Difference in gut microbial dysbiotic patterns between body-first and brain-first Parkinson's disease.

BACKGROUND: This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes. METHODS: In this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls. RESULTS: Significant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently. CONCLUSIONS: Our findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies.

Scapholunate Ligament Reconstruction With Internal Brace Augmentation Techniques for Chronic Scapholunate Dissociation: A Clinical Follow-up Study.

INTRODUCTION: The scapholunate ligament is the most important stabilizer of the scapholunate articulation. The management of chronic irreversible injuries of this ligament in the absence of preexisting arthritis of the wrist joint remains controversial. Recently, surgeons introduced a novel surgical technique using an internal brace (IB). Several biomechanical studies on this technique have been conducted using cadavers; however, very few studies have discussed the results in detail in actual clinical practice. Therefore, herein, we investigated the radiological and functional results of patients who underwent IB augmentation as a treatment for chronic scapholunate dissociation. METHODS: This retrospective study was conducted from April 2018 to May 2022. Twenty-two patients with chronic scapholunate dissociation were treated using the IB augmentation technique, of whom 17 were followed-up for at least 1 year. Radiological results, including scapholunate distance, scapholunate angle, and radioscaphoid angle, were collected. Furthermore, clinical parameters, such as the visual analog scale (preoperative and at final follow-up), the Disabilities of the Arm, Shoulder, and Hand scores (preoperatively and at 3, 6, and 12 months postoperatively), and Mayo wrist scores (preoperative and at final follow-up), were measured. RESULTS: The scapholunate distance increased significantly in the affected wrist compared to the unaffected wrist, which improved after reconstruction in all wrist positions ( P < 0.05). Compared to the unaffected wrist, the scapholunate angle increased significantly in all positions ( P < 0.05) except for extension ( P = 0.535) and improved after reconstruction in all wrist positions. The radioscaphoid angle significantly increased compared to the angle of the unaffected wrist in all positions ( P < 0.05) except for extension ( P = 0.602) and clenched fist ( P = 0.556). This angle improved after reconstruction in all wrist positions except for extension ( P = 0.900). The visual analog scale score (7-2, preoperatively and at final follow-up) and Mayo wrist score (53-82, preoperatively and at final follow-up) improved after surgery. The Disabilities of the Arm, Shoulder, and Hand scores also improved after surgery (68, 53, 30, 7, preoperatively and at 3, 6, and 12 months postoperatively). CONCLUSIONS: This study revealed that scapholunate ligament reconstruction using an autologous tendon and suture tape is a good reconstruction technique that can improve clinical symptoms and radiographic parameters with a shorter operation time and fewer complications than other reconstruction methods.

What Is the Optimal Method of Fixation for Scaphoid Nonunion Relative to the Location of the Lesion?

INTRODUCTION: Scaphoid nonunion is a typical complication of scaphoid fractures, with the nonunion rate varying by the location of the scaphoid. The current widely used method for treating scaphoid nonunion, which is challenging for surgeons, is the headless compression screw (HCS). Various surgical approaches, such as the scaphoid plate, have been proposed to address the problem of screw fixation; however, no consensus exists regarding the optimal treatment method. This study focused on analyzing appropriate treatment methods based on the anatomical location of the scaphoid nonunion. METHODS: Ninety-seven patients with scaphoid nonunion were treated between 2008 and 2023. All patients underwent treatment using 1 HCS or scaphoid volar locking plate with nonvascularized bone graft from the distal radius depending on the scaphoid's location. The scaphoid angle and bone union were confirmed using radiological examinations. The clinical evaluations included range of motion, pain, grip strength, and functional wrist scores. RESULTS: Fifty-seven patients were included in the final analysis. In the screw group, 26 patients (26/42 [62%]) obtained a bone union, and all 15 patients (15/15 [100%]) in the plate group obtained a union (P = 0.005). In the waist group, 16 patients with screw (16/25 [64%]) and 8 using a plate (8/8 [100%]) showed bony healing. In the proximal group, 3 patients with HCS (3/9 [33%]) and 4 using plate (4/4 [100%]) showed bone union. In the distal group, 7 patients with a screw (7/8 [87%]) and 3 with the plate (3/3 [100%]) showed bone union. Significant differences were found in the waist (P = 0.047) and proximal groups (P = 0.026), but not in the distal group (P = 0.521). All groups showed improved radiological angles associated with the scaphoid and better clinical outcomes postoperatively. CONCLUSIONS: Plate fixation was overall superior to screw fixation for scaphoid nonunion, especially in the waist and proximal poles, providing better union rates and stability. For the distal group, both methods are effective, with the choice depending on the surgeon's expertise and patient factors. The results highlight the importance of the lesion's anatomical location in selecting the appropriate fixation method.

Effect of bowel preparation completion time on bowel cleansing efficacy: Prospective randomized controlled trial of different bowel preparation completion times precolonoscopy.

OBJECTIVES: The elapse time between the completion of bowel cleansing and colonoscopy is one of the important factors for proper bowel cleansing. Although several studies have reported that a short time interval resulted in a favorable bowel cleansing, no randomized controlled trial (RCT) has been conducted to determine the effect of the elapse time. Consequently, we performed an RCT to investigate the efficacy of bowel preparation of participants who underwent colonoscopy according to the different time intervals between the completion of bowel preparation and colonoscopy. METHODS: In this single-center RCT, study participants were randomized to complete bowel preparation either 2-4 h or 4-8 h before colonoscopy. The primary end-point was successful bowel preparation, rated using the Boston Bowel Preparation Scale (BBPS). RESULTS: A total of 504 individuals were included (2-4 h, 255; 4-8 h, 249). The rate of successful bowel preparation in the 2-4 h group showed noninferiority compared with that of the 4-8 h group (97.6% vs. 95.2%; rate difference, 2.5% [-0.8% to 5.7%]; Pfor noninferiority < 0.001, Pfor superiority = 0.136). The rate for perfect cleansing (a BBPS score of 9) was higher in the 2-4 h group (56.5% vs. 39.8%, P < 0.001). CONCLUSION: When bowel cleansing was finished 2-4 h before the start of colonoscopy, the overall bowel cleansing was noninferior, and perfect cleansing was superior, compared to that when cleansing was finished 4-8 h before colonoscopy.

Assessing cognitive impairment and disability in older adults through the lens of whole brain white matter patterns.

INTRODUCTION: This study aimed to explore the potential of whole brain white matter patterns as novel neuroimaging biomarkers for assessing cognitive impairment and disability in older adults. METHODS: We conducted an in-depth analysis of magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) scans in 454 participants, focusing on white matter patterns and white matter inter-subject variability (WM-ISV). RESULTS: The white matter pattern ensemble model, combining MRI and amyloid PET, demonstrated a significantly higher classification performance for cognitive impairment and disability. Participants with Alzheimer's disease (AD) exhibited higher WM-ISV than participants with subjective cognitive decline, mild cognitive impairment, and vascular dementia. Furthermore, WM-ISV correlated significantly with blood-based biomarkers (such as glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]), and cognitive function and disability scores. DISCUSSION: Our results suggest that white matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making and determining cognitive impairment and disability. HIGHLIGHTS: The ensemble model combined both magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET) and demonstrated a significantly higher classification performance for cognitive impairment and disability. Alzheimer's disease (AD) revealed a notably higher heterogeneity compared to that in subjective cognitive decline, mild cognitive impairment, or vascular dementia. White matter inter-subject variability (WM-ISV) was significantly correlated with blood-based biomarkers (glial fibrillary acidic protein and phosphorylated tau-217 [p-tau217]) and with the polygenic risk score for AD. White matter pattern analysis has significant potential as an adjunct neuroimaging biomarker for clinical decision-making processes and determining cognitive impairment and disability.

Is arthritis an associated risk factor for trigger finger occurrence after carpal tunnel release? A nationwide, population-based study in Korea.

PURPOSE: We hypothesized that increased friction between the flexor tendon and surrounding structures due to hand arthritis is an important risk factor for trigger finger (TF) after carpal tunnel release (CTR). Therefore, we compared TF development according to the presence or absence of arthritis in carpal tunnel syndrome (CTS) patients treated with CTR. METHODS: This retrospective study was based on data collected from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) in the Republic of Korea between January 1, 2002, and December 31, 2015. Patients diagnosed with TF between one month and one year after the CTR date or with a history of surgery were included in the study. During subsequent follow-up, the patients were divided into subgroups of those (1) with TF and (2) without TF. Sex, age, arthritis, and TF-related comorbidities were compared between the subgroups. RESULTS: The subgroup with TF had a higher proportion of women (9.43% vs 90.57%), the highest age range between 50 and 59 years, more cases of arthritis (32.55% vs 16.79%), and a higher proportion of patients with hypothyroidism (10.85% vs 4.60%) than the group without TF. The association between arthritis and TF after CTR was examined using a multivariate logistic regression model, showing arthritis to be a significant risk factor for TF after CTR (odds ratio, 1.35; P = 0.049). CONCLUSIONS: We identified arthritis as an important risk factor for the development of TF after CTR.

Comparative analysis of tension band wiring and hook plate fixation in ulnar styloid fractures: a focus on fracture type.

INTRODUCTION: Various surgical techniques for ulnar styloid fractures (USFs) fixation have recently been developed, the actual clinical outcomes have not been discussed in detail. This study aimed to compare the outcomes of tension band wiring (TBW) and hook plate fixation in the treatment of USFs and to explore effective management strategies for these fractures. MATERIALS AND METHODS: We retrospectively reviewed 109 patients with styloid process fractures from March 2016 to July 2020. Among them, patients aged 21-75 years who required surgical intervention for USFs with distal radioulnar joint (DRUJ) instability, with or without accompanying distal radius fracturs (DRFs), were included. The patients were treated with either TBW (group T) or hook plate fixation (group P). The fractures were classified into four types based on their location and complexity. Postoperative assessments were conducted using radiographic analysis to monitor fracture healing. Clinical evaluations, including range of motion (ROM), grip strength, and patient-reported outcomes using the disabilities of the arm, shoulder, and hand scores and the visual analog scale for pain, were performed, at multiple time points up to a year after surgery. Statistical analyses were conducted to compare outcomes across fracture types and treatment methods. RESULTS: Osseous union was achieved in 96% of the patients. Specifically, the time to union in types 3 and 4 fractures was significantly shorter in group P than in group T. Functionally, ROM assessments showed similar flexion-extension in both groups but better pronation-supination in group T. Grip strength and patient-reported outcomes did not show significant differences between the groups. CONCLUSIONS: TBW offers slight ROM benefits for type 2 USFs, whereas hook plate fixation provides superior stability for complex types 3 and 4 USFs. Despite the minimal differences in ROM, the enhanced advantages of the hook plate fixation make it the preferred choice for severe fractures, ensuring faster healing.

Three-Dimensional Bowing Measurement of Distal Femur at Actual Size and Clinical Implications of Total Knee Arthroplasty.

Background and Objectives: To assess femoral shaft bowing (FSB) in coronal and sagittal planes and introduce the clinical implications of total knee arthroplasty (TKA) by analyzing a three-dimensional (3D) model with virtual implantation of the femoral component. Materials and Methods: Sixty-eight patients (average age: 69.1 years) underwent 3D model reconstruction of medullary canals using computed tomography (CT) data imported into Mimics® software (version 21.0). A mechanical axis (MA) line was drawn from the midportion of the femoral head to the center of the intercondylar notch. Proximal/distal straight centerlines (length, 60 mm; diameter, 1 mm) were placed in the medullary canal's center. Acute angles between these centerlines were measured to assess lateral and anterior bowing. The acute angle between the distal centerline and MA line was measured for distal coronal and sagittal alignment in both anteroposterior (AP) and lateral views. The diameter of curve (DOC) along the posterior border of the medulla was measured. Results: The mean lateral bowing in the AP view was 3.71°, and the mean anterior bowing in the lateral view was 11.82°. The average DOC of the medullary canal was 1501.68 mm. The average distal coronal alignment of all femurs was 6.40°, while the distal sagittal alignment was 2.66°. Overall, 22 femurs had coronal bowing, 42 had sagittal bowing, and 15 had both. Conclusions: In Asian populations, FSB can occur in coronal, sagittal, or both planes. Increased anterolateral FSB may lead to cortical abutment in the sagittal plane, despite limited space in the coronal plane. During TKA, distal coronal alignment guides the distal femoral valgus cut angle, whereas distal sagittal alignment aids in predicting femoral component positioning to avoid anterior notching. However, osteotomies along the anterior cortical bone intended to prevent notching may result in outliers due to differences between the distal sagittal alignment and the distal anterior cortical axis.

Dual-phase 18 F-FP-CIT positron emission tomography and cardiac 123 I-MIBG scintigraphy of Parkinson's disease patients with GBA mutations: evidence of the body-first type?

BACKGROUND AND PURPOSE: Parkinson's disease (PD) with glucocerebrosidase (GBA) gene mutation (GBA-PD) is known to show more rapid clinical progression than sporadic PD without GBA mutation (sPD). This study was performed to delineate the specific patterns of cortical hypoperfusion, dopamine transporter uptake and cardiac meta-iodobenzylguanidine (MIBG) uptake of GBA-PD in comparison to sPD. METHODS: Through next-generation sequencing analysis targeting 41 genes, a total of 16 GBA-PD and 24 sPD patients (sex, age matched) were enrolled in the study, and the clinical, dual-phase [18 F]-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane (1 8 F-FP-CIT) positron emission tomography (PET) and cardiac 123 I-MIBG scintigraphy results were compared between the two groups. RESULTS: The GBA-PD group had higher rates of rapid eye movement sleep behavior disorder, orthostatic hypotension and neuropsychiatric symptoms than the sPD group. Early-phase 18 F-FP-CIT PET showed significantly lower standard uptake value ratio on bilateral posterior parietal cortex (0.94 ± 0.05 vs. 1.02 ± 0.04, p = 0.011) and part of the occipital cortex (p < 0.05) in the GBA-PD group than the sPD group. In striatal dopamine transporter uptake, the regional standard uptake value ratio, asymmetry index and caudate-to-putamen ratio were similar between the two groups. The GBA-PD group had a lower heart-to-mediastinum uptake ratio in 123 I-MIBG scintigraphy than the sPD group. CONCLUSIONS: The GBA-PD patients showed decreased regional perfusion in the bilateral posterior parietal and occipital cortex. Cardiac sympathetic denervation and non-motor symptoms (orthostatic hypotension, rapid eye movement sleep behavior disorder) were more common in GBA-PD than sPD. These findings suggest that GBA-PD patients have more widespread peripheral (extranigral) α-synuclein accumulation, representing a body-first PD subtype.

The clinical necessity of a distal forearm DEXA scan for predicting distal radius fracture in elderly females: a retrospective case-control study.

BACKGROUND: Recent studies have demonstrated that the distal forearm dual-energy X-ray absorptiometry (DEXA) scan might be a better method for screening bone mineral density (BMD) and the risk of a distal forearm fracture, compared with a central DEXA scan. Therefore, the purpose of this study was to determine the effectiveness of a distal forearm DEXA scan for predicting the occurrence of a distal radius fracture (DRF) in elderly females who were not initially diagnosed with osteoporosis after a central DEXA scan. METHODS: Among the female patients who visited our institutes and who were over 50 years old and underwent DEXA scans at 3 sites (lumbar spine, proximal femur, and distal forearm), 228 patients with DRF (group 1) and 228 propensity score-matched patients without fractures (group 2) were included in this study. The patients' general characteristics, BMD, and T-scores were compared. The odds ratios (OR) of each measurement and correlation ratio among BMD values of the different sites were evaluated. RESULTS: The distal forearm T-score of the elderly females with DRF (group 1) was significantly lower than that of the control group (group 2) (p < 0.001 for the one-third radius and ultradistal radius measurements). BMD measured during the distal forearm DEXA scan was a better predictor of DRF risk than BMD measured during the central DEXA (OR = 2.33; p = 0.031 for the one-third radius, and OR = 3.98; p < 0.001 for the ultradistal radius). The distal one-third radius BMD was correlated with hip BMD, rather than lumbar BMD (p < 0.05 in each group). CONCLUSION: Performing a distal forearm DEXA scan in addition to a central DEXA scan appears to be clinically significant for detecting the low BMD in the distal radius, which is associated with osteoporotic DRF in elderly females. LEVEL OF EVIDENCE: III; case-control study.

Management of Hardware-Exposed Soft Tissue Defects Using Dermal Substitutes and Negative Pressure Wound Therapy.

INTRODUCTION: Reconstruction of complex injuries of the extremities with full-thickness wounds is a challenging but important task. If primary closure is not feasible, more complex procedures are required, such as split-thickness skin graft or flap surgery. Recently, several studies have shown good results when combined with negative pressure wound therapy (NPWT) and artificial dermal replacement therapy after extensive surgical debridement and NPWT administration for severe complex wounds accompanied by tendon or bone exposure. However, flap surgery remains the only treatment for wounds in which the hardware is exposed after fracture fixation. Therefore, in this study, we attempted to prove the usefulness of the combined treatment using artificial dermal substitutes (MatriDerm) and NPWT by focusing on hardware-exposed wounds, which have not been studied before. METHODS: From 2019 to 2021, we treated with our wound management procedure 14 patients with hardware-exposing wounds after internal fixation using plates, out of 48 patients with full-thickness posttraumatic skin defect. Before skin grafting, after surgical debridement and thorough washouts, MatriDerm was placed and NPWT was applied over it. This staged approach aimed at conditioning even the most complex wounds so that closure with MatriDerm-augmented skin grafting would become possible in a one-step approach. RESULTS: We stratified the duration of treatment and number of replacements in NPWT according to the type of injury. Cases with open fractures required significantly longer NPWT than those with closed fractures (P = 0.01); however, there was no significant difference between the Gustilo-Anderson classification within open fractures (P > 0.05). Patients with open fractures underwent a mean of 6.6 changes while those with closed fractures underwent 2.5 (P = 0.002) until the final wound closure with MatriDerm-augmented skin grafting was performed. There was no significant difference in the treatment period based on the location and size of the wound, and there was no significant difference in the number of NPWT replacements. Skin grafting was successful in all 14 patients. CONCLUSIONS: This study revealed that NPWT and artificial dermis-augmented skin grafting after combined treatment with NPWT and artificial dermis were sufficiently useful for hardware-exposed wounds, where flap surgery has been considered the only treatment to date.

Impact of the Voltage-Gated Calcium Channel Antagonist Nimodipine on the Development of Oligodendrocyte Precursor Cells.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). While most of the current treatment strategies focus on immune cell regulation, except for the drug siponimod, there is no therapeutic intervention that primarily aims at neuroprotection and remyelination. Recently, nimodipine showed a beneficial and remyelinating effect in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Nimodipine also positively affected astrocytes, neurons, and mature oligodendrocytes. Here we investigated the effects of nimodipine, an L-type voltage-gated calcium channel antagonist, on the expression profile of myelin genes and proteins in the oligodendrocyte precursor cell (OPC) line Oli-Neu and in primary OPCs. Our data indicate that nimodipine does not have any effect on myelin-related gene and protein expression. Furthermore, nimodipine treatment did not result in any morphological changes in these cells. However, RNA sequencing and bioinformatic analyses identified potential micro (mi)RNA that could support myelination after nimodipine treatment compared to a dimethyl sulfoxide (DMSO) control. Additionally, we treated zebrafish with nimodipine and observed a significant increase in the number of mature oligodendrocytes (* p≤ 0.05). Taken together, nimodipine seems to have different positive effects on OPCs and mature oligodendrocytes.

Cavity-dumped mode-locked Alexandrite laser oscillator with 100 mJ pulses stabilized by using a double trigger system.

We report a mode-locked Alexandrite single pulse laser with cavity dumping. Mode locking was achieved by using an AOM and an EOM was used for Q-switching and cavity dumping. The instability of the single pulse laser energy output was reduced down to a tenth of that of the conventional single trigger system by introducing a novel double trigger system. The single pulse laser energy and pulse width were 100 mJ and 475 ps in multiple mode and 12.5 mJ and 275 ps in single mode, obtained without a laser amplifier.

Color gamut change by optical crosstalk in high-resolution organic light-emitting diode microdisplays.

Herein, the color gamut change by optical crosstalk between sub-pixels in high-resolution full-color organic light-emitting diode (OLED) microdisplays was numerically investigated. The color gamut of the OLED microdisplay decreased dramatically as the pixel density of the panel increased from 100 pixels per inch (PPI) to 3000 PPI. In addition, the increase in thickness of the passivation layer between the bottom electrode and the top color filter results in a decrease in the color gamut. We also calculated the color gamut change depending on the pixel structures in the practical OLED microdisplay panel, which had an aspect ratio of 32:9 and a pixel density of 2,490 PPI. The fence angle and height, refractive index of the passivation layer, black matrix width, and white OLED device structure affect the color gamut of the OLED microdisplay panel because of the optical crosstalk effect.

The Analyses of Cetacean Virus-Responsive Genes Reveal Evolutionary Marks in Mucosal Immunity-Associated Genes.

Viruses are the most common and abundant organisms in the marine environment. To better understand how cetaceans have adapted to this virus-rich environment, we compared cetacean virus-responsive genes to those from terrestrial mammals. We identified virus-responsive gene sequences in seven species of cetaceans, which we compared with orthologous sequences in seven terrestrial mammals. As a result of evolution analysis using the branch model and the branch-site model, 21 genes were selected using at least one model. IFN-ε, an antiviral cytokine expressed at mucous membranes, and its receptor IFNAR1 contain cetacean-specific amino acid substitutions that might change the interaction between the two proteins and lead to regulation of the immune system against viruses. Cetacean-specific amino acid substitutions in IL-6, IL-27, and the signal transducer and activator of transcription (STAT)1 are also predicted to alter the mucosal immune response of cetaceans. Since mucosal membranes are the first line of defense against the external environment and are involved in immune tolerance, our analysis of cetacean virus-responsive genes suggests that genes with cetacean-specific mutations in mucosal immunity-related genes play an important role in the protection and/or regulation of immune responses against viruses.

α-Poly-L-lysine functions as an adipogenic inducer in 3T3-L1 preadipocytes.

α-Poly-L-lysine (PLL) has been used for various purposes such as cell attachment, immunization, and molecular delivery, and is known to be cytotoxic to several cell lines. Here, we studied the effect of PLL on the adipogenesis of 3T3-L1 cells and investigated the underlying mechanism. Differentiation media containing PLL with a molecular weight (MW) greater than 4 kDa enhanced lipid droplet formation and increased adipogenic marker levels, indicating an increase in adipocyte differentiation. PLL with a molecular weight between 30 and 70 kDa was more effective than PLL of other sizes in 3T3-L1 cell differentiation. Moreover, PLL induced 3T3-L1 adipogenesis in insulin-free adipocyte differentiation medium. Incubation with insulin and PLL exhibited greater adipogenesis than insulin treatment only even at a high concentration. PLL stimulated insulin signaling and augmented the signaling pathway when it was added with insulin. While PLL did not activate the glucocorticoid receptor, which is phosphorylated by dexamethasone (DEX), it showed a positive effect on the cAMP signal pathway when preadipocytes were treated with PLL and 3-isobutyl-1-methylxanthine (IBMX). Consistent with these results, incubation with PLL and DEX without IBMX induced adipocyte differentiation. We also observed that the mitotic clonal expansion phase was the critical stage in adipogenesis for inducing the effects of PLL. These results suggest that PLL functions as an adipogenic inducer in 3T3-L1 preadipocytes and PLL has a direct effect on insulin signaling, one of the main regulatory pathways.

Plasma neurofilament light chain level and orthostatic hypotension in early Parkinson's disease.

To delineate the impact of non-motor markers (REM sleep behavior disorder (RBD), orthostatic hypotension (OH), cardiac sympathetic denervation, hyposmia) on neuronal injury in early-stage Parkinson's disease (PD), we measured the plasma neurofilament light chain (NFL) level of PD patients and evaluated its relationship with these markers. The study population comprised a cohort of 77 patients with PD and 54 controls. OH was assessed using 5-min head-up tilt-table test. Other clinical parameters such as RBD, Unified Parkinson's Disease Rating Scale (UPDRS), cognition, Cross-Cultural Smell Identification Test (CCSIT), white matter hyperintensity (WMH), cardiac metaiodobenzylguanidine (MIBG) and striatal dopamine transporter (DAT) uptake were assessed. Plasma NFL levels were measured using Simoa platform. During mean 24.8 months of follow-up, 70 patients remained PD, 5 patients converted to Parkinson-plus syndrome (P + converter), and 2 were lost to follow-up. NFL level did not differ between PD and control groups (age-adjusted means 10.40 pg/mL vs 9.51 pg/mL, p = 0.151), but PD patients with OH (median 15.31 pg/mL) had higher levels compared with those without OH (median 9.2 pg/mL, p = 0.008), as well as the control group (median 9.7 pg/mL, p = 0.002). P + converter group had the highest plasma NFL level (38.17 pg/mL, p < 0.001). In a multiple regression analysis, OH, age, and disease duration independently correlated with plasma NFL level. This finding adds biomarker-based evidence for poor clinical outcomes associated with OH in patients with PD.

Comparison of bone single-photon emission computed tomography (SPECT)/CT and bone scintigraphy in assessing knee joints.

BACKGROUND: This study attempted to compare the radiopharmaceutical uptake findings of planar bone scintigraphy (BS) and single photon emission computed tomography (SPECT)/computed tomography (CT) performed on knee joints. METHODS: We retrospectively included 104 patients who underwent bone SPECT/CT and BS 4 h after the intravenous administration of technetium-99m-hydroxymethylene diphosphonate (99mTc-HDP) for pain in the knee joint. The uptake degree of each of the knee regions (medial femoral, lateral femoral, medial tibial, lateral tibial, and patellar area) in planar images and SPECT/CT were evaluated by visual (grades 0 to 2) and quantitative analyses (uptake counts for planar image and standardized uptake values [SUVs] for SPECT/CT). RESULTS: The uptake grades assessed visually on the planar images differed significantly from the uptake grades on SPECT/CT images in all areas of the knee (all p < 0.001), and SPECT/CT imaging revealed a larger number of uptake lesions than those noted in planar imaging for each patient (3.3 ± 2.0 vs 2.4 ± 2.3, p < 0.0001). In all regions of the knee, all of the quantitative values, including uptake counts obtained from the planar image as well as the maximum SUV (SUVmax) and mean SUV (SUVmean) obtained from SPECT/CT, showed statistically higher values as their visual grades increased (all p < 0.001). However, when analyzed for each area, only the SUVmax showed a significant difference by grade in all knee regions. Quantitative uptake values obtained from planar images were moderately correlated with SUVs of SPECT/CT images (r = 0.58 for SUVmean and r = 0.53 for SUVmax, all p < 0.001) in the total knee regions. Looking at each area, there was a significant but low correlation between the uptake counts of the planar images and the SUVs on SPECT/CT in the right lateral tibial region (r = 0.45 for SUVmean, r = 0.31 for SUVmax, all p < 0.001). CONCLUSIONS: In assessing knee joints, the findings of planar images and SPECT/CT images differ both visually and quantitatively, and more lesions can be found in SPECT/CT than in the planar images. The SUVmax could be a reliable value to evaluate knee joint uptake activity.

Development of a standardized new cigarette smoke generating (SNCSG) system for the assessment of chemicals in the smoke of new cigarette types (heat-not-burn (HNB) tobacco and electronic cigarettes (E-Cigs)).

To systematically regulate new types of cigarettes for which their safety has yet to be verified, such as heat-not-burn (HNB) products and electronic cigarettes (E-Cigs), the identification of chemicals in the new cigarette smoke is necessary. However, this is challenging due to the large number of new cigarette types and their different vaporization approaches. To address this issue, we herein report the development of a standardized new cigarette smoke generating (SNCSG) system based on heating-temperature control, which is able to generate smoke for all types of new cigarettes. Validation of the developed system was also carried out through analysis of the carbonyl compounds (e.g., formaldehyde and acetaldehyde) in the new cigarette smoke of HNB products and E-Cigs generated by the SNCSG system under different heating temperatures. The analytical results were used to validate the SNCSG system by comparison with those of previous studies. In all new cigarette smoke samples, the formaldehyde and acetaldehyde concentrations increased dramatically upon increasing the heating temperatures, especially over the reference heating range of each HNB device (mean concentration (µg/cigarette, n = 5 (HNB and E-Cig samples)): formaldehyde = 0.373-5.841 (250-320 °C), and acetaldehyde = 0.088-27.60 (250-320 °C). In the case of the HNB samples, the concentration differences determined by the heating temperatures of the tobacco stick were statistically significant, with p-values (ANOVA) of 1.85E-10 (formaldehyde) and 1.73E-08 (acetaldehyde). In the majority of smoke samples, acrolein and propionaldehyde were detected under relatively high heating temperature conditions (>250 °C) at 0.50 ± 1.76 µg/(cigarette or 10 µL), while acetone was detected under low heating temperature conditions (<250 °C) at 0.09 ± 0.17 µg/(cigarette or 10 µL). These results indicate that the developed SNCSG system could be suitable for application in the regulation of new types of cigarettes, regardless of the cigarette type and heating approach.

Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer's disease evaluated by ß-amyloid positron emission tomography imaging.

OBJECTIVE: We evaluated the effects of bone marrow-derived mesenchymal stem cells in a model of Alzheimer's disease using serial [18F]Florbetaben positron emission tomography. METHODS: 3xTg Alzheimer's disease mice were treated with intravenously injected bone marrow-derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and ß-amyloid-reactive cells. RESULTS: Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow-derived mesenchymal stem cells-treated group (n = 28). In contrast, there was no change in the ratio in control mice (n = 25) at any time point. In addition, mice that received bone marrow-derived mesenchymal stem cell therapy also exhibited significantly better memory function and less ß-amyloid-immunopositive plaques compared to controls. CONCLUSION: The therapeutic effect of intravenously injected bone marrow-derived mesenchymal stem cells in a mouse model of Alzheimer's disease was confirmed by ß-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.