A brain-specific angiogenic mechanism enabled by tip cell specialization.

Vertebrate organs require locally adapted blood vessels1,2. The gain of such organotypic vessel specializations is often deemed to be molecularly unrelated to the process of organ vascularization. Here, opposing this model, we reveal a molecular mechanism for brain-specific angiogenesis that operates under the control of Wnt7a/b ligands-well-known blood-brain barrier maturation signals3-5. The control mechanism relies on Wnt7a/b-dependent expression of Mmp25, which we find is enriched in brain endothelial cells. CRISPR-Cas9 mutagenesis in zebrafish reveals that this poorly characterized glycosylphosphatidylinositol-anchored matrix metalloproteinase is selectively required in endothelial tip cells to enable their initial migration across the pial basement membrane lining the brain surface. Mechanistically, Mmp25 confers brain invasive competence by cleaving meningeal fibroblast-derived collagen IV α5/6 chains within a short non-collagenous region of the central helical part of the heterotrimer. After genetic interference with the pial basement membrane composition, the Wnt-ß-catenin-dependent organotypic control of brain angiogenesis is lost, resulting in properly patterned, yet blood-brain-barrier-defective cerebrovasculatures. We reveal an organ-specific angiogenesis mechanism, shed light on tip cell mechanistic angiodiversity and thereby illustrate how organs, by imposing local constraints on angiogenic tip cells, can select vessels matching their distinctive physiological requirements.

The cytoskeleton adaptor protein Sorbs1 controls the development of lymphatic and venous vessels in zebrafish.

BACKGROUND: Lymphangiogenesis, the formation of lymphatic vessels, is tightly linked to the development of the venous vasculature, both at the cellular and molecular levels. Here, we identify a novel role for Sorbs1, the founding member of the SoHo family of cytoskeleton adaptor proteins, in vascular and lymphatic development in the zebrafish. RESULTS: We show that Sorbs1 is required for secondary sprouting and emergence of several vascular structures specifically derived from the axial vein. Most notably, formation of the precursor parachordal lymphatic structures is affected in sorbs1 mutant embryos, severely impacting the establishment of the trunk lymphatic vessel network. Interestingly, we show that Sorbs1 interacts with the BMP pathway and could function outside of Vegfc signaling. Mechanistically, Sorbs1 controls FAK/Src signaling and subsequently impacts on the cytoskeleton processes regulated by Rac1 and RhoA GTPases. Inactivation of Sorbs1 altered cell-extracellular matrix (ECM) contacts rearrangement and cytoskeleton dynamics, leading to specific defects in endothelial cell migratory and adhesive properties. CONCLUSIONS: Overall, using in vitro and in vivo assays, we identify Sorbs1 as an important regulator of venous and lymphatic angiogenesis independently of the Vegfc signaling axis. These results provide a better understanding of the complexity found within context-specific vascular and lymphatic development.

Clinical efficacy and patients' perception of virtual reality during wound care in adults: A systematic review with meta-analysis of randomised clinical trials.

This study was aimed to review Virtual Reality's (VR) impact on pain, anxiety, opioid usage, physiological and behavioural responses, and patients' experience during wound care (WC) in adults. We searched multiple databases (Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, CINAHL, Scopus and Google Scholar) from inception until January 27th, 2023. Included studies compared VR alone or as an adjunct to standard WC with standard WC or other distraction methods, in adults with burn or non-burn-related wounds. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomised parallel-group and crossover trials. The review followed PRISMA guidelines for reporting. Fourteen studies were eligible for inclusion. The meta-analysis was limited to studies comprising solely of adult participants. VR reduced pain intensity compared to standard WC in all study designs. Despite not being included in the meta-analysis due to reasons such as mixed population or lack of sufficient statistical data, other studies showed significant pain reduction using VR. Additionally, VR improved patients' experience of WC. No clear effect was found on other outcomes including anxiety, opioid usage and physiological and behavioural responses. VR shows promise in reducing acute pain and enhancing patients' experience of WC. The observed variations in the effects of VR at group and individual levels indicate the need for a personalised treatment plan by selecting the right VR for the right patient given at the right time.

Engineered Wnt ligands enable blood-brain barrier repair in neurological disorders.

The blood-brain barrier (BBB) protects the central nervous system (CNS) from harmful blood-borne factors. Although BBB dysfunction is a hallmark of several neurological disorders, therapies to restore BBB function are lacking. An attractive strategy is to repurpose developmental BBB regulators, such as Wnt7a, into BBB-protective agents. However, safe therapeutic use of Wnt ligands is complicated by their pleiotropic Frizzled signaling activities. Taking advantage of the Wnt7a/b-specific Gpr124/Reck co-receptor complex, we genetically engineered Wnt7a ligands into BBB-specific Wnt activators. In a "hit-and-run" adeno-associated virus-assisted CNS gene delivery setting, these new Gpr124/Reck-specific agonists protected BBB function, thereby mitigating glioblastoma expansion and ischemic stroke infarction. This work reveals that the signaling specificity of Wnt ligands is adjustable and defines a modality to treat CNS disorders by normalizing the BBB.

Ability to detect antibodies to beak and feather disease virus in blood on filter paper decreases with duration of storage.

BACKGROUND: Beak and feather disease virus (BFDV) is a circovirus that infects captive and wild psittacine birds, and is of conservation concern. The haemagglutination inhibition (HI) assay is used to determine antibody titres against BFDV, and the use of dried blood spots (DBS) on filter paper stored at room temperature has been suggested to be an equally valid technique to the use of frozen serum. However, research on other pathogens has found variable results when investigating the longevity of antibodies stored on DBS at room temperature. Consequently, we aimed to test the temporal stability of antibodies to BFDV in DBS samples stored long-term at room temperature. A further goal was to add to the current knowledge of antibody response to naturally acquired BFDV infection in crimson rosellas (Platycercus elegans). METHODS: Blood was collected from wild P. elegans in Victoria, Australia, that had been live-trapped (n = 9) or necropsied (n = 11). BFDV virus load data were obtained from blood stored in ethanol by real-time quantitative PCR (qPCR); antibody titres were obtained by HI assay from either DBS or serum samples, which had been collected concurrently. All HI assays were performed commercially by the Veterinary Diagnostic Laboratory (VDL) in Charles Sturt University, Australia, who were blind to BFDV blood status. RESULTS: HI titres from DBS stored at room temperature declined significantly over time (~80 weeks). By contrast, frozen serum samples assayed after 80 weeks in storage all had high HI titres, only varying up to one dilution step from the initial HI titres obtained from DBS at 3-6 weeks after sampling. Weak HI titres from DBS samples all came back negative when the test was repeated only nine weeks later. Novel high HI titres were reported in P. elegans, and while most birds with high antibody titres had corresponding negative qPCR results, a single subadult presented with high HI titres and virus load simultaneously. CONCLUSION: Detection of antibodies on filter paper stored at room temperature decreases over time, increasing the chances of false negatives in these samples, and in repeated testing of samples with weak HI titres. Consequently, serum should be the preferred sample type to use for seroepidemiological studies on BFDV in parrots and other bird species. When not possible, it may help to store DBS on filter paper at -20 °C or lower. However, prompt testing of DBS samples (e.g., <6 weeks in storage) is recommended pending further research on antibody temporal stability. We also show that P. elegans, especially adults, can produce high antibody titres against BFDV, which may help them resist infection.

The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging.

Skeletal muscle dysfunction, articular cartilage degeneration, and bone loss occur essentially in parallel during aging. Mechanisms contributing to this systemic musculoskeletal decline remain incompletely understood, limiting progress toward developing effective therapeutics. Because the progression of human musculoskeletal aging is slow, researchers rely on rodent models to identify mechanisms and test interventions. The Dunkin Hartley guinea pig is an outbred strain that begins developing primary osteoarthritis by 4 months of age with a progression and pathology similar to aging humans. The purpose of this study was to determine if skeletal muscle remodeling during the progression of osteoarthritis in these guinea pigs resembles musculoskeletal aging in humans. We compared Dunkin Hartley guinea pigs to Strain 13 guinea pigs, which develop osteoarthritis much later in the lifespan. We measured myofiber type and size, muscle density, and long-term fractional protein synthesis rates of the gastrocnemius and soleus muscles in 5, 9, and 15-month-old guinea pigs. There was an age-related decline in skeletal muscle density, a greater proportion of smaller myofibers, and a decline in type II concomitant with a rise in type I myofibers in the gastrocnemius muscles from Dunkin Hartley guinea pigs only. These changes were accompanied by age-related declines in myofibrillar and mitochondrial protein synthesis in the gastrocnemius and soleus. Collectively, these findings suggest Dunkin Hartley guinea pigs experience myofiber remodeling alongside the progression of osteoarthritis, consistent with human musculoskeletal aging. Thus, Dunkin Hartley guinea pigs may be a model to advance discovery and therapeutic development for human musculoskeletal aging.

Senescence of song revealed by a long-term study of the Seychelles warbler (Acrocephalus sechellensis).

Senescence is widespread in nature, often resulting in diminishing survival or reproduction with age, but its role in age-dependent variation in sexual traits is often poorly understood. One reason is that few studies of sexual traits consider non-linear relationships with age, or only consider a narrow range of years relative to the life span of the species. Birdsong has evolved to allow assessment of conspecific quality in numerous bird species. Whilst theory and empirical work suggests that song may become more elaborate with age, there are a paucity of long-term studies testing whether song is associated with age or longevity. In particular, the occurrence of song senescence has rarely been demonstrated. Using an exceptional long-term dataset for the Seychelles warbler (Acrocephalus sechellensis), we analysed relationships between male song, age, survival, and longevity. This species is a long-lived songbird with early life increases, followed by senescent declines, in survival and reproduction. The study population (Cousin Island, Seychelles) is a closed population, with no depredation of adults, providing an excellent opportunity to study senescence in free-living animals. We tested whether song traits were related to age at recording, future survival, longevity, and territory quality. We found age-dependent changes in five song traits (duration, maximum frequency, peak frequency of songs, and duration and frequency bandwidth of trills). Relationships with age were quadratic, indicating reversal in the expression of song coinciding with the onset of senescence in reproduction and survival in this species. One song trait (trill bandwidth) had a quadratic relationship with future survival, but no song traits were related to longevity, suggesting age-related patterns were not the result of selective disappearance. Our study provides one of the first examples of functional senescence in song, offering new insights into avian senescence. Late-life declines in avian song, and possibly other sexual traits, may be more common than currently known, and may play a fundamental role in age-dependent changes in reproductive success.

[Complications of coronary invasive procedures in nonagenarians: A case-control study]. / Complications des procédures invasives coronaires chez les nonagénaires : une étude cas-témoins.

INTRODUCTION: Coronary heart disease is the leading cause of morbidity and mortality in nonagenarians, whose numbers have doubled in twenty years. In the absence of recommendations, the place of coronary invasive strategy in this population remains a therapeutic challenge and its interest as well as its risks are poorly established. The aim of our study was to evaluate the safety of coronary invasive practice in the nonagenarian population for all indications. POPULATION AND METHODS: This was a monocentric case-control study conducted from January 1, 2010 to May 30, 2019. The patients included were all nonagenarians who had undergone coronary angiography at the centre hospitalier de Troyes during this period. For each patient included, two controls matched on sex, date of procedure and procedure were drawn at random. The main judgment criterion was the occurrence of immediate per- or post-procedure complications during the stay in which the procedure was performed. The main secondary outcome measures were average length of stay, occurrence of intercurrent events during the stay (nosocomial infections, confusional syndrome), and loss of autonomy. RESULTS: In all, 59 nonagenarians and 118 controls were included in our study. We identified 30.5% major complications in the nonagenarians versus 10.2% in the controls (P=0.001; OR=0.26 [0.1-0.6]), with a significant difference in the occurrence of cardiogenic shock (P=0.04), heart failure (P=0.02) and ventricular rhythm disorders (P=0.04). Post-procedure acute renal failure was greater in the nonagenarians (P=0.02; OR=0.20 [0.05-1.57]). The mean length of stay was on average twice as long in the nonagenarians. CONCLUSION: Nonagenarian patients are subject to more complications when undergoing coronary invasive procedures compared to patients under 75.

Photoredox/Nickel Dual-Catalyzed Reductive Cross Coupling of Aryl Halides Using an Organic Reducing Agent.

A successful protocol for the reductive aryl-aryl cross-coupling of polyfluorinated arenes with a broad range of aryl halides has been developed. Sequential carbon-fluorine bond cleavage and carbon-carbon bond formation are two of the important features of the reaction. Addition of an aryl radical anion to a nickel intermediate was achieved for the first time using polyfluoroarenes as radical precursors. This, in combination with the excellent para selectivity, paves the way for the synthesis of various new multifluorinated biaryl compounds.

Disruption of the Extracellular Matrix Progressively Impairs Central Nervous System Vascular Maturation Downstream of ß-Catenin Signaling.

Objective- The Wnt/ß-catenin pathway orchestrates development of the blood-brain barrier, but the downstream mechanisms involved at different developmental windows and in different central nervous system (CNS) tissues have remained elusive. Approach and Results- Here, we create a new mouse model allowing spatiotemporal investigations of Wnt/ß-catenin signaling by induced overexpression of Axin1, an inhibitor of ß-catenin signaling, specifically in endothelial cells ( Axin1 iEC- OE). AOE (Axin1 overexpression) in Axin1 iEC- OE mice at stages following the initial vascular invasion of the CNS did not impair angiogenesis but led to premature vascular regression followed by progressive dilation and inhibition of vascular maturation resulting in forebrain-specific hemorrhage 4 days post-AOE. Analysis of the temporal Wnt/ß-catenin driven CNS vascular development in zebrafish also suggested that Axin1 iEC- OE led to CNS vascular regression and impaired maturation but not inhibition of ongoing angiogenesis within the CNS. Transcriptomic profiling of isolated, ß-catenin signaling-deficient endothelial cells during early blood-brain barrier-development (E11.5) revealed ECM (extracellular matrix) proteins as one of the most severely deregulated clusters. Among the 20 genes constituting the forebrain endothelial cell-specific response signature, 8 ( Adamtsl2, Apod, Ctsw, Htra3, Pglyrp1, Spock2, Ttyh2, and Wfdc1) encoded bona fide ECM proteins. This specific ß-catenin-responsive ECM signature was also repressed in Axin1 iEC- OE and endothelial cell-specific ß-catenin-knockout mice ( Ctnnb1-KOiEC) during initial blood-brain barrier maturation (E14.5), consistent with an important role of Wnt/ß-catenin signaling in orchestrating the development of the forebrain vascular ECM. Conclusions- These results suggest a novel mechanism of establishing a CNS endothelium-specific ECM signature downstream of Wnt-ß-catenin that impact spatiotemporally on blood-brain barrier differentiation during forebrain vessel development. Visual Overview- An online visual overview is available for this article.

Do glucocorticoids or carotenoids mediate plumage coloration in parrots? An experiment in Platycercus elegans.

Conspicuous coloration can indicate phenotypic quality, and may reflect exposure or vulnerability to stress, or access to essential nutrients such as pigments. Although the production of pigmented colours is well understood, much less is known about how structural colours are affected by physiological state. In this study, we tested whether glucocorticoids (corticosterone) predicted expression of plumage coloration in an Australian parrot, the crimson rosella (Platycercus elegans). Parrots provide an interesting and unique test, as they possess conspicuous coloration produced by distinctive pigments known as psittacofulvins, in addition to structural coloration. We have previously documented that coloration in P. elegans is condition-dependent and responds to dietary manipulation. Here, n = 21 P. elegans underwent a dietary manipulation (including food restriction or carotenoid supplementation) during which they moulted, and the change in reflectance was measured for three structural and three pigmentary plumage patches. Stress-induced corticosterone (10 min after handling) measured at the start of the experiment predicted change in coloration in two pigmentary patches (crown and front). We also found that change in stress-induced corticosterone during the experiment was associated with the change in coloration of the crown and two structural patches (cheek and epaulette). Baseline corticosterone (<3 min after handling) was not associated with any measure of coloration. We found no effects of dietary manipulation on baseline or stress-induced corticosterone, but carotenoid supplementation was associated with an increase in a measure of chronic stress (heterophil/lymphocyte ratio), and the corticosterone response to handling decreased over the course of the study. Our results suggest that corticosterone may be linked to colour expression more broadly than previously recognised, including psittacofulvin and structural coloration in parrots, and they confirm the independence of plumage pigmentation in parrots from carotenoid accumulation. Moreover, our study provides new insight into the stress responses of Psittaciformes, one of the most highly threatened avian orders.

Gait and electromyographic alterations due to early onset of injury and eventual rupture of the cranial cruciate ligament in dogs: A pilot study.

OBJECTIVE: Identify relevant electromyography (EMG), kinematic, and kinetic changes resulting from monopolar radiofrequency energy (MRFE)-induced cranial cruciate ligament (CCL) injury and eventual rupture in dogs. STUDY DESIGN: Experimental, repeated measures. ANIMALS: Five purpose-bred female dogs free of orthopedic and neurologic disease. METHODS: Surface EMG, joint kinematics, and ground reaction forces were assessed at a trot in the pelvic limbs at baseline, at 2 and 4 weeks after unilateral MRFE-induced CCL injury, and at 4, 8, and 16 weeks after CCL rupture (CCLR). RESULTS: After MRFE-induced injury, average hip joint range of motion (ROM) during stance decreased within the untreated pelvic limb. After CCLR, stifle flexion angles decreased within the treated limb at 8 weeks and within the untreated pelvic limb at all time points, whereas average tarsal joint ROM decreased in the treated limb and increased in the untreated limb. Peak vertical ground reaction force and impulse decreased within the treated limb. Qualitative alterations of many EMG values were noted after MRFE-induced injury and CCLR, although significant differences between limbs or from baseline values were not detected. CONCLUSION: Monopolar radiofrequency energy-induced injury altered contralateral hip kinematics, suggesting early regional compensatory gait alterations. After CCLR, additional compensatory gait patterns occurred in both pelvic limbs. CLINICAL IMPACT: The qualitative analysis of trial-averaged EMG data in this small population supports a relationship between neuromuscular function and induced CCL injury leading to rupture.

Brønsted Base Assisted Photoredox Catalysis: Proton Coupled Electron Transfer for Remote C-C Bond Formation via Amidyl Radicals.

The synthesis of alkyne- and alkene-decorated lactams has been achieved through a photoredox-initiated radical cascade reaction. The developed Brønsted base assisted, photoredox-catalyzed, intramolecular 5-exo-trig cyclization/intermolecular radical addition/elimination reaction provides facile access to functionalized γ-lactams, with good functional group tolerance and high yields.

Effect of Rear Wheel Suspension on Tilt-in-Space Wheelchair Shock and Vibration Attenuation.

BACKGROUND: Suspension systems are designed to reduce shock and vibration exposure. An aftermarket rear-wheel suspension system is now available for manual tilt-in-space wheelchairs. OBJECTIVE: To compare quantifiable shock and vibration on a rigid manual tilt-in-space wheelchair to published data on manual wheelchairs and to determine whether aftermarket rear suspension system will significantly decrease shock exposure when traversing common obstacles. DESIGN: Cross-sectional. SETTING: Research laboratory. PARTICIPANTS: Ten healthy non-wheelchair users. METHODS: Subjects seated in a manual tilt-in-space wheelchair were pushed over 4 different obstacles (an exterior door threshold, truncated domes, 2-cm descent, and 2-cm ascent) with the chair as manufactured and with the suspension system installed. MAIN OUTCOME MEASUREMENTS: Superior/inferior and anterior/posterior accelerations were assessed at the seat pan with and without the use of ISO 2631-1 standards. Peak accelerations were analyzed from the door threshold, 2-cm descent and 2-cm ascent. Root mean square acceleration (RMSa) values were analyzed from the truncated domes, and vibration dose value (VDV) was analyzed for all surfaces. RESULTS: There were no differences in time spent over the 4 obstacles between rigid and suspended conditions (P≥.064). Suspension decreased the peak acceleration at the rear wheel when it initially impacted the door threshold, and when the rear wheel traversed the 2-cm descent and ascent (P≤.043). ISO 2631-1 frequency weighting, placing emphasis on frequencies most harmful to humans, also supports suspension reducing peak accelerations at the rear wheel both when it initially impacted and left the door threshold, and when the rear wheel descended 2 cm (P≤.049). Suspension also reduced the truncated dome RMSa as well as the door threshold, 2-cm descent, and total VDV (P≤.041). CONCLUSIONS: The results indicate that rigid manual tilt-in-space wheelchairs respond to rough surfaces in a similar fashion to previously studied rigid wheelchairs. Furthermore, the aftermarket suspension system reduces some aspects of shock and vibration exposure, also consistent with previously studied suspension systems. LEVEL OF EVIDENCE: NA.

Functional factors that are important correlates to physical activity in people with multiple sclerosis: a pilot study.

PURPOSE: Identify functional factors that are important correlates to physical activity levels among people with multiple sclerosis. METHODS: A total of eight functional tests were conducted and physical activity was objectively measured (Actigraph GT3X accelerometer) for one week in 34 people with multiple sclerosis. A corrected Akaike Information Criterion analysis was performed to identify the strongest correlates with moderate-to-vigorous physical activity, total activity and sedentary time. RESULTS: The multiple regression analysis converged on a model for moderate-to-vigorous physical activity (R2 = 0.31, F = 6.97, p= 0.003) that included total strength of the less-affected leg (partial r = 0.46, p = 0.007) and average peg test performance (partial r = -0.30, p = 0.087). The model for total activity (R2 = 0.40, F = 10.51, p < 0.001) included five times sit-to-stand performance (partial r= -0.44, p = 0.010) and total strength of the less-affected leg (partial r = 0.31, p = 0.077). The model for sedentary time (R2=0.22, F = 9.23, p = 0.005) only included total strength of the more affected leg (r= -0.47, p = 0.005). CONCLUSION: These results suggest that leg strength, manual dexterity and the ability to perform functional tasks may be important correlates with physical activity levels in people with multiple sclerosis. The findings of this pilot study can inform future investigations aiming to increase physical activity levels or develop improved rehabilitation protocols for people with multiple sclerosis. Implications for Rehabilitation Physical activity is an effective means of improving the symptoms associated with multiple sclerosis. Participation in physical activity by people with multiple sclerosis may be affected by functional factors such as leg strength, manual dexterity and the ability to rise from a seated position. Bilateral leg strength differences should be assessed and addressed in people with multiple sclerosis.

Long-distance flights and high-risk breeding by nomadic waterbirds on desert salt lakes.

Understanding and conserving mobile species presents complex challenges, especially for animals in stochastic or changing environments. Nomadic waterbirds must locate temporary water in arid biomes where rainfall is highly unpredictable in space and time. To achieve this they need to travel over vast spatial scales and time arrival to exploit pulses in food resources. How they achieve this is an enduring mystery.  We investigated these challenges in the colonial-nesting Banded Stilt (Cladorhynchus leucocephalus), a nomadic shorebird of conservation concern. Hitherto, Banded Stilts were hypothesized to have only 1-2 chances to breed during their long lifetime, when flooding rain fills desert salt lakes, triggering mass-hatching of brine shrimp. Over 6 years, we satellite tagged 57 individuals, conducted 21 aerial surveys to detect nesting colonies on 14 Australian desert salt lakes, and analyzed 3 decades of Landsat and MODIS satellite imagery to quantify salt-lake flood frequency and extent. Within days of distant inland rainfall, Banded Stilts flew 1,000-2,000 km to reach flooded salt lakes. On arrival, females laid over half their body weight in eggs. We detected nesting episodes across the species' range at 7 times the frequency reported during the previous 80 years. Nesting colonies of thousands formed following minor floods, yet most were subsequently abandoned when the water rapidly evaporated prior to egg hatching. Satellite imagery revealed twice as many flood events sufficient for breeding-colony initiation as recorded colonies, suggesting that nesting at remote sites has been underdetected. Individuals took risk on uncertain breeding opportunities by responding to frequent minor flood events between infrequent extensive flooding, exemplifying the extreme adaptability and trade-offs of species exploiting unstable environments. The conservation challenges of nest predation by overabundant native gulls and anthropogenic modifications to salt lakes filling frequencies require investigation, as do the physiological and navigational mechanisms that enable such extreme strategies.

Host heterozygosity and genotype rarity affect viral dynamics in an avian subspecies complex.

Genetic diversity at community, population and individual levels is thought to influence the spread of infectious disease. At the individual level, inbreeding and heterozygosity are associated with increased risk of infection and disease severity. Host genotype rarity may also reduce infection risk if pathogens are co-adapted to common or local hosts, but to date, no studies have investigated the relative importance of genotype rarity and heterozygosity for infection in a wild, sexually reproducing vertebrate. With beak and feather disease virus (BFDV) infection in a wild parrot (Platycercus elegans), we show that both heterozygosity and genotype rarity of individual hosts predicted infection, but in contrasting ways. Heterozygosity was negatively associated with probability of infection, but not with infection load. In contrast, increased host genotype rarity was associated with lower viral load in infected individuals, but did not predict infection probability. These effects were largely consistent across subspecies, but were not evident at the population level. Subspecies and age were also strongly associated with infection. Our study provides novel insights into infection dynamics by quantifying rarity and diversity simultaneously. We elucidate roles that host genetic diversity can play in infection dynamics, with implications for understanding population divergence, intraspecific diversity and conservation.

Longitudinal Assessment of Bone Mineral Density and Body Composition in Competitive Cyclists.

Baker, BS and Reiser II, RF. A longitudinal assessment of bone mineral density and body composition in competitive cyclists. J Strength Cond Res 31(11): 2969-2976, 2017-Competitive cycling has been associated with low bone mineral density (BMD); however, BMD is a multifaceted issue. The purpose of this study was to investigate how age (18-49 years), sex, USA Cycling Category (elite-4), and racing type (road and multiple bikes), influenced body composition across a season in competitive cyclists. February marked the preseason, where 42 participants (22 males, 20 females) completed a health history and cycling questionnaire, 4-day dietary log and a dual-energy X-ray absorptiometry scan, and repeated the measures 180 ± 11 days later. Preseason BMD and Z-Scores were within healthy ranges and similar between sexes, age groups, competition levels and racing-type groups (p ≥ 0.053). Age was significantly correlated with whole group BMD (r = 0.309; p = 0.047). Postseason analysis revealed very encouraging findings as no significant changes in BMD or Z-Score were observed in any group (p ≥ 0.067). A significant main effect for time was found in all groups as lean mass (LM) decreased and fat mass increased across the season (p ≤ 0.001). Additional analysis showed a significant time × group interaction as cat. 1 riders decreased body mass and body mass index, whereas cat. 4 riders responded in the opposite direction (p ≤ 0.037). Postseason correlations highlighted significant positive relationships between BMD and age, LM, and Kcal ingested (r ≥ 0.309; p ≤ 0.047). The only significant negative correlate of BMD was percent body fat (r = -0.359; p = 0.020). Armed with this information, cyclists and coaches should aim to prioritize balance between body mass and caloric intake while meeting the demands of training to minimize risk of cycling related low bone mass.

Biomechanical and histologic evaluation of the effects of underwater treadmill exercise on horses with experimentally induced osteoarthritis of the middle carpal joint.

OBJECTIVE To evaluate the effects of exercise in an underwater treadmill (UWT) on forelimb biomechanics and articular histologic outcomes in horses with experimentally induced osteoarthritis of the middle carpal joint. ANIMALS 16 horses. PROCEDURES An osteochondral fragment was induced arthroscopically (day 0) in 1 middle carpal joint of each horse. Beginning on day 15, horses were assigned to exercise in a UWT or in the UWT without water (simulating controlled hand walking) at the same speed, frequency, and duration. Thoracic and pelvic limb ground reaction forces, thoracic limb kinematics, and electromyographic results for select thoracic limb muscles acting on the carpi were collected on days -7 (baseline), 14, 42, and 70. Weekly evaluations included clinical assessments of lameness, response to carpal joint flexion, and goniometric measurements of thoracic limb articulations. At study conclusion, articular cartilage and synovial membrane from the middle carpal joints was histologically examined. RESULTS Exercise in a UWT significantly reduced synovial membrane inflammation and resulted in significant clinical improvements with regard to symmetric thoracic limb loading, uniform activation patterns of select thoracic limb muscles, and return to baseline values for carpal joint flexion, compared with results for horses with simulated hand walking. CONCLUSIONS AND CLINICAL RELEVANCE Overall improvements in thoracic limb function, joint range of motion, and synovial membrane integrity indicated that exercise in a UWT was a potentially viable therapeutic option for the management of carpal joint osteoarthritis in horses.