Disentangling Acid-Base Chemistry through Blue Shifting Hydrogen Bond Contributions.

The blue shifting of vibrational frequencies in hydrogen bonded molecules, as observed in aqueous environments, has been attributed to local partial charge transfer from solvation. Here, we extrapolate the blue shift model to the stronger ionic interactions between hydrogen bond acceptors associated with protonation through augmented pH levels and competitive interactions with counter ion pairing. The chemical model we utilize in this work is the aqueous pyridine-pyridinium equilibrium to characterize the blue shifts observed in the pyridinium chloride ionic system. The observed agreement between observed experimental and calculated spectral shifts shows that the blue shifting model can be extrapolated to stronger interactions and accurately describe the nature of the hydrogen bond.

High angular resolution diffusion imaging (HARDI) of porcine menisci: a comparison of diffusion tensor imaging and generalized q-sampling imaging.

Background: Diffusion magnetic resonance imaging (MRI) allows for the quantification of water diffusion properties in soft tissues. The goal of this study was to characterize the 3D collagen fiber network in the porcine meniscus using high angular resolution diffusion imaging (HARDI) acquisition with both diffusion tensor imaging (DTI) and generalized q-sampling imaging (GQI). Methods: Porcine menisci (n=7) were scanned ex vivo using a three-dimensional (3D) HARDI spin-echo pulse sequence with an isotropic resolution of 500 µm at 7.0 Tesla. Both DTI and GQI reconstruction techniques were used to quantify the collagen fiber alignment and visualize the complex collagen network of the meniscus. The MRI findings were validated with conventional histology. Results: DTI and GQI exhibited distinct fiber orientation maps in the meniscus using the same HARDI acquisition. We found that crossing fibers were only resolved with GQI, demonstrating the advantage of GQI over DTI to visualize the complex collagen fiber orientation in the meniscus. Furthermore, the MRI findings were consistent with conventional histology. Conclusions: HARDI acquisition with GQI reconstruction more accurately resolves the complex 3D collagen architecture of the meniscus compared to DTI reconstruction. In the future, these technologies have the potential to nondestructively assess both normal and abnormal meniscal structure.

Development of Nontargeted Workflow of Occupational Exposure by Infrared Ion Spectroscopy and Silicone Wristbands' Passive Sampling.

A new approach using orthogonal analytical techniques is developed for chemical identification. High resolution mass spectrometry and infrared ion spectroscopy are applied through a 5-level confidence paradigm to demonstrate the effectiveness of nontargeted workflow for the identification of hazardous organophosphates. Triphenyl phosphate is used as a surrogate organophosphate for occupational exposure, and silicone wristbands are used to represent personal samplers. Spectral data of a target compound is combined with spectral data of the sodium adduct and quantum chemical calculations to achieve a confirmed identification. Here, we demonstrate a nontargeted workflow that identifies organophosphate exposure and provides a mechanism for selecting validated methods for quantitative analyses.

Calculated Medicine: Seven Decades of Accelerating Growth.

The field of Calculated Medicine has grown substantially over the last 7 decades. Comprised of objective, evidence-based medical decision tools, Calculated Medicine has broad application in medical practice, medical research, and health care management. This article reviews the history and varied methodologies of Calculated Medicine, starting with the 1953 Apgar score and concluding with a look into modern computational tools of the field: machine learning, natural language processing, artificial intelligence, and in silico research techniques. We'll also review and quantify the rapidly accelerating growth of Calculated Medicine in the medical literature. Our database of journal articles referring to the field has accumulated over 1.8 million citations, with more than 460 new citations (on average) posted every day. Using natural language processing, we examine and analyze this burgeoning database. Lastly, we examine an important new direction of Calculated Medicine: self-reflection on its potential effect on racial and ethnic disparities in health care. Our field is making great strides promoting health care egality, and some of the most prominent contributions will be reviewed.

Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice.

Aging is a complex progression of changes best characterized as the chronic dysregulation of cellular processes leading to deteriorated tissue and organ function. Although aging cannot currently be prevented, its impact on life- and healthspan in the elderly can potentially be minimized by interventions that aim to return these cellular processes to optimal function. Recent studies have demonstrated that partial reprogramming using the Yamanaka factors (or a subset; OCT4, SOX2, and KLF4; OSK) can reverse age-related changes in vitro and in vivo. However, it is still unknown whether the Yamanaka factors (or a subset) are capable of extending the lifespan of aged wild-type (WT) mice. In this study, we show that systemically delivered adeno-associated viruses, encoding an inducible OSK system, in 124-week-old male mice extend the median remaining lifespan by 109% over WT controls and enhance several health parameters. Importantly, we observed a significant improvement in frailty scores indicating that we were able to improve the healthspan along with increasing the lifespan. Furthermore, in human keratinocytes expressing exogenous OSK, we observed significant epigenetic markers of age reversal, suggesting a potential reregulation of genetic networks to a younger potentially healthier state. Together, these results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly.

Global fine-resolution data on springtail abundance and community structure.

Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.

Influence of running on femoroacetabular joint bone-to-bone distances.

There is limited data quantifying the influence of running on hip cartilage mechanics. The goal of this investigation was to quantify changes in hip joint bone-to-bone distance in response to a 3-mile treadmill run. We acquired magnetic resonance (MR) images of the dominant hip of eight young, asymptomatic runners (five males, three females) before and immediately after they ran 3 miles at a self-selected pace on a level treadmill. The femoral heads and acetabula were semiautomatically segmented from the pre- and post-exercise MR images to generate three-dimensional models of each participant's hip that were used to compute changes in the bone-to-bone distances incurred by the running exercise. We observed a significant 3% decrease in bone-to-bone distance from 3.47 ± 0.20 to 3.36 ± 0.22 mm between the femoral head and acetabulum after a 3-mile treadmill run (mean ± 95% confidence interval; p = 0.03). These findings provide new baseline data describing how running impacts the hip joint in young, asymptomatic runners.

The effects of a 6-month weight loss intervention on physical function and serum biomarkers in older adults with and without osteoarthritis.

Objective: To examine the effects of a 6-month weight loss intervention on physical function, inflammatory biomarkers, and metabolic biomarkers in both those with and without osteoarthritis (OA). Design: 59 individuals ≥60 years old with obesity and a functional impairment were enrolled into this IRB approved clinical trial and randomized into one of two 6-month weight loss arms: a higher protein hypocaloric diet or a standard protein hypocaloric diet. All participants were prescribed individualized 500-kcal daily-deficit diets, with a goal of 10% weight loss. Additionally, participants participated in three, low-intensity, exercise sessions per week. Physical function, serum biomarkers and body composition data were assessed at the baseline and 6-month timepoints. Statistical analyses assessed the relationships between biomarkers, physical function, body composition, and OA status as a result of the intervention. Results: No group effects of dietary intervention were detected on any outcome measures (multiple p â€‹> â€‹0.05). During the 6-month trial, participants lost 6.2 â€‹± â€‹4.0% of their bodyweight (p â€‹< â€‹0.0001) and experienced improved physical function on the Short-Performance-Physical-Battery (p â€‹< â€‹0.0001), 8-foot-up-and-go (p â€‹< â€‹0.0001), and time to complete 10-chair-stands (p â€‹< â€‹0.0001). Adiponectin concentrations (p â€‹= â€‹0.0480) were elevated, and cartilage oligomeric matrix protein (COMP) concentrations (p â€‹< â€‹0.0001) were reduced; further analysis revealed that reductions in serum COMP concentrations were greater in OA-negative individuals. Conclusions: These results suggest that weight loss in older adults with and without OA may provide a protective effect to cartilage and OA. In particular, OA-negative individuals may be able to mitigate changes associated with OA through weight loss.

Chemical Composition of Four Industrial Hemp (Cannabis sativa L.) Pollen and Bee Preference.

Apart from its economic value, industrial hemp (Cannabis sativa L.) is a prolific pollen producer, serving as a food source for bees. However, little is known regarding the extent to which varietal differences in hemp pollen chemistry influences bee preference. Here, we report the chemical profile of pollen from four hemp varieties (Canda, CFX-2, Henola, and Joey) and bee abundance and diversity, using direct visual counts and pan traps. The number and type of bees on each variety was recorded and the chemical composition (proximate analysis and mineral, amino, and fatty acid profiles) of pollen from each hemp variety was determined. During the entire sampling period, three bee types (bumble bees, honey bees, and sweat bees) were recorded, with a combined total of 1826. Among these, sweat bees and bumble bees were the most prevalent and were highest on the Joey variety. The four varieties expressed protein content ranging from 6.05% to 6.89% and the highest in Henola. Seventeen amino acids were expressed in all varieties, with leucine recording the highest content ranging from 4.00 mg/g in Canda to 4.54 mg/g in Henola. In general, Henola expressed high protein, amino acid, and saturated and monosaturated fatty acid contents and recorded significantly fewer bees compared with Joey, which had a low content of these components and a high content of polyunsaturated fatty acids. Our findings suggest that, while industrial hemp offers abundant and accessible pollen that would promote bee health and sustainability of their ecosystem services, the nutritional quality may not be adequate for bee growth and development as an exclusive pollen source.

Non-local dielectric effects in nanoscience.

The physical properties of charges and excitations in nanoscale materials are influenced both by the dielectric properties of the material itself and the surrounding environment. This non-local dielectric effect was first discussed in the context of molecules in solvents over a century ago. In this perspective, we discuss non-local dielectric effects in zero-dimensional, one-dimensional, and two-dimensional nanoscale systems.

Automated segmentation and prediction of intervertebral disc morphology and uniaxial deformations from MRI.

Objective: The measurement of in vivo intervertebral disc (IVD) mechanics may be used to understand the etiology of IVD degeneration and low back pain (LBP). To this end, our lab has developed methods to measure IVD morphology and uniaxial compressive deformation (% change in IVD height) resulting from dynamic activity, in vivo, using magnetic resonance images (MRI). However, due to the time-intensive nature of manual image segmentation, we sought to validate an image segmentation algorithm that could accurately and reliably reproduce models of in vivo tissue mechanics. Design: Therefore, we developed and evaluated two commonly employed deep learning architectures (2D and 3D U-Net) for the segmentation of IVDs from MRI. The performance of these models was evaluated for morphological accuracy by comparing predicted IVD segmentations (Dice similarity coefficient, mDSC; average surface distance, ASD) to manual (ground truth) measures. Likewise, functional reliability and precision were assessed by evaluating the intraclass correlation coefficient (ICC) and standard error of measurement (SEm) of predicted and manually derived deformation measures. Results: Peak model performance was obtained using the 3D U-net architecture, yielding a maximum mDSC â€‹= â€‹0.9824 and component-wise ASDx â€‹= â€‹0.0683 â€‹mm; ASDy â€‹= â€‹0.0335 â€‹mm; ASDz â€‹= â€‹0.0329 â€‹mm. Functional model performance demonstrated excellent reliability ICC â€‹= â€‹0.926 and precision SEm â€‹= â€‹0.42%. Conclusions: This study demonstrated that a deep learning framework can precisely and reliably automate measures of IVD function, drastically improving the throughput of these time-intensive methods.

2001: An artificial heart odyssey.

The quest to replace the natural heart with an artificial one as a permanent system is among the remaining holy grails in medicine and surgery. Beginning in 1969, when the first total artificial heart (TAH) was implanted into a human, to the present, several types have been developed-the AbioCor was among them. On November 5th, 2001, our team at Hahnemann University Hospital in Philadelphia, Pennsylvania placed the world's fifth AbioCor. Excerpts of that moment in time were recorded and serve as a memorial to the past and a testimony to the present and future quest of this elusive holy grail.

Occupational Risk Factors for SARS-CoV-2 Seropositivity in Healthcare Workers: Results of a Longitudinal Cohort.

OBJECTIVE: The aim of the study is to evaluate COVID-19 risk factors among healthcare workers (HCWs) before vaccine-induced immunity. METHODS: We conducted a longitudinal cohort study of HCWs ( N = 1233) with SARS-CoV-2 immunoglobulin G quantification by ELISA and repeated surveys over 9 months. Risk factors were assessed by multivariable-adjusted logistic regression and Cox proportional hazards models. RESULTS: SARS-CoV-2 immunoglobulin G was associated with work in internal medicine (odds ratio [OR], 2.77; 95% confidence interval [CI], 1.05-8.26) and role of physician-in-training (OR, 2.55; 95% CI, 1.08-6.43), including interns (OR, 4.22; 95% CI, 1.20-14.00) and resident physicians (OR, 3.14; 95% CI, 1.24-8.33). Odds were lower among staff confident in N95 use (OR, 0.55; 95% CI, 0.31-0.96) and decreased over the follow-up. CONCLUSIONS: Excess COVID-19 risk observed among physicians-in-training early in the COVID-19 pandemic was reduced with improved occupational health interventions before vaccinations.

Auto-segmentation of the tibia and femur from knee MR images via deep learning and its application to cartilage strain and recovery.

The ability to efficiently and reproducibly generate subject-specific 3D models of bone and soft tissue is important to many areas of musculoskeletal research. However, methodologies requiring such models have largely been limited by lengthy manual segmentation times. Recently, machine learning, and more specifically, convolutional neural networks, have shown potential to alleviate this bottleneck in research throughput. Thus, the purpose of this work was to develop a modified version of the convolutional neural network architecture U-Net to automate segmentation of the tibia and femur from double echo steady state knee magnetic resonance (MR) images. Our model was trained on a dataset of over 4,000 MR images from 34 subjects, segmented by three experienced researchers, and reviewed by a musculoskeletal radiologist. For our validation and testing sets, we achieved dice coefficients of 0.985 and 0.984, respectively. As further testing, we applied our trained model to a prior study of tibial cartilage strain and recovery. In this analysis, across all subjects, there were no statistically significant differences in cartilage strain between the machine learning and ground truth bone models, with a mean difference of 0.2 ± 0.7 % (mean ± 95 % confidence interval). This difference is within the measurement resolution of previous cartilage strain studies from our lab using manual segmentation. In summary, we successfully trained, validated, and tested a machine learning model capable of segmenting MR images of the knee, achieving results that are comparable to trained human segmenters.

Elevated In Vivo ACL Strain Is Associated With a Straight Knee in Both the Sagittal and the Coronal Planes.

BACKGROUND: Noncontact anterior cruciate ligament (ACL) injuries typically occur during deceleration movements such as landing or cutting. However, conflicting data have left the kinematic mechanisms leading to these injuries unclear. Quantifying the influence of sagittal and coronal plane knee kinematics on in vivo ACL strain may help to elucidate noncontact ACL injury mechanisms. PURPOSE/HYPOTHESIS: The purpose of this study was to measure in vivo sagittal and coronal plane knee kinematics and ACL strain during a single-leg jump. We hypothesized that ACL strain would be modulated primarily by motion in the sagittal plane and that limited coronal plane motion would be measured during this activity. STUDY DESIGN: Descriptive laboratory study. METHODS: Seventeen healthy participants (8 male/9 female) underwent magnetic resonance imaging (MRI) followed by high-speed biplanar radiography, obtained as participants performed a single-leg jump. Three-dimensional models of the femur, tibia, and associated ACL attachment site footprints were created from the MRIs and registered to the radiographs to reproduce the position of the knee during the jump. ACL strain, knee flexion/extension angles, and varus/valgus angles were measured throughout the jump. Spearman rank correlations were used to assess relationships between mean ACL strain and kinematic variables. RESULTS: Mean ACL strain increased with decreasing knee flexion angle (ρ = -0.3; P = .002), and local maxima in ACL strain occurred with the knee in a straight position in both the sagittal and the coronal planes. In addition, limited coronal plane motion (varus/valgus angle) was measured during this activity (mean ± SD, -0.5°± 0.3°). Furthermore, we did not detect a statistically significant relationship between ACL strain and varus/valgus angle (ρ = -0.01; P = .9). CONCLUSION: ACL strain was maximized when the knee was in a straight position in both the sagittal and coronal planes. Participants remained in <1° of varus/valgus position on average throughout the jump. As a ligament under elevated strain is more vulnerable to injury, landing on a straight knee may be an important risk factor for ACL rupture. CLINICAL RELEVANCE: These data may improve understanding of risk factors for noncontact ACL injury, which may be useful in designing ACL injury prevention programs.

The Interplay of Biomechanical and Biological Changes Following Meniscus Injury.

PURPOSE OF REVIEW: Meniscus injury often leads to joint degeneration and post-traumatic osteoarthritis (PTOA) development. Therefore, the purpose of this review is to outline the current understanding of biomechanical and biological repercussions following meniscus injury and how these changes impact meniscus repair and PTOA development. Moreover, we identify key gaps in knowledge that must be further investigated to improve meniscus healing and prevent PTOA. RECENT FINDINGS: Following meniscus injury, both biomechanical and biological alterations frequently occur in multiple tissues in the joint. Biomechanically, meniscus tears compromise the ability of the meniscus to transfer load in the joint, making the cartilage more vulnerable to increased strain. Biologically, the post-injury environment is often characterized by an increase in pro-inflammatory cytokines, catabolic enzymes, and immune cells. These multi-faceted changes have a significant interplay and result in an environment that opposes tissue repair and contributes to PTOA development. Additionally, degenerative changes associated with OA may cause a feedback cycle, negatively impacting the healing capacity of the meniscus. Strides have been made towards understanding post-injury biological and biomechanical changes in the joint, their interplay, and how they affect healing and PTOA development. However, in order to improve clinical treatments to promote meniscus healing and prevent PTOA development, there is an urgent need to understand the physiologic changes in the joint following injury. In particular, work is needed on the in vivo characterization of the temporal biomechanical and biological changes that occur in patients following meniscus injury and how these changes contribute to PTOA development.

The Predicted Position of the Knee Near the Time of ACL Rupture Is Similar Between 2 Commonly Observed Patterns of Bone Bruising on MRI.

BACKGROUND: Bone bruises observed on magnetic resonance imaging (MRI) can provide insight into the mechanisms of noncontact anterior cruciate ligament (ACL) injury. However, it remains unclear whether the position of the knee near the time of injury differs between patients evaluated with different patterns of bone bruising, particularly with regard to valgus angles. HYPOTHESIS: The position of the knee near the time of injury is similar between patients evaluated with 2 commonly occurring patterns of bone bruising. STUDY DESIGN: Descriptive laboratory study. METHODS: Clinical T2- and T1-weighted MRI scans obtained within 6 weeks of noncontact ACL rupture were reviewed. Patients had either 3 (n = 20) or 4 (n = 30) bone bruises. Patients in the 4-bone bruise group had bruising of the medial and lateral compartments of the femur and tibia, whereas patients in the 3-bone bruise group did not have a bruise on the medial femoral condyle. The outer contours of the bones and associated bruises were segmented from the MRI scans and used to create 3-dimensional surface models. For each patient, the position of the knee near the time of injury was predicted by moving the tibial model relative to the femoral model to maximize the overlap of the tibiofemoral bone bruises. Logistic regressions (adjusted for sex, age, and presence of medial collateral ligament injury) were used to assess relationships between predicted injury position (quantified in terms of knee flexion angle, valgus angle, internal rotation angle, and anterior tibial translation) and bone bruise group. RESULTS: The predicted injury position for patients in both groups involved a flexion angle <20°, anterior translation >20 mm, valgus angle <10°, and internal rotation angle <10°. The injury position for the 3-bone bruise group involved less flexion (odds ratio [OR], 0.914; 95% CI, 0.846-0.987; P = .02) and internal rotation (OR, 0.832; 95% CI, 0.739-0.937; P = .002) as compared with patients with 4 bone bruises. CONCLUSION: The predicted position of injury for patients displaying both 3 and 4 bone bruises involved substantial anterior tibial translation (>20 mm), with the knee in a straight position in both the sagittal (<20°) and the coronal (<10°) planes. CLINICAL RELEVANCE: Landing on a straight knee with subsequent anterior tibial translation is a potential mechanism of noncontact ACL injury.

Immune Defense in Hypoxic Waters: Impacts of CO2 Acidification.

AbstractPeriodic episodes of low oxygen (hypoxia) and elevated CO2 (hypercapnia) accompanied by low pH occur naturally in estuarine environments. Under the influence of climate change, the geographic range and intensity of hypoxia and hypercapnic hypoxia are predicted to increase, potentially jeopardizing the survival of economically and ecologically important organisms that use estuaries as habitat and nursery grounds. In this review we synthesize data from published studies that evaluate the impact of hypoxia and hypercapnic hypoxia on the ability of crustaceans and bivalve molluscs to defend themselves against potential microbial pathogens. Available data indicate that hypoxia generally has suppressive effects on host immunity against bacterial pathogens as measured by in vitro and in vivo assays. Few studies have documented the effects of hypercapnic hypoxia on crustaceans or bivalve immune defense, with a range of outcomes suggesting that added CO2 might have additive, negative, or no interactions with the effects of hypoxia alone. This synthesis points to the need for more partial pressure of O2 × low pH factorial design experiments and recommends the development of new host∶pathogen challenge models incorporating natural transmission of a wide range of viruses, bacteria, and parasites, along with novel in vivo tracking systems that better quantify how pathogens interact with their hosts in real time under laboratory and field conditions.