Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

Isolation of myeloid-derived suppressor cells (MDSC) from endometriotic mice model and their immunomodulatory functions.

Endometriosis is a chronic, painful disease whose etiology remains unknown. The development of novel therapies and diagnostic tools for endometriosis has been limited due in part to challenges in studying the disease. Recently, a few reports have shown that immunosuppressive cells, such as myeloid-derived suppressor cell (MDSC), may promote the progression of endometriosis. MDSCs are a heterogeneous group of myeloid cells with potent immunosuppressive and angiogenic properties. Here, in this chapter, we provide a detailed protocol to phenotype MDSC as well as to isolate and assess the functionality from the peritoneal cavity of a mouse model of surgically induced endometriosis. Importantly, the current mouse model has been widely used to study how the immune system, hormones, and environmental factors affect endometriosis as well as the effects of endometriosis on fertility and pain.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus. Angiogenesis is a major pathophysiology in endometriosis. Our previous studies have demonstrated that the prodrug of epigallocatechin gallate (ProEGCG) exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate (EGCG). However, their direct binding targets and underlying mechanisms for the differential effects remain unknown. In this study, we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis. Additionally, 1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin (MTDH) and PX domain containing serine/threonine kinase-like (PXK) as novel binding targets of EGCG and ProEGCG, respectively. Computational simulation and BioLayer interferometry were used to confirm their binding affinity. Our results showed that MTDH-EGCG inhibited protein kinase B (Akt)-mediated angiogenesis, while PXK-ProEGCG inhibited epidermal growth factor (EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor (HIF-1a)/vascular endothelial growth factor (VEGF) pathway. In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways. Moreover, our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

Antiviral Effects and Mechanisms of Green Tea Catechins on Influenza: A Perception on Combating Symptoms from COVID-19.

Over the centuries, influenza and its associated epidemics have been a serious public health problem. Although vaccination and medications (such as neuraminidase inhibitors) are the mainstay of pharmacological approaches to prevent and treat influenza, however, frequent mutations in the influenza genome often result in treatment failure and resistance to standard medications which limit their effectiveness. In recent years, green tea catechins have been evaluated as potential anti-influenza agents. Herein, in this review, we highlighted the effects and mechanisms underlying the inhibitory effects of epigallocatechin 3-gallate (EGCG), the most abundant ingredient in green tea, against different influenza viral infections, and their clinical benefits toward prevention and treatment. In addition, as the severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) causes the outbreak of COVID-19 pandemic, our review also delineates the current perspective on SARS-CoV-2 and future insights as to the potential application of EGCG on suppressing the flu-like symptoms caused by COVID-19.

Serum vitamin D insufficiency is correlated with quadriceps neuromuscular functions in patients with anterior cruciate ligament injury: A preliminary study.

Background: This study aimed to investigate the correlations of serum vitamin D insufficiency with quadriceps neuromuscular function in patients with anterior cruciate ligament (ACL) injury. Methods: A cross-sectional study was conducted. Eighteen patients with a primary, unilateral ACL injury who had insufficient serum vitamin D concentrations (<30 ng/ml) were recruited for the study. Bilateral quadriceps neuromuscular function, including maximal strength, the speed of rapid contraction, and inhibition, were measured on an isokinetic dynamometer with the hip and the knee joint flexion at 90° and 45°, respectively. Quadriceps strength was measured by maximal voluntary isometric contractions (MVIC); the speed of rapid contraction was quantified by the rate of torque development (RTD), which was divided into the early (RTD0-50) and the late phase (RTD100-200); quadriceps inhibition was quantified by the central activation ratio (CAR). Serum vitamin D concentration was quantitatively determined by serum 25(OH)D concentration measured by the 25(OH)D ELISA kit. The Spearman rank correlation analysis was used to examine the correlation between the vitamin D concentration and bilateral quadriceps MVIC, RTD0-50, RTD100-200, and CAR, respectively. Results: The results of Spearman rank correlation analyses showed that the serum 25(OH)D concentration was significantly correlated with bilateral quadriceps MVIC (injured: r = 0.574, p = 0.013; uninjured: r = 0.650, p = 0.003) and RTD0-50 (r = 0.651, p = 0.003), and CAR (r = 0.662, p = 0.003) on the uninjured limb. However, no significant correlations were found between the serum 25(OH)D concentration and the other outcomes. Conclusions: The serum vitamin D concentration correlates with quadriceps neuromuscular function in patients with ACL injury who had vitamin D insufficiency.

Effect of eccentric isokinetic exercise on muscle strength and functional recovery after anterior cruciate ligament reconstruction.

Background: Previous studies have shown isokinetic exercise forms an important part in reconditioning the patients after anterior cruciate ligament reconstruction (ACLR) in regaining muscle strength and knee function. Although eccentric isokinetic training has been shown to enhance quadriceps muscle strength, the application toward benefiting patients after ACLR remains controversial. The present study aims to investigate the benefits of eccentric over concentric isokinetic exercises on knee muscle strength and its value in later stage of rehabilitation, including the return-to-sport. Methods: Thirty-six patients who had undergone ACLR for 4-to-6 months were assigned to receive either eccentric or concentric isokinetic training weekly for six weeks on top of their standardized post-operative exercise programme. The assessments include isokinetic test on the peak torques of quadriceps and hamstrings, single-leg hop test and ability to return-to-sport. Results: Both groups demonstrated significant gains on peak torques in quadriceps and hamstrings after training. At post-intervention, the peak torques for both quadriceps (p = 0.005) and hamstrings (p = 0.017) of the ACL-reconstructed limb from eccentric training were significantly higher than concentric training. The significant improvement was similarly demonstrated in the limb symmetry index (LSI) in hamstrings (p = 0.016) of the ACL-reconstructed limb from eccentric training. Moreover, eccentric group performed significantly better in single-leg hop tests (p = 0.042). Most importantly, eccentric group have higher percentages of return-to-sport (55.6 %) than concentric group (27.8 %). Conclusion: A 6-week course of eccentric isokinetic training was more effective than concentric isokinetic training in increasing quadriceps and hamstrings strength in terms of peak torques. Importantly, the better functional performance after the eccentric isokinetic exercise account for higher return-to-sport ratio.

Surgical accuracy of image-free versus image-based robotic-assisted total knee arthroplasty.

BACKGROUND: This study investigated the accuracy in achieving proper lower limb alignment and component positions after total knee replacement (TKR) with image-free and image-based robotic-assisted TKR. METHODS: A total of 129 patients (166 knees) suffering from end-stage knee arthritis who underwent TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Radiological outcomes were compared between image-free and image-based robotic-assisted surgical systems. RESULTS: There were significant differences between the two robotic systems when comparing the mean planned component alignment and the mean measured alignment on radiographs, in which the image-free robotic-assisted system was more varus, whereas the image-based robotic-assisted system was more valgus for both the mean femoral and tibial component coronal alignment (p < 0.001). For tibial component sagittal alignment, the image-based group had a larger deviation from the planned posterior slope (p < 0.001). CONCLUSION: Image-free and image-based robotic assisted TKR had differing accuracy in femoral and tibial alignment.

The effectiveness of robotic-assisted upper limb rehabilitation to improve upper limb function in patients with cervical spinal cord injuries: a systematic literature review.

Background: Spinal Cord Injury (SCI) damages corticospinal tracts and descending motor pathways responsible for transmitting signals from the brain to the spinal cord, leading to temporary or permanent changes in sensation, motor function, strength, and body function below the site of injury. Cervical SCI (cSCI), which leads to tetraplegia, causes severe functional upper limb (UL) impairments that increase falls risk, limits independence, and leads to difficulties with activities of daily living (ADLs). Robotic therapy (RT) has been developed in recent decades as a new treatment approach for people with cervical spinal cord injuries (cSCI). The present review aimed to explore current available evidence and studies regarding the effectiveness of RT for individuals with cSCI in improving UL function, identify current research gaps and future research directions. Method: This review was conducted by searching PubMed, CINAHL, Medline, Embase, and APA PsycInfo for relevant studies published from January 2010 to January 2022. Selected studies were analyzed with a focus on the patients' self-perception of limited UL function and level of independence in activities of daily living. In addition, the JBI Critical Appraisal checklist was used to assess study quality. Results: A total of 7 articles involving 87 patients (74 males and 13 females) were included in the analysis, with four studies utilizing exoskeleton and three studies utilizing end-effector robotic devices, respectively. The quality of these studies varied between JBI Critical Appraisal scores of 4 to 8. Several studies lacked blinding and a control group which affected internal validity. Nevertheless, four out of seven studies demonstrated statistically significant improvements in outcome measurements on UL function and strength after RT. Conclusion: This review provided mixed evidence regarding the effectiveness of RT as a promising intervention approach to improve upper limb function in participants with cSCI. Although RT was shown to be safe, feasible, and reduces active therapist time, further research on the long-term effects of UL RT is still needed. Nevertheless, this review serves as a useful reference for researchers to further develop exoskeletons with practical and plausible applications toward geriatric orthopaedics.

Myeloid-derived suppressor cells: A new emerging player in endometriosis.

Endometriosis is a common gynecological disorder defined by the presence of endometrial tissue outside the uterus. This is commonly associated with chronic pelvic pain, infertility, and dysmenorrhea, which occurs in approximately 10% of women of reproductive age. Although the exact mechanism remains uncertain, it has been widely accepted to be an estrogen-dependent and inflammatory disease. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune cells with immunosuppressive capacity and non-immunological functions. They have been found to be aggressively involved in the pathologies of various disorders. In regards to tumors, the functions of MDSCs have been profoundly shown to inhibit tumor immune response and to promote angiogenesis, tumor metastasis, fibrosis, and epithelial-mesenchymal transition (EMT). In recent years, the elevation of MDSCs in endometriosis was reported by several studies that provoke the assumption that MDSCs might exert similar roles to promote the development of endometriosis. Such that, precision treatments targeting MDSCs might be a promising direction for future study. Herein, we will review the research progress of MDSCs in endometriosis and its potential relevance to the pathogenesis, progression, and therapeutics strategy of endometriosis.

Therapeutic effects of green tea on endometriosis.

Endometriosis is a chronic disorder characterized by the presence of endometrial glands and stroma outside the uterine cavity. It affects 8%-10% of women in their reproductive years, and represents a major clinical problem with deleterious social, sexual and reproductive consequences. Current treatment options include pain relief, hormonal intervention and surgical removal. However, these treatments are deemed unsatisfactory owing to varying success, significant side effects and high recurrence rates. Green tea and its major bioactive component, (-)-epigallocatechin gallate (EGCG), possess diverse biological properties, particularly anti-angiogenic, anti-proliferation, anti-metastasis, and apoptosis induction. In recent years, preclinical studies have proposed the use of green tea to inhibit the growth of endometriosis. Herein, the aim of this review is to summarize the potential therapeutic effects of green tea on molecular and cellular mechanism through inflammation, oxidative stress, invasion and adhesion, apoptosis and angiogenesis in endometriosis.

The role of paraspinal muscle degeneration in coronal imbalance in patients with degenerative scoliosis.

Background: Coronal imbalance in degenerative scoliosis is common and is highly correlated with health-related quality of life. Paraspinal muscle is critical to spine stability, but little is known about its contribution to coronal imbalance in degenerative scoliosis. This study aims to investigate the relationship between paraspinal muscle (PSM) degeneration and coronal imbalance in patients with degenerative scoliosis (DS). Methods: This is a retrospective cohort study. A total of 117 patients with DS were retrospectively reviewed. Parameters of PSM (bilateral cross-sectional area, CSA; fat infiltration rate, FI%) at the apical disc and adjacent levels were quantitatively evaluated using MRI. Standing whole-spine radiograph was used to evaluate the coronal (Cobb angle, CA; coronal balance distance, CBD) and sagittal (thoracic kyphosis, TK; lumbar lordosis, LL; sagittal vertical axis, SVA) parameters. Patients were divided into 3 groups: coronal balanced (Type A), coronal imbalanced shifting to concavity (Type B), and coronal imbalanced shifting to convexity (Type C). Results: Based on our criteria, 56 patients were assigned to Type A, 34 patients to Type B, and 27 patients to Type C. There was no significant difference on the sagittal profiles and CSA between the groups. However, Type A showed significantly lower FI% than Type B and Type C on both concavity and convexity (Concave side: Type A vs. Type B vs. Type C, 30.8±8.1 vs. 45.1±7.7 vs. 38.7±12.5, P=0.001; Convex side: Type A vs. Type B vs. Type C, 32.6±10.9 vs. 46.3±7.3 vs. 40.7±11.8, P=0.004). Specifically, Cobb angle was negatively correlated with CSA, mainly at convexity (R=-0.415, P=0.008). Similarly, the increase of CBD significantly correlated with FI% at concavity (R=0.491, P=0.001) and convexity (R=0.354, P=0.025). Conclusions: DS patients with coronal imbalance demonstrated a worse PSM degeneration when compared with those without coronal imbalance. Besides, PSM degeneration strongly correlated with coronal imbalance, which implies that PSM degeneration may contribute to the coronal imbalance in patients with DS.

Melatonin in Endometriosis: Mechanistic Understanding and Clinical Insight.

Endometriosis is defined as the development of endometrial glands and stroma outside the uterine cavity. Pathophysiology of this disease includes abnormal hormone profiles, cell survival, migration, invasion, angiogenesis, oxidative stress, immunology, and inflammation. Melatonin is a neuroendocrine hormone that is synthesized and released primarily at night from the mammalian pineal gland. Increasing evidence has revealed that melatonin can be synthesized and secreted from multiple extra-pineal tissues where it regulates immune response, inflammation, and angiogenesis locally. Melatonin receptors are expressed in the uterus, and the therapeutic effects of melatonin on endometriosis and other reproductive disorders have been reported. In this review, key information related to the metabolism of melatonin and its biological effects is summarized. Furthermore, the latest in vitro and in vivo findings are highlighted to evaluate the pleiotropic functions of melatonin, as well as to summarize its physiological and pathological effects and treatment potential in endometriosis. Moreover, the pharmacological and therapeutic benefits derived from the administration of exogenous melatonin on reproductive system-related disease are discussed to support the potential of melatonin supplements toward the development of endometriosis. More clinical trials are needed to confirm its therapeutic effects and safety.

A novel image-based machine learning model with superior accuracy and predictability for knee arthroplasty loosening detection and clinical decision making.

Background: Loosening is the leading cause of total knee arthroplasty (TKA) revision. This is a heavy burden toward the healthcare system owing to the difficulty in diagnosis and complications occurring from the delay management. Based on automatic analytical model building, machine learning, may potentially help to automatically recognize the risk of loosening based on radiographs alone. The aim of this study was to build an image-based machine-learning model for detecting TKA loosening. Methods: Image-based machine-learning model was developed based on ImageNet, Xception model and a TKA patient X-ray image dataset. Based on a dataset with TKA patient clinical parameters, another system was then created for developing the clinical-information-based machine learning model with random forest classifier. In addition, the Xception Model was pre-trained on the ImageNet database with python and TensorFlow deep learning library for the prediction of loosening. Class activation maps were also used to interpret the prediction decision made by model. Two senior orthopaedic specialists were invited to assess loosening from X-ray images for 3 attempts in setting up comparison benchmark. Result: In the image-based machine learning loosening model, the precision rate and recall rate were 0.92 and 0.96, respectively. While for the accuracy rate, 96.3% for visualization classification was observed. However, the addition of clinical-information-based model, with precision rate of 0.71 and recall rate of 0.20, did not further showed improvement on the accuracy. Moreover, as class activation maps showed corresponding signals over bone-implant interface that is loosened radiographically, this confirms that the current model utilized a similar image recognition pattern as that of inspection by clinical specialists. Conclusion: The image-based machine learning model developed demonstrated high accuracy and predictability of knee arthroplasty loosening. And the class activation heatmap matched well with the radiographic features used clinically to detect loosening, which highlighting its potential role in assisting clinicians in their daily practice. However, addition of clinical-information-based machine-learning model did not offer further improvement in detection. As far as we know, this is the first report of pure image-based machine learning model with high detection accuracy. Importantly, this is also the first model to show relevant class activation heatmap corresponding to loosening location. Translational potential: The finding in this study indicated image-based machine learning model can detect knee arthroplasty loosening with high accuracy and predictability, which the class activation heatmap can potentially assist surgeons to identify the sites of loosening.

Determination of (-)-epigallocatechin-3-gallate octaacetate and its metabolites in plasma of rats for pharmacokinetic study by ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry.

(-)-Epigallocatechin-gallate octaacetate (pro-EGCG), a prodrug of epigallocatechin-gallate (EGCG), has been used for pre-clinical study for the treatment of endometriosis. A validated analytical method has been developed for the determination of plasma pro-EGCG and its metabolites after oral administration using ultra-performance-liquid-chromatography coupled to quadrupole-time-of-flight-mass-spectrometry (UPLC-Qtof-MS). This method is more robust, rapid, sensitive, simpler, and able to detect pro-EGCG metabolites compared to our previous method. Pro-EGCG in the plasma was stabilized from rapid degradation by formic acid, extracted by isopropanol/methyl-tert-butyl ether mixture, separated by UPLC core column, and quantified by an exact mass method with Qtof-MS. The lower limit of quantification (LLOQ), intra-day and inter-day precision, and accuracy for the range of 0.01-2.5 µg/mL were within acceptable limits. The sensitivity was improved by 25 folds using pro-EGCG ammonium adduct [M + NH4]+. This is the first report on the pharmacokinetics of oral administration with maximum-concentration (Cmax) was 0.067 ± 0.04 µg/mL, time-of-maximum-concentration (Tmax) was 1.33 h, area-under-curve (AUC) was 0.20 ± 0.05 h × µg/mL, and elimination-rate was 0.20 ± 0.11 hr-1. The pharmacokinetic profiles of pro-EGCG metabolites, (-)-epigallocatechin-gallate (EGCG) diacetates and EGCG triacetates, were also presented. This method is robust, rapid, and sensitive for the pharmacokinetic study of pro-EGCG and metabolites.

A prospective study comparing the inflammation-related cytokine and chemokine profile from the day of blastocyst transfer to 7 weeks of gestation between pregnancies that did or did not result in a miscarriage.

The dynamics of maternal immunomodulation is essential in early pregnancy. In our previous study, successful implantation is characterized by a transient increase of pro-inflammatory cytokines followed by a switch to an anti-inflammatory state in peripheral blood around 3-6 days after embryo transfer (ET). In this study, we aimed to extend the time points to compare the cytokine and chemokine profiles between women who did or did not subsequently miscarry. We utilized precisely timed serum samples on the day of ET and 3, 6, 9, 16, 23 and 30 days after ET in women undergoing single blastocyst transfer. Our analysis revealed a significant alteration in cytokine profile after day ET+ 9 between the two groups. Regarding pro-inflammatory cytokine profile, there was a significant increase in IL-17 on days ET+ 16, + 23, and + 30 (50.60 ± 9.97 vs 37.09 ± 3.25, 53.20 ± 8.13 vs 36.51 ± 3.34, 57.06 ± 8.83 vs 33.04 ± 3.11 pg/mL), TNF-α on days ET+ 23 and + 30 (73.90 ± 12.42 vs 50.73 ± 3.55, 74.16 ± 12.46 vs 46.59 ± 3.21 pg/mL), IFN-γ on day ET+ 30 (69.52 ± 13.19 vs 42.28 ± 7.76 pg/mL) in women who miscarried compared to women who had a live birth. In contrast, the concentrations of anti-inflammatory cytokines IL-10 on days ET+ 23 and + 30 (26.23 ± 2.11 vs 38.30 ± 4.64, 23.77 ± 2.06 vs 39.16 ± 4.99 pg/mL) and TGF-ß1 on day ET+ 30 (20.30 ± 1.25 vs 23.81 ± 0.88 ng/mL) were significantly decreased in women who miscarried compared to women who had a live birth. While for the chemokine profile, there was no significant alteration observed between the two groups across all the time points. These findings suggest that a sustained anti-inflammatory milieu is concomitant with the maintenance of early pregnancy, while the remarkable pro-inflammatory shift as early as day ET+ 16 in women who subsequently miscarried was observed before the diagnosis of miscarriage.

Effect of pulsed electromagnetic field as an intervention for patients with quadriceps weakness after anterior cruciate ligament reconstruction: a double-blinded, randomized-controlled trial.

BACKGROUND: The ultimate goal of anterior cruciate ligament reconstructions (ACLR) is to fulfil the return-to-play (RTP) criteria. Quadriceps muscle strength is one of the key determinants for a patient's successful return-to-play after ACLR. Quadriceps muscle atrophy can persist beyond the completion of the rehabilitation program in almost half the patients and the reason behind this is still unknown. There are emerging evidences showing that pulsed electromagnetic field (PEMF) can modulate mitochondrial activities for muscle gain. PEMF exposure on top of regular exercise training may promote muscle regeneration and tissue healing. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of PEMF treatment during the postoperative period on quadriceps muscle strength in ACL injured patient. Adult patients (aged 18-30) with a unilateral ACL injury, total quadriceps muscle volume is equal or more than 7% deficit on involved leg compared with uninvolved leg, sporting injury with a Tegner score of 7+, and both knees without a history of injury/prior surgery will be recruited. To estimate the improvement of patients, isokinetic muscle assessment, ultrasound imaging and MRI for quadriceps muscle thickness, self-reported outcomes with questionnaires, KT-1000 for knee laxity and biomechanical analysis, and Xtreme CT for bone mineral density will be performed. To investigate the mechanism of PEMF therapy on increasing quadriceps strength, samples of blood serum will be drawn before and after intervention. DISCUSSION: This is the first trial evaluating the effects of PEMF on quadriceps muscle recovery after ACLR. The proposed study addresses a huge research gap by evaluating practical use of PEMF as part of rehabilitation. The proposed study will provide much needed scientific support in the use of this noninvasive treatment modality to facilitate recovery of quadriceps strength after PEMF. TRIAL REGISTRATION: ClinicalTrials.gov NCT05184023. Registered on 5 January 2022.

Simultaneous Measurement of Patellofemoral Joint Kinematics and Contact Mechanics in Intact Knees: A Cadaveric Study.

OBJECTIVE: Patellofemoral kinematics and contact mechanics are important measurements for the assessment of patellofemoral joint (PFJ) problems. Simultaneously measuring PFJ contact pressures and kinematics is a challenging task. The purpose of this study was to simultaneously measure the kinematics and mean/peak contact pressures in the PFJs of cadaveric knees. METHODS: This was a comparative study performed on fresh cadaveric knees. The kinematic data was acquired for nine cadaveric knees using an optical tracking system. Data about the contact pressure and contact area in the PFJ was obtained at knee flexion angles of 0°, 30°, 60°, 90°, and 120° using a pressure sensor. Intraclass correlation coefficients (ICCs) and minimal detectable differences (MDDs) of six degrees of freedom (6 DOF) in the PFJs were calculated. ICCs and the MDDs of contact pressure, peak pressure, and contact area in the PFJs were also analyzed. We also compared the kinematics of the cadaveric knees before and after the insertion of the pressure sensor. RESULTS: All ICC values of 6 DOF in the PFJs were found to be greater than or equal to 0.924. Regarding medial-lateral rotation, the patellar showed a simplified movement pattern that demonstrated progressive lateral rotation of 4.8° ± 3.4° at 120° of knee flexion. While for patellar tilting, the patella showed medial tilting that peaked at 7.2 ± 2.5° at 30° of knee flexion. Whereas no significant differences in PFJ kinematics were found between with and without the placement of the pressure sensor at all knee flexions (P > 0.05). Most of the ICC values for contact pressure, peak contact pressure, and contact area ranged from 0.8 to 0.9. The MDDs for rotational displacement were 0.9° and 0.6 mm for translational displacement. No statistical differences in patellar kinematics were found before and after the insertion of the pressure sensor. CONCLUSIONS: The setup in the present study enables researchers to simultaneously and synchronously collect real-time PFJ kinematics and tibiofemoral joint (TFJ) biomechanical kinematic data with high reliability. The low MDDs enabled the researchers to obtain an accurate interpretation of the kinematic and contact mechanics measurement using the experimental setting used in the present study.

Morphological changes of Intervertebral Disc detectable by T2-weighted MRI and its correlation with curve severity in Adolescent Idiopathic Scoliosis.

BACKGROUND: Our previous studies found disproportionate anteroposterior vertebral size is associated with severity of the scoliotic curves in adolescent idiopathic scoliosis (AIS) patients. Subsequent studies showed wedging of vertebral bodies (VB) had less contribution than intervertebral discs (IVD) to the anterior-posterior vertebral column length discrepancy in severe-AIS. However, the exact morphological changes of IVD were not clearly defined. This study aimed to evaluate the morphological and pathological changes of IVD and VB in AIS girls and healthy female controls. METHODS: This study included 33 age-matched female controls and 76 AIS girls with a right-sided thoracic curvature. Wedge angle, height ratio and distance ratio of VB and IVD were measured on the best midline coronal and sagittal planes from reformatted MRI spine. Volumes of VB, IVD and nucleus pulposus (NP) were also evaluated on volumetric images. One-way ANOVA with Bonferroni correction and Pearson correlation tests were used. RESULTS: There was significant difference in wedge angle and height ratio of VB and IVD between AIS and controls. In severe-AIS, the position of NP was significantly shifted to the convexity when compared with non-severe AIS and controls. Whereas, the volume of IVD and NP in severe-AIS was found to be significantly smaller. In addition, Cobb angle was significantly correlated with wedge angle and height ratio, and inversely correlated with the volume of NP. CONCLUSIONS: In addition to wedging of VB and IVD, there was significantly reduced volume of IVD and NP in AIS patients with severe curve, insinuating the mechanical effect of scoliosis leads to a compression on both IVD and NP before significant disc desiccation occurs. We postulate that the compression of IVD and NP can contribute to curve progression in severe-AIS, these patients are more prone to disc degeneration in adulthood if no operative treatment is offered. Further longitudinal study on these parameters is still warranted.

Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer.

With a rich abundance of natural polyphenols, green tea has become one of the most popular and healthiest nonalcoholic beverages being consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the predominant catechin found in green tea, which has been shown to promote numerous health benefits, including metabolic regulation, antioxidant, anti-inflammatory, and anticancer. Clinical studies have also shown the inhibitory effects of EGCG on cancers of the male and female reproductive system, including ovarian, cervical, endometrial, breast, testicular, and prostate cancers. Autophagy is a natural, self-degradation process that serves important functions in both tumor suppression and tumor cell survival. Naturally derived products have the potential to be an effective and safe alternative in balancing autophagy and maintaining homeostasis during tumor development. Although EGCG has been shown to play a critical role in the suppression of multiple cancers, its role as autophagy modulator in cancers of the male and female reproductive system remains to be fully discussed. Herein, we aim to provide an overview of the current knowledge of EGCG in targeting autophagy and its related signaling mechanism in reproductive cancers. Effects of EGCG on regulating autophagy toward reproductive cancers as a single therapy or cotreatment with other chemotherapies will be reviewed and compared. Additionally, the underlying mechanisms and crosstalk of EGCG between autophagy and other cellular processes, such as reactive oxidative stress, ER stress, angiogenesis, and apoptosis, will be summarized. The present review will help to shed light on the significance of green tea as a potential therapeutic treatment for reproductive cancers through regulating autophagy.

The effectiveness of telerehabilitation in patients after total knee replacement: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Total knee replacement is a commonly adopted surgical intervention to reduce physical limitations and pain in advanced-stage knee osteoarthritis. However, these patients may experience physical dysfunction to limit their access during conventional rehabilitation after total knee replacement. The use of telemedicine may be the promising solution. This study aims to compare the effectiveness of telerehabilitation with conventional in-person rehabilitation in patients who underwent a total knee replacement. METHODS: For this systematic review on randomized controlled trials, PubMed, Medline, EMBASE, Cochrane Library, ScienceDirect and CINAHL databases were searched for eligible articles published between 1 January 2003 and 28 February 2022. The eligibility criteria were patients who underwent total knee replacement, randomized controlled trials and publications in English. The main outcome measures were focused on pain and physical function. Reference lists of relevant studies were also manually checked to find additional studies. Two independent reviewers conducted study selection separately. PEDro scale was used to assess the methodological quality of the included randomized controlled trials. A meta-analysis was performed on the collected data. Review Manager (RevMan, version 5.3) was used for all analyses. RESULTS: A total of 11 studies met the eligibility criteria and included 1825 participants in the systematic review. Overall, the results revealed that the effectiveness of telerehabilitation is comparable to conventional in-person rehabilitation in improving various pain and functional outcomes in patients who underwent a total knee replacement. In the meta-analysis with the fixed-effects model, no significant difference was found in the improvement of pain and physical function in patients with knee osteoarthritis compared with conventional rehabilitation (Standardized Mean Difference (SMD) -0.15, 95% CI -0.47 to 0.16, P = 0.34 and SMD -0.04, 95% CI -0.19 to 0.12, P = 0.62, respectively). In addition, the utilization of hospital resources and costs were significantly lower in telerehabilitation when compared with in-person rehabilitation. CONCLUSION: Telerehabilitation was comparable to conventional in-person rehabilitation in improving clinical outcomes following total knee replacement. However, it might be a more preferable alternative rehabilitation intervention for patients following total knee replacement given the significantly lower cost of telerehabilitation.