Lipopolysaccharide-binding protein expression is increased by stress and inhibits monoamine synthesis to promote depressive symptoms.

Monoamine insufficiency is suggested to be associated with depressive features such as sadness, anhedonia, insomnia, and cognitive dysfunction, but the mechanisms that cause it are unclear. We found that the acute-phase protein lipopolysaccharide-binding protein (LBP) inhibits monoamine biosynthesis by acting as an endogenous inhibitor of dopamine-ß-hydroxylase (DBH) and aromatic-L-amino-acid-decarboxylase (DDC). LBP expression was increased in individuals with depression and by diverse stress challenges in mice. LBP antibodies and LBP knockdown inhibited monoamine insufficiency and depression-like features in mice, which worsened with LBP overexpression or administration. Monoamine insufficiency and depression-like symptoms were not induced by stressful stimuli in LBP-deficient mice, further highlighting a role for LBP in stress-induced depression, and a peptide we designed that blocks LBP-DBH and LBP-DDC interactions showed anti-depression effects in mice. This study reveals an important role for LBP in regulating monoamine biosynthesis and suggests that targeting LBP may have potential as a treatment for some individuals with depression.

Reconstruction of LPS Transfer Cascade Reveals Structural Determinants within LBP, CD14, and TLR4-MD2 for Efficient LPS Recognition and Transfer.

Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, binds Toll-like receptor 4 (TLR4)-MD2 complex and activates innate immune responses. LPS transfer to TLR4-MD2 is catalyzed by both LPS binding protein (LBP) and CD14. To define the sequential molecular interactions underlying this transfer, we reconstituted in vitro the entire LPS transfer process from LPS micelles to TLR4-MD2. Using electron microscopy and single-molecule approaches, we characterized the dynamic intermediate complexes for LPS transfer: LBP-LPS micelles, CD14-LBP-LPS micelle, and CD14-LPS-TLR4-MD2 complex. A single LBP molecule bound longitudinally to LPS micelles catalyzed multi-rounds of LPS transfer to CD14s that rapidly dissociated from LPB-LPS complex upon LPS transfer via electrostatic interactions. Subsequently, the single LPS molecule bound to CD14 was transferred to TLR4-MD2 in a TLR4-dependent manner. The definition of the structural determinants of the LPS transfer cascade to TLR4 may enable the development of targeted therapeutics for intervention in LPS-induced sepsis.

COVID-19 detection from chest X-ray images using CLAHE-YCrCb, LBP, and machine learning algorithms.

BACKGROUND: COVID-19 is a disease that caused a contagious respiratory ailment that killed and infected hundreds of millions. It is necessary to develop a computer-based tool that is fast, precise, and inexpensive to detect COVID-19 efficiently. Recent studies revealed that machine learning and deep learning models accurately detect COVID-19 using chest X-ray (CXR) images. However, they exhibit notable limitations, such as a large amount of data to train, larger feature vector sizes, enormous trainable parameters, expensive computational resources (GPUs), and longer run-time. RESULTS: In this study, we proposed a new approach to address some of the above-mentioned limitations. The proposed model involves the following steps: First, we use contrast limited adaptive histogram equalization (CLAHE) to enhance the contrast of CXR images. The resulting images are converted from CLAHE to YCrCb color space. We estimate reflectance from chrominance using the Illumination-Reflectance model. Finally, we use a normalized local binary patterns histogram generated from reflectance (Cr) and YCb as the classification feature vector. Decision tree, Naive Bayes, support vector machine, K-nearest neighbor, and logistic regression were used as the classification algorithms. The performance evaluation on the test set indicates that the proposed approach is superior, with accuracy rates of 99.01%, 100%, and 98.46% across three different datasets, respectively. Naive Bayes, a probabilistic machine learning algorithm, emerged as the most resilient. CONCLUSION: Our proposed method uses fewer handcrafted features, affordable computational resources, and less runtime than existing state-of-the-art approaches. Emerging nations where radiologists are in short supply can adopt this prototype. We made both coding materials and datasets accessible to the general public for further improvement. Check the manuscript's availability of the data and materials under the declaration section for access.

The Association of Intestinal Leak with Sarcopenia and Physical Disability in Patients with Various Stages of Chronic Kidney Disease.

Sarcopenia is related to disease severity in chronic kidney disease (CKD) patients; however, its pathophysiology remains poorly known. We investigated the associations of biomarkers of intestinal leak with sarcopenia in various stages of CKD. We recruited 61-76-year-old male controls and patients with various stages of CKD (n = 36-57/group) for measuring plasma lipopolysaccharide-binding protein (LBP) and zonulin (markers of intestinal leak), handgrip strength (HGS), skeletal mass index (SMI), and gait speed (markers of sarcopenia), and short physical performance battery (SPPB; marker of physical capacity). CKD stages 4 and 5 were associated with lower HGS, SMI, gait speed, and cumulative SPPB scores and a higher sarcopenia prevalence than controls and patients with CKD stages 1 and 2 (all p < 0.05). CKD patients (stages 1 and 2) had elevated plasma zonulin and LBP when compared with CKD stages 4 and 5. Plasma zonulin and LBP exhibited significant correlations with renal function, HGS, gait speed, SPPB scores, and oxidative stress markers in CKD stages 4 and 5 (all p < 0.05). However, similar relations were not found in early CKD. Collectively, intestinal leak may be contributing to sarcopenia and physical disability in the advanced stages of CKD.

Effective prediction of human skin cancer using stacking based ensemble deep learning algorithm.

Automated diagnosis of cancer from skin lesion data has been the focus of numerous research. Despite that it can be challenging to interpret these images because of features like colour illumination changes, variation in the sizes and forms of the lesions. To tackle these problems, the proposed model develops an ensemble of deep learning techniques for skin cancer diagnosis. Initially, skin imaging data are collected and preprocessed using resizing and anisotropic diffusion to enhance the quality of the image. Preprocessed images are fed into the Fuzzy-C-Means clustering technique to segment the region of diseases. Stacking-based ensemble deep learning approach is used for classification and the LSTM acts as a meta-classifier. Deep Neural Network (DNN) and Convolutional Neural Network (CNN) are used as input for LSTM. This segmented images are utilized to be input into the CNN, and the local binary pattern (LBP) technique is employed to extract DNN features from the segments of the image. The output from these two classifiers will be fed into the LSTM Meta classifier. This LSTM classifies the input data and predicts the skin cancer disease. The proposed approach had a greater accuracy of 97%. Hence, the developed model accurately predicts skin cancer disease.

What a pain in the back: a review of current treatment options with a focus on naproxen sodium.

Non-specific low back pain (LBP) represents a challenging and prevalent condition that is one of the most common symptoms leading to primary care physician visits. While established guidelines recommend prioritizing non-pharmacological approaches as the primary course of action, pharmacological treatments are advised when non-pharmacological approaches are ineffective or based on patient preference. These guidelines recommend non-steroidal anti-inflammatory drugs (NSAIDs) or skeletal muscle relaxers (SMRs) as the first-line pharmacological options for acute or subacute LBP, while NSAIDs are the exclusive first-line pharmacological option for chronic LBP. Although SMRs are generally effective for acute LBP, the available evidence does not support the view that they improve functional recovery, and their comparative efficacy to NSAIDs and other analgesics remains unknown, while studies have shown them to introduce adverse events without significantly reducing LBP. Moreover, opioids continue to be widely prescribed for LBP, despite limited evidence for effectiveness and known risks of addiction and overdose. Broader use of non-opioid pharmacotherapy, including the appropriate use of OTC options, is critical to addressing the opioid crisis. The balance of evidence indicates that NSAIDs have a favorable benefit-risk profile when compared to other available pharmacological treatment options for non-specific LBP, a condition that is primarily acute in nature and well-suited for self-treatment with OTC analgesics. While clinical guidelines do not differentiate between NSAIDs, evidence indicates that OTC naproxen sodium effectively relieves pain across multiple types of pain models, and furthermore, the 14-h half-life of naproxen sodium allows sustained, all day pain relief with reduced patient pill burden as compared to shorter acting options. Choosing the most appropriate approach for managing LBP, including non-pharmacological options, should be based on the patient's condition, severity of pain, potential risks, and individual patient preference and needs.

Standards for fecal microbiota transplant: Tools and therapeutic advances.

Fecal microbiota transplantation (FMT) has been demonstrated to be efficacious in preventing recurrent Clostridioides difficile (C. difficile) infections, and is being investigated for treatment of several other diseases including inflammatory bowel disease, cancer, obesity, liver disease, and diabetes. To speed up the translation of FMT into clinical practice as a safe and standardized therapeutic intervention, additional evidence-based technical and regulatory guidance is needed. To this end in May of 2022, the International Alliance for Biological Standardization (IABS) and the BIOASTER Microbiology Technology Institute hosted a second webinar to discuss key issues still impeding the advancement and standardization of FMT. The goal of this two-day webinar was to provide a forum for scientific experts to share and discuss data and key challenges with one another. Discussion included a focus on the evaluation of safety, efficacy, clinical trial design, reproducibility and accuracy in obtained microbiome measurements and data reporting, and the potential for standardization across these areas. It also focused on increasing the application potential and visibility of FMT beyond treating C. difficile infections.

Changes in surrogate markers of intestinal epithelial injury and microbial translocation in young and older men during prolonged occupational heat stress in temperate and hot conditions.

PURPOSE: Exertional heat stress can cause damage to the intestinal epithelium and disrupt gastrointestinal barrier integrity, leading to microbial translocation (MT) linked to the development of heat stroke. This study aimed to assess age-related differences in markers of intestinal epithelial injury and MT following non-heat stress and high-heat stress exercise in healthy young and older men. METHODS: Markers of intestinal epithelial injury (intestinal fatty acid-binding protein-'IFABP') and MT (soluble cluster of differentiation 14-'sCD14'; and lipopolysaccharide-binding protein-'LBP') were assessed in healthy young (18-30 y, n = 13) and older (50-70 y) men (n = 12). Blood samples were collected before, after 180 min of moderate-intensity (metabolic rate: 200 W/m2) walking and following 60 min recovery in either a non-heat stress [temperate: 21.9 °C, 35% relative humidity (RH)] or high-heat stress (hot: 41.4 °C, 35% RH) environment. RESULTS: There were no differences in IFABP and sCD14 between the young and older groups in the temperate condition, while LBP was greater in the older group (+ 0.66 ug/mL; + 0.08 to + 1.24 ug/mL). In the hot condition, the older group experienced greater increases in IFABP compared to the young group (+ 712 pg/mL/hr; + 269 to + 1154 pg/mL/hr). However, there were no clear between-group differences for sCD14 (+ 0.24 ug/mL/hr, - 0.22 to + 0.70 ug/mL/hr) or LBP (+ 0.86 ug/mL/hr, - 0.73 to + 2.46 ug/mL/hr). CONCLUSION: While older men may experience greater intestinal epithelial injury following exercise in the heat; this did not lead to a greater magnitude of microbial translocation relative to their younger counterparts.

Association between cup orientation and low back pain after total hip arthroplasty in patients with osteonecrosis of the femoral head.

BACKGROUND: Postoperative low back pain (LBP) following total hip arthroplasty (THA) is classified as secondary hip-spine syndrome. The purpose of this study was to explore the correlations between cup orientation of THA and postoperative LBP in patients with osteonecrosis of the femoral head (ONFH). METHODS: A retrospective cohort study included 364 ONFH patients who underwent bilateral THA between January 2011 and December 2020. Among them, 53 patients (14.6%) experienced postoperative LBP at the end of follow-up and were designated as pain group (PG). A control group (CG) consisting of 106 patients with similar age, sex, and body mass index (BMI) to those in the PG was selected. Postoperative LBP in the PG was assessed using the visual analogue scale (VAS). Demographic data, clinical information, and radiographic criteria were evaluated as potential predictors of LBP. RESULTS: Patients in PG (mean age, 47.3 years [range, 27 to 75 years]; 42 [79%] male) had a mean VAS score of 4.6 (range, 1 to 9) compared with 0 for the patients in CG (mean age, 47.6 years [range, 19 to 77 years]; 84 [79%] male). There were no significant differences in clinical data between the two groups (p > 0.05). Preoperative radiographic variables also showed no significant differences between the PG and CG (p > 0.05). However, the postoperative inclination, anteversion, and standing ante-inclination (AI) were significantly lower in the PG compared to the CG, whereas the sitting and standing sacral slope (SS) were significantly higher (p < 0.05). Moreover, the variations in standing AI, standing and sitting pelvic tilt (PT) were significantly lower in the PG compared to the CG, while the variations in standing and sitting SS and lumbar lordosis (LL) were significantly higher (p < 0.05). The variation in standing AI in the PG showed a significantly correlation with the variation of standing SS, standing PT, and LL (p < 0.05). CONCLUSION: Postoperative LBP in ONFH patients after bilateral THA is significantly associated with the intraoperative cup orientation. The variation in standing AI is correlated with the variations in standing SS, standing PT, and LL, potentially contributing to the development of postoperative LBP.

Natural Language Processing of Referral Letters for Machine Learning-Based Triaging of Patients With Low Back Pain to the Most Appropriate Intervention: Retrospective Study.

BACKGROUND: Decision support systems (DSSs) for suggesting optimal treatments for individual patients with low back pain (LBP) are currently insufficiently accurate for clinical application. Most of the input provided to train these systems is based on patient-reported outcome measures. However, with the appearance of electronic health records (EHRs), additional qualitative data on reasons for referrals and patients' goals become available for DSSs. Currently, no decision support tools cover a wide range of biopsychosocial factors, including referral letter information to help clinicians triage patients to the optimal LBP treatment. OBJECTIVE: The objective of this study was to investigate the added value of including qualitative data from EHRs and referral letters to the accuracy of a quantitative DSS for patients with LBP. METHODS: A retrospective study was conducted in a clinical cohort of Dutch patients with LBP. Patients filled out a baseline questionnaire about demographics, pain, disability, work status, quality of life, medication, psychosocial functioning, comorbidity, history, and duration of pain. Referral reasons and patient requests for help (patient goals) were extracted via natural language processing (NLP) and enriched in the data set. For decision support, these data were considered independent factors for triage to neurosurgery, anesthesiology, rehabilitation, or minimal intervention. Support vector machine, k-nearest neighbor, and multilayer perceptron models were trained for 2 conditions: with and without consideration of the referral letter content. The models' accuracies were evaluated via F1-scores, and confusion matrices were used to predict the treatment path (out of 4 paths) with and without additional referral parameters. RESULTS: Data from 1608 patients were evaluated. The evaluation indicated that 2 referral reasons from the referral letters (for anesthesiology and rehabilitation intervention) increased the F1-score accuracy by up to 19.5% for triaging. The confusion matrices confirmed the results. CONCLUSIONS: This study indicates that data enriching by adding NLP-based extraction of the content of referral letters increases the model accuracy of DSSs in suggesting optimal treatments for individual patients with LBP. Overall model accuracies were considered low and insufficient for clinical application.

Does Overhead Squat Performance Affect the Swing Kinematics and Lumbar Spine Loads during the Golf Downswing?

The performance of the overhead squat may affect the golf swing mechanics associated with golf-related low back pain. This study investigates the difference in lumbar kinematics and joint loads during the golf downswing between golfers with different overhead squat abilities. Based on the performance of the overhead squat test, 21 golfers aged 18 to 30 years were divided into the highest-scoring group (HS, N = 10, 1.61 ± 0.05 cm, and 68.06 ± 13.67 kg) and lowest-scoring group (LS, N = 11, 1.68 ± 0.10 cm, and 75.00 ± 14.37 kg). For data collection, a motion analysis system, two force plates, and TrackMan were used. OpenSim 4.3 software was used to simulate the joint loads for each lumbar joint. An independent t-test was used for statistical analysis. Compared to golfers demonstrating limitations in the overhead squat test, golfers with better performance in the overhead squat test demonstrated significantly greater angular extension displacement on the sagittal plane, smaller lumbar extension angular velocity, and smaller L4-S1 joint shear force. Consequently, the overhead squat test is a useful index to reflect lumbar kinematics and joint loading patterns during the downswing and provides a good training guide reference for reducing the risk of a golf-related lower back injury.

Comparison of Integrase Strand Transfer Inhibitors (INSTIs) and Protease-Boosted Inhibitors (PIs) on the Reduction in Chronic Immune Activation in a Virally Suppressed, Mainly Male Population Living with HIV (PLWH).

Background and Objectives: The success of combined antiretroviral therapy (cART) has led to a dramatic improvement in the life expectancy of people living with HIV (PLWH). However, there has been an observed increase in cardiometabolic, bone, renal, hepatic, and neurocognitive manifestations, as well as neoplasms, known as serious non-AIDS events/SNAEs, compared to the general population of corresponding age. This increase is linked to a harmful phenomenon called inflammaging/immunosenescence, which is driven by chronic immune activation and intestinal bacterial translocation. In this study, we examined immunological and metabolic parameters in individuals receiving current cART. Materials and Methods: The study was conducted at Laiko General Hospital in Athens, Greece. Plasma concentrations of sCD14, IL-6, SuPAR, I-FABP, and LBP were measured in virally suppressed PLWH under cART with at least 350 CD4 lymphocytes/µL. We compared these levels between PLWH receiving integrase strand transfer inhibitors (INSTIs) and protease inhibitors (PIs) and attempted to correlate them with chronic immune activation and metabolic parameters. Results: Data from 28 PLWH were analyzed, with a mean age of 52 and 93% being males. Among the two comparison groups, IL-6 levels were higher in the PIs group (5.65 vs. 7.11 pg/mL, p = 0.03). No statistically significant differences were found in the other measured parameters. A greater proportion of PLWH under INSTIs had normal-range LBP (33% vs. 0%, p = 0.04). When using inverse probability of treatment weighting, no statistically significant differences in the measured parameters were found between the two groups (sCD14 p = 0.511, IL-6 p = 0.383, SuPAR p = 0.793, I-FABP p = 0.868, and LBP p = 0.663). Glucose levels were found to increase after viral suppression in the entire sample (92 mg/dL vs. 98 mg/dL, p = 0.009). Total (191 mg/dL vs. 222 mg/dL, p = 0.005) and LDL cholesterol (104 mg/dL vs. 140 mg/dL, p = 0.002) levels were higher in the PIs group. No significant differences were observed in liver and renal function tests. Conclusions: Further investigation is warranted for PLWH on cART-containing INSTI regimens to explore potential reductions in chronic immune activation and intestinal bacterial translocation.

Review Article: Safety of Live Biotherapeutic Products Used for the Prevention of Clostridioides difficile Infection Recurrence.

Live biotherapeutic products (LBPs) represent a new class of therapeutics indicated to prevent the recurrence of Clostridioides difficile infection (CDI) in adults. However, microbiota-based therapies have been used in CDI management before the Food and Drug Administration (FDA) designated this new drug class. The regulation of these microbiome-based therapies has varied, and several safety concerns have arisen over time. Requirements established by the FDA regarding the development of LBPs minimizes many of these prior concerns, and phase III trials have proven the safety and efficacy of 2 stool donor-derived LBPs: fecal microbiota, live-jslm (Rebyota™; formerly RBX2660) and fecal microbiota spores, live-brpk (Vowst™; formerly SER-109). Mild gastrointestinal side effects are common, but no severe drug-related adverse events have been reported with their use to date. A third LBP entering phase III clinical trials, VE303, follows a novel approach by sourcing bacterial strains from clonal cell banks and has demonstrated a similarly favorable safety profile.

Effect of time restricted feeding on anthropometric measures, eating behavior, stress, serum levels of BDNF and LBP in overweight/obese women with food addiction: a randomized clinical trial.

BACKGROUND & AIM: Food addiction (FA) as a specific food-related behavior may play an essential role in the pathogenesis of obesity. Brain-derived neurotrophic factor (BDNF) and gut microbiota (GM) alterations probably through fasting are closely related to brain function, affecting eating behaviors and body weight management. This study aimed to evaluate the effect of time-restricted feeding (TRF) on serum BDNF levels and eating behaviors in overweight and obese women with FA. METHODS AND DESIGN: This clinical trial was performed with a 2-month follow-up on 56 obese and overweight women with FA. Participants were randomly divided into two groups receiving a low-calorie diet (n = 27) and a group receiving a low-calorie diet with TRF (n = 29). Anthropometric measurements, biochemical markers, eating behavior, and stress were assessed during the study period. RESULTS: The reductions in weight, body mass index (BMI), waist circumference, and body fat mass were significantly higher in the TRF group compared to the control group at week 8 (P = 0.018, P = 0.015. P = 0.03, and P = 0.036, respectively). The cognitive restriction score was higher in the TRF as compared with the control group (P = 0.002). The food addiction criteria score was significantly reduced in both groups (P < 0.001). Serum levels of BDNF were significantly increased in the TRF group (P < 0.001). In addition, BDNF levels had a positive and significant correlation with the cognitive restriction score (r = 0.468 and P < 0.001), While the correlation with FA was not significant (ß = 0.588 and P = 0.618). Lipopolysaccharide binding protein decreased significantly in both groups, but this decrease was significantly higher in the TRF group than in the control group (P < 0.001). CONCLUSION: The results of this study showed that a low-calorie diet with TRF is more effective in weight management than a low-calorie diet alone, probably through further modulating the GM and improving BDNF levels. More effective weight loss in the TRF is probably related to better management of eating behavior than FA. TRIAL REGISTRATION: Iranian Registry of Clinical Trials identifier: IRCT20131228015968N7.

Lipopolysaccharide-binding protein as a biomarker in oral and maxillofacial tumors.

Oral and maxillofacial tumors (OMTs), such as oral squamous cell carcinoma (SCC), pleomorphic adenoma, and ameloblastoma, are common head and neck tumors. Lipopolysaccharide-binding protein (LBP) is a type I acute reactive protein, which participates in body inflammatory response modulation through lipopolysaccharide (LPS)-induced signaling pathway by targeting macrophages (expressing cluster of differentiation 204 [CD204]). Although it is well established that LBP is associated with the development of multiple types of cancer, little is known about the role of LBP in OMTs. This study aims to explore the expression of LBP in OMTs. Here, immunohistochemical (IHC) double staining of LBP and CD204 and enzyme-linked immunosorbent assay (ELISA) were conducted to explore the LBP expression in OMTs. The findings demonstrated that the LBP expression in OMTs was significantly elevated (p < 0.001). In addition, the LBP expression was associated with the clinical stage (p < 0.001), T classification (p < 0.001), and lymph node metastasis (p < 0.001, except ELISA) but independent of histological grade of SCC, gender, and age in patients with SCC. The optional cutoff of the LBP serum level is 0.721 µg/ml. To conclude, LBP contributes to the development of OMTs and could be a biomarker in the screening and predicting metastasis in patients with OMTs.

Bacterial translocation markers and toll-like receptors in biliary atresia following successful portoenterostomy.

AIM: The gut-liver axis may contribute to pathophysiology of cholestatic liver disorders like biliary atresia (BA) by bacterial translocation (BT). Toll-like receptors (TLR) are pattern recognition receptors known to activate innate immunity and secretion of inflammatory cytokines. Herein, we examined BT-associated biomarkers and TLRs in relation to liver injury after successful portoenterostomy (SPE) in BA. METHODS: Serum levels of lipopolysaccharide-binding protein (LBP), CD14, LAL, TNF-α, IL-6 and FABP2 along with liver expression of TLRs (TLR1, TLR4, TLR7 and TLR9), LBP and CD14 were measured during median 4.9 (1.7-10.6) years follow-up after SPE in 45 BA patients. RESULTS: Serum LBP, CD14, TNF-α and IL-6 all increased after SPE whereas LAL and FABP-2 remained unchanged. Serum LBP correlated positively with CD14 and markers of hepatocyte injury and cholestasis, but not with Metavir fibrosis stage, transcriptional markers for fibrosis (ACTA2) or ductular reaction. Serum CD14 concentration was significantly higher in patients with portal hypertension than without. While liver expression of TLR4 and LBP remained low, TLR7 and TLR1 showed marked BA-specific increases, and TLR7 correlated with Metavir fibrosis stage and ACTA2. CONCLUSION: BT does not seem to play a significant role in liver injury after SPE in our series of BA patients.

Metabolomics analysis of the serum metabolic signature of nonalcoholic fatty liver disease combined with prediabetes model rats after the intervention of Lycium barbarum polysaccharides combined with aerobic activity.

Metabolic disorders accompany nonalcoholic fatty liver disease (NAFLD), associated with prediabetes. Lycium barbarum polysaccharides (LBP) seem to be a potential prebiotic, and aerobic exercise has shown protective effects on NAFLD with prediabetes. However, their combined effects on NAFLD and prediabetes remain unclear. This study investigated the effects of LBP and aerobic exercise alone, and their combined effects on the metabolomics of serum, and explored the potential mechanisms utilizing a high-fat diet-induced rat model of NAFLD and prediabetes. It provided the metabolic basis for the pathogenesis and early diagnosis of prediabetes complicated with NAFLD. Untargeted metabolomics profiling was performed using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap mass spectrometry to analyze the changes in overall metabolites in each group of samples. An orthogonal partial least squares-discriminant analysis model with variable importance on projection >1 and p < 0.05 were used as the screening criteria to screen the significant differential metabolites and analyze the expression changes and functional pathways. Different intervention treatments showed clear discrimination by univariate and multivariate analyses. The model group had a high relative level of expression of lipids. Comparison between the two groups showed steroids with high expression after LBP and aerobic exercise treatment separately and alkaloids and fatty acyls with high expression after aerobic exercise and the combination intervention, respectively. Comparison of the five groups showed some of the metabolites to be differently expressed after the intervention improved lipid and fatty acid metabolism. The three types of intervention had sound effects on the changes in liver index for the diseases studied. Furthermore, the combination treatment may be a better choice for disease prevention and treatment than a single treatment. Our analysis of metabolomics confirmed that the different treatments had significant regulatory effects on the metabolic pathways. Our findings strongly support the possibility that aerobic exercise combined with LBP can be regarded as a potential therapeutic method for NAFLD in prediabetics.

How Back Pain Affects Patient Satisfaction After Primary Total Knee Arthroplasty.

BACKGROUND: Although back pain (BP) has been shown to be a predictor of dissatisfaction after total knee arthroplasty (TKA) in some reports, these studies did not use a scale to quantify the degree of pain. The purpose of this study was to quantify the effect of BP intensity on patient satisfaction reported at 1 year after TKA. METHODS: A multicenter prospective cohort was taken in which 9,057 patients undergoing primary unilateral TKA were enrolled in FORCE-TJR and demographic and clinical data were collected. Back pain (BP) intensity was assessed using the Oswestry back disability index (ODI) pain intensity questionnaire. Patients were classified into 4 categories based on the severity of BP. Patient-reported outcomes (PROs) were collected preoperatively and postoperatively after 1 year including the Knee injury and Osteoarthritis Outcome Score (KOOS) (total score, pain, Activities of Daily Living (ADL), and Quality of Life (QOL), Short-Form health survey 36-item (SF-36) Physical Component Score (PCS), and Mental Component Score (MCS)). We used a validated 5-point Likert satisfaction scale. Univariate analyses of the difference between the satisfied and dissatisfied patients' groups was performed. Multivariate logistic regression models with 95% confidence interval (CI) were used to quantify the effect of BP intensity on patient dissatisfaction at 1 year. Receiver operating characteristic (ROC) analyses were performed with measurement of area under curve (AUC). RESULTS: At 1 year, a total of 1,657 TKA patients (18.3%) were dissatisfied. A total of 4,765 patients (52.6%) reported back pain at the time of surgery, including mild BP in 2,264 patients (24.9%), moderate BP in 1,844 patients (20.3%), and severe BP in 657 patients (7.2%). Severe back pain was significantly associated with patient dissatisfaction at 1 year after TKA (P = .0006). The multivariate regressions showed that patients who had severe BP were 1.6 times more likely to be dissatisfied when compared to patients who had no BP [odds ratio (OR) 1.63; 95% confidence interval (CI) (1.23-2.16), P = .0006]. While patients who had mild BP [OR 0.98; 95% CI (0.82-1.17), P = .87] or moderate BP [OR 0.97; 95% CI (0.80-1.18), P = .78] were not associated with an increased likelihood of dissatisfaction. Other predictive variables for dissatisfaction, include age [OR for younger patients <65 years versus older patients ≥65 years, 0.74; 95% CI (0.59-0.92)], educational level [OR for post high school versus less, 0.83; 95% CI (0.71, 0.97)], smoking [OR for nonsmoker versus current smoker, 0.63; 95% CI (0.45, 0.87)], and Charlson comorbidity index [OR for CCI ≥2 versus 0, 1.25; 95% CI (1.05, 1.49)]. CONCLUSION: Increased BP intensity was associated with increased risk of dissatisfaction 1 year after TKA. Only patients who had severe BP were 1.6 times more likely to be dissatisfied. The data presented here can help to improve shared decision-making and patient counseling before surgery. Surgeons should consider a spine evaluation in patients who have severe BP prior to TKA.

Facial Expression Recognition Methods in the Wild Based on Fusion Feature of Attention Mechanism and LBP.

Facial expression methods play a vital role in human-computer interaction and other fields, but there are factors such as occlusion, illumination, and pose changes in wild facial recognition, as well as category imbalances between different datasets, that result in large variations in recognition rates and low accuracy rates for different categories of facial expression datasets. This study introduces RCL-Net, a method of recognizing wild facial expressions that is based on an attention mechanism and LBP feature fusion. The structure consists of two main branches, namely the ResNet-CBAM residual attention branch and the local binary feature (LBP) extraction branch (RCL-Net). First, by merging the residual network and hybrid attention mechanism, the residual attention network is presented to emphasize the local detail feature information of facial expressions; the significant characteristics of facial expressions are retrieved from both channel and spatial dimensions to build the residual attention classification model. Second, we present a locally improved residual network attention model. LBP features are introduced into the facial expression feature extraction stage in order to extract texture information on expression photographs in order to emphasize facial feature information and enhance the recognition accuracy of the model. Lastly, experimental validation is performed using the FER2013, FERPLUS, CK+, and RAF-DB datasets, and the experimental results demonstrate that the proposed method has superior generalization capability and robustness in the laboratory-controlled environment and field environment compared to the most recent experimental methods.

Cross-cultural adaptation of The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire: A methodological systematic review.

BACKGROUND: The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) is a reliable and sensitive measure of disability to determine functional status and evaluate curative effects in low back pain, it has now been cross-cultural translated into many other languages and adapted for use in different countries. We aim to evaluate the translation procedures and measurement properties of cross-cultural adaptations of the JOABPEQ. METHODS: Studies related to cross-cultural adaptation of the JOABPEQ in a specific language/culture were searched in PubMed, Embase, CINAHL, SciELO, PsycINFO, SinoMed, and Web of Science from their inception to March 2022. The Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and the Consensus-based Standards for the Selection of Health Status Measurement Instruments guideline were used for evaluation. RESULTS: Nine different versions of cross-cultural JOABPEQ adaptations in 8 different languages/cultures were included. The adaptation process was not strictly performed, such as standard forward translation and expert committee review were rarely reported. Content validity (8/9), floor and ceiling effects (3/9), reliability (4/9), and interpretability (6/9) were assessed in most of the adaptations, while agreement (2/9), responsiveness (2/9), and the internal consistency (2/9) were not. JOABPEQ can replace functional and quality of life score to reduce the burden of scientific research. CONCLUSION: We recommend Persian-Iranian, simplified Chinese-Chinese Mandarin, Thai and Gunaydin G's Turkish adaptations for application. The numerical pain rating scale/visual analogue scale in low back pain and lower extremities, as well as numbness in lower extremities could not be neglected in JOABPEQ adaptations.