Adaptation of FDMT to include process-based models and consider regional aspects following radionuclide deposition events.

Experience from earlier nuclear accidents has clearly shown the need for maintaining and developing appropriate modelling capabilities. Dealing with complex issues such as human exposure following a nuclear accident necessitates the implementation of a set of interconnected models such as FDMT. FDMT is an integrated module within the two main European decision support systems for radiological emergency preparedness, ARGOS and JRODOS, to simulate the transfer of radionuclides along terrestrial food chains and to predict their activity concentrations in foodstuffs. In order to make the module more fit-for-purpose, FDMT has been implemented in a new modelling platform (ECOLEGO) which provides a high degree of flexibility with regard to conducting developmental work. This paper presents improvements in FDMT further through either the incorporation of new models or further elaboration of existing ones, as well as updates in default parameters. Models have also been made more fit-for-purpose through consideration of regional-specific parameters. Specific improvements include modelling developments related to dry deposition, radioactive particle weathering, radiocaesium transfer influenced by soil characteristics and, for a region-specific case, animal uptake. In addition, the paper presents new pathways and parameters (and updated values) to be considered for making FDMT more adapted for Norwegian conditions. Overall, the improvements made in the present work should significantly reduce the uncertainties associated with the outputs of the FDMT models.

Efficacy, Safety and Acceptability of a Very-Low-Energy Diet in Adolescents with Obesity: A Fast Track to Health Sub-Study.

The aim of this study was to determine the efficacy, safety and acceptability of a 4-week very-low-energy diet (VLED) program for adolescents with obesity. Adolescents (13-17 years) with obesity and ≥1 obesity-related complication were Fast Track to Health 52-week randomized controlled trial participants. Adolescents undertook a 4-week micronutrient-complete VLED (800 kcal/day), with weekly dietitian support. Anthropometric data were recorded at baseline and week-4 and side-effects at day 3-4, week-1, -2, -3 and -4. Adolescents completed an acceptability survey at week-4. A total of 134 adolescents (14.9 ± 1.2 years, 50% male) had a 5.5 ± 2.9 kg (p < 0.001) mean weight loss at week-4: 95% experienced ≥1 and 70% experienced ≥3 side-effects during the VLED program, especially during the first week. Hunger, fatigue, headache, irritability, loose stools, constipation and nausea were most common. Reporting more side-effects at day 3-4 correlated with greater weight loss at week-4 (r = -0.188, p = 0.03). Adolescents reported 'losing weight' (34%) and 'prescriptive structure' (28%) as the most positive aspects of VLED, while 'restrictive nature' (45%) and 'meal replacement taste' (20%) were least liked. A dietitian-monitored short-term VLED can be implemented safely and is acceptable for many adolescents seeking weight loss, despite frequent side-effects. Investigating predictors of acceptability and effectiveness could determine adolescents most suited to VLED programs.

Unicortical Button Fixation Provide Higher Strength Compared with Transosseous Repair for Subscapularis Tendon in Total Shoulder Arthroplasty.

BACKGROUND: Subscapularis tendon (SSc) dysfunction following total shoulder arthroplasty (TSA) results in poor functional outcomes. There have been numerous SSc repair constructs tested biomechanically and clinically, however, none has been demonstrated as superior. Newer techniques and implants have emerged, but have not been fully tested. HYPOTHESIS: We hypothesized that the unicortical button (UB) fixation will provide significantly improved restoration of the anatomic footprint and biomechanical properties when compared to transosseous (TO) repair of the SSc. METHODS: A digital footprint of SSc humeral insertion was obtained in 6 pairs of fresh-frozen cadaveric shoulders using a three-dimensional (3-D) digitizer. A complete SSc tear was created, and each pair of shoulders was randomized to either SSc repair with UB or TO repair. Each specimen underwent a cyclic loading protocol followed by pull-to-failure. The failure load, elongation at failure, gapping failure, number of cycles until failure, the load at key gapping points (1 mm, 3 mm, 5 mm, and 10 mm) and the failure mode were recorded using high-resolution video recording. 3-D surfaces of the insertion footprint and repair site were obtained, and surface areas were calculated using a custom MATLAB script and laser scanner. Paired t-tests were conducted to compare differences between two repair groups. RESULTS: Failure load was significantly higher in the UB group (382.4 N ± 56.5 N) than in the TO group (253.6 N ± 103.4 N, p=0.005). TO repair provided higher gapping at failure (28.8 mm ± 8.2 mm) than UB repair (10.4 mm ± 6.8 mm, p=0.0017). UB repair had significantly higher load at the 1-mm, 5-mm, and 10-mm gapping compared with TO repair with p=0.042, p=0.033, and p=0.0076, respectively. There were no significant differences between elongation failure, the difference in footprint area from native to repair states, or the percentage of restored footprint area between groups. (p=0.26, p=0.18 and p=0.21 respectively) CONCLUSION: The UB fixation showed a significantly lower gap at failure, higher failure load and number of cycles until failure, and higher gap loads compared with the traditional TO repair for SSc. Although more clinical research is necessary, the UB fixation that utilizes cortical bone presents promising results.

Trichinella murrelli identified in red foxes (Vulpes vulpes) in Pennsylvania, USA.

Trichinella infections have been eliminated from pork where pigs are raised in biosecure facilities, but wildlife infections persist. Trichinella murrelli is the primary zoonotic species in wild carnivores in the United States, having been identified in several species of omnivores and carnivores. Here, we document its occurrence in seven of 21 (33.3%) red foxes (Vulpes vulpes) from six counties in Pennsylvania. Encysted Trichinella larvae were detected in muscle squashes (<5 g samples) of all seven foxes, and in histological sections of the tongue and limb muscle of three. Larvae from muscle squashes were pooled and tested in a multiplex PCR capable of differentiating all Trichinella species native to the USA; all samples contained only T. murrelli. This is the first identification of T. murrelli in red foxes from Pennsylvania, and the first such survey performed in the last three decades. Results indicate that Trichinella remains endemic in Pennsylvania wildlife and a threat to the health of those who consume wild game.

Exercise and nutrition to improve cancer Treatment-Related outcomes (ENICTO).

Chemotherapy treatment-related side-effects are common and increase the risk of suboptimal outcomes. Exercise interventions during cancer treatment improve self-reported physical functioning, fatigue, anxiety, and depression, but it is unclear whether these interventions improve important clinical outcomes, such as chemotherapy relative dose intensity (RDI). The National Cancer Institute funded the Exercise and Nutrition to Improve Cancer Treatment-Related Outcomes (ENICTO) Consortium, to address this knowledge gap. This paper describes the mechanisms hypothesized to underpin intervention effects on clinically-relevant treatment outcomes, briefly outlines each project's distinct research aims, summarizes the scope and organizational structure of ENICTO, and provides an overview of the integrated common data elements used to pursue research questions collectively. In addition, the paper includes a description of consortium-wide activities and broader research community opportunities for collaborative research. Findings from the ENICTO Consortium have the potential to accelerate a paradigm shift in oncology care such that cancer patients could receive exercise and nutrition programming as the standard of care in tandem with chemotherapy to improve RDI for a curative outcome.

How Strong Is the Ligamentum Teres of the Hip? A Biomechanical Analysis.

BACKGROUND: Intraarticular hip pain represents a substantial clinical challenge, with recent studies implicating lesions in the ligamentum teres as potential contributors. Even more so, damage to the ligamentum teres is particularly prevalent among young patients undergoing joint-preserving interventions. Although several studies have investigated the biomechanical attributes of the ligamentum teres, inconsistencies in reported findings and reliance on cadaveric or animal models have raised concerns regarding the extrapolation of results to clinical practice. Furthermore, there is a lack of research examining ligamentum teres biomechanics specifically within the relevant patient cohort-individuals who benefit from joint-preserving surgical interventions. QUESTIONS/PURPOSES: We sought (1) to determine the biomechanical properties (ultimate load to failure, tensile strength, stiffness, and elastic modulus) of fresh-frozen ligaments from patients undergoing surgical hip dislocation, and (2) to identify patient-specific factors that are associated with them. METHODS: This was an institutional review board-approved study on intraoperatively harvested ligamentum teres from 74 consecutive patients undergoing surgical hip dislocation for joint preservation (August 2021 to September 2022). After the exclusion of patients with previous surgery, posttraumatic deformities, avascular necrosis, slipped capital femoral epiphysis, and Perthes disease, 31 ligaments from 31 patients were analyzed. The mean age of the study group was 27 ± 8 years, and 61% (19) of participants were male. The main indication for surgery was femoroacetabular impingement. Standardized AP pelvic and axial radiographs and CT scans were performed in all patients for better radiological description of the population and to identify associated radiological factors. The ligament was thoroughly transected at its origin on the fossa acetabuli and at the insertion area on the fovea capitis and stored at -20°C until utilization. Specimens were mounted to a materials testing machine via custom clamps that minimized slippage and the likelihood of failure at the clamp. Force-displacement and stress-strain curves were generated. Ultimate failure load (N), tensile strength (MPa), stiffness (N/mm), and elastic modulus (MPa) were determined. Using a multivariate regression analysis and a subgroup analysis, we tested demographic, degenerative, and radiographic factors as potential associated factors. RESULTS: The ligamentum teres demonstrated an ultimate load to failure of 126 ± 92 N, and the tensile strength was 1 ± 1 MPa. The ligaments exhibited a stiffness of 24 ± 15 N/mm and an elastic modulus of 7 ± 5 MPa. After controlling for potential confounding variables like age, fossa/fovea degeneration, and acetabular/femoral morphologies, we found that female sex was an independent factor for higher tensile strength, stiffness, and elastic modulus. Excessive femoral version was independently associated with lower load to failure (HR 122 [95% CI 47 to 197]) and stiffness (HR 15 [95% CI 2 to 27]). Damage to the acetabular fossa was associated with reduced load to failure (HR -93 [95% CI -159 to -27]). CONCLUSION: Overall, the ligamentum teres is a relatively weak ligament. Sex, degeneration, and excessive femoral version are influencing factors on strength of the ligamentum teres. The ligamentum teres exhibits lower strength compared with other joint-stabilizing ligaments, which calls into question its overall contribution to hip stability. CLINICAL RELEVANCE: Young patients undergoing hip-preserving surgery are the population at risk for ligamentum teres lesions. Baseline values for load to failure, tensile strength, elastic modulus, and stiffness are needed to better understand those lesions in this cohort of interest.

Inflammation, Physical Activity, and Disease-Free Survival in Stage III Colon Cancer: CALGB/SWOG 80702 (Alliance).

BACKGROUND: Both inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. METHODS: This cohort study was nested within the CALGB/SWOG 80702 (Alliance) randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. RESULTS: The 3-year disease-free survival rate was 88.4% among patients with low inflammation and sufficient physical activity (referent group for all comparisons), 84.9% with low inflammation and insufficient physical activity [absolute risk difference (RD): -3.5%, 95% Confidence Interval (CI): -11.3, 4.3; P = .38], 78.0% with intermediate inflammation and insufficient physical activity (RD: -10.4%, 95% CI: -17.4, -3.3; P = .007), and 79.7% with high inflammation and insufficient physical activity (RD: -8.7%, 95% CI: -15.7, -1.6; P = .022). In contrast, the 3-year disease-free survival rate was 87.3% among patients with intermediate inflammation and sufficient physical activity (RD: -1.1%, 95% CI: -7.5, 5.3; P = .74) and 84.4% with high inflammation and sufficient physical activity (RD: -4.0%, 95% CI: -12.3, 4.3; P = .34). CONCLUSION: In this observational study of stage III colon cancer patients, physical activity was associated with improved disease-free survival despite high inflammation. Patients with intermediate or high inflammation who were physically active had disease-free survival rates that were not statistically significantly different from those with low inflammation.

Nutritional Mechanisms of Cancer Cachexia.

Cancer cachexia is a complex systemic wasting syndrome. Nutritional mechanisms that span energy intake, nutrient metabolism, body composition, and energy balance may be impacted by, and may contribute to, the development of cachexia. To date, clinical management of cachexia remains elusive. Leaning on discoveries and novel methodologies from other fields of research may bolster new breakthroughs that improve nutritional management and clinical outcomes. Characteristics that compare and contrast cachexia and obesity may reveal opportunities for cachexia research to adopt methodology from the well-established field of obesity research. This review outlines the known nutritional mechanisms and gaps in the knowledge surrounding cancer cachexia. In parallel, we present how obesity may be a different side of the same coin and how obesity research has tackled similar research questions. We present insights into how cachexia research may utilize nutritional methodology to expand our understanding of cachexia to improve definitions and clinical care in future directions for the field.

Intermittent Energy Restriction for Adolescents With Obesity: The Fast Track to Health Randomized Clinical Trial.

Importance: Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management. Objective: To examine the effectiveness of 2 diet therapies, delivered as part of an intensive behavioral weight management intervention, in adolescents with metabolic complications associated with obesity. Design, Setting, and Participants: This multisite, 52-week randomized clinical trial was conducted from January 31, 2018, to March 31, 2023, at 2 tertiary pediatric centers in Australia. Adolescents (aged 13-17 years) with obesity and 1 or more associated complications were included. Interventions: Intensive behavioral interventions, delivered by a multidisciplinary team, comparing intermittent energy restriction (IER) or continuous energy restriction (CER), with 3 phases: very low-energy diet (weeks 0-4), intensive intervention (weeks 5-16), and continued intervention and/or maintenance (weeks 17-52). Main Outcomes and Measures: The primary outcome was body mass index (BMI) z score at 52 weeks in the IER vs CER group. Anthropometry, body composition, and cardiometabolic health were assessed at baseline and 52 weeks. The BMI z score and percentiles were determined using Centers for Disease Control and Prevention growth charts. Insulin resistance, dyslipidemia, and elevated hepatic function were assessed. Results: A total of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) were enrolled, 71 in the IER group and 70 in the CER group, and 97 (68.8%) completed the intervention, 43 in the IER group and 54 in the CER group. At week 52, both groups had reduced BMI z scores (estimated marginal mean change, -0.28 [95% CI, -0.37 to -0.20] for IER and -0.28 [95% CI, -0.36 to -0.20] for CER) and reduced BMI expressed as a percentage of the 95th percentile (estimated marginal mean change, -9.56 [95% CI, -12.36 to -6.83] for IER and -9.23 [95% CI, -11.82 to -6.64] for CER). No differences were found in body composition or cardiometabolic outcomes between the groups. Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). No differences were found in dyslipidemia or hepatic function between groups. Conclusions and Relevance: These findings suggest that for adolescents with obesity-associated complications, IER can be incorporated into a behavioral weight management program, providing an option in addition to CER and offering participants more choice. Trial Registration: http://anzctr.org.au Identifier: ACTRN12617001630303.

Symptoms of Depression, Eating Disorders, and Binge Eating in Adolescents With Obesity: The Fast Track to Health Randomized Clinical Trial.

Importance: Depression and eating disorders are heightened for adolescents with obesity. Clinical reviews alongside self-report questionnaires are important to ensure appropriate intervention. Objective: To evaluate changes in self-report symptoms of depression, eating disorders, and binge eating in adolescents with obesity during the Fast Track to Health trial. Design, Setting, and Participants: This was a randomized clinical trial conducted from 2018 to 2023. It was a multisite trial conducted at children's hospitals in Sydney, New South Wales, and Melbourne, Victoria, Australia, and included adolescents (13-17 years) with obesity (defined as adult equivalent body mass index ≥30; calculated as weight in kilograms divided by height in meters squared) and 1 or more related complications. Interventions: Duration was 52 weeks including a very low energy diet for 4 weeks followed by intermittent energy restriction (IER) or continuous energy restriction (CER). Main Outcomes and Measures: Self-report symptoms of depression (Center for Epidemiologic Studies Depression Scale-Revised 10-Item Version for Adolescents [CESDR-10]; scores 0-30), eating disorders (Eating Disorder Examination Questionnaire [EDE-Q]; scores 0-6), and binge eating (Binge Eating Scale [BES]; scores 0-46) were assessed. Adolescents were screened for depression and eating disorders (weeks 0, 4, 16, and 52) and monitored for the onset of new symptoms of disordered eating during dietetic consults. Results: Of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) enrolled, median baseline EDE-Q score was 2.28 (IQR, 1.43-3.14), median baseline CESDR-10 score was 9.00 (IQR, 4.00-14.50), and median baseline BES score was 11.00 (IQR, 5.00-17.00). There were no differences between groups for change in CESDR-10 (mean difference at week 52, 0.75; 95% CI, -1.86 to 3.37), EDE-Q (mean difference at week 52, 0.02; 95% CI, -0.41 to 0.45), or BES (mean difference at week 52, -2.91; 95% CI, -5.87 to 0.05). The within-group reductions at week 4 were maintained at week 52, for CESDR-10 and EDE-Q, indicating reduced symptoms of depression and eating disorders. Within-group reductions on the BES were maintained in the IER group only. Seventeen adolescents (12.1%) required support or referral for depression and/or disordered eating, including 7 (5%; 5 IER, 2 CER) adolescents who experienced the onset or reemergence of symptoms during the intervention. Conclusions and Relevance: Results suggest that many treatment-seeking adolescents with obesity self-reported symptoms of depression and eating disorders. Although symptoms reduced for most, some required additional support. Obesity treatment is an opportune time to screen and monitor for depression and disordered eating. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12617001630303.

Comparison of Butorphanol-Azaperone-Medetomidine and Nalbuphine-Medetomidine-Azaperone in Free-Ranging Elk (Cervus canadensis) in Pennsylvania, USA.

Chemical immobilization is commonly used to capture and handle free-ranging elk (Cervus canadensis). Butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A) are compounded drug combinations that are lower-scheduled in the US than drugs historically used for elk immobilizations. We compared BAM and NalMed-A for immobilization of free-ranging elk using free-darting and Clover trapping. From January 2020 to April 2022, 196 female elk were immobilized in Pennsylvania, USA. We report vital rates, induction and recovery times, and the need for supplemental drugs. We built mixed-effects logistic regression models to describe differences between drug choice based on induction and recovery times, capture method, and individual variation. Several models were competing, including our null model, which suggests that BAM and NalMed-A are comparable based on the parameters we evaluated. Supplemental drug administration was more frequently needed in NalMed-A immobilizations (21.2%) than in BAM immobilizations (9.0%). Overall, we found minor differences between BAM and NalMed-A, both of which appear to be effective for immobilizing elk in both free-darting and Clover trapping scenarios when performing moderately invasive, minimally painful procedures on free-ranging elk.

Effect of resistance training on physical function during chemotherapy in colon cancer.

BACKGROUND: The decline of physical function during chemotherapy predicts poor quality of life and premature death. It is unknown if resistance training prevents physical function decline during chemotherapy in colon cancer survivors. METHODS: This multicenter trial randomly assigned 181 colon cancer survivors receiving postoperative chemotherapy to home-based resistance training or usual care control. Physical function outcomes included the short physical performance battery, isometric handgrip strength, and the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire. Mixed models for repeated measures quantified estimated treatment differences. RESULTS: At baseline, participants had a mean (SD) age of 55.2 (12.8) years; 67 (37%) were 60 years or older, and 29 (16%) had a composite short physical performance battery score of no more than 9. Compared with usual care control, resistance training did not improve the composite short physical performance battery score (estimated treatment difference = -0.01, 95% confidence interval [CI] = -0.32 to 0.31; P = .98) or the short physical performance battery scores for balance (estimated treatment difference = 0.01, 95% CI = -0.10 to 0.11; P = .93), gait speed (estimated treatment difference = 0.08, 95% CI = -0.06 to 0.22; P = .28), and sit-to-stand (estimated treatment difference = -0.08, 95% CI = -0.29 to 0.13; P = .46). Compared with usual care control, resistance training did not improve isometric handgrip strength (estimated treatment difference = 1.50 kg, 95% CI = -1.06 to 4.05; P = .25) or self-reported physical function (estimated treatment difference = -3.55, 95% CI = -10.03 to 2.94); P = .28). The baseline short physical performance battery balance score (r = 0.21, 95% CI = 0.07 to 0.35) and handgrip strength (r = 0.23, 95% CI = 0.09 to 0.36) correlated with chemotherapy relative dose intensity. CONCLUSION: Among colon cancer survivors with relatively high physical functioning, random assignment to home-based resistance training did not prevent physical function decline during chemotherapy. CLINICAL TRIAL REGISTRATION: NCT03291951.

Osteointegration of Ti Bone Implants: A Study on How Surface Parameters Control the Foreign Body Response.

The integration of titanium (Ti)-based implants with bone is limited, resulting in implant failure. This lack of osteointegration is due to the foreign body response (FBR) that occurs after the implantation of biodevices. The process begins with protein adsorption, which is governed by implant surface properties, e.g., chemistry, charge, wettability, and/or topography. The distribution and composition of the protein layer in turn influence the recruitment, differentiation, and modulation of immune and bone cells. The subsequent events that occur at the bone-material interface will ultimately determine whether the implant is encapsulated or will integrate with bone. Despite the numerous studies evaluating the influence of surface properties in the various stages of the FBR, the factors that affect tissue-material interactions are often studied in isolation or in small correlations due to the technical challenges involved in assessing them in vitro or in vivo. Consequently, the influence of protein conformation on the Ti bone implant surface design remains an unresolved research question. The objective of this review is to comprehensively evaluate the existing literature on the effect of surface parameters of Ti and its alloys in the stages of FBR, with a particular focus on protein adsorption and osteoimmunomodulation. This evaluation aims to systematically describe these effects on bone formation.

Diversity of Babesia spp. in skunks from selected states in the United States of America.

Babesia species are intraerythrocytic protozoan parasites that infect a variety of hosts. The goal of this study was to evaluate the piroplasm species present in skunks in various states in the United States and determine whether there was any geographic variation. Spleen, whole blood, or blood on filter paper were received from Pennsylvania, Kentucky, North Carolina, South Carolina, Georgia, Missouri, Louisiana, Texas, Kansas, and California, and were tested for Babesia sp. We tested four species of skunks including striped skunk (Mephitis mephitis, n = 72), eastern spotted skunk (Spilogale putorius, n = 28), western spotted skunk (Spilogale gracilis, n = 15), and hog-nosed skunk (Conepatus leuconotus, n = 11). A PCR assay targeting the 18S rRNA region and cox1 region were used to determine if skunks were infected with piroplasms and for phylogenetic analyses. A total of 48.4% (61/126) of skunks tested positive for a Babesia species. Both the 18S and cox1 analysis supported a skunk-specific Babesia microti-like sp. of carnivores as well as a species in the B. microti complex that is phylogenetically unique from both B. microti of humans and the B. microti-like sp. of carnivores. In the 18S analysis, there was a third species of Babesia in hog-nosed skunks in the western piroplasm group. This study shows that at least three species of piroplasms occur in skunk species in the United States and further highlights the importance of phylogenetic analyses and the use of multiple gene targets when studying piroplasms.

Title: Diversité des Babesia spp. chez des mouffettes provenant d'États sélectionnés des États-Unis. Abstract: Les espèces de Babesia sont des protozoaires parasites intraérythrocytaires qui infectent divers hôtes. Le but de cette étude était d'évaluer les espèces de piroplasmes présentes chez les mouffettes dans divers états des États-Unis et de déterminer s'il existait une variation géographique. Des rates, du sang total ou du sang sur papier filtre ont été reçus de Pennsylvanie, du Kentucky, de Caroline du Nord, de Caroline du Sud, de Géorgie, du Missouri, de Louisiane, du Texas, du Kansas et de Californie, et ont été testés pour Babesia sp. Nous avons testé quatre espèces de mouffettes, dont la mouffette rayée (Mephitis mephitis, n = 72), la mouffette tachetée de l'Est (Spilogale putorius, n = 28), la mouffette tachetée de l'Ouest (Spilogale gracilis, n = 15) et la mouffette à nez plat (Conepatus leuconotus, n = 11). Un test PCR ciblant la région de l'ARNr 18S et la région cox1 a été utilisé pour déterminer si les mouffettes étaient infectées par des piroplasmes et pour des analyses phylogénétiques. Au total, 48,4 % (61/126) des mouffettes ont été testées positives pour une espèce de Babesia. Les analyses du 18S et du cox1 ont toutes deux confirmé une espèce de type Babesia microti de carnivores spécifique aux mouffettes ainsi qu'une espèce du complexe B. microti qui est phylogénétiquement unique à la fois par rapport à B. microti de l'homme et à l'espèce des carnivores. Dans l'analyse 18S, il y avait une troisième espèce de Babesia chez les mouffettes à nez plat du groupe des piroplasmes de l'ouest. Cette étude montre qu'au moins trois espèces de piroplasmes sont présentes chez les espèces de mouffettes aux États-Unis et souligne en outre l'importance des analyses phylogénétiques et de l'utilisation de plusieurs cibles génétiques lors de l'étude des piroplasmes.

Novel Technologies to Address the Lower Motor Neuron Injury and Augment Reconstruction in Spinal Cord Injury.

Lower motor neuron (LMN) damage results in denervation of the associated muscle targets and is a significant yet under-appreciated component of spinal cord injury (SCI). Denervated muscle undergoes a progressive degeneration and fibro-fatty infiltration that eventually renders the muscle non-viable unless reinnervated within a limited time window. The distal nerve deprived of axons also undergoes degeneration and fibrosis making it less receptive to axons. In this review, we describe the LMN injury associated with SCI and its clinical consequences. The process of degeneration of the muscle and nerve is broken down into the primary components of the neuromuscular circuit and reviewed, including the nerve and Schwann cells, the neuromuscular junction, and the muscle. Finally, we discuss three promising strategies to reverse denervation atrophy. These include providing surrogate axons from local sources; introducing stem cell-derived spinal motor neurons into the nerve to provide the missing axons; and finally, instituting a training program of high-energy electrical stimulation to directly rehabilitate these muscles. Successful interventions for denervation atrophy would significantly expand reconstructive options for cervical SCI and could be transformative for the predominantly LMN injuries of the conus medullaris and cauda equina.

Fundamentals of wildlife dosimetry and lessons learned from a decade of measuring external dose rates in the field.

Methods for determining the radiation dose received by exposed biota require major improvements to reduce uncertainties and increase precision. We share our experiences in attempting to quantify external dose rates to free-ranging wildlife using GPS-coupled dosimetry methods. The manuscript is a primer on fundamental concepts in wildlife dosimetry in which the complexities of quantifying dose rates are highlighted, and lessons learned are presented based on research with wild boar and snakes at Fukushima, wolves at Chornobyl, and reindeer in Norway. GPS-coupled dosimeters produced empirical data to which numerical simulations of external dose using computer software were compared. Our data did not support a standing paradigm in risk analyses: Using averaged soil contaminant levels to model external dose rates conservatively overestimate the dose to individuals within a population. Following this paradigm will likely lead to misguided recommendations for risk management. The GPS-dosimetry data also demonstrated the critical importance of how modeled external dose rates are impacted by the scale at which contaminants are mapped. When contaminant mapping scales are coarse even detailed knowledge about each animal's home range was inadequate to accurately predict external dose rates. Importantly, modeled external dose rates based on a single measurement at a trap site did not correlate to actual dose rates measured on free ranging animals. These findings provide empirical data to support published concerns about inadequate dosimetry in much of the published Chernobyl and Fukushima dose-effects research. Our data indicate that a huge portion of that literature should be challenged, and that improper dosimetry remains a significant source of controversy in radiation dose-effect research.

Murine Progeria Model Exhibits Delayed Fracture Healing with Dysregulated Local Immune Response.

Background: Bone fracture is one of the most globally prevalent injuries, with an estimated 189 million bone fractures occurring annually. Delayed union or nonunion occurs in up to 15% of fractures and involves the interruption or complete failure of bone continuity following fracture. Preclinical testing is essential to support the translation of novel strategies to promote improved fracture repair treatment, but there is a paucity of small animal models that recapitulate clinical attributes associated with delayed fracture healing. This study explores whether the Zmpste24 -/- (Z24 -/- ) knockout mouse model of Hutchinson-Gilford progeria syndrome presents with delayed fracture healing. Leveraging the previously characterized Z24 -/- phenotype of genomic instability, epigenetic changes, and fragility, we hypothesize that these underlying alterations will lead to significantly delayed fracture healing relative to age-matched wild type (WT) controls. Methods: WT and Z24 -/- mice received intramedullary fixed tibia fractures at ∼12 weeks of age. Mice were sacrificed throughout the time course of repair for the collection of organs that would provide information regarding the local (fracture callus, bone marrow, inguinal lymph nodes) versus peripheral (peripheral blood, contralateral tibia, abdominal organs) tissue microenvironments. Analyses of these specimens include histomorphometry, µCT, mechanical strength testing, protein quantification, gene expression analysis, flow cytometry for cellular senescence, and immunophenotyping. Results: Z24 -/- mice demonstrated a significantly delayed rate of healing compared to WT mice with consistently smaller fracture calli containing higher proportion of cartilage and less bone after injury. Cellular senescence and pro-inflammatory cytokines were elevated in the Z24 -/- mice before and after fracture. These mice further presented with a dysregulated immune system, exhibiting generally decreased lymphopoiesis and increased myelopoiesis locally in the bone marrow, with more naïve and less memory T cell but greater myeloid activation systemically in the peripheral blood. Surprisingly, the ipsilateral lymph nodes had increased T cell activation and other pro-inflammatory NK and myeloid cells, suggesting that elevated myeloid abundance and activation contributes to an injury-specific hyperactivation of T cells. Conclusion: Taken together, these data establish the Z24 -/- progeria mouse as a model of delayed fracture healing that exhibits decreased bone in the fracture callus, with weaker overall bone quality, immune dysregulation, and increased cellular senescence. Based on this mechanism for delayed healing, we propose this Z24 -/- progeria mouse model could be useful in testing novel therapeutics that could address delayed healing. The Translational Potential of this Article: This study employs a novel animal model for delayed fracture healing that researchers can use to screen fracture healing therapeutics to address the globally prevalent issue of aberrant fracture healing.

Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.

BACKGROUND: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. METHODS: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. RESULTS: Randomization to exercise increased leukaemia inhibitory factor (1.26 pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P = 0.001) and interleukin-15 (2.23 pg/mL, 95% CI: 0.87, 3.60; adjusted P = 0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (-2.69 pg/mL, 95% CI: -4.31, -1.07; adjusted P = 0.014) and interleukin-15 (-1.74 pg/mL, 95% CI: -2.79, -0.69; adjusted P = 0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. CONCLUSIONS: This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.

RAPID POINT-OF-CARE TESTING FOR DETECTION OF ANTIBODIES TO TOXOPLASMA GONDII IN BLACK VULTURES AND RING-BILLED GULLS FROM PENNSYLVANIA.

Toxoplasma gondii is a zoonotic protozoan parasite that infects most warm-blooded animals, including birds. Scavenging birds are epidemiologically important hosts because they can serve as indicators of environmental T. gondii levels. A rapid point-of-care (POC) test that detects antibodies to T. gondii in humans is commercially available. In this research, we assessed the ability of the human POC test to detect anti-T. gondii antibodies in 106 black vultures (Coragyps atratus) and 23 ring-billed gulls (Larus delawarensis) from Pennsylvania, USA. Serum samples were tested with the POC test and compared to the modified agglutination test (MAT) in a blinded study. Overall, anti-T. gondii antibodies were detected in 2.8% (3/106) of black vultures and 60.9% (14/23) of ring-billed gulls by the POC test. One false-positive POC test occurred in a black vulture that was negative by MAT. False-negative results were obtained in 2 black vultures and 4 ring-billed gulls that had MAT titers of 1:25 or 1:50. The sensitivity and specificity of the POC for both black vultures and ring-billed gulls combined were 95.7% and 95.5%, respectively. This is the first study using human POC tests to detect antibodies to T. gondii in birds. Further study of the rapid test as a screening tool for serological surveillance of T. gondii in birds is warranted.