ABSTRACT
The accumulation of misfolded and aggregated proteins is a hallmark of neurodegenerative proteinopathies. Although multiple genetic loci have been associated with specific neurodegenerative diseases (NDs), molecular mechanisms that may have a broader relevance for most or all proteinopathies remain poorly resolved. In this study, we developed a multi-layered network expansion (MLnet) model to predict protein modifiers that are common to a group of diseases and, therefore, may have broader pathophysiological relevance for that group. When applied to the four NDs Alzheimer's disease (AD), Huntington's disease, and spinocerebellar ataxia types 1 and 3, we predicted multiple members of the insulin pathway, including PDK1, Akt1, InR, and sgg (GSK-3ß), as common modifiers. We validated these modifiers with the help of four Drosophila ND models. Further evaluation of Akt1 in human cell-based ND models revealed that activation of Akt1 signaling by the small molecule SC79 increased cell viability in all models. Moreover, treatment of AD model mice with SC79 enhanced their long-term memory and ameliorated dysregulated anxiety levels, which are commonly affected in AD patients. These findings validate MLnet as a valuable tool to uncover molecular pathways and proteins involved in the pathophysiology of entire disease groups and identify potential therapeutic targets that have relevance across disease boundaries. MLnet can be used for any group of diseases and is available as a web tool at http://ssbio.cau.ac.kr/software/mlnet.
Subject(s)
Alzheimer Disease , Huntington Disease , Proteostasis Deficiencies , Animals , Humans , Mice , Alzheimer Disease/genetics , Glycogen Synthase Kinase 3 beta , Huntington Disease/genetics , Signal TransductionABSTRACT
This study investigated the preventive effects of peptides derived from milk fermented with the probiotic strain Lactobacillus gasseri 505 (505) against stress-related brain damage and anxiety-like behavior. The peptides MKPWIQPKTKVIPYVRYL (Pep14) and VYQHQKAMKPWIQPKTKVIPYVRYL (Pep21), which exhibit high antioxidant and anti-inflammatory activities, were administered to stressed mice. The results showed that the stress mechanism in the gut-brain axis was regulated by pretreatment with both peptides, leading to inhibition of neurodevelopment and neuroinflammation through the hypothalamic-pituitary-adrenal (HPA) axis, based on the expression of related mRNA and proteins. The expression of colonic inflammation-related mRNA and proteins was also reduced. Moreover, anxiety-like behavior was significantly reduced in mice treated with Pep14 and Pep21. These results indicate that the bioactive peptides Pep14 and Pep21, derived from milk fermented with 505, may prevent stress-induced brain damage and anxiety-like behavior via regulation of the HPA axis.
Subject(s)
Brain Diseases , Gastrointestinal Diseases , Peptides , Stress, Physiological , Animals , Mice , Gastrointestinal Diseases/therapy , Hypothalamo-Hypophyseal System/physiology , Milk , Peptides/pharmacology , Pituitary-Adrenal System/physiology , RNA, Messenger , Probiotics , Brain Diseases/therapy , Fermented FoodsABSTRACT
PURPOSE: Previous studies have reported that a high critical shoulder angle (CSA) is associated with rotator cuff tears (RCTs). However, the available evidence concerning the strength of the association of these parameters with the pathogenesis of RCTs is conflicting. The aim in the present meta-analysis was to assess the diagnostic performance of CSA for detecting RCTs. METHODS: The PubMed and EMBASE databases were searched for diagnostic accuracy studies of CSA for detecting RCT. Quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We calculated the pooled diagnostic accuracy of CSA, including diagnostic odd ratios (DORs) with 95% confidence intervals (CIs). Bivariate random-effect modeling with forest plots and hierarchical summary receiver operating characteristic curves was performed to evaluate the pooled sensitivity and specificity of CSA. For heterogeneity exploration, we performed meta-regression analyses. RESULTS: Eight studies including 902 patients (460 patients with RCT and 442 control patients) were included. According to DOR, CSA was an informative feature for RCT (DOR 8; 95% CI 4-16). The overall diagnostic performance of CSA for RCT was good (sensitivity 71% [95% CI 61-80%]; specificity, 77% [95% CI 65-86%]). Meta-regression analyses revealed that the sensitivity of CSA could be higher for differentiating full-thickness RCTs and normal patients. Furthermore, the specificity of CSA could be higher using a cut-off value of 35°. CONCLUSION: CSA on plain radiographs has good diagnostic performance for RCTs. A cut-off value of 35° is recommended for more accurate diagnosis of full-thickness RCTs. Measuring CSA on plain radiographs may provide clinicians with a readily available and reliable method for detecting RCT in daily practice. LEVEL OF EVIDENCE: Diagnostic studies, Level III.
Subject(s)
Rotator Cuff Injuries/diagnostic imaging , Rotator Cuff/diagnostic imaging , Humans , Odds Ratio , ROC Curve , Radiography , Sensitivity and Specificity , Shoulder , Shoulder JointABSTRACT
OBJECTIVE: To compare the image quality, radiation dose, and diagnostic performance between low-dose (LD) and ultra-low-dose (ULD) lumbar-spine (L-spine) CT with iterative reconstruction (IR) for patients with chronic low back pain (LBP). METHODS: In total, 260 patients with chronic LBP who underwent L-spine CT between November 2015 and September 2016 were prospectively enrolled. Of these, 143 underwent LD-CT with IR and 117 underwent ULD-CT with IR. The patients were divided according to their body mass index (BMI) into BMI1 (<22.9 kg/m2), BMI2 (23.0-24.9 kg/m2), and BMI3 (≥25 kg/m2) groups. Two blinded radiologists independently evaluated the signal-to-noise ratio (SNR), qualitative image quality, and final diagnoses (lumbar disc disease and facet joint osteoarthritis). L-spine MRIs interpreted by consensus were used as the reference standard. All data were statistically analyzed. RESULTS: ULD protocol showed significantly lower SNR for all patients (p < 0.001) except the vertebral bodies and lower qualitative image quality for BMI3 patients (p ≤ 0.033). There was no statistically significant difference between ULD (sensitivity, 95.1-98.1%; specificity, 92.5-98.7%; accuracy, 94.6-98.0%) and LD protocols (sensitivity, 95.6-100%; specificity, 95.5-98.9%; accuracy, 97.4-98.1%), (all p≥0.1) in the BMI1 and BMI2; while dose was 60-68% lower with the ULD protocol. Interobserver agreements were excellent or good with regard to image quality and final diagnoses. CONCLUSIONS: For the BM1 and BMI2 groups, ULD-CT provided an acceptable image quality and exhibited a diagnostic accuracy similar to that of LD-CT. These findings suggest that it is a useful diagnostic tool for patients with chronic LBP who exhibit a BMI of <25 kg/m2.
Subject(s)
Intervertebral Disc Displacement/diagnostic imaging , Low Back Pain/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Magnetic Resonance Imaging/methods , Osteoarthritis/diagnostic imaging , Tomography, X-Ray Computed/methods , Zygapophyseal Joint/diagnostic imaging , Adult , Aged , Aged, 80 and over , Body Mass Index , Chronic Disease , Female , Humans , Intervertebral Disc Displacement/pathology , Low Back Pain/pathology , Lumbar Vertebrae/pathology , Male , Middle Aged , Osteoarthritis/pathology , Prospective Studies , Radiation Dosage , Sensitivity and Specificity , Signal-To-Noise Ratio , Zygapophyseal Joint/pathologyABSTRACT
PURPOSE: The purpose of this study was to conduct a meta-analysis to determine whether the locking plate or non-locking plate results in better opening-wedge high tibial osteotomy (OWHTO) outcomes. METHODS: The MEDLINE, EMBASE, COCHRANE, and KOREAMED register databases were searched for studies. The eligibility criteria for inclusion in the review were studies that compared the locking plate with the non-locking plate for OWHTO, and those that provided clear descriptions of surgical techniques and outcomes. The key outcomes of interest were union rate, correction loss angle, correction loss rate, and full weight-bearing starting point. The statistical software "RevMan" was used in statistical analysis. RESULTS: Five studies were included in the meta-analysis. Among their reported results, there were no differences in the incidence of union [risk ratio (RR) = 1.01, p = 0.34], non-locking plate was associated with lower incidence of correction maintenance (RR = 1.13, p = 0.0006) and greater angle of correction loss [mean difference (MD) = -2.06, p < 0.00001], and locking plate was associated with a significant improvement in Knee society score and function score (MD = 5.77, p < 0.0001; MD = 7.50, p = 0.0005). CONCLUSIONS: Locking plate provides better clinical outcomes and reduced correction loss rates and angles as compared to non-locking plate for fixation with OWHTO. LEVEL OF EVIDENCE: IV.
Subject(s)
Bone Plates , Osteoarthritis, Knee/surgery , Osteotomy/methods , Tibia/surgery , Humans , Knee/physiopathology , Middle Aged , Weight-BearingABSTRACT
PURPOSE: To compare the clinical outcomes between medial soft-tissue surgery and medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation without any evident predisposing factors. METHODS: A literature search was performed on the established medical databases MEDLINE, EMBASE, and the Cochrane register. The inclusion criteria were as follows: English-language papers for recurrent patellar dislocation without any evident predisposing factors, clinical trial(s) with clear description of surgical technique, adult subjects, medial soft-tissue surgery or MPFL reconstruction without combined surgery, and a follow-up longer than 2 years. The methodological quality of all articles was assessed by 2 authors according to the Coleman methodology score. RESULTS: Thirteen studies (mean Coleman methodology score value, 74.1; standard deviation, 11.5) were included in the analysis. Five studies reported the outcomes of patients undergoing medial soft-tissue surgery, compared with 7 studies reporting MPFL reconstruction. Overall, 109 patients underwent medial soft-tissue surgery with a minimum 2-years follow-up, compared with 308 patients of MPFL reconstruction. There was one direct comparative study between medial soft-tissue surgery and MPFL reconstruction. Of the patients who received medial soft-tissue surgery, 0 to 9.7% experienced redislocation, compared with 0 to 10.7% of the MPFL reconstruction group. The ranges of differences in Kujala scores were 23.6 to 31.7 points in patients who underwent medial soft-tissue surgery and 23.11 to 38.8 points in patients who underwent MPFL reconstruction. The ranges of postoperative congruence angles were -14.4° to 8.2° for medial soft-tissue surgery and -7.7° to -5.2° for MPFL reconstruction. The ranges of postoperative lateral patellofemoral angles were 7.9° to 9.4° for medial soft-tissue surgery and 5° to 5.3° for MPFL reconstruction. CONCLUSIONS: All studies on medial soft-tissue surgery and MPFL reconstruction for recurrent patellar dislocation without predisposing factors showed satisfactory outcomes despite the use of numerous surgical techniques, graft types, and follow-up periods. LEVEL OF EVIDENCE: Level IV, Systematic Review.
Subject(s)
Ligaments, Articular/surgery , Orthopedic Procedures/methods , Patellar Dislocation/surgery , Plastic Surgery Procedures/methods , Humans , RecurrenceABSTRACT
PURPOSE: The purpose of this study was to analyze clinical outcomes in patients who underwent posterior cruciate ligament reconstruction (PCLR) with and without remnant preservation. METHODS: A search of the literature was performed with the established medical databases Medline, Embase, and the Cochrane Register. Two authors screened the selected articles for title, abstract, and full text in accordance with predefined inclusion and exclusion criteria. The inclusion criteria were as follows: English-language articles on isolated posterior cruciate ligament injury; clinical trials with a clear description of surgical technique; outcome evaluation using a well-defined knee score, arthrometry, and posterior stress radiography; follow-up longer than 2 years; and a Coleman Methodology Score (CMS) of 65 points or greater. The methodologic quality of all articles was assessed by 2 authors according to the CMS. RESULTS: Eleven studies were included, with a mean CMS of 78.9 points (SD, 5.37 points). There was no direct comparative study between remnant-preserving PCLR and standard PCLR. At final follow-up, the knees of 72% to 100% of patients who underwent remnant-preserving PCLR and 41% to 95% of patients who underwent standard PCLR were rated as normal or nearly normal on the International Knee Documentation Committee subjective knee assessment. Patients who underwent remnant-preserving PCLR showed an increase of 16.4 to 47 points in Lysholm scores, and patients who underwent standard PCLR showed an increase of 22 to 29 points. The ranges of mean postoperative side-to-side differences on KT-1000 (MEDmetric, San Diego, CA) testing were 0.7 to 2.8 mm in patients who underwent remnant-preserving PCLR and 1 to 3.5 mm in patients who underwent standard PCLR. The ranges of mean postoperative side-to-side differences on stress radiography were 2.2 to 5 mm in patients who underwent remnant-preserving PCLR and 4.7 to 6 mm in patients who underwent standard PCLR. CONCLUSIONS: All studies on PCLR with remnant preservation showed satisfactory outcomes despite using numerous surgical techniques, graft types, intervals from injury to surgery, and follow-up periods. LEVEL OF EVIDENCE: Level IV, systematic review of Level II through IV studies.
Subject(s)
Arthroscopy/methods , Knee Joint/surgery , Posterior Cruciate Ligament/surgery , Humans , Joint Instability/surgery , Range of Motion, Articular , Treatment OutcomeABSTRACT
Recently, natural herbs have gained increasing attention owing to their comparatively low toxicity levels and the abundance of historical medical documentation regarding their use. Nevertheless, owing to a lack of knowledge regarding these herbs and their compounds, attempts to find those that could be beneficial for treating diseases have often been ad hoc; thus, there is now a growing demand for an in silico method to identify beneficial herbs. In this study, we present a computational approach for identifying natural herbs specifically effective in treating cognitive decline in Alzheimer's disease (AD) sufferers, which analyzes the similarities between herbal compounds and known drugs targeting AD-related proteins. Our in silico method suggests that Corydalis ternata can improve cognitive decline in AD sufferers. Behavioral tests with an AD mouse model for the confirmation of the in silico prediction reveals that C. ternata significantly alleviated the cognitive decline (memory and motor functions) caused by neurodegeneration. Further pathology analyses reveal that C. ternata decreases the level of Aß plaques, reduces neuroinflammation, and promotes autophagy flux, and thus C. ternata can be clinically effective for preventing mild cognitive impairment during the early stages of AD. These findings highlight the potential utility of our in silico method and the potential clinical application of the identified natural herb in treating and preventing AD.
Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Cognitive Dysfunction , Corydalis , Plant Extracts , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Animals , Corydalis/chemistry , Cognitive Dysfunction/drug therapy , Amyloid beta-Peptides/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Disease Models, Animal , Mice , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/pathology , Mice, Transgenic , Autophagy/drug effects , Male , Computer SimulationABSTRACT
Fermented mixed grain (FG) has beneficial anti-cancer, antioxidant, and anti-inflammatory effects. In this study, we investigated the effects of FG on gut inflammation, brain dysfunction, and anxiety/depression-like behavior induced by unpredictable chronic mild stress (UCMS) in mice. Mice were administered mixed grain or FG for 3 weeks and were then exposed to UCMS for 4 weeks. FG administration ameliorated stress-induced anxiety/despair-like behavior. FG administration also prevented UCMS-induced memory impairment. Additionally, the mRNA levels of 5-HTR1A and IL-6 were restored to normal levels in the brains of FG-administered mice. FG administration also inhibited intestinal damage in stressed mice compared with that in the UCMS (without FG) group. These results suggest that FG can alleviate stress-induced intestinal damage, brain dysfunction, and cognitive impairment.
ABSTRACT
Autoinhibition, a crucial allosteric self-regulation mechanism in cell signaling, ensures signal propagation exclusively in the presence of specific molecular inputs. The heightened focus on autoinhibited proteins stems from their implication in human diseases, positioning them as potential causal factors or therapeutic targets. However, the absence of a comprehensive knowledgebase impedes a thorough understanding of their roles and applications in drug discovery. Addressing this gap, we introduce Autoinhibited Protein Database (AiPD), a curated database standardizing information on autoinhibited proteins. AiPD encompasses details on autoinhibitory domains (AIDs), their targets, regulatory mechanisms, experimental validation methods, and implications in diseases, including associated mutations and post-translational modifications. AiPD comprises 698 AIDs from 532 experimentally characterized autoinhibited proteins and 2695 AIDs from their 2096 homologs, which were retrieved from 864 published articles. AiPD also includes 42 520 AIDs of computationally predicted autoinhibited proteins. In addition, AiPD facilitates users in investigating potential AIDs within a query sequence through comparisons with documented autoinhibited proteins. As the inaugural autoinhibited protein repository, AiPD significantly aids researchers studying autoinhibition mechanisms and their alterations in human diseases. It is equally valuable for developing computational models, analyzing allosteric protein regulation, predicting new drug targets, and understanding intervention mechanisms AiPD serves as a valuable resource for diverse researchers, contributing to the understanding and manipulation of autoinhibition in cellular processes. Database URL: http://ssbio.cau.ac.kr/databases/AiPD.
Subject(s)
Databases, Protein , Humans , Proteins/metabolism , Proteins/chemistry , Protein Domains , Data Curation/methodsABSTRACT
PURPOSE: The purpose of this cadaveric study was to study the effect of plane of osteotomy on incidence of lateral cortex fracture and to define a "safe zone" through which medial open-wedge high tibial osteotomy (HTO) could be performed with minimal risk of lateral cortex fracture. METHODS: Medial open HTO was performed in nine fresh frozen human cadavers (18 knees) with each specimen randomly assigned to a "safe zone" osteotomy (group A, between the tip of the fibular head and the circumference line of the fibular head), or a lower level osteotomy (group B, distal to the circumference line of the fibular head). RESULTS: Six out of nine knees developed lateral cortex fracture in group B compared to none in group A (P = 0.009) when the osteotomy site was distracted to a maximum of 20 mm. CONCLUSION: Directing the plane of the osteotomy toward the "safe zone" significantly reduces the risk of lateral cortex fracture compared to an osteotomy, which is directed at a lower level. Confining the plane of a medial open HTO to within the "safe zone" can prevent lateral cortex fracture and subsequent loss of correction.
Subject(s)
Knee Joint/surgery , Osteotomy/methods , Tibia/surgery , Tibial Fractures/prevention & control , Adult , Aged , Female , Humans , Incidence , Male , Middle Aged , Osteotomy/adverse effects , Tibia/injuries , Tibial Fractures/epidemiology , Tibial Fractures/etiology , Treatment OutcomeABSTRACT
Growing evidence indicates a crucial role of the gut microbiota in physiological functions. Gut-brain axis imbalance has also been associated with neuropsychiatric and neurodegenerative disorders. Studies have suggested that probiotics regulate the stress response and alleviate mood-related symptoms. In this study, we investigated the effects of the probiotic Lacticaseibacillus rhamnosus IDCC3201 (L3201) on the behavioral response and fecal metabolite content in an unpredictable chronic mild stress (UCMS) mouse model. Our study shows that chronic stress in mice for three weeks resulted in significant changes in behavior, including lower locomotor activity, higher levels of anxiety, and depressive-like symptoms, compared to the control group. Metabolomic analysis demonstrated that disrupted fecal metabolites associated with aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis by UCMS were restored with the administration of L3201. Oral administration of the L3201 ameliorated the observed changes and improved the behavioral alterations along with fecal metabolites, suggesting that probiotics play a neuroprotective role.
ABSTRACT
The medial habenula (mHb), a subregion of the habenula, is involved in diverse brain functions, such as nicotine addiction, anxiety, and anhedonia. We recently reported that TMEM16A deficiency, a calcium-activated chloride channel, decreased the activity of mHb cholinergic neurons. Since downregulated activity in cholinergic neurons of the mHb is involved in anhedonia-like behavior, we here investigated whether conditional deletion of TMEM16A in mHb cholinergic neurons also displays anhedonia-like behavior. The conditional deletion of TMEM16A in the mHb cholinergic neurons of mice (TMEM16A cKO mice) was generated by crossing ChaT-Cre (+) with floxed TMEM16A f/f mice. TMEM16A cKO mice displayed significantly reduced social interaction, sucrose preference, female urine sniffing, and increased marble burying. These behavioral data suggest the potential role of TMEM16A in anhedonic-like behavior in mice. Taken together, the presented data suggest that TMEM16A-mediated mHb activity might be a therapeutic target for anhedonia-related symptoms.
Subject(s)
Habenula , Anhedonia , Animals , Anxiety , Cholinergic Neurons , Female , Habenula/physiology , Mice , Mice, Inbred C57BLABSTRACT
For a long time, the central nervous system was believed to be the only regulator of cognitive functions. However, accumulating evidence suggests that the composition of the microbiome is strongly associated with brain functions and diseases. Indeed, the gut microbiome is involved in neuropsychiatric diseases (e.g., depression, autism spectrum disorder, and anxiety) and neurodegenerative diseases (e.g., Parkinson's disease and Alzheimer's disease). In this review, we provide an overview of the link between the gut microbiome and neuropsychiatric or neurodegenerative disorders. We also introduce analytical methods used to assess the connection between the gut microbiome and the brain. The limitations of the methods used at present are also discussed. The accurate translation of the microbiome information to brain disorder could promote better understanding of neuronal diseases and aid in finding alternative and novel therapies.
ABSTRACT
Chronic stress is a major cause of mental health problems and primary medical issues. Milk has been studied for its stress-reducing effects. Tryptophan, which is abundant in milk, is a precursor of the neuroactive compounds serotonin and melatonin. This study investigated the preventive effects of milk casein on brain dysfunction and anxiety-like behavior induced by chronic stress. Mice were exposed to unpredictable chronic mild stress (UCMS) and milk casein was administered for 10 weeks. Milk casein significantly reduced stress-induced changes in serum corticosterone and serotonin levels. The negative effects of UCMS on the expression of proteins associated with neuroendocrine function, neurodegeneration, neuronal inflammation, and barrier function of the blood-brain barrier were statistically normalized by casein treatment. Pretreatment with casein significantly prevented anxiety-like behavior induced by UCMS. These results suggest that milk casein has the potential to prevent stress-induced brain dysfunction and anxiety-like behavior.
Subject(s)
Caseins , Stress, Psychological , Animals , Behavior, Animal , Brain , Corticosterone , Depression , Disease Models, Animal , Mice , MilkABSTRACT
BACKGROUND: The clinical importance of meniscal ramp lesions in patients with anterior cruciate ligament (ACL) tear has emerged as a major issue. However, the diagnostic accuracy of magnetic resonance imaging (MRI) for detecting ramp lesions has a wide range. PURPOSE: To perform a systematic review and meta-analysis of the diagnostic performance of MRI for diagnosing ramp lesion in patients with ACL tear. STUDY DESIGN: Systematic review and meta-analysis. METHODS: A literature search of PubMed, EMBASE, and the Cochrane Library was performed based on the revised guidelines for the PRISMA DTA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Accuracy Studies) statement. Diagnostic performance studies using MRI as the index test and arthroscopy as the reference standard for ramp lesion were included. Bivariate and hierarchical summary receiver operating characteristic modeling was used to evaluate the diagnostic performance. Meta-regression analyses were performed to identify potential sources of heterogeneity. RESULTS: The review and meta-analysis included 9 studies from 8 articles (883 patients with ACL tear and reconstruction). The summary sensitivity, summary specificity, and area under the hierarchical summary receiver operating characteristic for ramp lesion were 0.71 (95% CI, 0.59-0.81), 0.94 (95% CI, 0.88-0.97), and 0.90 (95% CI, 0.87-0.92), respectively. Among the potential covariates, magnet strength (P < .01), patient knee position (P = .04), and MRI interpreter (P = .04) were associated with heterogeneity in terms of sensitivity, whereas magnet strength (P = .03) was associated with heterogeneity in terms of specificity. CONCLUSION: MRI demonstrated moderate sensitivity and excellent specificity for diagnosing ramp lesion. Routine arthroscopic assessment is recommended for the presence of ramp lesion, regardless of whether it is suspected on MRI. Further clinicoradiological studies of diagnostic algorithms are needed for identifying ramp lesion, including high-resolution MRI with appropriate knee position.
Subject(s)
Anterior Cruciate Ligament Injuries , Meniscus , Tibial Meniscus Injuries , Anterior Cruciate Ligament Injuries/diagnostic imaging , Arthroscopy , Humans , Magnetic Resonance Imaging , Meniscus/diagnostic imaging , Meniscus/injuries , Sensitivity and Specificity , Tibial Meniscus Injuries/diagnostic imagingABSTRACT
This study aimed to investigate the effects of glycated milk casein (Gc) fermented with Lactobacillus rhamnosus 4B15 (FGc) on the intestinal microbiota and physiological and behavioral properties in mice under chronic stress. Mice were administered Gc or FGc for 10 weeks and then exposed to unpredictable chronic mild stress (UCMS) for 7 weeks. FGc administration restored alterations of gut microbiota induced by UCMS. Moreover, FGc significantly reduced the stress-induced increase in serum corticosterone and decrease in serotonin levels. Anxiety-like behaviors induced by UCMS were also significantly decreased in the FGc group. UCMS-induced dysregulation of gene and protein expression related to neuroendocrine function, neuronal development, and inflammation, and gut-blood-brain barrier function was controlled by FGc pre-treatment. These results strongly suggest the protective effects of FGc targeting of intestinal microbiota for abnormal brain activity, which is consistent with the view that FGc plays an important role in regulating stress-related gut-brain axis disorders.
Subject(s)
Cognition , Lacticaseibacillus rhamnosus/metabolism , Milk Proteins/metabolism , Stress, Psychological/diet therapy , Stress, Psychological/psychology , Animals , Bacteria/classification , Bacteria/genetics , Bacteria/metabolism , Brain/physiopathology , Cattle , Corticosterone/blood , Cultured Milk Products/microbiology , Fermentation , Gastrointestinal Microbiome , Humans , Male , Mice, Inbred C57BL , Polysaccharides/metabolism , Serotonin/blood , Serotonin/metabolism , Stress, Psychological/blood , Stress, Psychological/microbiologyABSTRACT
PURPOSE: To compare the clinical outcomes between the open posterior approach and arthroscopic suture fixation for displaced posterior cruciate ligament (PCL) avulsion fractures. METHODS: A literature search was performed on MEDLINE, EMBASE, and the Cochrane Library databases. The inclusion criteria were as follows: papers written in English on displaced PCL avulsion fractures, clinical trial(s) with clear description of surgical technique, adult subjects, a follow-up longer than 12 months and modified Coleman methodology score (CMS) more than 60 points. RESULTS: Twelve studies were included with a mean CMS value of 72.4 (standard deviation, 7.6). Overall, 134 patients underwent the open posterior approach with a minimum 12-month follow-up, and 174 patients underwent arthroscopic suture fixation. At final follow-up, the range of Lysholm score was 85-100 for the open approach and 80-100 for the arthroscopic approach. Patients who were rated as normal or nearly normal in the International Knee Documentation Committee subjective knee assessment were 92%-100% for the open approach and 90%-100% for the arthroscopic approach. The range of side-to-side difference was 0-5 mm for both approaches. CONCLUSIONS: Both arthroscopic and open methods for the treatment of PCL tibial-side avulsion injuries resulted in comparably good clinical outcomes, radiological healing, and stable knees.
ABSTRACT
PURPOSE: To compared the diagnostic performance of low-dose (LD) lumbar-spine (L-spine) CT with that of standard-dose (SD) L-spine CT. METHODS: Patients who underwent SD (nâ¯=â¯76) or LD (nâ¯=â¯68) L-spine CT using model-based iterative reconstruction were included. Two reviewers independently analyzed 10 anatomical regions on both CT scans. Also, suggested treatment decision between both CT scans was compared. RESULTS: LD L-spine CT showed an excellent diagnostic accuracy (98.1-98.2%) that was comparable to that of SD L-spine CT (98.4-99.1%). The suggested treatment decision was not different between both CT scans. CONCLUSION: LD L-spine CT can be used as a potential first-line diagnostic tool.
Subject(s)
Lumbar Vertebrae/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted , Spinal Fractures/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Decision Making , Emergency Service, Hospital , Female , Humans , Lumbar Vertebrae/injuries , Male , Middle Aged , Radiation DosageABSTRACT
OBJECTIVE: To compare the image quality (IQ), radiation dose and diagnostic reliability of standard-dose and low-dose lumbar spine (L-spine) multi-detector CT (SDCT and LDCT, respectively) with iterative reconstruction (IR) in trauma patients. METHODS: We retrospectively analysed the data of 263 consecutive patients (male:female, 133:130; mean age, 44.3 years) who underwent SDCT (200-300mAs; 120 kVp) with IR (n = 126) or LDCT (80-150mAs; 120kVp) with IR (n = 137) for suspected L-spine fractures between November 2015 and September 2016. Patients were categorized according to their body mass index, as follows: Group 1,~22.9 kg m-2; Group 2, 23-24.9 kg m-2 or Group 3,≥25 kg m-2. We compared the quantitative IQ (signal-to-noise ratio), qualitative IQ (subjective image noise and diagnostic acceptability [4-point rating scale; score 1-4], image sharpness [5-point rating scale; score 1-5]) and diagnostic accuracy between the two scan types. Interobserver agreement was also calculated. RESULTS: Overall, SDCT exhibited slightly better diagnostic performance than did LDCT (sensitivity, 96.7-100%vs94-98.5%; specificity, 95.6-97.0%vs both 95.7%; accuracy, 96.0-98.4%vs94.9-97.1%). However, none of these parameters was significantly different between SDCT and LDCT, either in the whole cohort (p ≥ 0.50) or among the three body mass index groups (p ≥ 0.49). All interobserver agreements were excellent or good (range, 0.776-0.985). CONCLUSIONS: The diagnostic performance of LDCT with IR for L-spine fractures was comparable to that of SDCT with IR, with a 47-69% reduction in the radiation dose. Advances in knowledge: LDCT scan can be used as a diagnostic imaging tool for evaluating trauma patients with suspected L-spine fractures.