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Georges F Hatoum,1,* H Thomas Temple,2,* Silvio A Garcia,1 Yi Zheng,1,3 Fouad Kfoury,4 Jill Kinley,5 Xiaodong Wu1,3 1Department of Radiation Oncology, HCA Florida JFK Medical Center Comprehensive Cancer Institute, Lake Worth, FL, USA; 2Department of Orthopedic Surgery, University of Miami Miller School of Medicine, Miami, FL, USA; 3Department of Research and Development, Executive Medical Physics Associates, North Miami Beach, FL, USA; 4Pharmacy Department, South Miami Hospital, South Miami, FL, USA; 5Department of Clinical Research, HCA Florida JFK Medical Center, Atlantis, FL, USA*These authors contributed equally to this workCorrespondence: Xiaodong Wu, Executive Medical Physics Associates, 19470 NE 22nd Road, North Miami Beach, FL, 33179, USA, Tel +1 305 775 0333, Email drxiaodongwu@yahoo.comPurpose: To report a case of large extremity soft tissue sarcoma (2933 cc), safely treated with a novel approach of interdigitating high-dose LATTICE radiation therapy (LRT) with standard radiation therapy as a neoadjuvant treatment to surgery.Patients and Methods: Four sessions of high-dose LRT were delivered in a weekly interval, interdigitated with standard radiation therapy. The LRT plan consisted of 15 high-dose vertices receiving a dose > 12 Gy per session, with 2– 3 Gy to the peripheral margin of the tumor. The patient underwent surgical excision 2 months after the new regimen of induction radiation therapy.Results and Discussion: The patient tolerated the radiation therapy regimen well. The post-operative assessment revealed a negative surgical margin and over 95% necrosis of the total tumor volume. The post-surgical wound complication was mitigated by outpatient wound care. Interdigitating multiple sessions of high-dose LATTICE radiation treatments with standard neoadjuvant radiation therapy as a neoadjuvant therapy for soft tissue sarcoma was feasible and did not incur additional toxicity in this clinical case. A phase-I/II trial will be conducted to further evaluate the toxicity and efficacy of the new treatment strategy with the intent to increase the rate of pathologic necrosis, which has been shown to positively correlate with the overall survival.Keywords: sarcoma, SFRT, LATTICE radiotherapy, LRT, chemotherapy, surgery, necrosis

The purpose was to (1) compare the effect of a walking bout on femoral cartilage deformation between limbs with and without anterior cruciate ligament reconstruction (ACLR) and (2) examine the association between gait kinetics and the magnitude of cartilage deformation. A total of 30 individuals with primary unilateral ACLR completed this study [14 male, 16 female; age = 22.57 (3.78) years; body mass index (BMI) = 25.88 (5.68) kg/m 2 ; time since ACLR = 61.00 (16.43) months]. Overground walking biomechanics were assessed on day 1, and a 30-min walking bout or 30-min resting bout (control) were completed on days 2 and 3 (counterbalanced order). Femoral cartilage thickness was measured using ultrasound before, immediately following, and 30-min following each intervention. Linear mixed effects models compared the effect of walking on cartilage thickness between the ACLR and contralateral limbs after adjusting for sex, BMI, speed, and the number of steps. Stepwise regression examined the association between the external knee flexion and adduction moments and cartilage deformation following walking. There was a significant limb × time interaction for medial cartilage thickness. Post hoc analyses indicated that cartilage thickness decreased immediately following walking in the contralateral but not ACLR limb. Main effects of limb were observed for medial, central, and lateral cartilage thickness indicating thicker cartilage in the ACLR compared with contralateral limb. A higher knee adduction moment was associated with greater cartilage deformation in the ACLR limb. Femoral cartilage in the ACLR limb exhibited a less dynamic response to walking than the uninvolved limb, which may be due to habitual underloading during gait., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Both high body mass index (BMI) and anterior cruciate ligament reconstruction (ACLR) independently influence knee osteoarthritis risk. Preliminary evidence shows the combination of these risk factors leads to poorer recovery and altered biomechanical outcomes after ACLR, but few studies have directly evaluated early changes in cartilage health between normal-BMI and high-BMI groups in this population., Purpose: To evaluate ultrasound-based measures of cartilage strain and compositional changes (via echo-intensity [EI]) in response to an incline walking stress test between normal-BMI and high-BMI individuals with ACLR. A secondary evaluation was conducted of associations between habitual walking biomechanics (ie, ground-reaction forces, sagittal knee kinetics and kinematics) and cartilage strain and EI outcomes., Study Design: Controlled laboratory study., Methods: Gait biomechanics and femoral trochlear ultrasound analyses were evaluated in 64 participants with ACLR who had normal BMI (BMI < 27.0; n = 40) and high BMI (BMI ≥ 27.0; n = 24). Ultrasound images were collected bilaterally before and after an incline treadmill walk, and medial and lateral trochlear strain and EI changes pre-post exercise were used to compare BMI groups and limbs. Gait outcomes included ground-reaction forces, peak sagittal plane knee moments, angles, and excursions and were used to determine associations with cartilage outcomes in the entire cohort., Results: High-BMI individuals with ACLR exhibited greater medial trochlear cartilage strain in the ACLR limb compared with normal-BMI individuals (approximately 6%; P < .01). In those with high BMI, the ACLR limb exhibited greater medial trochlear strain relative to non-ACLR limbs (approximately 4%; P < .05), but between-limb differences were not observed in the normal-BMI group ( P > .05). Medial trochlear EI changes were greater bilaterally in those with high BMI compared with normal-BMI ACLR counterparts (approximately 10%; P < .01). Last, individuals who walked with greater peak knee flexion angles exhibited less medial cartilage strain (Δ R 2 = 0.06; P = .025)., Conclusion: The data suggested that high BMI affects cartilage functional properties after ACLR, whereas smaller knee flexion angles were associated with larger medial cartilage strain., Clinical Relevance: High-BMI individuals with ACLR may represent a subset of patients exhibiting earlier declines in cartilage functional integrity in response to loading, necessitating additional or more targeted interventions to mitigate disease development., Competing Interests: The authors declared that they have no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto. This study was approved by the Medical Institutional Review Board (IRBMED) at the University of Michigan (HUM00169174), and data were collected at the University of Michigan Orthopedic Rehabilitation Biomechanics (ORB) Laboratory.

Context: Knee joint effusion and quadriceps strength and activation deficits are common consequences of anterior cruciate ligament (ACL) injury and reconstruction. The presence of an effusion may initiate or worsen the quadriceps dysfunction present after ACL trauma. In simulated effusion studies, evidence indicates an inverse relationship between effusion size and quadriceps dysfunction. While this relationship was not found in patients after ACL injury, prior research was limited by a subjective clinical assessment of effusion grade., Objective: The purpose of this study was to determine if the size of the knee joint effusion, measured via ultrasound, after ACL injury and reconstruction influences quadriceps strength and activation., Design: Descriptive Laboratory Study., Setting: Research Laboratory., Patients or Other Participants: 41 individuals (23 females, age=21.8±7.5years, height =171.7±7.9cm, 15 mass =72.3±14.2kg), with an ACL injury reported for 2 sessions [one before 16 reconstruction and one ∽16 weeks after ACL reconstruction]., Main Outcome Measure: Three ultrasound images of the suprapatellar pouch and three trials of quadriceps strength and activation using the interpolated twitch technique were gathered from the ACL knee. Effusion cross-sectional area was measured using ImageJ, averaged and inputted into linear regression models to predict muscle strength and interpolated twitch activation. Analyses were considered significant at p≤0.05., Results: No relationship was found between effusion size and strength (R2 = 0.086) or activation (R2=0.056) after ACL injury (p>0.05). After reconstruction, however, there was a small negative relationship between effusion size 24 and activation (R2=0.122; Standardized β=-0.349; p=0.025), while no relationship was found for effusion size and strength (R2=0.000; p≤0.05)., Conclusions: The size of the effusion after ACL injury does not influence strength or activation. However, after ACL reconstruction, effusion size does have a small influence on quadriceps activation, with a larger effusion being related to lower activation. Prior research using simulated effusions appear to overestimate the effects of effusion on quadriceps function.

Objectives: Monitoring cavitation during ultrasound therapy is crucial for assessing the procedure safety and efficacy. This work aims to develop a self-sensing and low-complexity approach for robust cavitation detection in moving organs such as the heart., Methods: An analog-to-digital converter was connected onto one channel of the therapeutic transducer from a clinical system dedicated to cardiac therapy, allowing to record signals on a computer. Acquisition of successive echoes backscattered by the cavitation cloud on the therapeutic transducer was performed at a high repetition rate. Temporal variations of the backscattered echoes were analyzed with a Singular-Value Decomposition filter to discriminate signals associated to cavitation, based on its stochastic nature. Metrics were derived to classify the filtered backscattered echoes. Classification of raw backscattered echoes was also performed with a machine learning approach. The performances were evaluated on 155 in vitro acquisitions and 110 signals acquired in vivo during transthoracic cardiac ultrasound therapy on 3 swine., Results: Cavitation detection was achieved successfully in moving tissues with high signal to noise ratio in vitro (cSNR = 25±5) and in vivo (cSNR = 20±6) and outperformed conventional methods (cSNR = 11±6). Classification methods were validated with spectral analysis of hydrophone measurements. High accuracy was obtained using either the clutter filter-based method (accuracy of 1) or the neural network-based method (accuracy of 0.99)., Conclusion: Robust self-sensing cavitation detection was demonstrated to be possible with a clutter filter-based method and a machine learning approach., Significance: The self-sensing cavitation detection method enables robust, reliable and low complexity cavitation activity monitoring during ultrasound therapy.

Background: Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa., Methods: Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents. We used Bayesian mixed-effects spatial regression to model urban key population size estimates as a proportion of the gender-matched, year-matched, and area-matched population aged 15-49 years. We modelled subnational key population HIV prevalence and ART coverage with age-matched, gender-matched, year-matched, and province-matched total population estimates as predictors., Findings: We extracted 2065 key population size data points, 1183 HIV prevalence data points, and 259 ART coverage data points. Across national urban populations, a median of 1·65% (IQR 1·35-1·91) of adult cisgender women were female sex workers, 0·89% (0·77-0·95) were men who have sex with men, 0·32% (0·31-0·34) were men who injected drugs, and 0·10% (0·06-0·12) were women who were transgender. HIV prevalence among key populations was, on average, four to six times higher than matched total population prevalence, and ART coverage was correlated with, but lower than, the total population ART coverage with wide heterogeneity in relative ART coverage across studies. Across sub-Saharan Africa, key populations were estimated as comprising 1·2% (95% credible interval 0·9-1·6) of the total population aged 15-49 years but 6·1% (4·5-8·2) of people living with HIV., Interpretation: Key populations in sub-Saharan Africa experience higher HIV prevalence and lower ART coverage, underscoring the need for focused prevention and treatment services. In 2024, limited data availability and heterogeneity constrain precise estimates for programming and monitoring trends. Strengthening key population surveys and routine data within national HIV strategic information systems would support more precise estimates., Funding: UNAIDS, Bill & Melinda Gates Foundation, and US National Institutes of Health., Competing Interests: Declaration of interests SB has received funding from the US National Institutes of Health (NIH). FC has received funding from the Wellcome Trust, the Medical Research Council, NIH, Unitaid, and the Bill & Melinda Gates Foundation. LD has received untied educational grants for the study of new opioid medications in Australia from Indivior and Sequirus. EF has received funding from the UK Research and Innovation Medical Research Council, the Royal Society, and the Centre for Sexual Health and HIV/AIDS Research Zimbabwe. JWI-E acknowledges funding from UNAIDS, NIH, the Gates Foundation, UK Research and Innovation, and BAO Systems, and has received support to attend meetings from UNAIDS, the South African Centre for Epidemiological Modelling and Analysis, the International AIDS Society, and the Gates Foundation. KR and MM-G have received support to attend meetings from UNAIDS. JS has received funding from UNAIDS. OS has received funding from UNAIDS. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: High body mass index (BMI) is a strong predictor of posttraumatic osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR). Altered gait mechanics are independently affected by BMI and ACLR, and influence OA risk. Yet, evidence directly assessing the impact of high BMI on gait or cartilage characteristics after ACLR are limited. Here, we evaluated if high BMI moderates associations between gait and trochlear cartilage structure in individuals with ACLR., Methods: Treadmill walking biomechanics were evaluated in 40 normal BMI and 24 high BMI participants with ACLR at self-selected speeds. Normalized and absolute peak and cumulative loads (i.e., impulse) were extracted for peak knee flexion and adduction moments (KFM, KAM) and vertical ground reaction force (GRF). Medial and lateral femoral cartilage thickness and medial/lateral thickness ratios were assessed via ultrasound., Results: Those with ACLR and high BMI walked with reduced normalized peak vertical GRFs, and greater absolute peak and cumulative loads compared with normal BMI individuals with ACLR. Those with ACLR and high BMI also exhibited thinner cartilage and greater medial/lateral ratios in ACLR limbs compared with contralateral limbs whereas normal BMI individuals with ACLR exhibited thicker ACLR limb cartilage. Lastly, greater peak KAM and KAM cumulative load were associated with thicker lateral cartilage and lesser medial/lateral thickness ratios, but only in the high BMI group., Conclusions: We observed those with high BMI after ACLR exhibited trochlear cartilage structural alterations not observed in normal BMI patients, whereas differential associations between loading outcomes and cartilage thickness in ACLR knees were observed between groups. Those with high BMI after ACLR may require different therapeutic strategies to optimize joint health in this subset of patients., (Copyright © 2024 by the American College of Sports Medicine.)

The respiratory syncytial virus (RSV) M2-1 protein is a transcriptional antitermination factor crucial for efficiently synthesizing multiple full-length viral mRNAs. During RSV infection, M2-1 exists in a complex with mRNA within cytoplasmic compartments called inclusion body-associated granules (IBAGs). Prior studies showed that M2-1 can bind along the entire length of viral mRNAs instead of just gene-end (GE) sequences, suggesting that M2-1 has more sophisticated RNA recognition and binding characteristics. Here, we analyzed the higher oligomeric complexes formed by M2-1 and RNAs in vitro using size exclusion chromatography (SEC), electrophoretic mobility shift assays (EMSA), negative stain electron microscopy (EM), and mutagenesis. We observed that the minimal RNA length for such higher oligomeric assembly is about 14 nucleotides for polyadenine sequences, and longer RNAs exhibit distinct RNA-induced binding modality to M2-1, leading to enhanced particle formation frequency and particle homogeneity as the local RNA concentration increases. We showed that particular cysteine residues of the M2-1 cysteine-cysteine-cystine-histidine (CCCH) zinc-binding motif are essential for higher oligomeric assembly. Furthermore, complexes assembled with long polyadenine sequences remain unaffected when co-incubated with ribonucleases or a zinc chelation agent. Our study provided new insights into the higher oligomeric assembly of M2-1 with longer RNA.IMPORTANCERespiratory syncytial virus (RSV) causes significant respiratory infections in infants, the elderly, and immunocompromised individuals. The virus forms specialized compartments to produce genetic material, with the M2-1 protein playing a pivotal role. M2-1 acts as an anti-terminator in viral transcription, ensuring the creation of complete viral mRNA and associating with both viral and cellular mRNA. Our research focuses on understanding M2-1's function in viral mRNA synthesis by modeling interactions in a controlled environment. This approach is crucial due to the challenges of studying these compartments in vivo . Reconstructing the system in vitro uncovers structural and biochemical aspects and reveals the potential functions of M2-1 and its homologs in related viruses. Our work may contribute to identifying targets for antiviral inhibitors and advancing RSV infection treatment., Competing Interests: The authors declare no conflict of interest.

The actions of the retinoic acid nuclear receptor gamma (RARγ) agonist, palovarotene, on pre-existing osteochondromas were investigated using a mouse multiple osteochondroma model. This approach was based on the knowledge that patients often present to the clinic after realizing the existence of osteochondroma masses, and the findings from preclinical investigations are the effects of drugs on the initial formation of osteochondromas. Systemic administration of palovarotene, with increased doses (from 1.76 to 4.0 mg/kg) over time, fully inhibited tumor growth, keeping the tumor size (0.31 ± 0.049 mm 3 ) similar to the initial size (0.27 ± 0.031 mm 3 , p = 0.66) while the control group tumor grew (1.03 ± 0.23 mm 3 , p = 0.023 to the drug-treated group). Nanoparticle (NP)-based local delivery of the RARγ agonist also inhibited the growth of osteochondromas at an early stage (Control: 0.52 ± 0.11 mm 3 ; NP: 0.26 ± 0.10, p = 0.008). Transcriptome analysis revealed that the osteoarthritis pathway was activated in cultured chondrocytes treated with palovarotene (Z-score = 2.29), with the upregulation of matrix catabolic genes and the downregulation of matrix anabolic genes, consistent with the histology of palovarotene-treated osteochondromas. A reporter assay performed in cultured chondrocytes demonstrated that the Stat3 pathway, but not the Stat1/2 pathway, was stimulated by RARγ agonists. The activation of Stat3 by palovarotene was confirmed using immunoblotting and immunohistochemistry. These findings suggest that palovarotene treatment is effective against pre-existing osteochondromas and that the Stat3 pathway is involved in the antitumor actions of palovarotene.

Background: Articular cartilage is important for knee function and can be imaged using ultrasound. The purpose was to compare femoral cartilage thickness and echo intensity (EI) measured at 90° and 140° of knee flexion and between limbs in a cohort with unilateral anterior cruciate ligament reconstruction (ACLR). We also examined associations between gait biomechanics and cartilage outcomes., Methods: Twenty-seven individuals with primary unilateral ACLR participated (12 men, 15 women; age = 22.3 ± 3.8 years; time since ACLR = 71.2 ± 47.2 months). Ultrasound was used to obtain femoral cartilage measurements. Gait outcomes included peak KFA (knee flexion angle) and peak external knee flexion moment (KFM). Cartilage outcomes were compared using a 2 ( position ) × 2 ( limb ) repeated measures ANOVA (analysis of variance). Gait and cartilage associations were assessed using linear regression., Findings: There were no position × limb interactions for any cartilage outcome (all P > 0.05). Medial ( P = 0.038) and central cartilage ( P < 0.001) were thicker, whereas central ( P = 0.029) and lateral cartilage EI ( P = 0.003) were lower when measured at 90° than those at 140° of knee flexion. Medial cartilage was thicker in the ACLR than that in the contralateral limb ( P = 0.016). A larger KFM was associated with thicker medial cartilage (ΔR 2 = 0.146, P = 0.021) and central cartilage (ΔR 2 = 0.159, P = 0.039) measured at 140° of knee flexion in the ACLR limb but not at 90°., Interpretation: Findings suggest that imaging position influences cartilage thickness and EI measurements in individuals with ACLR and should be considered in study designs and clinical evaluation. A greater KFM was associated with thicker cartilage within specific portions of the distal femur., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Body mass index (BMI) and history of anterior cruciate ligament reconstruction (ACLR) independently influence gait biomechanics and knee osteoarthritis risk, but the interaction between these factors is unclear. The purpose of this study was to compare gait biomechanics between individuals with and without ACLR, and with and without overweight/obesity. We examined 104 individuals divided into four groups: with and without ACLR, and with low or high BMI (n = 26 per group). Three-dimensional gait biomechanics were evaluated at preferred speed. The peak vertical ground reaction force, knee flexion angle and excursion, external knee flexion moment, and external knee adduction moment were extracted for analysis. Gait features were compared between groups using 2 (with and without overweight/obesity) × 2 (with and without ACLR) analysis of variance. Primary findings indicated that those with ACLR and high BMI had a larger external knee adduction moment compared with those with low BMI and with (p = 0.004) and without ACLR (p = 0.005), and compared with those without ACLR and high BMI (p = 0.001). The main effects of ACLR and BMI group were found for the knee flexion moment, and those with ACLR and with high BMI had lower knee flexion moments compared with those without ACLR (p = 0.031) and with low BMI (p = 0.021), respectively. Data suggest that individuals with ACLR and high BMI may benefit from additional intervention targeting the knee adduction moment. Moreover, lower external knee flexion moments in those with high BMI and ACLR were consistent, but high BMI did not exacerbate deficits in the knee flexion moment in those with ACLR. [Correction added on 9 November 2022, after first online publication: In the preceding sentence, for clarity, the words "reductions in the lower" was removed from the initial sentence to read "Moreover, lower external knee flexion moments".]., (© 2022 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: Abnormal gait is common after anterior cruciate ligament reconstruction (ACLR) which may influence osteoarthritis risk in this population. Yet few gait retraining options currently exist in ACLR rehabilitation. Cueing cadence changes is a simple, low-cost method that can alter walking mechanics in healthy adults, but few studies have tested its effectiveness in an ACLR population. Here, we evaluated the acute effects of altering cadence on knee mechanics in patients 9 to 12 months post ACLR., Hypothesis: Cueing larger steps will facilitate larger knee angles and moments, while cueing smaller steps would induce smaller knee angles and moments., Study Design: Randomized cross-sectional design., Level of Evidence: Level 3., Methods: Twenty-eight patients with unilateral ACLR underwent gait assessments on a treadmill at preferred pace. Preferred walking gait was assessed first to obtain preferred cadence. Participants then completed trials while matching an audible beat set to 90% and 110% of preferred cadence in a randomized order. Three-dimensional sagittal and frontal plane biomechanics were evaluated bilaterally., Results: Compared with preferred cadence, cueing larger steps induced larger peak knee flexion moments (KFMs) and knee extension excursions bilaterally ( P < 0.01), whereas cueing smaller steps only reduced knee flexion excursions ( P < 0.01). Knee adduction moments remain unchanged across conditions and were similar between limbs ( P > 0.05). Peak KFMs and excursions were smaller in the injured compared with uninjured limb ( P < 0.01)., Conclusion: Frontal plane gait outcomes were unchanged across conditions suggesting acute cadence manipulations result in mainly sagittal plane adaptations. Follow-up studies using a longitudinal cadence biofeedback paradigm may be warranted to elucidate the utility of this gait retraining strategy after ACLR., Clinical Relevance: Cueing changes in walking cadence can target sagittal plane knee loading and joint range of motion in ACLR participants. This strategy may offer high clinical translatability given it requires relatively minimal equipment (ie, free metronome app) outside of a treadmill., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

Introduction: Epilepsy is a disease characterized by an excessive discharge in neurons generally provoked without any external stimulus, known as convulsions. About 2 million people are diagnosed each year in the world. This process is carried out by a neurological doctor using an electroencephalogram (EEG), which is lengthy., Method: To optimize these processes and make them more efficient, we have resorted to innovative artificial intelligence methods essential in classifying EEG signals. For this, comparing traditional models, such as machine learning or deep learning, with cutting-edge models, in this case, using Capsule-Net architectures and Transformer Encoder, has a crucial role in finding the most accurate model and helping the doctor to have a faster diagnosis., Result: In this paper, a comparison was made between different models for binary and multiclass classification of the epileptic seizure detection database, achieving a binary accuracy of 99.92% with the Capsule-Net model and a multiclass accuracy with the Transformer Encoder model of 87.30%., Conclusion: Artificial intelligence is essential in diagnosing pathology. The comparison between models is helpful as it helps to discard those that are not efficient. State-of-the-art models overshadow conventional models, but data processing also plays an essential role in evaluating the higher accuracy of the models., (© 2024. The Author(s).)

Background: Earlier studies have proposed a link between the Interpregnancy Interval (IPI) and unfavorable birth outcomes. However, it remains unclear if the outcomes of previous births could affect this relationship. We aimed to investigate whether the occurrence of adverse outcomes-small for gestational age (SGA), preterm birth (PTB), and low birth weight (LBW)-at the immediately preceding pregnancy could alter the association between IPI and the same outcomes at the subsequent pregnancy., Methods: We used a population-based linked cohort from Brazil (2001-2015). IPI was measured as the difference, in months, between the preceding birth and subsequent conception. Outcomes included SGA (<10th birthweight percentile for gestational age and sex), LBW (<2500 g), and PTB (gestational age <37 weeks). We calculated risk ratios (RRs), using the IPI of 18-22 months as the reference IPI category, we also stratified by the number of adverse birth outcomes at the preceding pregnancy., Findings: Among 4,788,279 births from 3,804,152 mothers, absolute risks for subsequent SGA, PTB, and LBW were higher for women with more adverse outcomes in the preceding delivery. The RR of SGA and LBW for IPIs <6 months were greater for women without previous adverse outcomes (SGA: 1.44 [95% Confidence Interval (CI): 1.41-1.46]; LBW: 1.49 [1.45-1.52]) compared to those with three previous adverse outcomes (SGA: 1.20 [1.10-1.29]; LBW: 1.24 [1.15-1.33]). IPIs ≥120 months were associated with greater increases in risk for LBW and PTB among women without previous birth outcomes (LBW: 1.59; [1.53-1.65]; PTB: 2.45 [2.39-2.52]) compared to women with three adverse outcomes at the index birth (LBW: 0.92 [0.78-1.06]; PTB: 1.66 [1.44-1.88])., Interpretation: Our study suggests that women with prior adverse outcomes may have higher risks for adverse birth outcomes in subsequent pregnancies. However, risk changes due to differences in IPI length seem to have a lesser impact compared to women without a prior event. Considering maternal obstetric history is essential in birth spacing counseling., Funding: Wellcome Trust225925/Z/22/Z., Competing Interests: All authors declare no conflict of interest., (© 2024 The Author(s).)

Background: Key populations (KPs), including female sex workers (FSWs), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as "infection ratios"). We recalculated these ratios using dynamic transmission models., Setting: One hundred seventy-eight settings (106 countries)., Methods: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020., Results: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n = 172 estimates) and 1.2 (0.8-1.8; n = 127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable with the previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n = 20) and 0.3 (0.2-0.4; n = 10) for partners of PWID across settings in Eastern and Southern Africa, lower than the corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher [5.1 (1.2-7.0; n = 8)] than the UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n = 29)., Conclusions: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence., Competing Interests: K.M.M. reports payments from Pfizer for teaching, outside the submitted work. The remaining authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder affecting multiple functional parameters. This study examined postural stability and associated gait and neuromuscular factors in young adults with PWS., Methods: Participants included 10 adults with PWS [7 M/3F; Body Fat % 40.61 ± 7.79]; ten normal weight (NW) adults [7 M/3F; Body Fat % 23.42 ± 7.0]; ten obese (OB) adults [7 M/3F; Body Fat % 42.40 ± 5.62]. Participants completed the Sensory Organization Test (SOT)®. Condition (C) specific and a composite equilibrium score (CES) were calculated (maximum = 100). Quadriceps strength was assessed using an isokinetic dynamometer. Three-dimensional gait analyses were completed along a 10 m walkway using a motion capture system and two force plates. A gait stability ratio (GSR) was computed from gait speed and step length (steps/m)., Results: The PWS group had lower scores for C1, C3, C4 and CES compared to the NW (p < .039 for all) and lower scores for C4 and CES than the OB (p < .019 for both) groups, respectively. In C5 (eyes closed, sway-referenced support) and C6 (sway-referenced vision and support), 33.3% of participants with PWS fell during the first trial in both conditions (X 2 [2] 7.436, p = .024) and (X 2 [2] 7.436, p = .024) but no participant in the other groups fell. Those with PWS showed higher GSR than participants with NW (p = .005) and those with obesity (p = .045)., Conclusion: Individuals with PWS had more difficulty maintaining standing balance when relying on information from the somatosensory (C3), visual-vestibular (C4) and vestibular systems (C5, C6). A more stable walk was related to shorter steps, slower velocity and reduced peak quadriceps torque. Participation in multisensory activities that require appropriate prioritization of sensory system(s) input for controlling balance in altered sensory environments should be routinely included. In addition, exercises targeting muscular force and power should be included as part of exercise programming in PWS., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest with the information presented in this manuscript., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Ultrathin strut coronary drug-eluting stents (DES) have demonstrated improved safety and efficacy in large contemporary trials. The evaluation of an ultrathin strut DES in a post-market United States (US) patient population was undertaken., Objective: The purpose of this post-approval study is to confirm that the clinical performance of an ultrathin strut bioresorbable polymer sirolimus-eluting stent (BP SES) in clinical practice is similar to that observed with BP SES in the BIOFLOW V pivotal trial., Methods: BIOFLOW VII is a prospective, multicenter, single-arm US post-market approval study to confirm the clinical performance of BP SES in a real-world setting. The primary endpoint of 1-year target lesion failure (TLF) was compared with a performance goal of 6.9% based on an adapted BIOFLOW V trial BP SES TLF rate and TLF rates from other US market-released DES utilizing the Society for Cardiovascular Angiography and Interventions definition for peri-procedural myocardial infarction (MI). Subjects undergoing percutaneous coronary intervention with BP SES were consented within 24 h post-index procedure with planned follow-up through 5 years., Results: Among 556 enrolled patients, clinical demographics included: 34.7% female, 35.6% with diabetes mellitus, and 56.8% with acute coronary syndromes. The average stent length (mean ± standard deviation) was 20.2 ± 11.8 mm, and the mean number of stents per patient was 1.3 ± 0.6. Procedure success was 99.1% (551/556), and device success was 99.9% (689/690). Among 531 subjects included in the primary endpoint analysis, the 1-year rate of TLF rate was 1.7% (9/531), and the primary endpoint was met compared with the performance goal (p < 0.0001, 95% confidence interval: 0.69%, 3.43%). Rates of target vessel MI and clinically driven target lesion revascularization were 1.3% (7/531) and 0.9% (5/531), with no occurrence of cardiac death. Definite stent thrombosis was observed for two cases (0.4%; 2/556) with one acute (≤24 h) and one late (>30 days and ≤1 year) event., Conclusion: In a post-approval study, 1-year clinical outcomes with BP SES were consistent with prior trials supporting the safety and effectiveness of ultrathin BP SES., (© 2023 Wiley Periodicals LLC.)

Purpose: Individuals with anterior cruciate ligament reconstruction (ACLR) generally exhibit limb underloading behaviors during walking, but most research focuses on per-step comparisons. Cumulative loading metrics offer unique insight into joint loading as magnitude, duration, and total steps are considered, but few studies have evaluated if cumulative loads are altered post-ACLR. Here, we evaluated if underloading behaviors are apparent in ACLR limbs when using cumulative load metrics and how load metrics change in response to walking speed modifications., Methods: Treadmill walking biomechanics were evaluated in 21 participants with ACLR at three speeds (self-selected (SS); 120% SS and 80% SS). Cumulative loads per step and per kilometer were calculated using knee flexion and adduction moment (KFM and KAM) and vertical ground reaction force (GRF) impulses. Traditional magnitude metrics for KFM, KAM, and GRF were also calculated., Results: The ACLR limb displayed smaller KFM and GRF in early and late stances, but larger KFM and GRF during midstance compared with the contralateral limb ( P < 0.01). Only GRF cumulative loads (per step and per kilometer) were reduced in the ACLR limb ( P < 0.01). In response to speed modifications, load magnitudes generally increased with speed. Conversely, cumulative load metrics (per step and per kilometer) decreased at faster speeds and increased at slow speeds ( P < 0.01)., Conclusions: Patients with ACLR underload their knee in the sagittal plane per step, but cumulatively over the course of many steps/distance, this underloading phenomenon was not apparent. Furthermore, cumulative load increased at slower speeds, opposite to what is identified with traditional single-step metrics. Assessing cumulative load metrics may offer additional insight into how load outcomes may be impacted in injured populations or in response to gait modifications., (Copyright © 2023 by the American College of Sports Medicine.)

Background: Walking biomechanics are commonly affected after anterior cruciate ligament reconstruction and differ compared to uninjured controls. Manipulating task difficulty has been shown to affect the magnitude of walking impairments in those early after knee surgery but it is unclear if patients in later phases post-op are similarly affected by differing task demands. Here, we evaluated the effects of manipulating walking speed on between-limb differences in ground reaction force and knee biomechanics in those with and without anterior cruciate ligament reconstruction., Methods: We recruited 28 individuals with anterior cruciate ligament reconstruction and 20 uninjured control participants to undergo walking assessments at three speeds (self-selected, 120%, and 80% self-selected speed). Main outcomes included sagittal plane knee moments, angles, excursions, and ground reaction forces (vertical and anterior-posterior)., Findings: We observed walking speed differentially impacted force and knee-outcomes in those with anterior cruciate ligament reconstruction. Between-limb differences increased at fast and decreased at slow speeds in those with anterior cruciate ligament reconstruction while uninjured participants maintained between-limb differences regardless of speed (partial η 2  = 0.13-0.33, p < 0.05). Anterior cruciate ligament reconstruction patients underloaded the surgical limb relative to both the contralateral, and uninjured controls in GRFs and sagittal plane knee moments (partial η 2 range = 0.13-0.25, p < 0.05)., Interpretation: Overall, our findings highlight the persistence of walking impairments in those with anterior cruciate ligament reconstruction despite completing formal rehabilitation. Further research should consider determining if those displaying larger changes in gait asymmetries in response to fast walking also exhibit poorer strength and/or joint health outcomes., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven Garcia reports financial support was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The incidence of osteopenia and osteoporosis is of concern in adults with Prader-Willi syndrome (PWS). Walking generates reaction forces that could stimulate bone mineralization and is popular in people with PWS. This study compared bone parameters and ground reaction forces (GRF) during gait between young adults with PWS and without PWS and explored associations between bone and GRFs during gait., Methods: 10 adults with PWS, 10 controls with obesity (OB) and 10 with normal weight (NW) matched on sex participated. Segmental and full body dual-energy x-ray absorptiometry scans provided femoral neck, spine, total body minus the head bone mineral density (BMD), bone mineral content (BMC). Vertical GRF, vertical impulse, posterior force and negative impulse were measured during 5 walking trials at a self-selected speed along a 10 m runway., Results: Multivariate analyses of variance showed that adults with PWS ( n  = 7-8) had hip and body BMD and BMC comparable ( p  > .050) to NW and lower ( p  < .050) than OB. Adults with PWS showed slower speed than NW (p < .050) but similar to OB ( p  > .050). Adults with PWS presented lower absolute vertical GRF, vertical impulse and negative impulse than OB ( p  < .050). Pearson r correlations ( p  < .050) in those with PWS (n = 7-8) indicated that femoral neck BMC was associated with vertical GRF ( r  = 0.716), vertical impulse ( r  = 0.780), posterior force ( r  = -0.805), and negative impulse ( r  = -0.748). Spine BMC was associated with speed ( r  = 0.829) and body BMD was associated with speed ( r  = 0.893), and posterior force ( r  = -0.780)., Conclusions: Increased BMC in the femoral neck and body were associated with larger breaking forces during walking, a phenomenon normally observed at greater gait speeds. Faster walking speed was associated with greater BMC in the spine and body. Our preliminary results suggest that young adults with PWS could potentially benefit from faster walking for bone health; however, larger prospective studies are needed to confirm this., Competing Interests: None., (© 2023 The Authors.)

Calmodulin (CaM) is a ubiquitous, calcium-sensing protein that regulates a multitude of processes throughout the body. In response to changes in [Ca 2+ ], CaM modifies, activates, and deactivates enzymes and ion channels, as well as many other cellular processes. The importance of CaM is highlighted by the conservation of an identical amino acid sequence in all mammals. Alterations to CaM amino acid sequence were once thought to be incompatible with life. During the last decade modifications to the CaM protein sequence have been observed in patients suffering from life-threatening heart disease (calmodulinopathy). Thus far, inadequate or untimely interaction between mutant CaM and several proteins (LTCC, RyR2, and CaMKII) have been identified as mechanisms underlying calmodulinopathy. Given the extensive number of CaM interactions in the body, there are likely many consequences for altering CaM protein sequence. Here, we demonstrate that disease-associated CaM mutations alter the sensitivity and activity of the Ca 2+ -CaM-enhanced serine/threonine phosphatase calcineurin (CaN). Biophysical characterization by circular dichroism, solution NMR spectroscopy, stopped-flow kinetic measurements, and MD simulations provide mechanistic insight into mutation dysfunction as well as highlight important aspects of CaM Ca 2+ signal transduction. We find that individual CaM point mutations (N53I, F89L, D129G, and F141L) impair CaN function, however, the mechanisms are not the same. Specifically, individual point mutations can influence or modify the following properties: CaM binding, Ca 2+ binding, and/or Ca 2+ kinetics. Moreover, structural aspects of the CaNCaM complex can be altered in manners that indicate changes to allosteric transmission of CaM binding to the enzyme active site. Given that loss of CaN function can be fatal, as well as evidence that CaN modifies ion channels already associated with calmodulinopathy, our results raise the possibility that altered CaN function contributes to calmodulinopathy., Competing Interests: Declaration of Competing Interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Hepatobiliary surgery bares obstacles to informed consent for the patients due to its complexity and related risk of postoperative complications. 3D visualization of the liver has been proven to facilitate comprehension of the spatial relationship between anatomical structures and to assist in clinical decision-making. Our objective is to utilize individual 3D-printed liver models to enhance patient satisfaction with surgical education in hepatobiliary surgery., Design, Setting: We conducted a prospective, randomized pilot study comparing 3D liver model-enhanced (3D-LiMo) surgical education against regular patient education during preoperative consultation at the department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Dresden, Germany., Participants: Of 97 screened patients, undergoing hepatobiliary surgery, 40 patients were enrolled from July 2020 to January 2022., Results: The study population (n = 40) was predominantly of male gender (62.5%) with a median age of 65.2 years and a high prevalence of preexisting diseases. Underlying disease, warranting hepatobiliary surgery, was malignancy in the majority of cases (97.5%). Patients in the 3D-LiMo group were more likely to feel very thoroughly educated and exhibited a higher level of satisfaction following surgical education than the control group (80 vs. 55%, n.s.; 90 vs. 65%, n.s.; respectively). Applying 3D models was also associated with enhanced understanding of the underlying disease with regard to amount (100% vs. 70%, p = 0.020) and location of liver masses (95 vs. 65%, p = 0.044). 3D-LiMo patients also demonstrated enhanced understanding of the surgical procedure (80 vs. 55%, n.s.), leading to better awareness for the occurrence of postoperative complications (88.9, vs. 68.4%, p = 0.052). Adverse event profiles were similar., Conclusion: In conclusion, individual 3D-printed liver models increase patient satisfaction with surgical education and facilitate patients' understanding of the surgical procedure as well as awareness of postoperative complications. Therefore, the study protocol is feasible to apply to an adequately powered, multicenter, randomized clinical trial with minor modifications., (© 2023. The Author(s).)

We propose a new VO2max test using a progressive staged protocol on an Assault Fitness AssaultBike. Twelve healthy males performed a traditional ramp cycle ergometer test (TRAD) and a progressively staged AssaultBike protocol (AB) in a counterbalanced order. AB elicited higher immediate post-exercise lactate, absolute and relative VO2max, and maximum heart rate than TRAD ( P = 0.006, P = 0.014, P = 0.007, and P = 0.001, respectively). The protocol outlined herein may provide a more accurate assessment of VO2max due to greater skeletal muscle mass recruitment that is more representative of the whole body.

Background: Transcatheter aortic valve replacement (TAVR) has become the standard of care for most patients with severe aortic stenosis (AS), but the impact of medical therapy prescribing patterns on post-TAVR patients has not been thoroughly investigated., Methods: We analyzed Optum claims data from 9,012 adults who received TAVR for AS (January 2014-December 2018). Pharmacy claims data were used to identify patients who filled ACEI/ARB and/or statin prescriptions during the study's 90-day landmark period post-TAVR. Kaplan-Meier and adjusted Cox Proportional Hazards models were used to evaluate the association of prescribing patterns with mortality during the 3-year follow-up period. Subgroup analyses were performed to examine the impact of 11 potential confounders on the observed associations., Results: A significantly lower adjusted 3-year mortality was observed for patients with post-TAVR prescription for ACEI/ARBs (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.74-0.91, P = .0003) and statins (HR = 0.85, 95% CI 0.77-0.94, P = .0018) compared to patients who did not fill prescriptions for these medications post-TAVR. Subgroup analyses revealed that the survival benefit associated with ACEI/ARB prescription was not affected by any of the potential confounding variables, except preoperative ACEI/ARB prescription was associated with significantly lower risk of mortality vs postoperative prescription only. No other subgroup variables had significant interactions associated with survival benefits, including preoperative use of statins., Conclusions: In this large-scale, real-world analysis of patients undergoing TAVR, the prescription of ACEI/ARB and statins was associated with a significantly lower risk of mortality at 3-years, especially in those where the medications were initiated preoperatively., Competing Interests: Conflict of interest Dr. Cubeddu reports receiving payments for occasional lectures from Edwards Lifesciences. Ms. Murphy reports current employment at Edwards Lifesciences; and being a stockholder at Edwards Lifesciences. Dr. Asher reports receiving royalties for educational Books from Wolters Kluwer Publishing Company. Dr. Garcia is supported by The Harold C. Schott Foundation Endowed Chair for Structural and Valvular Heart Disease and is proctor and steering committee member for Edwards Lifesciences. Dr. Granada has no disclosures to report. Dr. Don reports current participation on the data safety monitoring board (DSMB) of Statins for rheumatic heart disease-Nepal. Dr. Patel has no disclosures to report. Dr. Albaghdadi has no disclosures to report. Dr. Cavalcante reports receiving consulting fees from Abbott Structural, Aria CV, Boston Scientific, Edwards Lifesciences, Medtronic, Vdyne, W.L. Gore, and Xylocor. Dr. Coylewright reports receiving fees or honoraria for lectures, presentations, speakers bureau, manuscript writing or educational events from Medtronic, Abbott, Occlutech, CardioSmart, Edwards Lifesciences, and Boston Scientific. Dr. Hahn reports speaker fees from Abbott Structural, Baylis Medical, Edwards Lifesciences, and Philips Healthcare; she has institutional consulting contracts for which she receives no direct compensation with Abbott Structural, Edwards Lifesciences, Medtronic and Novartis; she is Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored tricuspid valve trials, for which she receives no direct industry compensation. Dr. Genereux reports receiving consultation fees and institution research grant from Edwards Lifesciences; and receiving payment or honoraria for lectures from Edwards Lifesciences. Dr. Yadav reports receiving consulting fees from Edwards Lifesciences and Abbott Vascular; receiving payment or honoraria for lectures, presentations, speakers bureau, manuscript writing or educational events from Edwards Lifesciences, Abbott Vascular, and Shockwave medical; and current participation on the DSMB or advisory board of Dasi simulations. Dr Thourani reports receiving grants from Edwards Lifesciences; and receiving payment or honoraria for lectures, presentations, speakers bureau, manuscript writing or educational events from Edwards Lifesciences. Dr. Leon reports receiving grants or contracts from Abbott Vascular, Medtronic, Boston Scientific, and Edwards Lifesciences; and receiving consulting fees from Bain Capital., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Maize is a staple food for many communities with high levels of iron deficiency anemia. Enhancing the iron concentrations and iron bioavailability of maize with traditional breeding practices, especially after cooking and processing, could help alleviate iron deficiency in many of these regions. Previous studies on a small number of maize genotypes and maize flour products indicated that degermination (germ fraction removed with processing) could improve the iron bioavailability of maize. This study expanded upon this research by evaluating the iron bioavailability, mineral concentrations, and phytate concentrations of 52 diverse maize genotypes before (whole kernels) and after degermination. Whole and degerminated maize samples were cooked, dried, and milled to produce corn flour. Iron bioavailability was evaluated with an in vitro digestion Caco2 cell bioassay. In 30 of the maize genotypes, bioavailable iron increased when degerminated, thus indicating a higher fractional iron uptake because the iron concentrations decreased by more than 70% after the germ fraction was removed. The remaining 22 genotypes showed no change or a decrease in iron bioavailability after degermination. These results confirm previous research showing that the germ fraction is a strong inhibitory component for many maize varieties. Phytate concentrations in maize flours were greatly reduced with degermination. However, the relationship between phytate concentrations and the iron bioavailability of processed maize flour is complex, acting as either inhibitor or promoter of iron uptake depending on the color of the maize kernels and processing method used to produce flour. Other factors in the maize endosperm fractions are likely involved in the effects of degermination on iron bioavailability, such as vitreous or floury endosperm compositions and the polyphenol content of the bran. This study demonstrates that iron nutrition from maize can be enhanced by selecting genotypes where the inhibitory effect of the bran color and endosperm fraction are relatively low, especially after processing via degermination., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Keigler, Wiesinger, Flint-Garcia and Glahn.)

This study compared femoral cartilage characteristics between age- and sex-matched individuals with (n = 48, age = 22.8 ± 3.5 years; body mass index [BMI] = 33.1 ± 4.1 kg/m 2 ) and without obesity (n = 48 age = 22.0 ± 2.6 years; BMI = 21.7 ± 1.7 kg/m 2 ) and evaluated the associations between body composition, quadriceps function, and gait kinetics with femoral cartilage characteristics. Medial and lateral femoral cartilage thickness, medial:lateral thickness ratio and medial and lateral cartilage echo intensity were measured using ultrasound imaging. Body composition was assessed using air displacement plethysmography. Quadriceps function was assessed via maximal isometric knee extension. Three-dimensional gait biomechanics were recorded to extract peak external knee flexion and adduction moments, and peak loading rate of the vertical ground reaction force. Cartilage outcomes were compared between groups using one-way multivariate analysis of variance. Stepwise moderated regression evaluated the association between body composition, quadriceps function, and gait kinetics with femoral cartilage outcomes in individuals with and without obesity. Medial (75.24 vs 65.84; P < .001, d = 1.02) and lateral (58.81 vs 52.22; P < .001, d = 0.78) femoral cartilage echo intensity were higher in individuals with compared with those without obesity. A higher body fat percentage was associated with higher medial and lateral cartilage echo intensity (ΔR 2  = 0.09-0.12) in individuals with obesity. A higher knee adduction moment was associated with a larger medial:lateral thickness ratio (ΔR 2  = 0.09) in individuals without obesity. No associations were found between quadriceps function and cartilage outcomes. These findings suggest that high body fat in adults with obesity is associated with cartilage echo intensity. The obese body mass index was also associated with a lack of a positive relationship between cartilage thickness and joint loading during walking., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Individuals with anterior cruciate ligament (ACL) reconstruction often display abnormal gait mechanics reflective of a "stiff-knee" gait (i.e., reduced knee flexion angles and moments). However, dynamic knee stiffness, which is the dynamic relationship between the position of the knee and the moment acting on it, has not been directly examined during walking in individuals with ACL reconstruction. Here, we aimed to evaluate dynamic knee stiffness in the involved compared to the uninvolved limb during weight-acceptance and mid-stance phases of walking. Twenty-six individuals who underwent ACL reconstruction (Age: 20.2 ± 5.1 yrs., Time post-op: 7.2 ± 0.9 mo.) completed an overground walking assessment using a three-dimensional motion capture system and two force plates. Dynamic knee stiffness (Nm/°) was calculated as the slope of the regression line during weight-acceptance and midstance, obtained by plotting the sagittal plane knee angle versus knee moment. Paired t-tests with Bonferroni corrections were used to compare differences in dynamic stiffness, knee excursions, and moment ranges between limbs during both stance phases. Greater dynamic knee stiffness was found in the involved compared with the uninvolved limb during weight-acceptance and mid-stance (p < 0.01). Knee flexion and extension excursions were reduced in the involved limb during both weight-acceptance and mid-stance, respectively (p < 0.01). Sagittal plane knee moment ranges were not different between limbs during weight-acceptance (p = 0.1); however, the involved limb moment range was reduced relative to the uninvolved limb during mid-stance (p < 0.01). These results indicate that individuals with ACL reconstruction walk with a stiffer knee throughout stance, which may influence knee contact forces and could contribute to the high propensity for post-traumatic knee osteoarthritis development in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Key Message: Moisture content during nixtamalization can be accurately predicted from NIR spectroscopy when coupled with a support vector machine (SVM) model, is strongly modulated by the environment, and has a complex genetic architecture. Lack of high-throughput phenotyping systems for determining moisture content during the maize nixtamalization cooking process has led to difficulty in breeding for this trait. This study provides a high-throughput, quantitative measure of kernel moisture content during nixtamalization based on NIR scanning of uncooked maize kernels. Machine learning was utilized to develop models based on the combination of NIR spectra and moisture content determined from a scaled-down benchtop cook method. A linear support vector machine (SVM) model with a Spearman's rank correlation coefficient of 0.852 between wet laboratory and predicted values was developed from 100 diverse temperate genotypes grown in replicate across two environments. This model was applied to NIR spectra data from 501 diverse temperate genotypes grown in replicate in five environments. Analysis of variance revealed environment explained the highest percent of the variation (51.5%), followed by genotype (15.6%) and genotype-by-environment interaction (11.2%). A genome-wide association study identified 26 significant loci across five environments that explained between 5.04% and 16.01% (average = 10.41%). However, genome-wide markers explained 10.54% to 45.99% (average = 31.68%) of the variation, indicating the genetic architecture of this trait is likely complex and controlled by many loci of small effect. This study provides a high-throughput method to evaluate moisture content during nixtamalization that is feasible at the scale of a breeding program and provides important information about the factors contributing to variation of this trait for breeders and food companies to make future strategies to improve this important processing trait., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The use of remote measurement technologies (RMTs) across mobile health (mHealth) studies is becoming popular, given their potential for providing rich data on symptom change and indicators of future state in recurrent conditions such as major depressive disorder (MDD). Understanding recruitment into RMT research is fundamental for improving historically small sample sizes, reducing loss of statistical power, and ultimately producing results worthy of clinical implementation. There is a need for the standardisation of best practices for successful recruitment into RMT research. The current paper reviews lessons learned from recruitment into the Remote Assessment of Disease and Relapse- Major Depressive Disorder (RADAR-MDD) study, a large-scale, multi-site prospective cohort study using RMT to explore the clinical course of people with depression across the UK, the Netherlands, and Spain. More specifically, the paper reflects on key experiences from the UK site and consolidates these into four key recruitment strategies, alongside a review of barriers to recruitment. Finally, the strategies and barriers outlined are combined into a model of lessons learned. This work provides a foundation for future RMT study design, recruitment and evaluation., (© 2022. The Author(s).)

Microglia have been implicated in multiple sclerosis (MS) pathogenesis. The fractalkine receptor CX3CR1 limits the activation of pathogenic microglia and the human polymorphic CX3CR1 I249/M280 (hCX3CR1 I249/M280 ) variant increases disease progression in models of MS. However, the role of hCX3CR1 I249/M280 variant on microglial activation and central nervous system repair mechanisms remains unknown. Therefore, using transgenic mice expressing the hCX3CR1 I249/M280 variant, we aimed to determine the contribution of defective CX3CR1 signaling to neuroinflammation and remyelination in the cuprizone model of focal demyelination. Here, we report that mice expressing hCX3CR1 I249/M280 exhibit marked demyelination and microgliosis following acute cuprizone treatment. Nanostring gene expression analysis in demyelinated lesions showed that hCX3CR1 I249/M280 but not CX3CR1-deficient mice up-regulated the cuprizone-induced gene profile linked to inflammatory, oxidative stress, and phagocytic pathways. Although CX3CR1-deficient (CX3CR1-KO) and fractalkine-deficient (FKN-KO) mice displayed a comparable demyelination and microglial activation phenotype to hCX3CR1 I249/M280 mice, only CX3CR1-deficient and CX3CR1-WT mice showed significant myelin recovery 1 week from cuprizone withdrawal. Confocal microscopy showed that hCX3CR1 I249/M280 variant inhibits the generation of cells involved in myelin repair. Our results show that defective fractalkine signaling contributes to regional differences in demyelination, and suggest that the CX3CR1 pathway activity may be a key mechanism for limiting toxic gene responses in neuroinflammation. Cover Image for this issue: https://doi.org/10.1111/jnc.15416., (© 2022 International Society for Neurochemistry.)

The purpose of this systematic review was to synthesize the results from current literature examining the effects of prior exercise on the postprandial triglyceride (TG) response to evaluate current literature and provide future direction. A quantitative review was performed using meta-analytic methods to quantify individual effect sizes. A moderator analysis was performed to investigate potential variables that could influence the effect of prior exercise on postprandial TG response. Two hundred and seventy-nine effects were retrieved from 165 studies for the total TG response and 142 effects from 87 studies for the incremental area under the curve TG response. There was a moderate effect of exercise on the total TG response (Cohen's d = -0.47; p < .0001). Moderator analysis revealed exercise energy expenditure significantly moderated the effect of prior exercise on the total TG response (p < .0001). Exercise modality (e.g., cardiovascular, resistance, combination of both cardiovascular and resistance, or standing), cardiovascular exercise type (e.g., continuous, interval, concurrent, or combined), and timing of exercise prior to meal administration significantly affected the total TG response (p < .001). Additionally, exercise had a moderate effect on the incremental area under the curve TG response (Cohen's d = -0.40; p < .0001). The current analysis reveals a more homogeneous data set than previously reported. The attenuation of postprandial TG appears largely dependent on exercise energy expenditure (∼2 MJ) and the timing of exercise. The effect of prior exercise on the postprandial TG response appears to be transient; therefore, exercise should be frequent to elicit an adaptation.

Individuals with Prader-Willi Syndrome (PWS) have reduced mobility, which may be due to altered gait biomechanics. This study compared lower extremity intersegmental coordination and joint kinetics in adults with and without PWS. Walking biomechanics were evaluated in 10 adults with PWS and 10 controls without and 10 with obesity. The foot-shank and shank-thigh coordination was evaluated using modified vector coding and compared between groups using Kruskal-Wallis and Mann-Whitney U tests. The total support moment was summed from the ankle, knee, and hip extensor moments; and relative joint contributions were expressed as a percentage and compared between groups using one-way MANOVA. The group with PWS had greater exclusive shank segment rotation during later stance compared with controls with (p < 0.001) and without obesity (p < 0.001). The group with PWS also had a smaller absolute total support moment than controls with obesity during early and late stance (both p < 0.001), and lower normalized total support moment compared to controls without obesity during early stance (p = 0.019) and compared to controls with obesity during late stance (p = 0.004). Extensor moment contributions was similar between groups during early and late stance (all p > 0.05). Findings suggest a flat-footed gait pattern in PWS during late stance, which may negatively influence propulsion and speed. Moreover, those with PWS had lower total support moments than controls during early and late stance, but similar relative extensor contributions when walking at self-selected speeds. As such, improving overall torque generation in the lower extremity may be useful to improve stability and mobility during gait in PWS., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The complexity of astrocyte morphology and syncytial coupling through gap junctions are crucial for astrocyte function in the brain. However, the ultrastructural details of astrocyte arborization and interactions between neighboring astrocytes remain unknown. While a prevailing view is that synapses selectively contact peripheral astrocyte processes, the precise spatial-location selectivity of synapses abutting astrocytes is unresolved. Additionally, knowing the location and quantity of vesicles and mitochondria are prerequisites to answer two emerging questions - whether astrocytes have a signaling role within the brain and whether astrocytes are highly metabolically active. Here, we provided structural context for these questions by tracing and 3D reconstructing three neighboring astrocytes using serial block-face scanning electron microscopy. Our reconstructions reveal a spongiform astrocytic morphology resulting from the abundance of reflexive and leaflet processes. At the interfaces, varying sizes of astrocyte-astrocyte contacts were identified. Inside an astrocyte domain, synapses contact the entire astrocyte, and synapse-astrocyte contacts increase from soma to terminal leaflets. In contrast to densely packed vesicles at synaptic boutons, vesicle-like structures were scant within astrocytes. Lastly, astrocytes contain dense mitochondrial networks with a mitochondrial volume ratio similar to that of neurites. Together, these ultrastructural details should expand our understanding of functional astrocyte-astrocyte and astrocyte-neuron interactions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Populations are locally adapted when they exhibit higher fitness than foreign populations in their native habitat. Maize landrace adaptations to highland and lowland conditions are of interest to researchers and breeders. To determine the prevalence and strength of local adaptation in maize landraces, we performed a reciprocal transplant experiment across an elevational gradient in Mexico. We grew 120 landraces, grouped into four populations (Mexican Highland, Mexican Lowland, South American Highland, South American Lowland), in Mexican highland and lowland common gardens and collected phenotypes relevant to fitness and known highland-adaptive traits such as anthocyanin pigmentation and macrohair density. 67k DArTseq markers were generated from field specimens to allow comparisons between phenotypic patterns and population genetic structure. We found phenotypic patterns consistent with local adaptation, though these patterns differ between the Mexican and South American populations. Quantitative trait differentiation ( Q ST ) was greater than neutral allele frequency differentiation ( F ST ) for many traits, signaling directional selection between pairs of populations. All populations exhibited higher fitness metric values when grown at their native elevation, and Mexican landraces had higher fitness than South American landraces when grown in these Mexican sites. As environmental distance between landraces' native collection sites and common garden sites increased, fitness values dropped, suggesting landraces are adapted to environmental conditions at their natal sites. Correlations between fitness and anthocyanin pigmentation and macrohair traits were stronger in the highland site than the lowland site, supporting their status as highland-adaptive. These results give substance to the long-held presumption of local adaptation of New World maize landraces to elevation and other environmental variables across North and South America., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Background: Biomechanical knee asymmetry is commonly present after anterior cruciate ligament (ACL) reconstruction. Factors that could assist in identification of asymmetrical biomechanics after ACL reconstruction could help clinicians in making return-to-play decisions. The purpose of this study is to determine factors that may contribute to knee biomechanical asymmetry present after ACL reconstruction., Hypothesis: We hypothesized that quadriceps strength and activation and patient-reported function would allow for identification of patients with symmetrical knee biomechanics., Study Design: Cross-sectional study., Level of Evidence: Level 3., Methods: Thirty-one subjects (18 women; time since ACL reconstruction = 284.4 ± 53.6 days) who underwent ACL reconstruction and were to return to activity were recruited. Participants completed bilateral assessments of isokinetic quadriceps strength, quadriceps activation using the superimposed burst technique, and biomechanical function testing during a single-leg forward hop. The International Knee Documentation Committee (IKDC) subjective knee form was also completed. Symmetry values were calculated for each variable. Decision trees were utilized to determine which input factors (quadriceps strength symmetry, quadriceps activation symmetry, IKDC score, age, sex, height, mass, graft type) were able to identify participants who had symmetrical knee flexion angles (KFAs) and extension moments. Angles and moments were considered symmetrical if symmetry values were ≥90%., Results: Quadriceps strength and activation symmetry were able to predict whether a patient landed with symmetrical or asymmetrical KFAs, with thresholds of 77.2% strength symmetry and 91.3% activation symmetry being established. Patient-reported function and quadriceps strength were factors that allowed for classification of participants with symmetrical/asymmetrical knee extension moments, with thresholds of 89.1 for the IKDC and 80.0% for quadriceps strength symmetry., Conclusions: Quadriceps strength contributed to both models and appears to be a critical factor for achieving symmetrical knee biomechanics. High patient-reported function and quadriceps activation are also important for restoring knee biomechanical symmetry after ACL reconstruction., Clinical Relevance: Quadriceps strength and activation and patient-reported function may be able to assist clinicians in identifying ACL patients with symmetrical/asymmetrical knee biomechanics.

Purpose: Prader-Willi Syndrome (PWS) is a form of congenital obesity characterized by excessive body fat, hypotonia, muscle weakness, and physical/cognitive disability. However, the sources of muscle dysfunction and their contribution to mobility are unclear. The purposes of this study were to 1) compare plantar flexor function between adults with and without PWS; and 2) to examine the relationship between plantar flexor function and gait speed in adults with PWS., Methods: Participants included 10 adults with PWS, 10 adults without PWS and with obesity, and 10 adults without PWS and without obesity (matched on age and sex). Plantar flexor function was assessed using isokinetic dynamometry (peak torque [PT], early/late rate of torque development [RTD]), Hoffman reflex (H/M ratio), ultrasound imaging (cross-sectional area [CSA], echo intensity, pennation angle, and fascicle length), and peak propulsive force and plantar flexor moment during gait. Outcomes were compared between groups using one-way MANOVA. Associations between plantar flexor outcomes and gait speed were assessed using Pearson correlation in the PWS group., Results: Adults with PWS had lower absolute and normalized early RTD, and lower H/M ratio than controls with and without obesity; lower absolute PT and late RTD than controls with obesity (all P < 0.05). Cross-sectional area, propulsive force, and plantarflexor moment were lower, and echo intensity was higher, in adults with PWS compared with controls without obesity (all P < 0.05). Greater absolute PT (r = 0.64), absolute early RTD (r = 0.62), absolute late RTD (r = 0.64), gastrocnemii CSA (r = 0.55), and propulsive force (r = 0.58) were associated with faster gait speed (all P < 0.05)., Conclusions: Adults with PWS have impaired plantar flexor function likely attributable to reduced neuromuscular function and altered muscle morphology, which are associated with slower gait speeds.

Background: Individuals with obesity have impaired gait and muscle function that may contribute to reduced mobility and increased fall risk., Research Questions: (1) what is the difference in spatiotemporal gait parameters and joint kinetics between individuals with and without obesity; (2) what is the association between spatiotemporal gait parameters, joint kinetics, and quadriceps function?, Methods: Forty-eight young adults with obesity (BMI = 33.0 ± 4.1 kg/m 2 ) and 48 without obesity (BMI = 21.6 ± 1.7 kg/m 2 ) completed assessments of quadriceps function (peak torque and early/late rate of torque development (RTD)) and walking biomechanics at self-selected speed. Spatiotemporal gait parameters (stance time, double support time, double support to stance ratio, step width, step length, cadence, and gait stability ratio (GSR)) and joint kinetics (total support moment, and relative contribution from extensor moments) were compared using one-way MANOVAs. Partial correlation examined the association between the total support moment and quadriceps function, and spatiotemporal gait parameters controlling for sex and speed., Results: Individuals with obesity walked with longer stance (p = 0.01), longer double-limb support (p < 0.001), wider steps (p < 0.001), lower cadence (p = 0.03), and a greater absolute (p < 0.001) but lesser normalized total support moment (p = 0.03) compared with adults without obesity. In those with obesity, greater PT was associated with less double limb support (p = 0.011) and smaller double support to stance ratio (p = 0.006); greater early RTD was associated with less double limb support (r = -0.455, p = 0.0021), less stance time (r = -0.384, p = 0.008), and a smaller double support to stance ratio (r = -0.371, p = 0.011). In those without obesity, a larger total support moment was associated with longer step length (r = 0.512, p < 0.001), lesser cadence (r = -0.497, p < 0.001), and smaller GSR (-0.460, p = 0.001)., Significance: Individuals with obesity walk with altered spatiotemporal gait parameters and joint kinetics that may compromise stability. Extended periods of support may be a strategy used by individuals with obesity to increase stability during gait and accomodate insufficient quadriceps function., (Copyright © 2021 Elsevier B.V. All rights reserved.)