receptor messenger RNA (mRNA) and protein, thus affecting the ability of androgens to control prostate function. AR-positive human prostate cancer cells, LNCaP, were incubated with either the calcium ionophore A23187 or the intracellular endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. Subsequently, AR mRNA and protein levels were assessed by Northern and Western blot analysis. Both A23187 and thapsigargin were found to down-regulate steady state AR mRNA levels in a time- and dose-dependent manner. AR mRNA began to decrease after 6-8 h of incubation with 10(-6) M A23187 or 10(-7) M thapsigargin, reaching a nadir at 16 and 10 h of incubation, respectively. In contrast, control mRNA (glyceraldehyde 3-phosphate dehydrogenase) did not change significantly during the treatments with either A23187 or thapsigargin. AR protein levels were found to be decreased after 12 h of incubation with either 10(-6) M A23187 or 10(-7) M thapsigargin. The decrease in AR mRNA and protein seemed to precede apoptosis, since neither A23187 (24 h) nor thapsigargin (30 h) was found to alter cell morphology within the treatment time. Cycloheximide and actinomycin D were unable to change the calcium-mediated decrease in AR mRNA, ruling out the necessity for de novo protein synthesis or a change in mRNA stability. Moreover, the decrease in AR mRNA induced by calcium does not seem to involve protein kinase C- or calmodulin-dependent pathways, since inhibitors of these cellular components had no effect. Nuclear run-on assays demonstrated little or no effects of either A23187 or thapsigargin treatment on AR gene transcription (8 h and 10 h). In conclusion, these studies show that intracellular calcium seems to be a potent regulator of AR gene expression in LNCaP cells

Performance evaluation of the Balcomb solar house

Additional instrumentation was added to the Balcomb solar house for a six-week period and up to 85 channels were recorded hourly. Some new findings based on an evaluation of these data are presented. (1) The thermal comfort characteristics of four rooms are documented. (2) Relative humidity in the living room varies from 30 to 50%; these data are used to infer an evaporation rate in the house of about 25 kg of water/day. The evaporation rate correlates reasonably well with greenhouse temperature. (3) Heat storage in the greenhouse floor is estimated at about 0.30 kWh/day-m/sup 2/ based on temperatures measured at four depths. (4) Several thermal characteristics of the rock bed are deduced but it is evident that the heat flow is not yet completely understood

Site investigation for the effects of vegetation on ground stability

The procedure for geotechnical site investigation is well established but little attention is currently given to investigating the potential of vegetation to assist with ground stability. This paper describes how routine investigation procedures may be adapted to consider the effects of the vegetation. It is recommended that the major part of the vegetation investigation is carried out, at relatively low cost, during the preliminary (desk) study phase of the investigation when there is maximum flexibility to take account of findings in the proposed design and construction. The techniques available for investigation of the effects of vegetation are reviewed and references provided for further consideration. As for general geotechnical investigation work, it is important that a balance of effort is maintained in the vegetation investigation between (a) site characterisation (defining and identifying the existing and proposed vegetation to suit the site and ground conditions), (b) testing (in-situ and laboratory testing of the vegetation and root systems to provide design parameters) and (c) modelling (to analyse the vegetation effects)

Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.</p

Stabilization of protein-protein interactions in drug discovery

Introduction: PPIs are involved in every disease and specific modulation of these PPIs with small molecules would significantly improve our prospects of developing therapeutic agents. Both industry and academia have engaged in the identification and use of PPI inhibitors. However in comparison, the opposite strategy of employing small-molecule stabilizers of PPIs is underrepresented in drug discovery. Areas covered: PPI stabilization has not been exploited in a systematic manner. Rather, this concept validated by a number of therapeutically used natural products like rapamycin and paclitaxel has been shown retrospectively to be the basis of the activity of synthetic molecules originating from drug discovery projects among them lenalidomide and tafamidis. Here, the authors cover the growing number of synthetic small-molecule PPI stabilizers to advocate for a stronger consideration of this as a drug discovery approach. Expert opinion: Both the natural products and the growing number of synthetic molecules show that PPI stabilization is a viable strategy for drug discovery. There is certainly a significant challenge to adapt compound libraries, screening techniques and downstream methodologies to identify, characterize and optimize PPI stabilizers, but the examples of molecules reviewed here in our opinion justify these efforts.</p

Physicality and Cooperative Design

CSCW researchers have increasingly come to realize that material work setting and its population of artefacts play a crucial part in coordination of distributed or co-located work. This paper uses the notion of physicality as a basis to understand cooperative work. Using examples from an ongoing fieldwork on cooperative design practices, it provides a conceptual understanding of physicality and shows that material settings and co-worker’s working practices play an important role in understanding physicality of cooperative design

First imaging results from the Iapetus B/C flyby of the Cassini spacecraft

Cassini had a relatively close flyby at Iapetus on New Year's Eve 2005. The 288 ISS images set various constraints on the origin theories of the dark/bright dichotomy, as revealed multiple surface structures at up to 740 m/pxl size

Towards Solving QCD - The Transverse Zero Modes in Light-Cone Quantization

We formulate QCD in (d+1) dimensions using Dirac's front form with periodic boundary conditions, that is, within Discretized Light-Cone Quantization. The formalism is worked out in detail for SU(2) pure glue theory in (2+1) dimensions which is approximated by restriction to the lowest {\it transverse} momentum gluons. The dimensionally-reduced theory turns out to be SU(2) gauge theory coupled to adjoint scalar matter in (1+1) dimensions. The scalar field is the remnant of the transverse gluon. This field has modes of both non-zero and zero {\it longitudinal} momentum. We categorize the types of zero modes that occur into three classes, dynamical, topological, and constrained, each well known in separate contexts. The equation for the constrained mode is explicitly worked out. The Gauss law is rather simply resolved to extract physical, namely color singlet states. The topological gauge mode is treated according to two alternative scenarios related to the In the one, a spectrum is found consistent with pure SU(2) gluons in (1+1) dimensions. In the other, the gauge mode excitations are estimated and their role in the spectrum with genuine Fock excitations is explored. A color singlet state is given which satisfies Gauss' law. Its invariant mass is estimated and discussed in the physical limit.Comment: LaTex document, 26 pages, one figure (obtainable by contacting authors). To appear in Physical. Review