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.

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.

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.

Design of a mouse restraint for synchrotron-based computed tomography imaging.

High-resolution computed tomography (CT) imaging of a live animal within a lead-lined synchrotron light hutch presents several unique challenges. In order to confirm that the animal is under a stable plane of anaesthesia, several physiological parameters (e.g. heart rate, arterial oxygen saturation, core body temperature and respiratory rate) must be remotely monitored from outside the imaging hutch. In addition, to properly scan the thoracic region using CT, the animal needs to be held in a vertical position perpendicular to the fixed angle of the X-ray beam and free to rotate 180°-360°. A new X-ray transparent mouse restraint designed and fabricated using computer-aided design software and three-dimensional rapid prototype printing has been successfully tested at the Biomedical Imaging and Therapy bending-magnet (BMIT-BM) beamline at the Canadian Light Source.

Little evidence for morphological change in a resilient endemic species following the introduction of a novel predator.

Human activities, such as species introductions, are dramatically and rapidly altering natural ecological processes and often result in novel selection regimes. To date, we still have a limited understanding of the extent to which such anthropogenic selection may be driving contemporary phenotypic change in natural populations. Here, we test whether the introduction of the piscivorous Nile perch, Lates niloticus, into East Africa's Lake Victoria and nearby lakes coincided with morphological change in one resilient native prey species, the cyprinid fish Rastrineobola argentea. Drawing on prior ecomorphological research, we predicted that this novel predator would select for increased allocation to the caudal region in R. argentea to enhance burst-swimming performance and hence escape ability. To test this prediction, we compared body morphology of R. argentea across space (nine Ugandan lakes differing in Nile perch invasion history) and through time (before and after establishment of Nile perch in Lake Victoria). Spatial comparisons of contemporary populations only partially supported our predictions, with R. argentea from some invaded lakes having larger caudal regions and smaller heads compared to R. argentea from uninvaded lakes. There was no clear evidence of predator-associated change in body shape over time in Lake Victoria. We conclude that R. argentea have not responded to the presence of Nile perch with consistent morphological changes and that other factors are driving observed patterns of body shape variation in R. argentea.

The Efficacy of Self-Report Measures in Predicting Social Phobia in African American Adults.

Empirical literature pertaining to anxiety in African Americans has been relatively sparse. More recent studies indicate that the construct of social fear is different in African Americans than in non-Hispanic Whites. Although some of these studies have examined factor structure utilizing self-report measures of anxiety in African American samples, none to date have examined the clinical utility of these measures in predicting anxiety diagnoses, particularly social phobia. A total of sixty-five African American adults from the community completed the Fear Survey Schedule-Second Edition (FSS-II), Social Anxiety Interaction Scale (SIAS), Social Phobia Scale (SPS), and Albany Panic and Phobia Questionnaire (APPQ). The Anxiety Disorder Interview Schedule-Fourth Edition (ADIS-IV) was administered to all participants to specify differential diagnoses of anxiety and related disorders. Twenty-three African American adults were diagnosed with social phobia leaving 42 diagnostic controls. Results suggest that the social anxiety factors were highly predictive of a social phobia diagnosis (AUC=.84 to .90; CI .73-.98, p<.01) and sensitivity and specificity rates revealed optimal cutoff scores for each measure. The optimal cutoff scores reveal the clinical utility of the social fear factor from these measures in screening for social phobia in African Americans. Future direction and implications are discussed. PUBLICATION INDICES: Psychinfo, PubMed, Medline.

Common characteristics shared by different differential phase contrast imaging methods.

There are many variations of differential phase contrast imaging methods. Although these imaging methods are different in configuration, they are alike in imaging by extracting differential phase information through the evaluation of the refraction angles. In this paper, we investigate common characteristics shared by various different differential phase contrast imaging methods.

Is handedness related to anxiety? New answers to an old question.

Is handedness related to anxiety? Two separable dimensions of handedness have been considered in previous studies: Direction of the preferred hand (left or right) and the consistency with which the preferred hand is used over the nonpreferred hand (consistent or inconsistent). Findings have included (1) left-handedness being associated with greater anxiety than right-handedness, (2) consistent-handedness being associated with greater anxiety than inconsistent-handedness and (3) neither dimension being associated with anxiety. Here, we administered measures of trait anxiety, state anxiety and worry to individuals classified as consistent-left, inconsistent-left, inconsistent-right or consistent-right. Neither direction nor consistency had a main effect on any measure. However, there was a direction by consistency interaction in trait and state anxiety measured on the State/Trait Anxiety Inventory. Among right-handers, inconsistent individuals reported less anxiety than consistent individuals. Among left-handers, consistency was unrelated to anxiety. In consequence of this pattern, inconsistent right-handers were less anxious than inconsistent left-handers. Hence, supporting prior studies, left-handedness was associated with greater anxiety than right-handedness (but only among inconsistent individuals) and consistency was associated with greater anxiety than inconsistency (but only among right-handers). These findings advance our understanding of handedness consistency as an important individual difference factor in personality and cognition.

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.

Outcome of laparoscopic inguinal hernia repair in a South African private practice setting.

OBJECTIVE: The aim of this study was to determine the recurrence and complication rates of laparoscopic inguinal hernia repair performed in a private practice in Cape Town. DESIGN AND SUBJECTS: An unselected cohort of 507 patients who underwent laparoscopic totally extraperitoneal (TEP) inguinal hernia repair before September 2005 were included in this study, thus ensuring a minimum 5-year follow-up. Patient demographic data, clinical notes, operating notes and outpatient follow-up notes were studied. Patients were interviewed telephonically regarding hernia recurrence, chronic pain and technique preference if they had previously undergone an open repair. All data collected were recorded on an electronic spreadsheet. The primary outcome parameter was recurrence. The secondary outcome parameters were postoperative and long-term complications. RESULTS: Of the 507 patients, 267 were contactable telephonically. There were 384 hernia repairs with a mean follow-up of 8.8 years. There were 9 recurrences (2.3%). The overall complication rate was 7.9%. Two per cent of patients suffered from chronic groin pain with gradual improvement since surgery. Sixteen per cent of patients had had previous open repair of an inguinal hernia, either on the ipsilateral or the contralateral side, and all judged the open repair to have been more painful. CONCLUSIONS: The recurrence and complication rates for laparoscopic TEP inguinal hernia repair in this practice are low and comparable to the best reported series. There is a low incidence of persistent postoperative pain with the laparoscopic technique, and it is the technique preferred by patients who previously underwent an open repair.

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.

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).

Genetic divergence in morphology-performance mapping between Misty Lake and inlet stickleback.

Different environments should select for different aspects of organismal performance, which should lead to correlated divergence in morphological traits that influence performance. The result should be genetic divergence in aspects of performance, morphology and associations ('maps') between morphology and performance. Testing this hypothesis requires quantifying performance and morphology in multiple populations after controlling for environmental differences, but this is rarely attempted. We used a common-garden experiment to examine morphology and several aspects of swimming performance within and between the lake and inlet populations of threespine stickleback (Gasterosteus aculeatus) from the Misty system, Vancouver Island, Canada. Controlling for body size, lake stickleback had shallower bodies, larger caudal fins and smaller pelvic girdles. With or without morphological covariates, lake stickleback showed greater performance in both sustained and burst swimming. In contrast, inlet stickleback showed greater manoeuverability than did lake stickleback in some analyses. Morphology-performance relationships were decoupled when considering variation within vs. between populations. Moreover, morphology-performance mapping differed between the two populations. Based on these observations, we advance a hypothesis for why populations adapting to different environments should show adaptive genetic divergence in morphology-performance mapping.

Identification of a human population infected with simian foamy viruses.

Studying the transmission of simian retroviruses to humans can help define the importance of these infections to public health. We identified a substantial prevalence (4/231, 1.8%) of infection with simian foamy viruses (SFV) among humans occupationally exposed to nonhuman primates. Evidence of SFV infection included seropositivity, proviral DNA detection and isolation of foamy virus. The infecting SFV originated from an African green monkey (one person) and baboons (three people). These infections have not as yet resulted in either disease or sexual transmission, and may represent benign endpoint infections.

Hypoxia and male behaviour in an African cichlid Pseudocrenilabrus multicolor victoriae.

This study tested the prediction that hypoxia may reduce the frequency of energetically expensive behaviours by quantifying male mating and aggressive displays in the cichlid Pseudocrenilabrus multicolor victoriae after long-term acclimation (5 months) to either high dissolved oxygen (DO) or low DO. Regardless of DO treatment, males engaged in more aggressive displays than mating displays; however, males acclimated to low DO reduced their total number of displays compared to high DO-acclimated males.

Periodic paralysis: an unusual presentation of thyrotoxicosis.

Thyrotoxic Periodic Paralysis (TPP) is a rare complication of thyrotoxicosis and is up to 20 times more common in males. Cases usually present with painless muscle weakness precipitated by heavy exercise, fasting, an alcohol binge or large carbohydrate meal. Serum potassium is low in the majority, but normokalaemic (or even hyperkalaemic) TPP is recognised. Acute treatment of any electrolyte disorder, administration of a beta-blocker and treatment of the thyrotoxicosis leads to complete resolution. This rare diagnosis should be considered by the Acute Physician when confronted with any case of muscle weakness.