MARCH5 promotes STING pathway activation by suppressing polymer formation of oxidized STING.

Stimulator of interferon genes (STING) is a core DNA sensing adaptor in innate immune signaling. STING activity is regulated by a variety of post-translational modifications (PTMs), including phosphorylation, ubiquitination, sumoylation, palmitoylation, and oxidation, as well as the balance between active and inactive polymer formation. It remains unclear, though, how different PTMs and higher order structures cooperate to regulate STING activity. Here, we report that the mitochondrial ubiquitin ligase MARCH5 (Membrane Associated Ring-CH-type Finger 5, also known as MITOL) ubiquitinates STING and enhances its activation. A long-term MARCH5 deficiency, in contrast, leads to the production of reactive oxygen species, which then facilitate the formation of inactive STING polymers by oxidizing mouse STING cysteine 205. We show that MARCH5-mediated ubiquitination of STING prevents the oxidation-induced STING polymer formation. Our findings highlight that MARCH5 balances STING ubiquitination and polymer formation and its control of STING activation is contingent on oxidative conditions.

The transcription factor NFIL3/E4BP4 regulates the developmental stage-specific acquisition of basophil function.

BACKGROUND: Basophils are rare but important effector cells in many allergic disorders. Contrary to their early progenitors, the terminal developmental processes of basophils in which they gain their unique functional properties are unknown. OBJECTIVE: We sought to identify a novel late-stage basophil precursor and a transcription factor regulating the terminal maturation of basophils. METHODS: Using flow cytometry, transcriptome analysis, and functional assays, we investigated the identification and functionality of the basophil precursors as well as basophil development. We generated mice with basophil-specific deletion of nuclear factor IL-3 (NFIL3)/E4BP4 and analyzed the functional impairment of NFIL3/E4BP4-deficient basophils in vitro and in vivo using an oxazolone-induced murine model of allergic dermatitis. RESULTS: We report a new mitotic transitional basophil precursor population (referred to as transitional basophils) that expresses the FcεRIα chain at higher levels than mature basophils. Transitional basophils are less responsive to IgE-linked degranulation but produce more cytokines in response to IL-3, IL-33, or IgE cross-linking than mature basophils. In particular, we found that the expression of NFIL3/E4BP4 gradually rises as cells mature from the basophil progenitor stage. Basophil-specific deletion of NFIL3/E4BP4 reduces the expression of genes necessary for basophil function and impairs IgE receptor signaling, cytokine secretion, and degranulation in the context of murine atopic dermatitis. CONCLUSIONS: We discovered transitional basophils, a novel late-stage mitotic basophil precursor cell population that exists between basophil progenitors and postmitotic mature basophils. We demonstrated that NFIL3/E4BP4 augments the IgE-mediated functions of basophils, pointing to a potential therapeutic regulator for allergic diseases.

Surface Crystal and Degradability of Shape Memory Scaffold Essentialize Osteochondral Regeneration.

The minimally invasive deployment of scaffolds is a key safety factor for the regeneration of cartilage and bone defects. Osteogenesis relies primarily on cell-matrix interactions, whereas chondrogenesis relies on cell-cell aggregation. Bone matrix expansion requires osteoconductive scaffold degradation. However, chondrogenic cell aggregation is promoted on the repellent scaffold surface, and minimal scaffold degradation supports the avascular nature of cartilage regeneration. Here, a material satisfying these requirements for osteochondral regeneration is developed by integrating osteoconductive hydroxyapatite (HAp) with a chondroconductive shape memory polymer (SMP). The shape memory function-derived fixity and recovery of the scaffold enabled minimally invasive deployment and expansion to fill irregular defects. The crystalline phases on the SMP surface inhibited cell aggregation by suppressing water penetration and subsequent protein adsorption. However, HAp conjugation SMP (H-SMP) enhanced surface roughness and consequent cell-matrix interactions by limiting cell aggregation using crystal peaks. After mouse subcutaneous implantation, hydrolytic H-SMP accelerated scaffold degradation compared to that by the minimal degradation observed for SMP alone for two months. H-SMP and SMP are found to promote osteogenesis and chondrogenesis, respectively, in vitro and in vivo, including the regeneration of rat osteochondral defects using the binary scaffold form, suggesting that this material is promising for osteochondral regeneration.

Socioeconomic and Other Risk Factors for Retear after Arthroscopic Surgery for Nontraumatic Rotator Cuff Tear.

Background and Objectives: Few studies have investigated the socioeconomic factors associated with retear after rotator cuff repair. This study aimed to identify the risk factors, including socioeconomic factors, for rotator cuff retear in patients who underwent arthroscopic rotator cuff repair. Materials and Methods: This retrospective study included 723 patients diagnosed with full-thickness rotator cuff tears who underwent arthroscopic rotator cuff repair from March 2010 to March 2021. The outcome variable was rotator cuff retear observed on postoperative magnetic resonance imaging or ultrasonography. Sex, age, obesity, diabetes, symptom duration, and tear size were the independent variables. Socioeconomic variables included occupation, educational level, type of medical insurance, and area of residence. We compared patients with and without retear and estimated the effects of the independent factors on retear risk. Results: The mean age of the patients, symptom duration, and tear size were 62.4 ± 8.0 years, 1.8 ± 1.7 years, and 21.8 ± 12.5 mm, respectively. The age, type of medical insurance, diabetes, tear size, and symptom duration differed significantly between patients with and without retearing (p < 0.05). Age, occupation, type of medical insurance, diabetes, initial tear size, and symptom duration significantly affected the risk of retear. Patients who performed manual labor had a significantly higher retear rate (p = 0.005; OR, 1.95; 95% CI, 1.23-3.11). The highest retear risk was seen in patients with Medicaid insurance (p < 0.001; OR, 4.34; 95% CI, 2.09-9.02). Conclusions: Age, initial tear size, and symptom duration significantly affect retear risk after arthroscopic rotator cuff repair. Occupation and type of medical insurance were also risk factors for retear. Socioeconomically vulnerable patients may be at a greater risk of retear. Proactive efforts are required to expand early access to medical care.

Usefulness of double plate fixation after failed ORIF for clavicle shaft fracture.

PURPOSE: We aimed to evaluate the clinical and radiological outcomes of double plate fixation for failed clavicle shaft fracture surgery. MATERIALS AND METHODS: We analyzed 14 patients who underwent double plate fixation due to plate failure after clavicle shaft fracture surgery from March 2016 to March 2021. The study used 3.5 mm locking compression plates for superior clavicle and anterior reconstruction in all patients. In addition, moldable allograft bone was used to fill the bone defect. Clinical and radiological evaluation was performed immediately, at 2 and 4 weeks, and 3, 6, 9, and 12 months postoperatively. The visual analog scale (VAS), University of California at Los Angeles (UCLA) shoulder scale, and American Shoulder and Elbow Surgeons (ASES) scores and range of motion of the shoulder were evaluated as clinical results. For radiological evaluation, anteroposterior, caudal, and cephalad views of both clavicles were used. Successful bone union was defined as complete adjoining of the fracture site through callus formation. RESULTS: Successful bone union was achieved in all patients, and the mean time to bone union was 16.7 ± 1.2 weeks (range, 12-24 weeks). Statistically significant improvement in forward flexion and external and internal rotation was observed from 135.5° ± 6.3, 45.2° ± 5.3, and 13° ± 2.3 preoperatively to 157.0° ± 9.3, 68.7° ± 6.3, and 9.8° ± 3.1 at the final follow-up, respectively. The VAS score improved from an average of 6.2 ± 2.8 preoperatively to 1.3 ± 0.7 at the final follow-up, which was statistically significant (P = 0.018). In addition, the ASES score significantly increased from a mean of 52.1 ± 6.3 points preoperatively to 83.6 ± 7.8 points at the final follow-up (P = 0.001). The average UCLA shoulder score was 16.7 ± 1.4 and 31.4 ± 2.2 points preoperatively and at the final follow-up, respectively, which was statistically significant (P = 0.001). CONCLUSION: Double plate fixation has shown good results after failed open reduction and internal fixation (ORIF) for clavicle shaft fractures. Therefore, in complicated situations after ORIF, double plate fixation is considered a surgical treatment option.

Asymmetric Ene-Reduction of α,ß-Unsaturated Compounds by F420-Dependent Oxidoreductases A Enzymes from Mycobacterium smegmatis.

The stereoselective reduction of alkenes conjugated to electron-withdrawing groups by ene-reductases has been extensively applied to the commercial preparation of fine chemicals. Although several different enzyme families are known to possess ene-reductase activity, the old yellow enzyme (OYE) family has been the most thoroughly investigated. Recently, it was shown that a subset of ene-reductases belonging to the flavin/deazaflavin oxidoreductase (FDOR) superfamily exhibit enantioselectivity that is generally complementary to that seen in the OYE family. These enzymes belong to one of several FDOR subgroups that use the unusual deazaflavin cofactor F420. Here, we explore several enzymes of the FDOR-A subgroup, characterizing their substrate range and enantioselectivity with 20 different compounds, identifying enzymes (MSMEG_2027 and MSMEG_2850) that could reduce a wide range of compounds stereoselectively. For example, MSMEG_2027 catalyzed the complete conversion of both isomers of citral to (R)-citronellal with 99% ee, while MSMEG_2850 catalyzed complete conversion of ketoisophorone to (S)-levodione with 99% ee. Protein crystallography combined with computational docking has allowed the observed stereoselectivity to be mechanistically rationalized for two enzymes. These findings add further support for the FDOR and OYE families of ene-reductases displaying general stereocomplementarity to each other and highlight their potential value in asymmetric ene-reduction.

Shape-Configurable Mesh for Hernia Repair by Synchronizing Anisotropic Body Motion.

Continuous progress has been made in elucidating the relationship between material property, device design, and body function to develop surgical meshes. However, an unmet need still exists wherein the surgical mesh can handle the body motion and thereby promote the repair process. Here, the hernia mesh design and the advanced polymer properties are tailored to synchronize with the anisotropic abdominal motion through shape configuration. The thermomechanical property of shape configurable polymer enables molding of mesh shape to fit onto the abdominal structure upon temperature shift, followed by shape fixing with the release of the heat energy. The microstructural design of mesh is produced through finite element modeling to handle the abdominal motion efficiently through the anisotropic longitudinal and transverse directions. The design effects are validated through in vitro, ex vivo, and in vivo mechanical analyses using a self-configurable, body motion responsive (BMR) mesh. The regenerative function of BMR mesh leads to effective repair in a rat hernioplasty model by effectively handling the anisotropic abdomen motion. Subsequently, the device-tissue integration is promoted by promoting healthy collagen synthesis with fibroblast-to-myofibroblast differentiation. This study suggests a potential solution to promote hernia repair by fine-tuning the relationship between material property and mesh design.

Asymmetric Ene-Reduction by F420 -Dependent Oxidoreductases B (FDOR-B) from Mycobacterium smegmatis.

Asymmetric reduction by ene-reductases has received considerable attention in recent decades. While several enzyme families possess ene-reductase activity, the Old Yellow Enzyme (OYE) family has received the most scientific and industrial attention. However, there is a limited substrate range and few stereocomplementary pairs of current ene-reductases, necessitating the development of a complementary class. Flavin/deazaflavin oxidoreductases (FDORs) that use the uncommon cofactor F420 have recently gained attention as ene-reductases for use in biocatalysis due to their stereocomplementarity with OYEs. Although the enzymes of the FDOR-As sub-group have been characterized in this context and reported to catalyse ene-reductions enantioselectively, enzymes from the similarly large, but more diverse, FDOR-B sub-group have not been investigated in this context. In this study, we investigated the activity of eight FDOR-B enzymes distributed across this sub-group, evaluating their specific activity, kinetic properties, and stereoselectivity against α,ß-unsaturated compounds. The stereochemical outcomes of the FDOR-Bs are compared with enzymes of the FDOR-A sub-group and OYE family. Computational modelling and induced-fit docking are used to rationalize the observed catalytic behaviour and proposed a catalytic mechanism.

Arthroscopic Superior Capsular Reconstruction With Tensor Fascia Lata Allograft for Irreparable Rotator Cuff Tears: Clinical and Radiologic Outcomes for a Minimum 1-Year Follow-Up.

PURPOSE: To confirm the radiologic and clinical outcomes after performing arthroscopic superior capsular reconstruction (ASCR) using a tensor fascia lata (TFL) allograft. METHODS: Thirty-three patients with irreparable rotator cuff tears were treated with ASCR with a TFL allograft. The mean age and follow-up period were 62 years and 20.1 months, respectively. TFL allografts were used as 3, 4, and 6 layers, and the graft thickness was 3.7, 3.9, and 5.4 mm, respectively. Range of motion, visual analog scale (VAS) pain score, American Shoulder and Elbow Surgeons score, and Constant score were evaluated preoperatively and at the final follow-up. The pre-, postoperative, and final acromiohumeral distances (AHD) were compared. The graft integrity was checked through a follow-up magnetic resonance imaging at least 6 months after surgery. RESULTS: Torn grafts were identified in 6 cases (19%). AHD significantly increased from 5.0 to 8.0 mm postoperatively (P < .0001). However, there was no significant difference of 5.0 mm at the final follow-up AHD. Five cases (83%) of torn grafts were induced in the 3-layered graft sheet group, but the difference was not statistically significant (P = .067). Visual analog scale, forward elevation, internal rotation, American Shoulder and Elbow Surgeons, and Constant scores significantly improved at the last follow-up. Two cases of early infection were confirmed and the graft materials were all removed. CONCLUSIONS: Despite the possibility of early infection, ASCR using TFL allograft is a reliable procedure for the irreparable rotator cuff tear. In particular, if the number of layers of TFL allograft increases, it is judged that it could become a more effective graft. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Retinal Thickness and Its Interocular Asymmetry Between Parkinson's Disease and Drug-Induced Parkinsonism.

BACKGROUND: Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging. Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson's disease (PD). METHODS: We investigated 97 de novo PD patients and 27 DIP patients using OCT and [18F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specific/non-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. RESULTS: No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all P values > 0.090). The mean SNBRAI was significantly higher in PD than in DIP (P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). CONCLUSION: Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

Correlations with REM sleep behavior disorder severity in isolated rapid eye movement sleep behavior disorders patients.

OBJECTIVES: The pathogenesis of isolated rapid eye movement sleep behavior disorders (iRBD) is poorly understood. The severity of RBD may reflect its pathogenesis. METHODS: We compared motor function and non-motor symptoms (NMSs) between iRBD patients and healthy volunteers. We correlated motor function, NMSs, and striatal dopaminergic activity with RBD severity using video-polysomnography. RESULTS: Twenty-one iRBD patients and 17 controls participated. The Unified Parkinson's Disease Rating Scale part III scores were higher in patients compared to controls (p < 0.001). There was no difference in upper extremity function between patients and controls (right, p = 0.220; left, p = 0.209), but gait was slower in iRBD patients (walking time, p < 0.001; number of steps, p < 0.001). The mean value of the Korean version of the Mini-Mental State Exam and Clinical Dementia Rating were lower in patients (p = 0.006, p = 0.003, respectively). Patients with were also more depressed (p = 0.002), had decreased olfactory function (p < 0.001), reported more frequent sleep/fatigue episodes (p < 0.001), worse attention/memory capacity (p < 0.001), gastrointestinal problems (p = 0.009), urinary problems (p = 0.007), and pain (p = 0.083). Further, iRBD patients reported more frequent sleep-related disturbances (p = 0.004), but no difference in daytime sleepiness (p = 0.663). Disease severity was correlated with pain (r = 0.686, p = 0.002) and visuospatial function (r= -0.507, p = 0.038). There were no correlations between RBD severity and striatal dopaminergic activities (p > 0.09). CONCLUSIONS: iRBD is a multisystem neurodegenerative disorder, and gait abnormalities may be a disease characteristic, possibly related to the akinetic-rigid phenotype of Parkinson's disease. The correlation between pain/visuospatial dysfunction and RBD severity may be related to its pathogenesis.

Editorial: Chronic Inflammation and Related Diseases: From Mechanisms to Therapies.

The purpose of this Special Issue is to identify the exact mechanism underlying inflammation to direct more effective strategies for inflammation management and to provide basic data for the development of anti-inflammatory and analgesic treatment methods for patients with inflammatory pain [...].

Factors associated with nonunion of the posttraumatic subtalar arthrodesis after displaced intra-articular calcaneal fractures.

BACKGROUND: This study investigated the incidence of and risk factors for nonunion in patients with posttraumatic subtalar arthrodesis (SA). METHODS: We retrospectively reviewed 165 posttraumatic SA cases. Nonunion was diagnosed at 6 months after surgery based on the findings of clinical evaluations, plain radiographs, and CT scans. Patient-specific factors and surgeon-specific factors were evaluated as potential risk factors. RESULTS: The overall nonunion rate was 13.3 % (22 of 165 cases). In the final multivariate logistic regression analysis, smoking (odds ratio [OR] = 3.64; 95 % confidence interval [CI] = 1.23-10.75), parallel screw configuration (OR = 5.70; 95 % CI = 1.62-20.06), and freeze dried iliac crest (OR = 9.16; 95 % CI = 2.28-36.79) were demonstrated as risk factors for nonunion of posttraumatic SA. CONCLUSION: Patients with a history of smoking, parallel screw configuration fixation, and those who received freeze dried iliac crest as an interpositional graft, had a significantly higher rate of nonunion.

Engineering of Surface Energy of Cell-Culture Platform to Enhance the Growth and Differentiation of Dendritic Cells via Vapor-Phase Synthesized Functional Polymer Films.

Although the dendritic cell (DC)-based modulation of immune responses has emerged as a promising therapeutic strategy for tumors, infections, and autoimmune diseases, basic research and therapeutic applications of DCs are hampered by expensive growth factors and sophisticated culture procedures. Furthermore, the platform to drive the differentiation of a certain DC subset without any additional biochemical manipulations has not yet been developed. Here, five types of polymer films with different hydrophobicity via an initiated chemical vapor deposition (iCVD) process to modulate the interactions related to cell-substrate adhesion are introduced. Especially, poly(cyclohexyl methacrylate) (pCHMA) substantially enhances the expansion and differentiation of conventional type 1 DCs (cDC1s), the prime DC subset for antigen cross-presentation, and CD8+ T cell activation, by 4.8-fold compared to the conventional protocol. The cDC1s generated from the pCHMA-coated plates retain the bona fide DC functions including the expression of co-stimulatory molecules, cytokine secretion, antigen uptake and processing, T cell activation, and induction of antitumor immune responses. To the authors' knowledge, this is the first report highlighting that the modulation of surface hydrophobicity of the culture plate can be an incisive approach to construct an advanced DC culture platform with high efficiency, which potentially facilitates basic research and the development of immunotherapy employing DCs.

Osteomyelitis on MR imaging as a key predictor of recurrent septic arthritis of the shoulder.

OBJECTIVES: To investigate the clinical and radiologic predictors of postoperative recurrent septic arthritis of the shoulder (SAS) using multivariable analysis. METHODS: Forty-three patients (mean age, 65 years; 24 women) who underwent surgery for SAS between January 2011 and October 2019 were retrospectively enrolled. An orthopedic surgeon assessed clinical (age, sex, comorbidity, duration from symptom onset to MR imaging and surgery, surgical method, antibiotic usage), laboratory (serum white blood cell [WBC] count, C-reactive protein [CRP] level, synovial cell count), and surgical findings (culture/biopsy results). Two musculoskeletal radiologists evaluated MR imaging findings (bone marrow [reactive bone marrow edema, osteomyelitis, osteochondral erosion] and soft tissue [synovitis, bursitis, muscle edema, abscess] abnormalities). Recurrent SAS was evaluated at ≥ 12 months postoperatively. Univariable and multivariable analyses were performed to determine the best predictor of recurrent SAS. RESULTS: The overall recurrent SAS rate was 33% (14/43). On univariable analysis, mean age (without recurrence vs. recurrence: 68 vs. 59 years, p = .04), mean duration from symptom onset to surgery (18 vs. 25 days, p = .02), serum WBC count (12,000 vs. 9,000 cells/mL3, p = .04), CRP level (13 vs. 6 mg/L, p = .01), and osteomyelitis on MR imaging (p < .01 for both readers) significantly differed between patients with and without recurrence; on multivariable analysis, only osteomyelitis on MR imaging was significantly associated with recurrent SAS for both readers (p = .02 and .01 for each reader respectively). The inter-reader agreement was good (κ = .62-1.0) for all MR imaging findings, except for muscle edema (fair, κ = .37). CONCLUSION: Osteomyelitis on MR imaging was the best predictor of recurrent SAS. KEY POINTS: • Osteomyelitis on preoperative MR imaging was the best predictor associated with recurrent septic arthritis of the shoulder on multivariable analysis including clinical, laboratory, and MR findings. • In multivariable analyses focused on each bone marrow abnormality, with adjustment for clinical and laboratory parameters, the presence of reactive bone marrow edema and osteochondral erosion on MR imaging showed no significant association with recurrent septic arthritis of the shoulder.

A prospective multi-centre study of susceptibility map-weighted MRI for the diagnosis of neurodegenerative parkinsonism.

OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.

Pain in atypical parkinsonism, vascular parkinsonism, and Parkinson's disease.

BACKGROUND: Pain is a common symptom in Parkinson's disease (PD) and is considered a pre-motor symptom suggesting sensory involvement in the pre-motor stage. Pain in other parkinsonian disorders such as atypical parkinsonism and vascular parkinsonism (VP) has been investigated in only a few studies. The characteristics of pain in other parkinsonian disorders, including the temporal relationships between pain and motor symptoms, were investigated in the present study. METHODS: A total of 236 PD, 42 multiple system atrophy (MSA), 31 progressive supranuclear palsy (PSP), and 38 VP patients were screened for pain. After excluding patients with dementia and pain not related to PD, the presence of pain, severity, onset, type, and location were compared among the four patient groups. RESULTS: Difference was not observed in pain presence (χ2 = 3, p = 0.186), severity (F = 1.534, p = 0.207), or type (χ2 = 6, p = 0.400) among the four groups. However, the temporal relationship between pain and motor symptoms differed (H(3) = 8.764, p = 0.033). Pain predated motor symptoms in PD, MSA, and VP but often followed motor symptoms in PSP. The pain location in the body was different among the four patient groups (χ2 = 21, p = 0.018), and leg involvement was more common in PSP. CONCLUSION: The present study results suggest that pain can be a pre-motor symptom in PD, MSA, and VP but not in PSP, implying different pain pathogeneses in these disorders. Pain locations were other for each group, which requires further investigation with a more extensive study cohort.

Cough Characteristics and Healthcare Journeys of Chronic Cough Patients in Community-Based Populations in South Korea and Taiwan.

PURPOSE: This study aimed to understand the cough characteristics and health journeys among community-based chronic cough (CC) patients, and their characteristics associated with healthcare visits. METHODS: A population-based cross-sectional study was conducted in 2020, using the South Korea and Taiwan National Health and Wellness Survey (NHWS) and CC surveys. Patients with current CC were defined by daily coughing for > 8 weeks in the past 12 months and currently coughing at the time of survey. The survey items pertained to CC patients' treatment journey and cough characteristics. RESULTS: Patients with current CC in South Korea and Taiwan, respectively, had cough duration for 3.45 ± 5.13 years and 5.75 ± 7.28 years and cough severity visual analogue scale (VAS) scores of 4.50 ± 2.15 and 4.46 ± 1.92 out of 0-10 scale, with 70.3% and 57.9% having spoken with a physician about cough. Compared to CC patients who had not visited healthcare professionals for cough, those who visited reported more severe cough (VAS: 3.89 ± 1.71 vs. 4.6 ± 2.02; p = 0.009), worse cough-specific quality of life (Leicester Cough Questionnaire: 16.20 ± 3.23 vs.13.45 ± 2.68, p < 0.001), greater symptom severity (Hull Airway Reflux Questionnaire: 16.73 ± 15.16 vs. 24.57 ± 13.38; p < 0.001), and more urinary incontinence (13.6 vs. 26.5%, p = 0.027). More than 50% of patients perceived cough medication(s) as not or a little useful and 25% felt their physicians did not well understand how CC impacts their life. CONCLUSION: Cough is frequently severe and persistent among community-based CC patients. They experience several issues in their health journey, including treatment ineffectiveness and physician's understanding. Further efforts are warranted to reduce CC burden in the community.

Factors affecting the occurrence of osseous lesions in septic shoulder arthritis and the recurrence rate after arthroscopic surgery.

HYPOTHESIS: The purpose of this study was to determine the incidence of osseous lesions and the recurrence rate after arthroscopic surgery in shoulder septic arthritis patients and evaluate the influencing factors. MATERIALS AND METHODS: We retrospectively reviewed 44 patients who underwent arthroscopic surgery for septic arthritis of the shoulder between January 2012 and September 2019. The average age of the patients was 65.57 ± 14.2 years, and 56.8% were female patients. The minimum follow-up period was 12 months (average, 32.8 ± 14.2 months; range, 12-72 months). We assessed variables including sex, age, underlying diseases, duration from symptom onset to magnetic resonance imaging (MRI), duration from symptom onset to surgery, radiologic results (radiography and MRI), history of injection therapy, and postoperative infection. The incidence of osseous lesions and the recurrence rate were calculated according to independent variables. In addition, multivariate logistic regression was performed to identify the risk factors for osseous lesions and recurrent infection after adjustment for other variables. RESULTS: Twenty-one patients had an osseous lesion on MRI, and 12 patients had evidence of bone erosion on radiographs. In univariate analyses, significant (P < .05) risk factors for the presence of osseous lesions were female sex, lower C-reactive protein level, and longer duration from symptom onset to MRI. The overall infection recurrence rate was 22.7% (10 of 44 patients). Culture results and the duration from symptom onset to surgery were significant risk factors for recurrent infection (P < .05). As the duration from symptom onset to MRI increased by 1 day, the probability of osseous lesions increased 1.31-fold (95% confidence interval, 1.08- to 1.59-fold; P = .007), and this probability was significantly higher after correction for other risk factors. CONCLUSIONS: To reduce the severity of septic shoulder infection, timely diagnosis and treatment are essential. Even if osseous lesions are present, good results can be obtained if meticulous débridement is performed through arthroscopic surgery. However, functional and radiologic long-term follow-up studies are needed in patients with osseous lesions.

Super-Resolving Methodology for Noisy Unpaired Datasets.

Although it is possible to acquire high-resolution and low-resolution paired datasets, their use in directly supervised learning is impractical in real-world applications. In the present work, we focus on a practical methodology for image acquisition in real-world conditions. The main method of noise reduction involves averaging multiple noisy input images into a single image with reduced noise; we also consider unpaired datasets that contain misalignments between the high-resolution and low-resolution images. The results show that when more images are used for average denoising, better performance is achieved in the super-resolution task. Quantitatively, for a fixed noise level with a variance of 60, the proposed method of using 16 images for average denoising shows better performance than using 4 images for average denoising; it shows 0.68 and 0.0279 higher performance for the peak signal-to-noise ratio and structural similarity index map metrics, as well as 0.0071 and 1.5553 better performance for the learned perceptual image patch similarity and natural image quality evaluator metrics, respectively.