Marmosets as model systems for the study of Alzheimer's disease and related dementias: substantiation of physiological Tau 3R and 4R isoform expression and phosphorylation.

INTRODUCTION: Marmosets have been shown to spontaneously develop pathological hallmarks of Alzheimer's disease (AD) during advanced age, including amyloid-beta plaques, positioning them as a model system to overcome the rodent-to-human translational gap for AD. However, Tau expression in the marmoset brain has been understudied. METHODS: To comprehensively investigate Tau isoform expression in marmosets, brain tissue from eight unrelated marmosets across various ages was evaluated and compared to human postmortem AD tissue. Microtubule-associated protein tau ( MAPT ) mRNA expression and splicing were confirmed by RT-PCR. Tau isoforms in the marmoset brain were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining. Synaptic Tau expression was analyzed from crude synaptosome extractions. RESULTS: 3R and 4R Tau isoforms are expressed in marmoset brains at both transcript and protein levels across ages. Results from western blot analysis were confirmed by mass spectrometry, which revealed that Tau peptides in marmoset corresponded to the 3R and 4R peptides in the human AD brain. 3R Tau was primarily enriched in neonate brains, and 4R enhanced in adult and aged brains. Tau was widely distributed in neurons with localization in the soma and synaptic regions. Phosphorylation residues were observed on Thr-181, Thr-217, and Thr-231, Ser202/Thr205, Ser396/Ser404. Paired helical filament (PHF)-like aggregates were also detected in aged marmosets. DISCUSSION: Our results confirm the expression of both 3R and 4R Tau isoforms and important phosphorylation residues in the marmoset brain. These data emphasize the significance of marmosets with natural expression of AD-related hallmarks as important translational models for the study of AD.

Mode of delivery and birth outcomes before and during COVID-19 -A population-based study in Ontario, Canada.

There is lack of clarity on whether pregnancies during COVID-19 resulted in poorer mode of delivery and birth outcomes in Ontario, Canada. We aimed to compare mode of delivery (C-section), birth (low birthweight, preterm birth, NICU admission), and health services use (HSU, hospitalizations, ED visits, physician visits) outcomes in pregnant Ontario women before and during COVID-19 (pandemic periods). We further stratified for pre-existing chronic diseases (asthma, eczema, allergic rhinitis, diabetes, hypertension). Deliveries before (Jun 2018-Feb 2020) and during (Jul 2020-Mar 2022) pandemic were from health administrative data. We used multivariable logistic regression analyses to estimate adjusted odds ratios (aOR) of delivery and birth outcomes, and negative binomial regression for adjusted rate ratios (aRR) of HSU. We compared outcomes between pre-pandemic and pandemic periods. Possible interactions between study periods and covariates were also examined. 323,359 deliveries were included (50% during pandemic). One in 5 (18.3%) women who delivered during the pandemic had not received any COVID-19 vaccine, while one in 20 women (5.2%) lab-tested positive for COVID-19. The odds of C-section delivery during the pandemic was 9% higher (aOR = 1.09, 95% CI: 1.08-1.11) than pre-pandemic. The odds of preterm birth and NICU admission were 15% (aOR = 0.85, 95% CI: 0.82-0.87) and 10% lower (aOR = 0.90, 95% CI: 0.88-0.92), respectively, during COVID-19. There was a 17% reduction in ED visits but a 16% increase in physician visits during the pandemic (aRR = 0.83, 95% CI: 0.81-0.84 and aRR = 1.16, 95% CI: 1.16-1.17, respectively). These aORs and aRRs were significantly higher in women with pre-existing chronic conditions. During the pandemic, healthcare utilization, especially ED visits (aRR = 0.83), in pregnant women was lower compared to before. Ensuring ongoing prenatal care during the pandemic may reduce risks of adverse mode of delivery and the need for acute care during pregnancy.

Large-scale Deep Proteomic Analysis in Alzheimer's Disease Brain Regions Across Race and Ethnicity.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non-Hispanic White (NHW) population. Here we aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial and ethnic groups. Methods: Dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) brain tissues were donated from multiple centers (Mayo Clinic, Emory University, Rush University, Mt. Sinai School of Medicine) and were harmonized through neuropathological evaluation, specifically adhering to the Braak staging and CERAD criteria. Among 1105 DLPFC tissue samples (998 unique individuals), 333 were from African American donors, 223 from Latino Americans, 529 from NHW donors, and the rest were from a mixed or unknown racial background. Among 280 STG tissue samples (244 unique individuals), 86 were African American, 76 Latino American, 116 NHW and the rest were mixed or unknown ethnicity. All tissues were uniformly homogenized and analyzed by tandem mass tag mass spectrometry (TMT-MS). Results: As a Quality control (QC) measure, proteins with more than 50% missing values were removed and iterative principal component analysis was conducted to remove outliers within brain regions. After QC, 9,180 and 9,734 proteins remained in the DLPC and STG proteome, respectively, of which approximately 9,000 proteins were shared between regions. Protein levels of microtubule-associated protein tau (MAPT) and amyloid-precursor protein (APP) demonstrated AD-related elevations in DLPFC tissues with a strong association with CERAD and Braak across racial groups. APOE4 protein levels in brain were highly concordant with APOE genotype of the individuals. Discussion: This comprehensive region resolved large-scale proteomic dataset provides a resource for the understanding of ethnoracial-specific protein differences in AD brain.

Long term impact of transjugular intrahepatic portosystemic shunt (TIPS) creation on hepatic morphology.

PURPOSE: The purpose of this study was to evaluate long-term morphologic changes occurring in the liver after TIPS creation with correlation with hepatic function to gain insight on the physiologic impact of TIPS on the liver. METHODS: This retrospective study included patients who underwent TIPS creation between 2005 and 2022 and had contrasted CT or MRI studies prior to and between 1 and 2 years post procedure. Strict exclusion criteria were applied to avoid confounding. Parenchymal volume and vessel measurements were assessed on the pre- and post-TIPS CT or MRI and MELD scores calculated. RESULTS: Of 580 patients undergoing TIPS creation, 65 patients (mean age, 55 years; 36 males) had pre-TIPS and post-TIPS imaging meeting inclusion criteria at median 16.5 months. After TIPS, the mean MELD score increased (12.9 to 15.4; p = 0.008) and total liver volume decreased (1730 to 1432 mL; p < 0.001). However, the magnitude of volume change did not correlate with MELD change. Neither portosystemic gradient nor TIPS laterality correlated with total or lobar hepatic volume changes or MELD changes. The main portal vein diameter increased (15.0 to 18.7 mm; p < 0.001). Thrombosis of the hepatic vein used for TIPS creation resulted in a mean increase in MELD of +4.1 compared to -2.1 in patients who had a patent and normal hepatic vein (p = 0.007). CONCLUSIONS: Given lack of correlation between portosystemic gradient, hepatic atrophy, hepatic function, and TIPS laterality, the alterations in portal flow dynamics after TIPS may not be impactful to hepatic function. However, hepatic vein patency after TIPS correlated with improved hepatic function.

eIF4A1 enhances LARP1-mediated translational repression during mTORC1 inhibition.

Eukaryotic translation initiation factor (eIF)4A-a DEAD-box RNA-binding protein-plays an essential role in translation initiation. Recent reports have suggested helicase-dependent and helicase-independent functions for eIF4A, but the multifaceted roles of eIF4A have not been fully explored. Here we show that eIF4A1 enhances translational repression during the inhibition of mechanistic target of rapamycin complex 1 (mTORC1), an essential kinase complex controlling cell proliferation. RNA pulldown followed by sequencing revealed that eIF4A1 preferentially binds to mRNAs containing terminal oligopyrimidine (TOP) motifs, whose translation is rapidly repressed upon mTORC1 inhibition. This selective interaction depends on a La-related RNA-binding protein, LARP1. Ribosome profiling revealed that deletion of EIF4A1 attenuated the translational repression of TOP mRNAs upon mTORC1 inactivation. Moreover, eIF4A1 increases the interaction between TOP mRNAs and LARP1 and, thus, ensures stronger translational repression upon mTORC1 inhibition. Our data show the multimodality of eIF4A1 in modulating protein synthesis through an inhibitory binding partner and provide a unique example of the repressive role of a universal translational activator.

A fear conditioned cue orchestrates a suite of behaviors in rats.

Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that - in addition to jumping, and rearing - is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of danger-specific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing - all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveal a fear conditioned cue to orchestrate a temporally organized suite of behaviors.

Proteomic changes in the human cerebrovasculature in Alzheimer's disease and related tauopathies linked to peripheral biomarkers in plasma and cerebrospinal fluid.

INTRODUCTION: Cerebrovascular dysfunction is a pathological hallmark of Alzheimer's disease (AD). Nevertheless, detecting cerebrovascular changes within bulk tissues has limited our ability to characterize proteomic alterations from less abundant cell types. METHODS: We conducted quantitative proteomics on bulk brain tissues and isolated cerebrovasculature from the same individuals, encompassing control (N = 28), progressive supranuclear palsy (PSP) (N = 18), and AD (N = 21) cases. RESULTS: Protein co-expression network analysis identified unique cerebrovascular modules significantly correlated with amyloid plaques, cerebrovascular amyloid angiopathy (CAA), and/or tau pathology. The protein products within AD genetic risk loci were concentrated within cerebrovascular modules. The overlap between differentially abundant proteins in AD cerebrospinal fluid (CSF) and plasma with cerebrovascular network highlighted a significant increase of matrisome proteins, SMOC1 and SMOC2, in CSF, plasma, and brain. DISCUSSION: These findings enhance our understanding of cerebrovascular deficits in AD, shedding light on potential biomarkers associated with CAA and vascular dysfunction in neurodegenerative diseases.

Adducin Regulates Sarcomere Disassembly During Cardiomyocyte Mitosis.

BACKGROUND: Recent interest in understanding cardiomyocyte cell cycle has been driven by potential therapeutic applications in cardiomyopathy. However, despite recent advances, cardiomyocyte mitosis remains a poorly understood process. For example, it is unclear how sarcomeres are disassembled during mitosis to allow the abscission of daughter cardiomyocytes. METHODS: Here, we use a proteomics screen to identify adducin, an actin capping protein previously not studied in cardiomyocytes, as a regulator of sarcomere disassembly. We generated many adeno-associated viruses and cardiomyocyte-specific genetic gain-of-function models to examine the role of adducin in neonatal and adult cardiomyocytes in vitro and in vivo. RESULTS: We identify adducin as a regulator of sarcomere disassembly during mammalian cardiomyocyte mitosis. α/γ-adducins are selectively expressed in neonatal mitotic cardiomyocytes, and their levels decline precipitously thereafter. Cardiomyocyte-specific overexpression of various splice isoforms and phospho-isoforms of α-adducin in identified Thr445/Thr480 phosphorylation of a short isoform of α-adducin as a potent inducer of neonatal cardiomyocyte sarcomere disassembly. Concomitant overexpression of this α-adducin variant along with γ-adducin resulted in stabilization of the adducin complex and persistent sarcomere disassembly in adult mice, which is mediated by interaction with α-actinin. CONCLUSIONS: These results highlight an important mechanism for coordinating cytoskeletal morphological changes during cardiomyocyte mitosis.

Effect of Estrogen Receptor Alpha on Cardiopulmonary Adaptation to Chronic Developmental Hypoxia in a Rat Model.

Humans living at high-altitude (HA) have adapted to this environment by increasing pulmonary vascular and alveolar growth. RNA sequencing data from a novel murine model that mimics this phenotypical response to HA suggested estrogen signaling via estrogen receptor alpha (ERα) may be involved in this adaptation. We hypothesized ERα was a key mediator in the cardiopulmonary adaption to chronic hypoxia and sought to delineate the mechanistic role ERα contributes to this process by exposing novel loss-of-function ERα mutant (ERαMut) rats to simulated HA. ERα mutant or wild type (wt) rats were exposed to normoxia or hypoxia starting at conception and continued postnatally until 6 weeks of age. Both wt and ERαMut animals born and raised in hypoxia exhibited lower body mass and higher hematocrits, total alveolar volumes (Va), diffusion capacities of carbon monoxide (DLCO), pulmonary arteriole (PA) wall thickness, and Fulton indices than normoxia animals. Right ventricle adaptation was maintained in the setting of hypoxia. While no major physiologic differences were seen between wt and ERαMut animals at either exposure, ERαMut animals exhibited smaller mean linear intercepts (MLI) and increased PA total and lumen areas. Hypoxia exposure or ERα loss-of-function did not affect lung mRNA abundance of vascular endothelial growth factor, angiopoietin 2 or apelin. Sexual dimorphisms were noted in PA wall thickness and lumen area in ERαMut rats. In summary, in room air-exposed rats and rats with peri- and postnatal hypoxia exposure, ERα loss-of-function was associated with decreased alveolar size (primarily driven by hypoxic animals) and increased PA remodeling.

First in vitro measurement of VHEE relative biological effectiveness (RBE) in lung and prostate cancer cells using the ARES linac at DESY.

Very high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE to inhomogeneities. This study explores how electrons in the VHEE range can be used to perform successful in vitro radiobiological studies. The ARES (accelerator research experiment at SINBAD) facility at DESY, Hamburg, Germany was used to deliver 154 MeV electrons to both prostate (PC3) and lung (A549) cancer cells in suspension. Dose was delivered to samples with repeatability and uniformity, quantified with Gafchromic film. Cell survival in response to VHEE was measured using the clonogenic assay to determine the biological effectiveness of VHEE in cancer cells for the first time using this method. Equivalent experiments were performed using 300 kVp X-rays, to enable VHEE irradiated cells to be compared with conventional photons. VHEE irradiated cancer cell survival was fitted to the linear quadratic (LQ) model (R2 = 0.96-0.97). The damage from VHEE and X-ray irradiated cells at doses between 1.41 and 6.33 Gy are comparable, suggesting similar relative biological effectiveness (RBE) between the two modalities. This suggests VHEE is as damaging as photon radiotherapy and therefore could be used to successfully damage cancer cells during radiotherapy. The RBE of VHEE was quantified as the relative doses required for 50% (D0.5) and 10% (D0.1) cell survival. Using these values, VHEE RBE was measured as 0.93 (D0.5) and 0.99 (D0.1) for A549 and 0.74 (D0.5) and 0.93 (D0.1) for PC3 cell lines respectively. For the first time, this study has shown that 154 MeV electrons can be used to effectively kill lung and prostate cancer cells, suggesting that VHEE would be a viable radiotherapy modality. Several studies have shown that VHEE has characteristics that would offer significant improvements over conventional photon radiotherapy for example, electrons are relatively easy to steer and can be used to deliver dose rapidly and with high efficiency. Studies have shown improved dose distribution with VHEE in treatment plans, in comparison to VMAT, indicating that VHEE can offer improved and safer treatment plans with reduced side effects. The biological response of cancer cells to VHEE has not been sufficiently studied as of yet, however this initial study provides some initial insights into cell damage. VHEE offers significant benefits over photon radiotherapy and therefore more studies are required to fully understand the biological effectiveness of VHEE.

Practical causal mediation analysis: extending nonparametric estimators to accommodate multiple mediators and multiple intermediate confounders.

Mediation analysis is appealing for its ability to improve understanding of the mechanistic drivers of causal effects, but real-world data complexities challenge its successful implementation, including (i) the existence of post-exposure variables that also affect mediators and outcomes (thus, confounding the mediator-outcome relationship), that may also be (ii) multivariate, and (iii) the existence of multivariate mediators. All three challenges are present in the mediation analysis we consider here, where our goal is to estimate the indirect effects of receiving a Section 8 housing voucher as a young child on the risk of developing a psychiatric mood disorder in adolescence that operate through mediators related to neighborhood poverty, the school environment, and instability of the neighborhood and school environments, considered together and separately. Interventional direct and indirect effects (IDE/IIE) accommodate post-exposure variables that confound the mediator-outcome relationship, but currently, no readily implementable nonparametric estimator for IDE/IIE exists that allows for both multivariate mediators and multivariate post-exposure intermediate confounders. The absence of such an IDE/IIE estimator that can easily accommodate both multivariate mediators and post-exposure confounders represents a significant limitation for real-world analyses, because when considering each mediator subgroup separately, the remaining mediator subgroups (or a subset of them) become post-exposure intermediate confounders. We address this gap by extending a recently developed nonparametric estimator for the IDE/IIE to allow for easy incorporation of multivariate mediators and multivariate post-exposure confounders simultaneously. We apply the proposed estimation approach to our analysis, including walking through a strategy to account for other, possibly co-occurring intermediate variables when considering each mediator subgroup separately.

Skeletal muscle architecture and aging: A comparison of ultrasound techniques and an assessment of intrarater reliability.

OBJECTIVE: To assess intrarater reliability of ultrasound-determined measurements of skeletal muscle characteristics across different measurement outcomes, imaging techniques, and age groups. METHODS: 2D ultrasound images (B-mode) of the quadriceps were obtained from young (26 ± 4 year, n = 8 M, 8 F) and older (70 ± 7 year, n = 7 M, 5 F) adults on two occasions, separated by 6 ± 3 days. With participants in both standing and supine postures, images were collected from five anatomical sites along the anterior (two sites) and lateral (three sites) compartments of the thigh corresponding to 56%, 39%, and 22% (lateral only) of femur length. Images were analysed for muscle thickness, pennation angle, and echogenicity. Intraclass correlation coefficients (ICC) were used to assess reliability. RESULTS: Muscle thickness values were higher (p < 0.05) on images collected in the stand versus supine posture only for muscles of the anterior compartment, independent of age. Echogenicity values were higher (p < 0.05) in the vastus intermedius on images collected in the supine versus stand posture only in older adults. Pennation angle values were not impacted by imaging posture (p > 0.05). ICC values for thickness, echogenicity, and pennation angle were generally higher for analyses conducted on images collected in the supine versus stand posture. Imaging posture generated a greater difference in ICC values in the lateral versus anterior muscles and in older versus younger participants. CONCLUSION: Our findings suggest that participant posture during imaging impacts the absolute values and intrarater reliability of ultrasound-determined muscle characteristics in a muscle-specific fashion, and this effect is greater in older compared to younger individuals.

Native-state proteomics of Parvalbumin interneurons identifies unique molecular signatures and vulnerabilities to early Alzheimer's pathology.

Dysfunction in fast-spiking parvalbumin interneurons (PV-INs) may represent an early pathophysiological perturbation in Alzheimer's Disease (AD). Defining early proteomic alterations in PV-INs can provide key biological and translationally-relevant insights. We used cell-type-specific in-vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state PV-IN proteomes. PV-IN proteomic signatures include high metabolic and translational activity, with over-representation of AD-risk and cognitive resilience-related proteins. In bulk proteomes, PV-IN proteins were associated with cognitive decline in humans, and with progressive neuropathology in humans and the 5xFAD mouse model of Aß pathology. PV-IN CIBOP in early stages of Aß pathology revealed signatures of increased mitochondria and metabolism, synaptic and cytoskeletal disruption and decreased mTOR signaling, not apparent in whole-brain proteomes. Furthermore, we demonstrated pre-synaptic defects in PV-to-excitatory neurotransmission, validating our proteomic findings. Overall, in this study we present native-state proteomes of PV-INs, revealing molecular insights into their unique roles in cognitive resiliency and AD pathogenesis.

Corrigendum: Early improvement predicts clinical outcomes similarly in 10 Hz rTMS and iTBS therapy for depression.

[This corrects the article DOI: 10.3389/fpsyt.2022.863225.].

The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle Implicates MYC as a Hypertrophic Regulator That is Sufficient for Growth.

Molecular control of recovery after exercise in muscle is temporally dynamic. A time course of biopsies around resistance exercise (RE) combined with -omics is necessary to better comprehend the molecular contributions of skeletal muscle adaptation in humans. Vastus lateralis biopsies before and 30 minutes, 3-, 8-, and 24-hours after acute RE were collected. A time-point matched biopsy-only group was also included. RNA-sequencing defined the transcriptome while DNA methylomics and computational approaches complemented these data. The post-RE time course revealed: 1) DNA methylome responses at 30 minutes corresponded to upregulated genes at 3 hours, 2) a burst of translation- and transcription-initiation factor-coding transcripts occurred between 3 and 8 hours, 3) global gene expression peaked at 8 hours, 4) ribosome-related genes dominated the mRNA landscape between 8 and 24 hours, 5) methylation-regulated MYC was a highly influential transcription factor throughout the 24-hour recovery and played a primary role in ribosome-related mRNA levels between 8 and 24 hours. The influence of MYC in human muscle adaptation was strengthened by transcriptome information from acute MYC overexpression in mouse muscle. To test whether MYC was sufficient for hypertrophy, we generated a muscle fiber-specific doxycycline inducible model of pulsatile MYC induction. Periodic 48-hour pulses of MYC over 4 weeks resulted in higher muscle mass and fiber size in the soleus of adult female mice. Collectively, we present a temporally resolved resource for understanding molecular adaptations to RE in muscle and reveal MYC as a regulator of RE-induced mRNA levels and hypertrophy.

Molecular recording of calcium signals via calcium-dependent proximity labeling.

Calcium ions serve as key intracellular signals. Local, transient increases in calcium concentrations can activate calcium sensor proteins that in turn trigger downstream effectors. In neurons, calcium transients play a central role in regulating neurotransmitter release and synaptic plasticity. However, it is challenging to capture the molecular events associated with these localized and ephemeral calcium signals. Here we present an engineered biotin ligase that generates permanent molecular traces in a calcium-dependent manner. The enzyme, calcium-dependent BioID (Cal-ID), biotinylates nearby proteins within minutes in response to elevated local calcium levels. The biotinylated proteins can be identified via mass spectrometry and visualized using microscopy. In neurons, Cal-ID labeling is triggered by neuronal activity, leading to prominent protein biotinylation that enables transcription-independent activity labeling in the brain. In summary, Cal-ID produces a biochemical record of calcium signals and neuronal activity with high spatial resolution and molecular specificity.

Concatenated ScaA and TSA56 Surface Antigen Sequences Reflect Genome-Scale Phylogeny of Orientia tsutsugamushi: An Analysis Including Two Genomes from Taiwan.

Orientia tsutsugamushi is an obligate intracellular bacterium associated with trombiculid mites and is the causative agent of scrub typhus, a life-threatening febrile disease. Strain typing of O. tsutsugamushi is based on its immunodominant surface antigen, 56-kDa type-specific antigen (TSA56). However, TSA56 gene sequence-based phylogenetic analysis is only partially congruent with core genome-based phylogenetic analysis. Thus, this study investigated whether concatenated surface antigen sequences, including surface cell antigen (Sca) proteins, can reflect the genome-scale phylogeny of O. tsutsugamushi. Complete genomes were obtained for two common O. tsutsugamushi strains in Taiwan, TW-1 and TW-22, and the core genome/proteome was identified for 11 O. tsutsugamushi strains. Phylogenetic analysis was performed using maximum likelihood (ML) and neighbor-joining (NJ) methods, and the congruence between trees was assessed using a quartet similarity measure. Phylogenetic analysis based on 691 concatenated core protein sequences produced identical tree topologies with ML and NJ methods. Among TSA56 and core Sca proteins (ScaA, ScaC, ScaD, and ScaE), TSA56 trees were most similar to the core protein tree, and ScaA trees were the least similar. However, concatenated ScaA and TSA56 sequences produced trees that were highly similar to the core protein tree, the NJ tree being more similar. Strain-level characterization of O. tsutsugamushi may be improved by coanalyzing ScaA and TSA56 sequences, which are also important targets for their combined immunogenicity.

Sex Differences in Quadriceps Atrophy After Anterior Cruciate Ligament Tear.

BACKGROUND: Female athletes lag behind their male counterparts in recovery from anterior cruciate ligament (ACL) injury. Quadriceps muscle size and strength are crucial factors for regaining function after ACL injury, but little is known about how these metrics vary due to biological sex. HYPOTHESIS: Female patients have reduced vastus lateralis fiber cross-sectional area (CSA) and lower quadriceps strength after ACL injury than male patients. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 60 participants with recent ACL tear were evaluated for vastus lateralis muscle fiber CSA, isometric quadriceps peak torque, and quadriceps rate of torque development. Linear mixed models were fit to determine differences across sex and limb for each variable of interest. RESULTS: The female group averaged almost 20% atrophy between limbs (P < 0.01), while the male group averaged just under 4% (P = 0.05). Strength deficits between limbs were comparable between female and male groups. CONCLUSION: Immediately after ACL injury, female patients have greater between-limb differences in muscle fiber CSA but between-limb strength deficits comparable with those of male patients. CLINICAL RELEVANCE: These results indicate that the underpinnings of strength loss differ based on biological sex, and thus individual patients could benefit from a sex-specific treatment approach to ACL injury.