A visual marker for early atrophy of the supraspinatus muscle on conventional MRI: introduction of the blackbird sign.

OBJECTIVES: The aim of this study was to introduce the blackbird sign as a fast, qualitative measure of early supraspinatus (SSP) muscle atrophy and to correlate the sign with quantitatively assessed muscle volume and intramuscular fat fraction (FF) in patients with full-thickness SSP tears. MATERIALS AND METHODS: The blackbird sign describes the asymmetric pattern of early SSP atrophy: on sagittal MR images, the supero-posterior contour of the muscle becomes concave, resembling the shape of a blackbird. MRIs of patients with full-thickness SSP tears were retrospectively reviewed for the presence of the blackbird and tangent signs. Patients were then divided into group 1: negative tangent sign and negative blackbird sign (n = 67), group 2: negative tangent sign and positive blackbird sign (n = 31), and group 3: positive tangent sign (n = 32). A 2-point Dixon sequence was acquired in all patients from which quantitative FF and muscle volumes were calculated. RESULTS: In total 130 patients (mean age 67 ± 11 years) were included. Mean SSP volume was significantly smaller in group 3 (15.8 ± 8.1 cm3) compared to group 2 (23.9 ± 7.0 cm3, p = 0.01) and group 1 (29.7 ± 9.1 cm3, p < 0.01). Significantly lower muscle volumes were also found in group 2 compared to group 1 (p = 0.02), confirming that the blackbird sign is able to identify early SSP atrophy. Mean FF in the SSP was significantly higher in group 3 (18.5 ± 4.4%) compared to group 2 (10.9 ± 4.7%, p < 0.01) and group 1 (6.1 ± 2.6%, p < 0.01). CONCLUSION: Visual assessment of early muscle atrophy of the SSP is feasible and reproducible using the blackbird sign, allowing the diagnosis of early SSP atrophy. CLINICAL RELEVANCE STATEMENT: In routine clinical practice, the blackbird sign may be a useful tool for assessing early muscle degeneration before the risk of postoperative rotator cuff re-tears increases with progressive muscle atrophy and fatty infiltration. KEY POINTS: Quantitative measurements of rotator cuff injuries require time, limiting clinical practicality. The proposed blackbird sign is able to identify early SSP atrophy. Reader agreement for the blackbird sign was substantial, demonstrating reproducibility and ease of implementation in the clinical routine.

Traditional Cardiovascular Risk Factors Associated with Diagonal Earlobe Crease (Frank Sign) in Mexican Adults: Aging, Obesity, Arterial Hypertension, and Being Male Are the Most Important.

Introduction: Cardiovascular risk factors such as obesity, type 2 diabetes, hypertension, smoking, and dyslipidemia enfold heart disease morbimortality. Diagonal earlobe crease has been proposed as a prognostic marker of extension and severity of illness in patients with acute coronary syndrome. But its usefulness remains unclear in patients with or without coronary disease. Methods: A case-control study was carried out on a total of 805 patients with and without cardiovascular risk factors or acute coronary syndrome. Univariate and multivariate binary logistic regression analyses were used to determine the probability of having diagonal earlobe crease with the presence of cardiovascular risk factors and acute coronary syndrome. Data were summarized as odds ratio with 95% confidence intervals and P values. Results: An unadjusted (univariate) analysis showed that being male, being older than 55 years, obesity, type 2 diabetes mellitus, arterial hypertension, smoking, and dyslipidemia, as well as having acute coronary syndrome, were associated with the presence of diagonal earlobe crease. The multivariate analysis showed that men (OR 1.6, 95% IC 1.1-2.4, P=0.007), being over 55 years old (OR 4.8, 95% IC 3.2-7.2, P < 0.001), being obese (OR 2.1, 95% IC 1.4-3.1, P < 0.001), having arterial hypertension (1.5, 95% IC 1.1-2.3, P=0.025), or suffering from acute coronary syndrome (OR 5.3, 95% IC 2.5-11.1, P < 0.001), were independent factors associated with diagonal earlobe crease. The rest of cardiovascular risk factors were not relevant in the multivariate model. Conclusions: In Mexican adults, having an acute coronary syndrome is not the only factor associated with diagonal earlobe crease but also being a man, older than 55 years, having high blood pressure and obesity. Diagonal earlobe crease may simply be caused by changes in the skin and connective tissues of the ears because of the aging process, obesity, and/or being male. These factors, by themselves, enfold cardiovascular risk due to well-known pathophysiological causes.

Does a postmortem redistribution affect the concentrations of the 7 azaindole-derived synthetic cannabinoid 5F-MDMB-P7AICA in tissues and body fluids following pulmonary administration to pigs?

Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC-MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.

Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder.

BACKGROUND: The understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI). METHODS: 67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[-]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance). RESULTS: MDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia. CONCLUSION: IR appears to be linked to depressive symptoms characteristic of the "metabolic" MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI.

Maxillary reconstruction with horizontally oriented scapular tip free flap: outcomes in orbital support and palate closure.

BACKGROUND: Current indications of maxillary reconstruction with scapular tip free flap (STFF) are palatoalveolar defects associated with zygomaticomaxillary buttress and/or orbital floor defects. STFF can be placed either horizontally or vertically. Horizontal placement usually allows ideal palatal conformation, preventing oronasal communication, but has been argued to compromise orbital support and projection of the midface, whereas vertical placement is advocated for midface support but may be insufficient for the complete closure of the palate. The present study focuses on the horizontal placing of STFF to allow complete palate reconstruction and fistulae prevention while still obtaining optimal midface projection and orbital support. MATERIALS AND METHODS: This study included 21 case complex maxillary reconstructions with this flap, in which the horizontally placed scapular tip component replaced the palate, a muscular flap component was included for midface volume restoration, and an alloplastic implant was utilized for supporting the orbital content when needed. RESULTS: None of the patients presented palatal fistulas or alterations in the orbital support. CONCLUSION: A multilevel approach was proposed according to the maxillectomy defect. This experience supported the horizontal insetting of STFF to allow palatal fistulae prevention while still obtaining an optimal midface projection and orbital support.

Persistent Luminescence Nanosensors: A Generalized Optode-Based Platform for Autofluorescence-Free Sensing in Biological Systems.

Fluorescent nanosensors have revolutionized diagnostics and our ability to monitor cellular dynamics. Yet, distinguishing sensor signals from autofluorescence remains a challenge. Here, we merged optode-based sensing with near-infrared-emitting ZnGa2O4:Cr3+ persistent luminescence nanoparticles (PLNPs) to create nanocomposites for autofluorescence-free "glow-in-the-dark" sensing. Hydrophobic modification and incorporation of the persistent luminescence nanoparticles into an optode-based nanoparticle core yielded persistent luminescence nanosensors (PLNs) for five analytes (K+, Na+, Ca2+, pH, and O2) via two distinct mechanisms. We demonstrated the viability of the PLNs by quantifying K+ in fetal bovine serum, calibrating the pH PLNs in the same, and ratiometrically monitoring O2 metabolism in cultures of Saccharomyces cerevisiae, all the while overcoming their respective autofluorescence signatures. This highly modular platform allows for facile tuning of the sensing functionality, optical properties, and surface chemistry and promises high signal-to-noise ratios in complex optical environments.

IL-23p19 in osteoarthritic pain and disease.

OBJECTIVE: We have previously reported that the interleukin-23 p19 subunit (IL-23p19) is required for experimental inflammatory arthritic pain-like behavior and disease. Even though inflammation is often a characteristic feature of osteoarthritis (OA), IL-23 is not usually considered as a therapeutic target in OA. We began to explore the role of IL-23p19 in OA pain and disease utilizing mouse models of OA and patient samples. DESIGN: The role of IL-23p19 in two mouse models of OA, namely collagenase-induced OA and monosodium iodoacetate-induced OA, was investigated using gene-deficient male mice. Pain-like behavior and arthritis were assessed by relative static weight distribution and histology, respectively. In knee synovial tissues from a small cohort of human OA patients, a correlation analysis was performed between IL-23A gene expression and Oxford knee score (OKS), a validated Patient Reported Outcome Measure. RESULTS: We present evidence that i) IL-23p19 is required for the development of pain-like behavior and optimal disease, including cartilage damage and osteophyte formation, in two experimental OA models and ii) IL-23A gene expression in OA knee synovial tissues correlates with a lower OKS (r = -0.742, p = 0.0057). CONCLUSIONS: The findings support the possible targeting of IL-23 as a treatment for OA pain and disease progression.

Diversity and molecular characterization of insect-specific flaviviruses in mosquitoes (Diptera: Culicidae) collected in central and northern Argentina.

The genus Flavivirus comprises approximately 80 different viruses. Phylogenetic relationships among its members indicate a clear ecological separation between those viruses transmitted by mosquitoes, ticks, with no known vector, and insect-specific Flaviviruses. The diversity and phylogenetic relationships among insect-specific flaviviruses circulating in the central and northern regions of Argentina were studied by performing molecular detection and characterization of the NS5 protein gene in mosquitoes collected in Córdoba, Chaco and Tucumán provinces. Overall, 68 out of 1776 pools were positive. CxFV, KRV and CFAV circulate in the 3 studied provinces. Several mosquito species (Aedes aegypti, Culex bidens, Cx. dolosus, Cx. interfor, Cx. quinquefasciatus, Cx. saltanensis, Haemagogus spegazzini) were found infected. A wide circulation of CxFV was observed in the central-northern region of Argentina. CxFV strains detected in our study clustered with strains circulating in Santa Fe and Buenos Aires provinces (Argentina), and other countries such as Indonesia, Mexico, Uganda and Taiwan. The presence of these viruses in mosquitoes could play an important role from the public health perspective, because it has been shown that previous CxFV infection can increase or block the infection of the mosquito by other pathogenic flaviviruses.

A simplified molecular tool for detecting the Chagas etiological agent using a vector feces sample in field conditions.

Triatomine bugs are vectors of Trypanosoma cruzi, the etiologic agent of Chagas disease in the American continent. Here, we have tested a loop-mediated isothermal amplification (LAMP) test for a direct detection of T. cruzi in feces of Triatoma infestans, the main vector of this parasite in the Southern Cone of America. The analytical evaluation showed positive results with samples of triatomine feces artificially inoculated with DNA from strains of T. cruzi corresponding to each Discrete Typing Units (I-VI), with a sensitivity of up to one parasite per reaction. Conversely, the reaction yielded negative results when tested with DNA from Trypanosoma rangeli and other phylogenetically related and unrelated organisms. In triatomines captured under real field conditions (from urban households), and defined as positive or negative for T. cruzi using the reference microscopy technique, the LAMP test achieved a concordance of 100 %. Our results demonstrate that this LAMP reaction exhibits excellent analytical specificity and sensitivity without interference from the fecal matrix, since all the reactions were conducted without purification steps. This simple molecular diagnostic technique can be easily used by vector control agencies under field conditions.

Association of neighborhood socioeconomic status with echocardiographic parameters and re-admission following transcatheter aortic valve replacement.

BACKGROUND: Data on predictors of poor hemodynamic presentation and rehospitalizations following transcatheter aortic valve replacement (TAVR) are limited. We evaluate the association between neighborhood socioeconomic status (NSES) on echocardiographic presentation and post-TAVR readmission at a high-volume institution. METHODS: All patients undergoing TAVR at a single institution between 2012 and 2022 were included. Patient addresses, baseline variables including Society of Thoracic Surgeons (STS) preoperative risk of mortality and frailty, and post-procedural outcomes were extracted from electronic health records. Using a validated US Census Bureau Index, the NSES of each patient (1-100) was tabulated, with lower values correlating to increased social deprivation. Patients were separated into four ranked groups based on NSES (rank 1: 1-25, rank 4: 76-100). Multivariable regression was performed to determine variables associated with number of days hospitalized in one-year following index TAVR procedure. RESULTS: A total of 2031 patients were included. The median NSES was 68 (IQR: 53-80). There was a total of 232 (11.4%) readmissions. The median number of days hospitalized in one year following TAVR was 4 (interquartile range [IQR]: 2-7) After adjusting for baseline variables including STS risk score and patient frailty, compared to patients in the lowest ranked socioeconomic group, patients of higher NSES were associated with lower aortic valve gradients at baselines (Exp[ß]=0.997, 95% CI: 0.993-0.999, P=0.049). Additionally, compared to patients in the lowest ranked socioeconomic group, patients of NSES were associated with shorter duration of readmission after risk-factor adjustments (Exp[ß]=0.996, 95% CI: 0.992-0.999, P=0.032). CONCLUSIONS: Patients of lower socioeconomic status are associated with higher aortic valve gradient at baseline and more days hospitalized in the first year after their index TAVR procedure after adjusting for other risk factors. As TAVR volume continues to expand, physicians and health systems must consider this independent factor when determining patient prognosis and readmission policies.

ACR Appropriateness Criteria® Acute Pelvic Pain in the Reproductive Age Group: 2023 Update.

This review focuses on the initial imaging in the reproductive age adult population with acute pelvic pain, including patients with positive and negative beta-human chorionic gonadotropin (ß-hCG) levels with suspected gynecological and nongynecological etiology. For all patients, a combination of transabdominal and transvaginal pelvic ultrasound with Doppler is usually appropriate as an initial imaging study. If nongynecological etiology in patients with negative ß-hCG is suspected, then CT of the abdomen and pelvis with or without contrast is also usually appropriate. In patients with positive ß-hCG and suspected nongynecological etiology, CT of the abdomen and pelvis with contrast and MRI of the abdomen and pelvis without contrast may be appropriate. In patients with negative ß-hCG and suspected gynecological etiology, CT of the abdomen and pelvis with contrast, MRI of pelvis without contrast, or MRI of pelvis with and without contrast may be appropriate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Correction: A novel power-amplified jumping behavior in larval beetles (Coleoptera: Laemophloeidae).

[This corrects the article DOI: 10.1371/journal.pone.0256509.].

Sequencing-guided design of genetically encoded small RNAs targeting CAG repeats for selective inhibition of mutant huntingtin.

Huntington's disease (HD) is an incurable neurodegenerative disorder caused by genetic expansion of a CAG repeat sequence in one allele of the huntingtin (HTT) gene. Reducing expression of the mutant HTT (mutHTT) protein has remained a clear therapeutic goal, but reduction of wild-type HTT (wtHTT) is undesirable, as it compromises gene function and potential therapeutic efficacy. One promising allele-selective approach involves targeting the CAG repeat expansion with steric binding small RNAs bearing central mismatches. However, successful genetic encoding requires consistent placement of mismatches to the target within the small RNA guide sequence, which involves 5' processing precision by cellular enzymes. Here, we used small RNA sequencing (RNA-seq) to monitor the processing precision of a limited set of CAG repeat-targeted small RNAs expressed from multiple scaffold contexts. Small RNA-seq identified expression constructs with high-guide strand 5' processing precision and promising allele-selective inhibition of mutHTT. Transcriptome-wide mRNA-seq also identified an allele-selective small RNA with a favorable off-target profile. These results support continued investigation and optimization of genetically encoded repeat-targeted small RNAs for allele-selective HD gene therapy and underscore the value of sequencing methods to balance specificity with allele selectivity during the design and selection process.

Qualitative study of new doctor induction and socialisation.

AIM: Junior doctors joining EDs are required to rapidly acquire new knowledge and skills, but there is little research describing how this process can be facilitated. We aimed to understand what would make ED formal induction and early socialisation more effective. METHODS: Qualitative study; informal interviews of junior doctors, consultants and nursing staff and direct observation of clinical interactions, induction and training in a single ED in an English Emergency Department between August and October 2018. We used constant comparison to identify and develop themes. FINDINGS: New junior doctors identified that early socialisation should facilitate patient safety and a safe learning space, with much of this process dependent on consultant interactions rather than formal induction. Clear themes around helpful and unhelpful consultant support and supervision were identified. Consultants who acknowledged their own fallibility and maintained approachability produced a safe learning environment, while consultants who lacked interest in their juniors, publicly humiliated them or disregarded the junior doctors' suggestions were seen as unhelpful and unconstructive. CONCLUSION: Effective socialisation, consistent with previous literature, was identified as critical. Junior doctors see consultant behaviours and interactions as key to creating a safe learning space.

Tumor-Like Distal Femoral Cortical Irregularities of the Knee in Adolescent Competitive Alpine Skiers: Longitudinal Assessment Over 48 Months.

BACKGROUND: Tumor-like distal femoral cortical irregularities (DFCIs) are a frequent incidental finding on knee magnetic resonance imaging (MRI) and are common in young competitive athletes. PURPOSE: To assess and compare the morphology and prevalence of DFCIs in competitive alpine skiers over 48 months during adolescence. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Adolescent competitive alpine skiers were prospectively recruited in 2018 and received bilateral 3-T MRI of the knee at baseline and after 48 months. All MRIs were evaluated for the presence and location of DFCIs, which were marked at 1 of 3 anatomic positions: (1) the femoral attachment of the medial head of the gastrocnemius muscle, (2) the lateral head of the gastrocnemius muscle, or (3) the attachment of the adductor magnus aponeurosis. The size of the DFCI was measured by 2 radiologists independently. The measurements were compared using the Wilcoxon signed-rank test, the interclass correlation coefficient (ICC), and Cohen Kappa. RESULTS: A total of 63 athletes (mean age at follow-up, 19.6 ± 1.2 years; n = 25 female) were included in the study. At baseline, DFCIs were detected in 84 out of 126 knees (67%). At the 48-month follow-up, DFCIs were found in 88 out of 126 knees (70%), with multiple DFCIs in 3 knees and no significant difference between male and female patients (n = 24 male, n = 19 female; P = .71). No significant increase was detected for the number (P = .21) and size of the DFCIs between the baseline and the 48-month follow-up (mean size: baseline, 3.7 ± 0.8 mm; 48-month follow-up: 3.6 ± 0.9 mm; P = .66). The interrater agreement for the mean size measurements of DFCIs was good to excellent (ICC 0.88). CONCLUSION: DFCIs remain a frequent finding on knee MRI in competitive alpine skiers after skeletal maturation and do not disappear during adolescence. The DFCI size was constant in athletes aged between 15 and 19 years. Moreover, DFCIs should not be mistaken for a pathologic finding.

Arecoline in buccal cells reflects Areca nut dose.

Areca nut (AN) is a carcinogen; its chewing cessation is, therefore, of worldwide interest. However, cessation biomarkers are lacking. We sought to establish arecoline in chewers' buccal cells (BCs) as a biomarker for AN dose. Self-reported AN doses, expressed as the average AN load ("AANL"), the product of AN amount, chewing time, and chewing frequency, were correlated by regression analysis with chewers' BC arecoline, measured by liquid chromatography mass spectrometry. We then determined whether associations differed between Class 1 chewers (who consume AN alone or with slaked lime, leaf, and/or spices) and Class 2 chewers (who consume any combination of the aforementioned ingredients plus tobacco). Among the 103 chewers, 28 Class 1 and 39 Class 2 chewers had detectable arecoline levels, which were used for analyses. A linear regression of cube-root transformed AANL on equally transformed BC arecoline levels provided the best model fit; resulting slopes and corresponding correlation coefficients were 0.86 and 0.40 (p < 0.01) for all; 1.09 and 0.51 (p < 0.01) for Class 1 chewers; 0.35 and 0.17 (p = 0.29) for Class 2 chewers; and 0.94 and 0.45 (p < 0.01), and 0.79 and 0.37 (p = 0.08), respectively, for those who included or excluded lime. Relationships between AANL and BC arecoline levels were similar between chewers who included or excluded lime (p = 0.76), but less between chewing classes (p = 0.14). This provides confidence that BC arecoline can generally act as a reliable biomarker for AN dose, useful for estimating efficacy in AN cessation studies and population-based chewing assessments.

A review of emerging health threats from zoonotic New World mammarenaviruses.

Despite repeated spillover transmission and their potential to cause significant morbidity and mortality in human hosts, the New World mammarenaviruses remain largely understudied. These viruses are endemic to South America, with animal reservoir hosts covering large geographic areas and whose transmission ecology and spillover potential are driven in part by land use change and agriculture that put humans in regular contact with zoonotic hosts.We compiled published studies about Guanarito virus, Junin virus, Machupo virus, Chapare virus, Sabia virus, and Lymphocytic Choriomeningitis virus to review the state of knowledge about the viral hemorrhagic fevers caused by New World mammarenaviruses. We summarize what is known about rodent reservoirs, the conditions of spillover transmission for each of these pathogens, and the characteristics of human populations at greatest risk for hemorrhagic fever diseases. We also review the implications of repeated outbreaks and biosecurity concerns where these diseases are endemic, and steps that countries can take to strengthen surveillance and increase capacity of local healthcare systems. While there are unique risks posed by each of these six viruses, their ecological and epidemiological similarities suggest common steps to mitigate spillover transmission and better contain future outbreaks.

Quantifying Tendon Degeneration Using Magic Angle Insensitive Ultra-Short Echo Time Magnetization Transfer: A Phantom Study in Bovine Tendons.

OBJECTIVES: The aim of this study was to qualitatively and quantitatively assess changes in bovine flexor tendons before and after collagen degradation and at different angles in relation to the static B0 field using 3-dimensional ultra-short echo time (UTE) magnetization transfer (MT) imaging within a clinically feasible acquisition time. MATERIALS AND METHODS: Eight bovine flexor tendons were examined at 3 T magnetic resonance imaging including 3-dimensional UTE MT and UTE T2* research application sequences (acquired within 4:04 and 6:38 minutes, respectively) before and after enzyme-induced degradation. The tendons were divided into 2 groups: group 1 (controls) treated with phosphate-buffered saline and group 2 treated with collagenase I to induce collagen degeneration. Magnetic resonance imaging was repeated at 0, 27, 55, and 90 degrees to the B0 field. To calculate quantitative tissue properties, all tendons were semiautomatically segmented, and changes in quantitative UTE T2* and UTE MT ratios (MTRs) were compared at different angles and between groups. In addition to descriptive statistics, the coefficient of variation was calculated to compare UTE MT and UTE T2* imaging. RESULTS: Ultra-short echo time MTR showed a significantly lower coefficient of variation compared with UTE T2* values, indicating a more robust imaging method (UTE MTR 9.64%-11.25%, UTE T2* 18.81%-24.06%, P < 0.001). Both methods showed good performance in detecting degenerated tendons using histopathology as reference standard, with UTE MT imaging having a better area under the curve than UTE T2* mapping (0.918 vs 0.865). Falsely high UTE T2* values were detected at the 55 degrees acquisition angle, whereas UTE MTR values were robust, that is, insensitive to the MAE. CONCLUSIONS: Ultra-short echo time MT imaging is a reliable method for quantifying tendon degeneration that is robust to the MAE and can be acquired in a clinically reasonable time.

Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity.

Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that cannot easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of 3 long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from 2 populations of genetic diversity. Additionally, we compared how intrabone relationships varied in the 2 populations. Our first population of genetic diversity included 72 females and 72 males from the 8 inbred founder strains used to create the Diversity Outbred (DO) population. These 8 strains together span almost 90% of the genetic diversity found in mice (Mus musculus). Our second population of genetic diversity included 25 genetically unique, outbred females and 25 males from the DO population. We show that multi-scale cortical bone traits vary significantly with genetic background; heritability values range from 21% to 99% indicating genetic control of bone traits across length scales. We show for the first time that lacunar shape and number are highly heritable. Comparing the 2 populations of genetic diversity, we show that each DO mouse does not resemble a single inbred founder, but instead the outbred mice display hybrid phenotypes with the elimination of extreme values. Additionally, intrabone relationships (eg, ultimate force vs. cortical area) were mainly conserved in our 2 populations. Overall, this work supports future use of these genetically diverse populations to discover novel genes contributing to cortical bone traits, especially at the lacunar length scale.