Ex vivo biomechanical evaluation of 2.4 mm LCP plate rod constructs versus 2.7 mm LCP applied to the feline tibia.

OBJECTIVE: To compare the stiffness and strength of three plate and rod fixation constructs applied to a feline tibial gap model. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Thirty-three unpaired tibiae obtained from skeletally mature cats. METHODS: The tibiae were randomly divided into three groups. The following implants were then applied to the feline tibiae prior to the creation of a 10 mm diaphyseal gap. Group 1: 2.4 mm locking compression plate (LCP) and 1.0 mm intramedullary pin (IMP). Group 2: 2.4 mm LCP and 1.6 mm IMP. Group 3: 2.7 mm LCP. Subsequently, each specimen was tested for torsion, axial compression, and axial load until construct failure. Student's t-tests were used to compare the torsional and axial stiffness, yield load, and maximum axial force. RESULTS: Group 2 had higher axial stiffness than group 3 (p = .013). Group 1 showed a lower maximum axial force and yield point than groups 2 and 3 (p < .01; p < .05, respectively). There were no among-group differences in torsional stiffness. CONCLUSION: Constructs with a 2.4 mm LCP and 1.6 mm IMP provided the strongest and most rigid constructs in a feline tibia gap model. CLINICAL SIGNIFICANCE: A plate-rod construct combining a 2.4 mm LCP and a 1.6 mm IMP is appropriate for achieving high implant stiffness and resisting maximum axial force in treatment of tibial fractures in cats.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Prolonged baleen hormone cycles suggest atypical reproductive endocrinology of female bowhead whales.

Serial measurements of hormone concentrations along baleen plates allow for reconstructions of mysticete whale reproductive histories. We assessed gestation and calving interval in bowhead whales (Balaena mysticetus) by measuring progesterone, oestradiol, corticosterone and nitrogen stable isotope ratios (δ15N) along baleen of 10 females from the eastern Canada-west Greenland population. Three immature females (body size < 14.32 m) had uniformly low progesterone concentrations across their baleen, while seven mature females (body size ≥ 14.35 m) had repeated, sustained elevations of progesterone indicative of pregnancies. The mean duration of progesterone elevations (23.6 ± 1.50 months) was considerably longer than the approximately 14 month gestation previously estimated for this species. We consider several possible explanations for this observation, including delayed implantation or sequential ovulations prior to gestation, strategies that would allow females to maximize their fitness in variable Arctic conditions, as well as suggest modified criteria defining gestation as a shorter component of the entire progesterone peak. Calving intervals varied within and among individuals (mean = 3.7 years; range = range 2.8-5.7 years), providing population-specific reproductive estimates for growth models used in bowhead whale management and conservation.

Age and Task Modulate Olfactory Sensitivity in the Florida Carpenter Ant Camponotus floridanus.

Age-related changes in behavior and sensory perception have been observed in a wide variety of animal species. In ants and other eusocial insects, workers often progress through an ordered sequence of olfactory-driven behavioral tasks. Notably, these behaviors are plastic, and workers adapt and rapidly switch tasks in response to changing environmental conditions. In the Florida carpenter ant, smaller minors typically perform most of the work needed to maintain the colony while the larger majors are specialized for nest defense and rarely engage in these routine tasks. Here, we investigate the effects of age and task group on olfactory responses to a series of odorant blends in minor and major worker castes. Consistent with their respective roles within the colony, we observed significant age-associated shifts in the olfactory responses of minors as they transitioned between behavioral states, whereas the responses of majors remained consistently low regardless of age. Furthermore, we identified a unitary compound, 3-methylindole, which elicited significantly higher responses and behavioral aversion in minor nurses than in similarly aged foragers suggesting that this compound may play an important role in brood care. Taken together, our results suggest that age- and task-associated shifts in olfactory physiology may play a critical role in the social organization of ant colonies. Simple Summary: Florida carpenter ants ( Camponotus floridanus ) live in colonies comprised of thousands of workers. The smallest workers, known as minors, engage in routine tasks such as nursing and foraging while the largest workers, known as majors, are thought to be soldiers specialized for defending the nest. How ant colonies allocate their workforce to address the dynamic and ever-changing needs of the colonies remains an open question in the field, but current evidence suggests that ant social behavior likely results from a combination of genetic/epigenetic, physiological, and systems-level processes. Here, we extend these studies by investigating the role of olfactory sensitivity in regulating ant behavior. Minor workers exhibited significant shifts in olfactory sensitivity and odor coding as they aged and switched tasks. The olfactory sensitivity of majors, however, remained relatively stable as they aged. From these studies, we also identified a single compound, 3-methylindole, which elicited significantly higher olfactory responses and aversive behavior in nurses compared to foragers, suggesting that this chemical may have a role in brood care. Overall, these studies support the hypothesis that changes in olfactory sensitivity play an important role in regulating social behavior in ants.

Hierarchical settlement behaviours of coral larvae to common coralline algae.

Natural regeneration of degraded reefs relies on the recruitment of larvae to restore populations. Intervention strategies are being developed to enhance this process through aquaculture production of coral larvae and their deployment as spat. Larval settlement relies on cues associated with crustose coralline algae (CCA) that are known to induce attachment and metamorphosis. To understand processes underpinning recruitment, we tested larval settlement responses of 15 coral species, to 15 species of CCA from the Great Barrier Reef (GBR). CCA in the family Lithophyllaceae were overall the best inducer across most coral species, with Titanoderma cf. tessellatum being the most effective species that induced at least 50% settlement in 14 of the coral species (mean 81%). Taxonomic level associations were found, with species of Porolithon inducing high settlement in the genus Acropora; while a previously understudied CCA, Sporolithon sp., was a strong inducer for the Lobophyllidae. Habitat-specific associations were detected, with CCA collected from similar light environment as the coral inducing higher levels of settlement. This study revealed the intimate relationships between coral larvae and CCA and provides optimal coral-algal species pairings that could be utilized to increase the success of larval settlement to generate healthy spat for reef restoration.

Olfactory sensitivity differentiates morphologically distinct worker castes in Camponotus floridanus.

BACKGROUND: Camponotus floridanus ant colonies are comprised of a single reproductive queen and thousands of sterile female offspring that consist of two morphologically distinct castes: smaller minors and larger majors. Minors perform most of the tasks within the colony, including brood care and food collection, whereas majors have fewer clear roles and have been hypothesized to act as a specialized solider caste associated with colony defense. The allocation of workers to these different tasks depends, in part, on the detection and processing of local information including pheromones and other chemical blends such as cuticular hydrocarbons. However, the role peripheral olfactory sensitivity plays in establishing and maintaining morphologically distinct worker castes and their associated behaviors remains largely unexplored. RESULTS: We examined the electrophysiological responses to general odorants, cuticular extracts, and a trail pheromone in adult minor and major C. floridanus workers, revealing that the repertoire of social behaviors is positively correlated with olfactory sensitivity. Minors in particular display primarily excitatory responses to olfactory stimuli, whereas major workers primarily manifest suppressed, sub-solvent responses. The notable exception to this paradigm is that both minors and majors display robust, dose-dependent excitatory responses to conspecific, non-nestmate cuticular extracts. Moreover, while both minors and majors actively aggress non-nestmate foes, the larger and physiologically distinct majors display significantly enhanced capabilities to rapidly subdue and kill their adversaries. CONCLUSIONS: Our studies reveal the behavioral repertoire of minors and majors aligns with profound shifts in peripheral olfactory sensitivity and odor coding. The data reported here support the hypothesis that minors are multipotential workers with broad excitatory sensitivity, and majors are dedicated soldiers with a highly specialized olfactory system for distinguishing non-nestmate foes. Overall, we conclude that C. floridanus majors do indeed represent a physiologically and behaviorally specialized soldier caste in which caste-specific olfactory sensitivity plays an important role in task allocation and the regulation of social behavior in ant colonies.

Physiological stretching induces a differential extracellular matrix gene expression response in acetabular labrum cells.

The acetabular labrum is a fibrocartilaginous ring surrounding the acetabulum and is important for hip stability and contact pressure dissipation through a sealing function. Injury of the labrum may contribute to hip-joint degeneration and development of secondary osteoarthritis. Understanding how extracellular matrix (ECM) production and remodelling is regulated is of key importance for successful tissue restoration. The present study hypothesised that physiological stretching enhanced the metabolic activity and altered the ECM gene expression in labrum cells. Primary bovine labrum cells were physiologically stretched for up to 5 d. 24 h after the last stretch cycle, changes in metabolic activity were measured using the PrestoBlue™ HS Cell Viability Reagent and ECM gene expression was examined using the quantitative polymerase chain reaction method. Targets of interest were further investigated using immunofluorescence and enzyme-linked immunosorbent assay. Metabolic activity was not affected by the stretching (0.9746 ± 0.0614, p > 0.05). Physiological stretching upregulated decorin (DCN) (1.8548 ± 0.4883, p = 0.002) as well as proteoglycan 4 (PRG4) (1.7714 ± 0.6600, p = 0.029) and downregulated biglycan (BGN) (0.7018 + 0.1567, p = 0.008), cartilage oligomeric matrix protein (COMP) (0.5747 ± 0.2650, p = 0.029), fibronectin (FN1) (0.5832 ± 0.0996, p < 0.001) and spondin 1 (SPON1) (0.6282 ± 0.3624, p = 0.044) gene expression. No difference in PRG4 and DCN abundance or release could be measured. The here identified mechanosensitive targets are known to play relevant roles in tissue organisation. Therefore, physiological stretching might play a role in labrum tissue homeostasis and regeneration.

Exposure-response relationship between K. brevis blooms and reporting of upper respiratory and neurotoxin-associated symptoms.

In southwest Florida, Karenia brevis (K. brevis) blooms occur frequently, can be very intense and persist over several years. Individuals living in coastal communities around the Gulf of Mexico are particularly vulnerable to brevetoxins released by K. brevis in seawater and carried inland within marine aerosol. Exposure to K. brevis occurs during residential, recreational, and occupational activities and has been associated with upper respiratory tract (URT) symptoms in healthy and medically vulnerable individuals. Additionally, ingestion of brevetoxin-contaminated seafood causes neurotoxic shellfish poisoning (NSP), and severe headaches prompting emergency department visits which occur in excess during K. brevis blooms. The current study examined a dose-response relationship between K. brevis in coastal waters and URT and NSP-like symptoms and headaches among southwest Florida residents. Data on past medical history (PMH) and medical symptoms were collected from the participants (n = 258) in five southwest Florida counties between June 2019 to August 2021. A dose-response relationship was observed between K. brevis blooms and reporting of URT and NSP-like symptoms and headaches. Reporting of NSP-like symptoms was higher among participants with a PMH of migraines, chronic fatigue syndrome (CFS) and mild memory loss, while the association of headaches with K. brevis blooms was accentuated among individuals with a PMH of migraines. These results suggest further investigations into the threshold of aerosolized brevetoxin dose required to elicit URT, headaches and/or NSP-like symptoms. These symptoms ultimately cause significant public health safety concerns, primarily among vulnerable populations with preexisting neurological conditions.

Absolute calibration of Fujifilm BAS-TR image plate response to laser driven protons up to 40 MeV.

Image plates (IPs) are a popular detector in the field of laser driven ion acceleration, owing to their high dynamic range and reusability. An absolute calibration of these detectors to laser-driven protons in the routinely produced tens of MeV energy range is, therefore, essential. In this paper, the response of Fujifilm BAS-TR IPs to 1-40 MeV protons is calibrated by employing the detectors in high resolution Thomson parabola spectrometers in conjunction with a CR-39 nuclear track detector to determine absolute proton numbers. While CR-39 was placed in front of the image plate for lower energy protons, it was placed behind the image plate for energies above 10 MeV using suitable metal filters sandwiched between the image plate and CR-39 to select specific energies. The measured response agrees well with previously reported calibrations as well as standard models of IP response, providing, for the first time, an absolute calibration over a large range of proton energies of relevance to current experiments.

Calibration of BAS-TR image plate response to GeV gold ions.

The response of the BAS-TR image plate (IP) was absolutely calibrated using a CR-39 track detector for high linear energy transfer Au ions up to ∼1.6 GeV (8.2 MeV/nucleon), accelerated by high-power lasers. The calibration was carried out by employing a high-resolution Thomson parabola spectrometer, which allowed resolving Au ions with closely spaced ionization states up to 58+. A response function was obtained by fitting the photo-stimulated luminescence per Au ion for different ion energies, which is broadly in agreement with that expected from ion stopping in the active layer of the IP. This calibration would allow quantifying the ion energy spectra for high energy Au ions, which is important for further investigation of the laser-based acceleration of heavy ion beams.

JIP3 links lysosome transport to regulation of multiple components of the axonal cytoskeleton.

Lysosome axonal transport is important for the clearance of cargoes sequestered by the endocytic and autophagic pathways. Building on observations that mutations in the JIP3 (MAPK8IP3) gene result in lysosome-filled axonal swellings, we analyzed the impact of JIP3 depletion on the cytoskeleton of human neurons. Dynamic focal lysosome accumulations were accompanied by disruption of the axonal periodic scaffold (spectrin, F-actin and myosin II) throughout each affected axon. Additionally, axonal microtubule organization was locally disrupted at each lysosome-filled swelling. This local axonal microtubule disorganization was accompanied by accumulations of both F-actin and myosin II. These results indicate that transport of axonal lysosomes is functionally interconnected with mechanisms that control the organization and maintenance of the axonal cytoskeleton. They have potential relevance to human neurological disease arising from JIP3 mutations as well as for neurodegenerative diseases associated with the focal accumulations of lysosomes within axonal swellings such as Alzheimer's disease.

The levonorgestrel intrauterine system for prevention of endometrial cancer in women with obesity: A cost-effectiveness study.

OBJECTIVE: To estimate the cost-effectiveness of the levonorgestrel intrauterine system (LNG-IUS) as an endometrial cancer prevention strategy in women with obesity. METHODS: A Markov decision-analytic model was used to compare 5 strategies in women with a body mass index of 30 or greater: 1) Usual care 2) LNG-IUS for 5 years 3) LNG-IUS for 7 years 4) LNG-IUS for 5 years, replaced once for a total of 10 years 5) LNG-IUS for 7 years, replaced once for a total of 14 years. Obesity was presumed to be associated with a 3-fold relative risk of endometrial cancer incidence and a 2.65-fold disease-specific mortality. The LNG-IUS was assumed to confer a 50% reduction in cancer incidence over the period of the LNG-IUS insertion. Outcomes were incremental cost-effectiveness ratios, calculated in 2019 Canadian dollars (CAD) per year of life saved. One-way and two-way sensitivity analyses were performed. RESULTS: The LNG-IUS strategy was considered cost-effective if the cost of the intervention is less than $66,400 CAD ($50,000 US dollars) per year of life saved. The strategy becomes cost-effective if the LNG-IUS is inserted at age 57 (strategy #2), at age 52 for strategy #3, at age 51 for strategy #4 and at age 45 for strategy #5, when compared to usual care. The results are stable to variations in cost but sensitive to the estimated risk reduction of the LNG-IUS and the impact of obesity on endometrial cancer incidence and disease-specific mortality. CONCLUSION: The LNG-IUS is a cost-effective method of endometrial cancer prevention in women with obesity.

Distinct populations of cortical pyramidal neurons mediate drug reward and aversion.

Processing within the anterior cingulate cortex (ACC) is crucial for the patterning of appropriate behavior, and ACC dysfunction following chronic drug use is thought to play a major role in drug addiction. However, cortical pyramidal projection neurons can be subdivided into two major types (intratelencephalic (IT) and pyramidal tract (PT)), with distinct inputs and projection targets, molecular and receptor profiles, morphologies and electrophysiological properties. Yet, how each of these cell populations modulate behavior related to addiction is unknown. We demonstrate that PT neurons regulate the positive features of a drug experience whereas IT neurons regulate the negative features. These findings support a revised theory of cortical function in addiction, with distinct cells and circuits mediating reward and aversion.

Perception versus Reality: The Relationship between Subjective and Objective Measures of Sleep When On-call under Simulated Laboratory Conditions.

BACKGROUND: On-call working arrangements have been shown to negatively impact sleep. However, workers may perceive their sleep to be worse than it actually is. The aim of this study was to compare participants' pre- and post-sleep estimates of sleep duration and sleep quality with objectively measured sleep when on-call under laboratory conditions. PARTICIPANTS: 72 healthy, adult males. METHODS: Analyses were performed on three interrelated studies, all of which consisted of four nights in a sleep laboratory. Following adaptation and baseline nights were two on-call nights (sleep opportunity 23:00 h - 07:00 h). Before and after each sleep opportunity, participants provided subjective estimates of sleep. Sleep was objectively measured using polysomnography. RESULTS: Estimated sleep duration (6.74 ± 1.13 h) and sleep onset latency (20.55 ± 14.85 min) were significantly poorer than objectively measured sleep outcomes (sleep duration 7.21 ± 1.25 h; sleep latency 13.20 ± 10.06 min). Of the variance in post-sleep estimated sleep duration, 14% was associated with objectively measured minutes of N3 (R2Δ = 0.55) and REM (R2Δ = 0.75). Additionally, 14% of post-sleep sleep quality estimation variance was associated with minutes of N2 (R2Δ = 0.60) and N3 (R2Δ = 0.79), measured by polysomnography. CONCLUSIONS: Some objective measures of sleep were associated with subjective estimates of sleep duration and sleep quality. However, individuals may overestimate sleep onset latency and underestimate sleep duration during on-call periods. It may be beneficial for on-call workers to actively reflect on feelings of fatigue/alertness for workplace fatigue management, rather than relying solely on estimates of sleep.

DYNLT1 gene expression is downregulated in whole blood of patients at different Huntington's disease stages.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG nucleotide expansion, which encodes the amino acid glutamine, in the huntingtin gene. HD is characterized by motor, cognitive, and psychiatric dysfunctions. In a previous study, we showed by qPCR that some genes altered in an HD mouse model were also altered in blood of HD patients. These alterations were mainly with respect to the dynein family. Therefore, this study aimed to investigate whether dynein light chain Tctex type 1 (DYNLT1) is altered in HD patients and if there is a correlation between DYNLT1 gene expression changes and disease progression. We assessed the DYNLT1 gene expression in the blood of 19 HD patients and 20 healthy age-matched controls. Also, in 6 of these patients, we analyzed the DYNLT1 expression at two time points, 3 years apart. The DYNLT1 gene expression in the whole blood of HD patients was significantly downregulated and this difference was widened in later stages. These data suggest that DYNLT1 could emerge as a peripheral prognostic indicator in HD and, also, might be a target for potential intervention in the future.

Perioperative outcomes of women with and without class III obesity undergoing hysterectomy for endometrioid endometrial cancer: A population-based study.

OBJECTIVE: Population-based data on perioperative complications among women with endometrial cancer and severe obesity are lacking. We evaluated 30-day complication rates among women with and without class III obesity (body mass index ≥ 40 kg/m2) undergoing primary surgical management for endometrioid endometrial cancer (EEC), and how outcomes differed according to surgical approach (open vs. minimally invasive). METHODS: We performed a retrospective population-based cohort study of women with EEC undergoing hysterectomy in Ontario, Canada, between 2006 and 2015. We evaluated perioperative complications in the whole cohort, and in a 1:1 matched analysis using hard and propensity score matching to ensure similar distributions of patient, tumour, provider and institution-level factors between women with and without class III obesity (identified using a surgical billing code). The primary outcome of interest was the 30-day perioperative complication rate. RESULTS: 12,112 women met inclusion criteria; 2697 (22.3%) had class III obesity. We matched 2320 (86%) women with class III obesity to those without. The composite complication rate was significantly higher among women with class III obesity (23.2% vs. 18.4%, standardized mean difference [SMD] = 0.12), primarily due to wound infection/disruption (12.1% vs. 6.2%). There was no difference in outcomes for women with and without class III obesity when a minimally invasive approach was used. CONCLUSIONS: Wound infection/disruption was increased for women with class III obesity compared to women without. Otherwise, perioperative complications were similar between the matched pairs. When minimally invasive approaches were used, women with class III obesity had a similar risk of complications as women without obesity.

Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats.

Drug addiction is a chronic disease defined by a complex set of characteristics, including loss of control over drug intake and persistent drug craving, which primarily affects a small percentage of people who try drugs. Although many models have been developed to study individual aspects of drug use, there is great translational value in having an animal model that encompasses multiple aspects of the human disease, including the variation in severity observed in humans. Here, we describe an intermittent access model of cocaine self-administration that produces a subset of rats that display many of the core features of addiction, including escalation of drug intake, a binge-like pattern of drug use, robust locomotor sensitization, and high levels of drug-seeking during cue-induced reinstatement. This group is compared with rats that have the same drug history but do not develop this pattern of drug-taking and drug-seeking, as well as rats that undergo a traditional continuous access paradigm. Finally, we observe that high levels of cocaine consumption produce long-term changes in intracellular calcium signaling in the dorsomedial striatum.

Lateral stability in healthy proximal interphalangeal joints versus surface replacement and silicone arthroplasty: Results of a three-dimensional motion analysis study.

The objective of this study was to quantify the lateral stability of healthy proximal interphalangeal (PIP) joints using a three-dimensional motion capture system and compare it to affected joints after surface replacement or silicone arthroplasty. Three study groups comprised healthy participants, patients with PIP joint osteoarthritis treated with a surface replacing implant (CapFlex-PIP) and those with a silicone arthroplasty. All participants were matched on gender and finger, and the two patient groups were also matched on length of follow-up. An optical tracking system was used to measure lateral stability. Radial and ulnar stability of the PIP joint was measured as the maximal lateral deviation angle of the middle phalanx under loads of 40 g, 90 g and 170g at 0°, 20° and 45° PIP joint flexion. Measurement reliability was evaluated with a test-retest trial [intraclass correlation coefficient (ICC)]. A total of 30 joints were assessed with 5 index and 5 middle fingers per test group. Lateral deviation increased proportionally with applied weight. Silicone arthroplasty joints had a higher median lateral deviation angle of 5.1° (range 0.7-7.9) than healthy [3.0° (0.5-11.0)] and surface replacement joints [3.3° (0.3-7.4)] at 45° flexion and under 170g load. Test-retest reliability was high with an ICC of 0.93. Lateral PIP joint stability is highly variable in both healthy participants and patients after PIP joint arthroplasty. PIP joint surface replacement arthroplasty tends to achieve better anatomical stability compared to flexible silicone implants.