MRI overestimates articular cartilage thickness and volume compared to synchrotron radiation phase-contrast imaging.

Accurate evaluation of morphological changes in articular cartilage are necessary for early detection of osteoarthritis (OA). 3T magnetic resonance imaging (MRI) has highly sensitive contrast resolution and is widely used clinically to detect OA. However, synchrotron radiation phase-contrast imaging computed tomography (SR-PCI) can also provide contrast to tissue interfaces that do not have sufficient absorption differences, with the added benefit of very high spatial resolution. Here, MRI was compared with SR-PCI for quantitative evaluation of human articular cartilage. Medial tibial condyles were harvested from non-OA donors and from OA patients receiving knee replacement surgery. Both imaging methods revealed that average cartilage thickness and cartilage volume were significantly reduced in the OA group, compared to the non-OA group. When comparing modalities, the superior resolution of SR-PCI enabled more precise mapping of the cartilage surface relative to MRI. As a result, MRI showed significantly higher average cartilage thickness and cartilage volume, compared to SR-PCI. These data highlight the potential for high-resolution imaging of articular cartilage using SR-PCI as a solution for early OA diagnosis. Recognizing current limitations of using a synchrotron for clinical imaging, we discuss its nascent utility for preclinical models, particularly longitudinal studies of live animal models of OA.

Daily administration of parathyroid hormone slows the progression of basic multicellular units in the cortical bone of the rabbit distal tibia.

Basic Multicellular Units (BMUs) conduct bone remodeling, a critical process of tissue turnover which, if imbalanced, can lead to disease, including osteoporosis. Parathyroid hormone (PTH 1-34; Teriparatide) is an osteoanabolic treatment for osteoporosis; however, it elevates the rate of intra-cortical remodeling (activation frequency) leading, at least transiently, to increased porosity. The purpose of this study was to test the hypothesis that PTH not only increases the rate at which cortical BMUs are initiated but also increases their progression (Longitudinal Erosion Rate; LER). Two groups (n = 7 each) of six-month old female New Zealand white rabbits were both administered 30 µg/kg of PTH once daily for a period of two weeks to induce remodeling. Their distal right tibiae were then imaged in vivo by in-line phase contrast micro-CT at the Canadian Light Source synchrotron. Over the following two weeks the first group (PTH) received continued daily PTH while the second withdrawal group (PTHW) was administrated 0.9 % saline. At four weeks all animals were euthanized, their distal tibiae were imaged by conventional micro-CT ex vivo and histomorphometry was performed. Matching micro-CT datasets (in vivo and ex vivo) were co-registered in 3D and LER was measured from 612 BMUs. Counter to our hypothesis, mean LER was lower (p < 0.001) in the PTH group (30.19 ± 3.01 µm/day) versus the PTHW group (37.20 ± 2.77 µm/day). Despite the difference in LER, osteonal mineral apposition rate (On.MAR) did not differ between groups indicating the anabolic effect of PTH was sustained after withdrawal. The slowing of BMU progression by PTH warrants further investigation; slowed resorption combined with elevated bone formation rate, may play an important role in how PTH enhances coupling between resorption and formation within the BMU. Finally, the prolonged anabolic response following withdrawal may have utility in terms of optimizing clinical dosing regimens.

Direct Assessment of Rabbit Cortical Bone Basic Multicellular Unit Longitudinal Erosion Rate: A 4D Synchrotron-Based Approach.

Cortical bone remodeling is carried out by basic multicellular units (BMUs), which couple resorption to formation. Although fluorochrome labeling has facilitated study of BMU formative parameters since the 1960s, some resorptive parameters, including the longitudinal erosion rate (LER), have remained beyond reach of direct measurement. Indeed, our only insights into this spatiotemporal parameter of BMU behavior come from classical studies that indirectly inferred LER. Here, we demonstrate a 4D in vivo method to directly measure LER through in-line phase contrast synchrotron imaging. The tibias of rabbits (n = 15) dosed daily with parathyroid hormone were first imaged in vivo (synchrotron micro-CT; day 15) and then ex vivo 14 days later (conventional micro-CT; day 29). Mean LER assessed by landmarking the co-registered scans was 23.69 ± 1.73 µm/d. This novel approach holds great promise for the direct study of the spatiotemporal coordination of bone remodeling, its role in diseases such as osteoporosis, as well as related treatments. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Profound Vagal Tone and Bradycardia Mimicking Asystole: A Resuscitation Case Report.

A 48-year-old man presented with dizziness. When he arrived at the emergency department, he collapsed and became pulseless. Prior to his collapse, he was asymptomatic and now even participated in multiple marathon and ultra-running events per year. However, he previously experienced a vasospastic inferior STEMI eight years prior from cocaine use. As a result, he had an ischaemic cardiomyopathy with LVEF of 45%. He never took any further illicit substances after the STEMI; instead, he changed his lifestyle completely and commenced extreme endurance sports. After one hour of alternations between VF/VT rhythms and asystole, a rhythm check demonstrated a single complex with a corresponding pulse. He had received 12 mg of epinephrine up to that point as per local resuscitation guidelines. Upon diagnosing extreme bradycardia, 2 mg of total atropine administration resulted in ROSC. We theorise that this bradycardia was a result of increased vagal tone as ROSC was quickly achieved following atropine administration.

International Foot and Ankle Osteoarthritis Consortium review and research agenda for diagnosis, epidemiology, burden, outcome assessment and treatment.

OBJECTIVE: To summarise the available evidence relating to the diagnosis, epidemiology, burden, outcome assessment and treatment of foot and ankle osteoarthritis (OA) and to develop an agenda to guide future research. METHOD: Members of the International Foot and Ankle Osteoarthritis Consortium compiled a narrative summary of the literature which formed the basis of an interactive discussion at the Osteoarthritis Research Society International World Congress in 2021, during which a list of 24 research agenda items were generated. Following the meeting, delegates were asked to rank the research agenda items on a 0 to 100 visual analogue rating scale (0 = not at all important to 100 = extremely important). Items scoring a mean of 70 or above were selected for inclusion. RESULTS: Of the 45 delegates who attended the meeting, 31 contributed to the agenda item scoring. Nineteen research agenda items met the required threshold: three related to diagnosis, four to epidemiology, four to burden, three to outcome assessment and five to treatment. CONCLUSIONS: Key knowledge gaps related to foot and ankle OA were identified, and a comprehensive agenda to guide future research planning was developed. Implementation of this agenda will assist in improving the understanding and clinical management of this common and disabling, yet relatively overlooked condition.

Wide field imaging energy dispersive X-ray absorption spectroscopy.

A new energy dispersive X-ray absorption spectroscopy (EDXAS) method is presented for simultaneous wide-field imaging and transmission X-ray absorption spectroscopy (XAS) to enable rapid imaging and speciation of elements. Based on spectral K-Edge Subtraction imaging (sKES), a bent Laue imaging system diffracting in the vertical plane was developed on a bend magnet beamline for selenium speciation. The high flux and small vertical focus, forming a wide horizontal line beam for projection imaging and computed tomography applications, is achieved by precise matching of lattice plane orientation and crystal surface (asymmetry angle). The condition generating a small vertical focus for imaging also provides good energy dispersion. Details for achieving sufficient energy and spatial resolution are demonstrated for both full field imaging and computed tomography in quantifying selenium chemical species. While this system has lower sensitivity as it uses transmission and may lack the flux and spatial resolution of a dedicated focused beamline system, it has significant potential in rapid screening of heterogeneous biomedical or environmental systems to correlate metal speciation with function.

Nebulized hypertonic saline triggers nervous system-mediated active liquid secretion in cystic fibrosis swine trachea.

Inhaled hypertonic saline (HTS) treatment is used to improve lung health in patients with cystic fibrosis (CF). The current consensus is that the treatment generates an osmotic gradient that draws water into the airways and increases airway surface liquid (ASL) volume. However, there is evidence that HTS may also stimulate active secretion of ASL by airway epithelia through the activation of sensory neurons. We tested the contribution of the nervous system and airway epithelia on HTS-stimulated ASL height increase in CF and wild-type swine airway. We used synchrotron-based imaging to investigate whether airway neurons and epithelia are involved in HTS treatment-triggered ASL secretion in CFTR-/- and wild-type swine. We showed that blocking parasympathetic and sensory neurons in airway resulted in ~50% reduction of the effect of HTS treatment on ASL volume in vivo. Incubating tracheal preparations with inhibitors of epithelial ion transport across airway decreased secretory responses to HTS treatment. CFTR-/- swine ex-vivo tracheal preparations showed substantially decreased secretory response to HTS treatment after blockage of neuronal activity. Our results indicated that HTS-triggered ASL secretion is partially mediated by the stimulation of airway neurons and the subsequent activation of active epithelia secretion; osmosis accounts for only ~50% of the effect.

Biodistribution of strontium and barium in the developing and mature skeleton of rats.

Bone acts as a reservoir for many trace elements. Understanding the extent and pattern of elemental accumulation in the skeleton is important from diagnostic, therapeutic, and toxicological perspectives. Some elements are simply adsorbed to bone surfaces by electric force and are buried under bone mineral, while others can replace calcium atoms in the hydroxyapatite structure. In this article, we investigated the extent and pattern of skeletal uptake of barium and strontium in two different age groups, growing, and skeletally mature, in healthy rats. Animals were dosed orally for 4 weeks with either strontium chloride or barium chloride or combined. The distribution of trace elements was imaged in 3D using synchrotron K-edge subtraction micro-CT at 13.5 µm resolution and 2D electron probe microanalysis (EPMA). Bulk concentration of the elements in serum and bone (tibiae) was also measured by mass spectrometry to study the extent of uptake. Toxicological evaluation did not show any cardiotoxicity or nephrotoxicity. Both elements were primarily deposited in the areas of active bone turnover such as growth plates and trabecular bone. Barium and strontium concentration in the bones of juvenile rats was 2.3 times higher, while serum levels were 1.4 and 1.5 times lower than adults. In all treatment and age groups, strontium was preferred to barium even though equal molar concentrations were dosed. This study displayed spatial co-localization of barium and strontium in bone for the first time. Barium and strontium can be used as surrogates for calcium to study the pathological changes in animal models of bone disease and to study the effects of pharmaceutical compounds on bone micro-architecture and bone remodeling in high spatial sensitivity and precision.

High-power-load DCLM monochromator for a computed tomography program at BMIT at energies of 25-150 keV.

The research program at the biomedical imaging facility requires a high-flux hard-X-ray monochromator that can also provide a wide beam. A wide energy range is needed for standard radiography, phase-contrast imaging, K-edge subtraction imaging and monochromatic beam therapy modalities. The double-crystal Laue monochromator, developed for the BioMedical Imaging and Therapy facility, is optimized for the imaging of medium- and large-scale samples at high energies with the resolution reaching 4 µm. A pair of 2 mm-thick Si(111) bent Laue-type crystals were used in fixed-exit beam mode with a 16 mm vertical beam offset and the first crystal water-cooled. The monochromator operates at energies from 25 to 150 keV, and the measured size of the beam is 189 mm (H) × 8.6 mm (V) at 55 m from the source. This paper presents our approach in developing a complete focusing model of the monochromator. The model uses mechanical properties of crystals and benders to obtain a finite-element analysis of the complete assembly. The modeling results are compared and calibrated with experimental measurements. Using the developed analysis, a rough estimate of the bending radius and virtual focus (image) position of the first crystal can be made, which is also the real source for the second crystal. On the other hand, by measuring the beam height in several points in the SOE-1 hutch, the virtual focus of the second crystal can be estimated. The focusing model was then calibrated with measured mechanical properties, the values for the force and torque applied to the crystals were corrected, and the actual operating parameters of the monochromator for fine-tuning were provided.

Ethnic Identity and Regional Differences in Mental Health in a National Sample of African American Young Adults.

Prior research has found that a strong positive ethnic identity is a protective factor against anxiety and depression in African Americans. In this study, ethnic identity is examined in a geographically representative sample of African American young adults (n = 242), using the Multigroup Ethnic Identity Measure (MEIM) (Phinney in J Adolescent Res 7:156-76, 15). The two-factor structure of the measure (Roberts et al. in J Early Adolescence 19:301-22, 1) was analyzed using a structural equation model and displayed an acceptable fit only when multiple error terms were correlated. A multigroup confirmatory factor analysis revealed measurement equivalence of the two-factor structure between African Americans from Southern and non-Southern regions of the USA. We found that significantly higher levels of ethnic identity were present among African American in the South compared to other regions, and region significantly predicted total ethnic identity scores in a linear regression, even when controlling for gender, age, urbanicity, and years of education. Furthermore, among African Americans, living in the South was significantly correlated with less help-seeking for diagnosed depression, anxiety, and/or obsessive-compulsive disorder, where help-seeking was defined as obtaining a diagnosis by a professional. The role of ethnic identity and social support are discussed in the context of African American mental health.

Cystic fibrosis swine fail to secrete airway surface liquid in response to inhalation of pathogens.

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR-/- swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease.Cystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface liquid secretion. Here the authors show that exposure to bacteria triggers secretion in wild-type but not in pig models of cystic fibrosis, suggesting an impaired response to pathogens contributes to infection.

Expression of BrpA in Streptococcus mutans is regulated by FNR-box mediated repression.

Our previous studies showed that brpA in Streptococcus mutans, which encodes a member of the LytR-CpsA-Psr family of proteins, can be co-transcribed with brpB upstream as a bicistronic operon, and the intergenic region also has strong promoter activity. To elucidate how brpA expression is regulated, the promoter regions were analyzed using polymerase chain reaction-based deletions and site-directed mutagenesis and a promoterless luciferase gene as a reporter. Allelic exchange mutagenesis was also used to examine genes encoding putative trans-acting factors, and the impact of such mutations on brpA expression was analyzed by reporter assays. Multiple elements in the short brpA promoter (nucleotide -1 to -344 relative to start cordon ATG) were shown to have a major impact on brpA expression, including an FNR-box, for a putative binding site of an FNR-type of transcriptional regulator. When compared with the intact brpA promoter, mutations of the highly conserved nucleotides in FNR-box from TTGATgtttAcCtt to TTACAgaaaGtTac resulted in 1362-fold increases of luciferase activity (P < .001), indicative of the FNR-box-mediated repression as a major mechanism in regulation of brpA expression. When luciferase reporter was fused to the upstream brpBA promoter (nucleotides -784 to -1144), luciferase activity was decreased by 4.5-fold (P < .001) in the brpA mutant, TW14D, and by 67.7-fold (P < .001) in the brpB mutant, JB409, compared with the wild-type, UA159. However, no such effects were observed when the reporter gene was fused to the short brpA promoter and its derivatives. These results also suggest that brpA expression in S. mutans is auto-regulated through the upstream brpBA promoter.

A systematic quality assessment of Environmental Impact Statements in the oil and gas industry.

The global economy relies heavily on oil and gas resources. However, hydrocarbon exploitation projects can cause significant impacts on the environment. But despite the production of numerous Environmental Impact Statements (EISs) to identify/mitigate such impacts, no study has specifically assessed the quality of EISs for both onshore and offshore oil and gas projects, with tested hypotheses. To address this research gap, our paper, for the first time, develops a modified Lee and Colley evaluation model to assess the quality of 19 sampled oil and gas project EISs produced from 1998 to 2008 in Nigeria. Our findings show that Project Description and Communication of Results are the main areas of strength. However, Environmental Impact Prediction, and Project Decommissioning, were among the key areas requiring attention. A key finding, though, is that Mann-Whitney tests suggest that there is no evidence that the quality of EISs for the latter period (2004-2008) is higher than that of the earlier period (1998-2004). We suggest that periodic systematic review of the quality of submitted/approved EISs (c. every 3-5years) should be established to monitor trends in EIS quality and identify strong and weak areas. This would help to drive continual improvement in both the EIA processes and the resultant EISs of technical engineering projects. Such reviews have the potential to illuminate some of the underlying problems of, and solutions to, oil and gas exploration, production and transportation, and their related environmental impacts. This suggested change would also be useful internationally, including for the burgeoning exploration and production of unconventional hydrocarbon resources.

Spectral K-edge subtraction imaging of experimental non-radioactive barium uptake in bone.

PURPOSE: To evaluate the feasibility of using non-radioactive barium as a bone tracer for detection with synchrotron spectral K-edge subtraction (SKES) technique. METHODS: Male rats of 1-month old (i.e., developing skeleton) and 8-month old (i.e., skeletally mature) were orally dosed with low dose of barium chloride (33mg/kg/day Ba2+) for 4weeks. The fore and hind limbs were dissected for imaging in projection and computed tomography modes at 100µm and 52µm pixel sizes. The SKES method utilizes a single bent Laue monochromator to prepare a 550eV energy spectrum to encompass the K-edge of barium (37.441keV), for collecting both 'above' and 'below' the K-edge data sets in a single scan. RESULTS: The SKES has a very good focal size, thus limits the 'crossover' and motion artifacts. In juvenile rats, barium was mostly incorporated in the areas of high bone turnover such as at the growth plate and the trabecular surfaces, but also in the cortical bone as the animals were growing at the time of tracer administration. However, the adults incorporated approximately half the concentration and mainly in the areas where bone remodeling was predominant and occasionally in the periosteal and endosteal layers of the diaphyseal cortical bone. CONCLUSIONS: The presented methodology is simple to implement and provides both structural and functional information, after labeling with barium, on bone micro-architecture and thus has great potential for in vivo imaging of pre-clinical animal models of musculoskeletal diseases to better understand their mechanisms and to evaluate the efficacy of pharmaceuticals.

Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis.

AIM: Metformin is the most widely used oral hypoglycaemic drug, but it may lower B12 status, which could have important clinical implications. We undertook a systematic review and meta-analysis of the relationship between metformin use and vitamin B12 deficiency in persons with type 2 diabetes. METHODS: Electronic database searches were undertaken (1st January 1957-1st July 2013) using the Cochrane library, Scopus, CINAHL, Grey literature databases, Pub Med Central, NICE Clinical Guidelines UK, and ongoing clinical trials. Included studies were of any study design, with data from patients with type 2 diabetes of any age or gender, taking any dose or duration of metformin. Planned primary outcomes were serum vitamin B12 levels, % prevalence or incidence of vitamin B12 deficiency and risk of vitamin B12 deficiency. RESULTS: Twenty-six papers were included in the review. Ten out of 17 observational studies showed statistically significantly lower levels of vitamin B12 in patients on metformin than not on metformin. Meta-analysis performed on four trials demonstrated a statistically significant overall mean B12 reducing effect of metformin of 57pmol/L [WMD (fixed)=-0.57 (95% CI: -35 to -79pmol/L)] after 6weeks to 3months of use. CONCLUSION: The evidence from this review demonstrates an association between metformin usage and lower levels of vitamin B12 by 57pmol/L, which leads to frank deficiency or borderline status in some patients with type 2 diabetes. This suggests that it is prudent to monitor B12 levels in these patients who are at increased risk of deficiency.

Psychometric properties of a brief version of the Penn State Worry Questionnaire in African Americans and European Americans.

The reliable and valid assessment of chronic worry in African Americans is vital when attempting to draw cross-cultural comparisons between African Americans and other ethnic groups. As such, the current study examined the psychometric properties of a brief version of a gold standard assessment of chronic worry, specifically the Penn State Worry Questionnaire-Abbreviated (PSWQ-A; Hopko et al., 2003) in a college sample of African Americans (n = 100) and European Americans (n = 121). Results indicated that the PSWQ-A total score has good internal consistency and convergent validity with another measure of anxiety, but less than favorable discriminant validity with a measure of depression in African American and European American students. Also, the 1-factor solution for the 8-item PSWQ-A had excellent model fit in our full sample and was partially invariant between ethnic groups. Collectively, the present study provides evidence that the PSWQ-A is a psychometrically sound option for assessing chronic worry and suggests that this brief measure may enhance the time efficiency and clinical utility of research and clinical assessments in ethnically diverse samples. (PsycINFO Database Record

Effects of habitat on mercury concentrations in fish: a case study of Nile perch (Lates niloticus) in Lake Nabugabo, Uganda.

This study focused on variation in fish mercury (Hg) concentrations in 185 Nile perch (Lates niloticus) samples collected across four different habitat types in Lake Nabugabo, Uganda, a tropical lake located proximate to Lake Victoria. We quantified the stomach contents of Nile perch using the % index of relative importance, as well as, nitrogen and carbon isotopic concentrations to assess the role of diet and trophic level on Hg concentrations. In each habitat, we also evaluated a suite of chemical and physical characteristics that are commonly associated with variation in Hg bioavailability in temperate systems. Using linear mixed models and ANOVA, we demonstrate that habitat of capture is an important predictor of Hg concentrations in Nile perch from Lake Nabugabo and that the relationship between habitat and Hg is size and diet dependent. Nile perch diet as well as dissolved oxygen concentration and pH were also correlated with observed differences in fish Hg. Overall, Hg concentrations in Nile perch were all well below the WHO/FAO recommended guideline of 500 ng/g (mean 13.6 ± 0.4 ng/g wet weight; range 4.9 and 29.3 ng/g wet weight). This work contributes to a growing awareness of intra-lake divergence in Nile perch, as well as, divergence in Hg concentrations between varying aquatic habitat types, particularly wetlands.

Diffraction-Enhanced Computed Tomographic Imaging of Growing Piglet Joints by Using a Synchrotron Light Source.

The objective of this project was to develop and test a new technology for imaging growing joints by means of diffraction-enhanced imaging (DEI) combined with CT and using a synchrotron radiation source. DEI-CT images of an explanted 4-wk-old piglet stifle joint were acquired by using a 40-keV beam. The series of scanned slices was later 'stitched' together, forming a 3D dataset. High-resolution DEI-CT images demonstrated fine detail within all joint structures and tissues. Striking detail of vasculature traversing between bone and cartilage, a characteristic of growing but not mature joints, was demonstrated. This report documents for the first time that DEI combined with CT and a synchrotron radiation source can generate more detailed images of intact, growing joints than can currently available conventional imaging modalities.