Microplastic continues to be an environmental concern, especially for filter feeding bivalves known to ingest these particles. It is important to understand the effects of microplastic particles on ...the physiological performance of these bivalves and many studies have investigated their impact on various physiological processes. This study investigated the effects of microplastic (10 mum) on digestive enzyme (amylase) activity of Mytilus galloprovincialis at 55,000 and 110,000 microplastic particles/L under laboratory conditions. Additionally, our study measured the expression of an isoform of Hsp70 in the gills to assess whether or not these particles may cause protein denaturation. Results revealed that this regime negatively affect the ability of M. galloprovincialis to digest starch under high food conditions but not low food conditions. Exposure to extreme levels of microplastic raised amylase activity. Furthermore, Hsp70 transcript abundance was not elevated in treatment mussels. These results show that mussels may be resilient to current microplastic pollution levels in nature.
Context
Qualitative research is widely accepted as a legitimate approach to inquiry in health professions education (HPE). To secure this status, qualitative researchers have developed a variety of ...strategies (e.g. reliance on post‐positivist qualitative methodologies, use of different rhetorical techniques, etc.) to facilitate the acceptance of their research methodologies and methods by the HPE community. Although these strategies have supported the acceptance of qualitative research in HPE, they have also brought about some unintended consequences. One of these consequences is that some HPE scholars have begun to use terms in qualitative publications without critically reflecting on: (i) their ontological and epistemological roots; (ii) their definitions, or (iii) their implications.
Objectives
In this paper, we share our critical reflections on four qualitative terms popularly used in the HPE literature: thematic emergence; triangulation; saturation, and member checking.
Methods
We discuss the methodological origins of these terms and the applications supported by these origins. We reflect critically on how these four terms became expected of qualitative research in HPE, and we reconsider their meanings and use by drawing on the broader qualitative methodology literature.
Conclusions
Through this examination, we hope to encourage qualitative scholars in HPE to avoid using qualitative terms uncritically and non‐reflexively.
Both chronic excess of PTH, as in hyperparathyroidism, and intermittent elevation of PTH (by daily injections) increase the number of osteoblasts; albeit, the former is associated with bone ...catabolism and the later with bone anabolism. Intermittent PTH increases osteoblast number by attenuating osteoblast apoptosis, an effect that requires the transcription factor Runx2. However, chronic elevation of PTH does not affect osteoblast apoptosis because it stimulates the proteasomal degradation of Runx2. Here, we studied the effects of PTH on Sost, a Runx2 target gene expressed in osteocytes (former osteoblasts embedded in the bone matrix), which antagonizes the pro-osteoblastogenic actions of bone morphogenetic proteins and Wnts. We report that continuous infusion of PTH to mice for 4 d decreased Sost mRNA expression in vertebral bone by 80–90%. This effect was accompanied by a comparable reduction of sclerostin, the product of Sost, in osteocytes, as determined by quantitative immunoblot analysis of bone extracts and by immunostaining. In contrast, a single injection of PTH caused a transient 50% reduction in Sost mRNA at 2 h, but four daily injections had no effect on Sost mRNA or sclerostin. PTH strongly decreased Sost expression in osteocytes formed in primary cultures of neonatal murine calvaria cells as well as in osteocytic MLO-A5 cells, demonstrating a direct effect of PTH on this cell type. These results, together with evidence that sclerostin antagonizes bone morphogenetic proteins and Wnts, strongly suggest that suppression of Sost by PTH represents a novel mechanism for hormonal control of osteoblastogenesis mediated by osteocytes.
Glucocorticoid administration to mice results in a rapid loss of bone mineral density due to an imbalance in osteoblast and osteoclast numbers. Whereas excess glucocorticoids reduce both osteoblast ...and osteoclast precursors, cancellous osteoclast number surprisingly does not decrease as does osteoblast number, presumably due to the ability of glucocorticoids to promote osteoclast life span. Whether glucocorticoids act directly on osteoclasts in vivo to promote their life span and whether this contributes to the rapid loss of bone with glucocorticoid excess remains unknown. To determine the direct effects of glucocorticoids on osteoclasts in vivo, we expressed 11β-hydroxysteroid dehydrogenase type 2, an enzyme that inactivates glucocorticoids, specifically in the osteoclasts of transgenic mice using the tartrate-resistant acid phosphatase promoter. Bone mass, geometry, and histomorphometry were similar in untreated wild-type and transgenic animals. Glucocorticoid administration for 7 d caused equivalent increases in cancellous osteoblast apoptosis, and equivalent decreases in osteoblasts, osteoid, and bone formation, in wild-type and transgenic mice. In contrast, glucocorticoids stimulated expression of the mRNA for calcitonin receptor, an osteoclast product, in wild-type but not transgenic mice. Consistent with the previous finding that glucocorticoids decrease osteoclast precursors and prolong osteoclast life span, glucocorticoids decreased cancellous osteoclast number in the transgenic mice but not wild-type mice. In accord with this decrease in osteoclast number, the loss of bone density observed in wild-type mice was strikingly prevented in transgenic mice. These results demonstrate for the first time that the early, rapid loss of bone caused by glucocorticoid excess results from direct actions on osteoclasts.
Staphylococcus aureus is an opportunistic pathogen, which can readily develop antibiotic resistance and result in severe disease. To combat antibiotic resistance, new treatment strategies are being ...developed with a particular focus on vaccine development. S. aureus vaccines that target humoral immunity alone do not provide sufficient protection from all disease phenotypes associated with this pathogen. Recent studies have identified the requirement for cellular immunity to provide a robust immune response to this infection. Driving conventional T cell responses has therefore become the focus of intense research in this area. Recently described ‘alternative’ T cells could provide a novel strategy for improving therapeutic efficacy and success in next-generation anti-S. aureus vaccine design.
Antibody responses alone are not sufficient to drive protective immunity to S. aureus infection; cellular immunity is also required.
γδ T cells are particularly important in the production of IL-17 at the early stages of S. aureus infections in mice. Similar human IL-17-producing γδ cells have yet to be described in S. aureus-infected individuals.
Other alternative lymphocyte subsets such as ILCs and MAIT cells, which can produce IFN-γ and IL-17, directly target infected cells and bacteria, and potentially have other immunomodulatory functions. These have also been implicated in the immune response to S. aureus.
Alternative lymphocyte subsets can develop a memory phenotype, are localised to specific tissues, and respond rapidly to stimuli, making them a first-line of defence, which could be targeted in vaccine formulations.
How alternative cells are involved in S. aureus infection and what potentially novel ligands they respond to has yet to be fully established and requires further study.
Summary In this systematic review, we summarize risk factors for low bone mineral density and bone loss in healthy men age 50 years or older. Consistent risk factors were: age, smoking, low weight, ...physical/functional limitations, and previous fracture. Data specific to men has clinical and policy implications. Introduction Osteoporosis is a significant health care problem in men as well as women, yet the majority of evidence on diagnosis and management of osteoporosis is focused on postmenopausal women. The objective of this systematic review is to examine risk factors for low bone mineral density (BMD) and bone loss in healthy men age 50 years or older. Materials and methods A systematic search for observational studies was conducted in MEDLINE, Cochrane Database of Systematic Reviews, DARE, CENTRAL, CINAHL and Embase, Health STAR. The three main search concepts were bone density, densitometry, and risk factors. Trained reviewers assessed articles using a priori criteria. Results Of 642 screened abstracts, 299 articles required a full review, and 25 remained in the final assessment. Consistent risk factors for low BMD/bone loss were: advancing age, smoking, and low weight/weight loss. Although less evidence was available, physical/functional limitations and prevalent fracture (after age 50) were also associated with low BMD/bone loss. The evidence was inconsistent or weak for physical activity, alcohol consumption, calcium intake, muscle strength, family history of fracture/osteoporosis, and height/height loss. Conclusion In this systematic review, we identified several risk factors for low BMD/bone loss in men that are measurable in primary practice.
There has recently been a great deal of interest in employing immiscible solutes to stabilize nanocrystalline microstructures. Existing modeling efforts largely rely on mesoscale Monte Carlo ...approaches that employ a simplified model of the microstructure and result in highly homogeneous segregation to grain boundaries. However, there is ample evidence from experimental and modeling studies that demonstrates segregation to grain boundaries is highly non-uniform and sensitive to boundary character. This work employs a realistic nanocrystalline microstructure with experimentally relevant global solute concentrations to illustrate inhomogeneous boundary segregation. Experiments quantifying segregation in thin films are reported that corroborate the prediction that grain boundary segregation is highly inhomogeneous. In addition to grain boundary structure modifying the degree of segregation, the existence of a phase transformation between low and high solute content grain boundaries is predicted. In order to conduct this study, new embedded atom method interatomic potentials are developed for Pt, Au, and the PtAu binary alloy.
Therapeutic decisions in atrial fibrillation (AF) are often influenced by assessment of bleeding risk. However, existing bleeding risk scores have limitations.
We sought to develop and validate a ...novel bleeding risk score using routinely available clinical information to predict major bleeding in a large, community-based AF population.
We analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a prospective registry that enrolled incident and prevalent AF patients at 176 US sites. Using Cox proportional hazards regression, we identified factors independently associated with major bleeding among patients taking oral anticoagulation (OAC) over a median follow-up of 2 years (interquartile range = 1.6-2.5). We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding. The predictive performance of the full model, the simple five-item score, and two existing risk scores (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly, HAS-BLED, and anticoagulation and risk factors in atrial fibrillation, ATRIA) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population, Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET-AF).
Among 7411 ORBIT-AF patients taking OAC, the rate of major bleeding was 4.0/100 person-years. The full continuous model (12 variables) and five-factor ORBIT risk score (older age 75+ years, reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) both had good ability to identify those who bled vs. not (C-index 0.69 and 0.67, respectively). These scores both had similar discrimination, but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial.
The five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores. The ORBIT risk score can provide a simple, easily remembered tool to support clinical decision making.
Understanding the relationship between biodiversity conservation and ecosystem services concepts is essential for evidence-based policy development. We used text mining augmented by topic modelling ...to analyse abstracts of 15 310 peer-reviewed papers (from 2000 to 2020). We identified nine major topics; “Research & Policy”, “Urban and Spatial Planning”, “Economics & Conservation”, “Diversity & Plants”, “Species & Climate change”, “Agriculture”, “Conservation and Distribution”, “Carbon & Soil & Forestry”, “Hydro-& Microbiology”. The topic “Research & Policy” performed highly, considering number of publications and citation rate, while in the case of other topics, the “best” performances varied, depending on the indicator applied. Topics with human, policy or economic dimensions had higher performances than the ones with ‘pure’ biodiversity and science. Agriculture dominated over forestry and fishery sectors, while some elements of biodiversity and ecosystem services were under-represented. Text mining is a powerful tool to identify relations between research supply and policy demand.
ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful ...therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2, DEseq2, EdgeR) for identification of differentially expressed genes (DEG's). Ingenuity Pathways Analysis (IPA) and Weighted Gene Co-expression Network Analysis (WGCNA) identified inflammatory processes as significantly elevated in our ALS samples, with tumor necrosis factor (TNF) found to be a major pathway regulator (IPA) and TNFα-induced protein 2 (TNFAIP2) as a major network "hub" gene (WGCNA). Using the oPOSSUM algorithm, we analyzed transcription factors (TF) controlling expression of the nine DEG/hub genes in the ALS samples and identified TF's involved in inflammation (NFkB, REL, NFkB1) and macrophage function (NR1H2::RXRA heterodimer). Transient expression in human iPSC-derived motor neurons of TNFAIP2 (also a DEG identified by all three algorithms) reduced cell viability and induced caspase 3/7 activation. Using high-density RNAseq, multiple algorithms for DEG identification, and an unsupervised gene co-expression network approach, we identified significant elevation of inflammatory processes in ALS spinal cord with TNF as a major regulatory molecule. Overexpression of the DEG TNFAIP2 in human motor neurons, the population most vulnerable to die in ALS, increased cell death and caspase 3/7 activation. We propose that therapies targeted to reduce inflammatory TNFα signaling may be helpful in ALS patients.
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