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1.
N Engl J Med ; 387(10): 905-915, 2022 09 08.
Article in English | MEDLINE | ID: mdl-36036496

ABSTRACT

BACKGROUND: There are limited data from randomized trials to guide a specific follow-up surveillance approach after myocardial revascularization. Whether a follow-up strategy that includes routine functional testing improves clinical outcomes among high-risk patients who have undergone percutaneous coronary intervention (PCI) is uncertain. METHODS: We randomly assigned 1706 patients with high-risk anatomical or clinical characteristics who had undergone PCI to a follow-up strategy of routine functional testing (nuclear stress testing, exercise electrocardiography, or stress echocardiography) at 1 year after PCI or to standard care alone. The primary outcome was a composite of death from any cause, myocardial infarction, or hospitalization for unstable angina at 2 years. Key secondary outcomes included invasive coronary angiography and repeat revascularization. RESULTS: The mean age of the patients was 64.7 years, 21.0% had left main disease, 43.5% had bifurcation disease, 69.8% had multivessel disease, 70.1% had diffuse long lesions, 38.7% had diabetes, and 96.4% had been treated with drug-eluting stents. At 2 years, a primary-outcome event had occurred in 46 of 849 patients (Kaplan-Meier estimate, 5.5%) in the functional-testing group and in 51 of 857 (Kaplan-Meier estimate, 6.0%) in the standard-care group (hazard ratio, 0.90; 95% confidence interval [CI], 0.61 to 1.35; P = 0.62). There were no between-group differences with respect to the components of the primary outcome. At 2 years, 12.3% of the patients in the functional-testing group and 9.3% in the standard-care group had undergone invasive coronary angiography (difference, 2.99 percentage points; 95% CI, -0.01 to 5.99), and 8.1% and 5.8% of patients, respectively, had undergone repeat revascularization (difference, 2.23 percentage points; 95% CI, -0.22 to 4.68). CONCLUSIONS: Among high-risk patients who had undergone PCI, a follow-up strategy of routine functional testing, as compared with standard care alone, did not improve clinical outcomes at 2 years. (Funded by the CardioVascular Research Foundation and Daewoong Pharmaceutical; POST-PCI ClinicalTrials.gov number, NCT03217877.).


Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Aftercare , Coronary Artery Bypass/adverse effects , Coronary Artery Disease/diagnosis , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Diagnostic Tests, Routine , Drug-Eluting Stents/adverse effects , Humans , Kaplan-Meier Estimate , Middle Aged , Myocardial Infarction/etiology , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Standard of Care , Treatment Outcome
2.
Nano Lett ; 24(6): 1891-1900, 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38150559

ABSTRACT

Two-dimensional (2D) transition metal dichalcogenide (TMD) layers are highly promising as field-effect transistor (FET) channels in the atomic-scale limit. However, accomplishing this superiority in scaled-up FETs remains challenging due to their van der Waals (vdW) bonding nature with respect to conventional metal electrodes. Herein, we report a scalable approach to fabricate centimeter-scale all-2D FET arrays of platinum diselenide (PtSe2) with in-plane platinum ditelluride (PtTe2) edge contacts, mitigating the aforementioned challenges. We realized a reversible transition between semiconducting PtSe2 and metallic PtTe2 via a low-temperature anion exchange reaction compatible with the back-end-of-line (BEOL) processes. All-2D PtSe2 FETs seamlessly edge-contacted with transited metallic PtTe2 exhibited significant performance improvements compared to those with surface-contacted gold electrodes, e.g., an increase of carrier mobility and on/off ratio by over an order of magnitude, achieving a maximum hole mobility of ∼50.30 cm2 V-1 s-1 at room temperature. This study opens up new opportunities toward atomically thin 2D-TMD-based circuitries with extraordinary functionalities.

3.
J Cogn Neurosci ; : 1-16, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39106162

ABSTRACT

Crossing a spatial boundary such as a doorway plays an important role in the temporal organization of episodic memory. However, despite the wealth of evidence showing that visual boundary structures in scenes affect our representation of space, no studies have tested the possibility that they also function as event boundaries even without active navigation. In this study, we used a nonnavigational scene-based memory task that required participants to remember a sequence of objects moving to various baskets in a scene. In the boundary condition, there was a freestanding boundary in the middle of the room, low enough to see the rest of the room beyond it. We found that the additional boundary within the scene was sufficient to trigger a larger response in the cortical visual scene network, the hippocampus, and their coordinated activity. These results suggest that active navigation across a spatial boundary such as a doorway into another room is not necessary to form an event boundary and that a visual representation of boundaries is sufficient to influence the organization of a hippocampal episodic memory.

4.
Neurobiol Dis ; 201: 106655, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39218360

ABSTRACT

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.

5.
Hum Brain Mapp ; 45(2): e26619, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38339822

ABSTRACT

The prefrontal cortex (PFC) has been extensively studied in relation to various cognitive abilities, including executive function, attention, and memory. Nevertheless, there is a gap in our scientific knowledge regarding the functionally dissociable neural dynamics across the PFC during a cognitive task and their individual differences in performance. Here, we explored this possibility using a delayed match-to-sample (DMTS) working memory (WM) task using NIRSIT, a high-density, wireless, wearable functional near-infrared spectroscopy (fNIRS) system. First, upon presentation of the sample stimulus, we observed an immediate signal increase in the ventral (orbitofrontal) region of the anterior PFC, followed by activity in the dorsolateral PFC. After the DMTS test stimulus appeared, the orbitofrontal cortex activated once again, while the rest of the PFC showed overall disengagement. Individuals with higher accuracy showed earlier and sustained activation of the PFC across the trial. Furthermore, higher network efficiency and functional connectivity in the PFC were correlated with individual WM performance. Our study sheds new light on the dynamics of PFC subregional activity during a cognitive task and its potential applicability in explaining individual differences in experimental, educational, or clinical populations. PRACTITIONER POINTS: Wearable functional near-infrared spectroscopy (fNIRS) captured dissociable temporal dynamics across prefrontal subregions during a delayed match-to-sample task. Anterior regions of the orbitofrontal cortex (OFC) activated first during the delay period, followed by the dorsolateral prefrontal cortex (PFC). PFC disengaged overall after the delay, but the OFC reactivated to the test stimulus. Earlier and sustained activation of PFC was associated with better accuracy. Functional connectivity and network efficiency also varied with task performance.


Subject(s)
Memory, Short-Term , Wearable Electronic Devices , Humans , Memory, Short-Term/physiology , Spectroscopy, Near-Infrared/methods , Cognition/physiology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiology
6.
Small ; 20(24): e2306738, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38161257

ABSTRACT

Adoptive immunotherapy utilizing natural killer (NK) cells has demonstrated remarkable efficacy in treating hematologic malignancies. However, its clinical intervention for solid tumors is hindered by the limited expression of tumor-specific antigens. Herein, lipid-PEG conjugated hyaluronic acid (HA) materials (HA-PEG-Lipid) for the simple ex-vivo surface coating of NK cells is developed for 1) lipid-mediated cellular membrane anchoring via hydrophobic interaction and thereby 2) sufficient presentation of the CD44 ligand (i.e., HA) onto NK cells for cancer targeting, without the need for genetic manipulation. Membrane-engineered NK cells can selectively recognize CD44-overexpressing cancer cells through HA-CD44 affinity and subsequently induce in situ activation of NK cells for cancer elimination. Therefore, the surface-engineered NK cells using HA-PEG-Lipid (HANK cells) establish an immune synapse with CD44-overexpressing MIA PaCa-2 pancreatic cancer cells, triggering the "recognition-activation" mechanism, and ultimately eliminating cancer cells. Moreover, in mouse xenograft tumor models, administrated HANK cells demonstrate significant infiltration into solid tumors, resulting in tumor apoptosis/necrosis and effective suppression of tumor progression and metastasis, as compared to NK cells and gemcitabine. Taken together, the HA-PEG-Lipid biomaterials expedite the treatment of solid tumors by facilitating a sequential recognition-activation mechanism of surface-engineered HANK cells, suggesting a promising approach for NK cell-mediated immunotherapy.


Subject(s)
Hyaluronan Receptors , Hyaluronic Acid , Immunotherapy , Killer Cells, Natural , Killer Cells, Natural/immunology , Hyaluronan Receptors/metabolism , Animals , Humans , Immunotherapy/methods , Hyaluronic Acid/chemistry , Cell Line, Tumor , Ligands , Mice , Polyethylene Glycols/chemistry , Neoplasms/therapy , Neoplasms/immunology
7.
Mamm Genome ; 35(3): 324-333, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38837040

ABSTRACT

Hypercholesterolemia raises the risk for cardiovascular complications and overall health. Hypercholesterolemia is common, affecting 10% of the general population of the US, and heritable. Most individuals with hypercholesterolemia have a polygenic predisposition to the condition. Previously we identified a quantitative trait locus, Tachol1, linked to hypercholesterolemia on mouse chromosome 1 (Chr1) in a cross between C57BL/6J (B6) and TALLYHO/JngJ (TH) mice, a polygenic model for human obesity, type 2 diabetes and hyperlipidemia. Subsequently, using congenic mice that carry a TH-derived genomic segment of Chr1 on a B6 background, we demonstrated that the distal segment of Chr1, where Tachol1 maps, is necessary to cause hypercholesterolemia, as well as diet-induced obesity. In this study, we generated overlapping subcongenic lines to the distal segment of congenic region and characterized subcongenic mice carrying the smallest TH region of Tachol1, ~ 16.2 Mb in size (B6.TH-Chr1-16.2 Mb). Both male and female B6.TH-Chr1-16.2 Mb mice showed a significantly increased plasma total cholesterol levels compared to B6 on both chow and high fat (HF) diet. B6.TH-Chr1-16.2 Mb mice also had greater fat mass than B6 on HF diet, without increasing food intake. The gene and protein expression levels of absent in melanoma 2 (Aim2) gene were significantly upregulated in B6.TH-Chr1-16.2 Mb mice compared to B6. In summary, we confirmed the effect of Tachol1 on hypercholesterolemia and diet-induced obesity using subcongenic analysis.


Subject(s)
Hypercholesterolemia , Mice, Inbred C57BL , Obesity , Quantitative Trait Loci , Animals , Obesity/genetics , Obesity/metabolism , Hypercholesterolemia/genetics , Hypercholesterolemia/metabolism , Mice , Male , Female , Chromosomes, Mammalian/genetics , Diet, High-Fat/adverse effects , Mice, Congenic , Disease Models, Animal , Genetic Predisposition to Disease
8.
Compr Psychiatry ; 129: 152447, 2024 02.
Article in English | MEDLINE | ID: mdl-38134553

ABSTRACT

BACKGROUND: Personalization is considered an important principle in virtual reality (VR) exposure therapy. We aimed to identify whether personalized VR exposure could provoke increased anxiety in patients with panic disorder and agoraphobia as it is considered the first step in successful treatment for anxiety. METHODS: We performed a double-arm, one-day preliminary study among 28 patients with panic disorder and agoraphobia. Three sessions of VR exposure, including a theater, train, and elevator scenario, were conducted in two groups. In the personalized group (n = 14), the brightness and crowd density were customized based on a pre-assessment. In the control group (n = 14), these conditions were fully randomized. Self-reported anxiety, heart rate, skin conductance, and electroencephalography were measured before, during, and after the VR sessions. RESULTS: In the later VR sessions, higher self-reported anxiety levels measured by the Visual Analogue Scale were observed in the personalized exposure group. Increased heart rates during and after the VR sessions were observed in the personalized group. The changes in skin conductance peaks were not significantly different between the groups, but the increase in skin conductance was associated with the participants' perception of presence. The electroencephalogram showed widespread increases in alpha waves in the frontal and temporal areas of the brain in the personalized group than in the control group. CONCLUSION: Personalized VR exposure elicits stronger anxiogenic effects in patients with panic disorder and agoraphobia as suggested by self-report and neurophysiological data. Personalization of VR exposure has the potential for effective behavioral therapy.


Subject(s)
Panic Disorder , Virtual Reality , Humans , Panic Disorder/diagnosis , Panic Disorder/therapy , Agoraphobia/diagnosis , Agoraphobia/therapy , Anxiety/therapy , Anxiety Disorders
9.
Lipids Health Dis ; 23(1): 165, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38835081

ABSTRACT

BACKGROUND: The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. METHODS: Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. RESULTS: ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50-1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20-29 years, HR 4.07 [95% CI 2.85-5.83]; 30-39 years, HR 2.39 [95% CI 1.83-3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16-1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. CONCLUSIONS: Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD.


Subject(s)
Cholesterol , Kidney Failure, Chronic , Triglycerides , Humans , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/blood , Male , Female , Middle Aged , Cholesterol/blood , Risk Factors , Adult , Triglycerides/blood , Cholesterol, HDL/blood , Retrospective Studies , Aged , Cholesterol, LDL/blood , Republic of Korea/epidemiology , Proportional Hazards Models
10.
J Shoulder Elbow Surg ; 33(8): 1724-1732, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38367925

ABSTRACT

BACKGROUND: The glenoid track concept has enabled the categorization of Hill-Sachs lesions (HSLs) into on-track lesions and off-track lesions. Furthermore, among the on-track lesions, further categorization has been established based on the distance from the medial edge of the Hill-Sachs lesion to the medial edge of the glenoid track, into peripheral-track lesions and central-track lesions. Recent studies on peripheral-track lesions and central-track lesions within the glenoid track have shown inconsistencies in failure rates, which deserves further investigation. METHODS: A retrospective cohort comparison of patients who underwent arthroscopic Bankart repair between 2015 and 2020 was performed. 102 patients with peripheral-track HSLs were included. The patients were divided into 2 groups based on the results of the postoperative apprehension test: the apprehension positive group (n = 30), and the apprehension negative group (n = 72). Using preoperative computed tomography (CT) and an image reconstruction program, 3-dimensional (3D) images were segmented to calculate the length, width, depth, and distance of the HSLs. A multivariate logistic regression was used to determine the risk factors of recurrence, for which odds ratio (OR) and 95% confidence interval (CI) were provided. RESULTS: A multivariate logistic regression analysis revealed that the length of the peripheral-track HSLs was a significant independent predictor of failure in this study. (OR 1.380; 95% CI 1.170-1.627; P < .001). The receiver operating characteristics curve (ROC) demonstrated a predictive power (area under the curve = 0.841) and a threshold value of 14.2 mm. CONCLUSION: Length was the only risk factor for the recurrent instability of peripheral-track HSLs after ABR. In the context of surgical decision-making, utilizing the glenoid track concept, medical practitioners may need to evaluate instability by considering the length as a continuous factor, while differentiating between peripheral-track and central-track classifications.


Subject(s)
Arthroscopy , Bankart Lesions , Joint Instability , Humans , Arthroscopy/methods , Male , Retrospective Studies , Female , Joint Instability/surgery , Adult , Bankart Lesions/surgery , Recurrence , Shoulder Joint/surgery , Young Adult , Tomography, X-Ray Computed
11.
J Sci Food Agric ; 104(9): 5010-5020, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38314949

ABSTRACT

BACKGROUND: Cruciferous vegetable sprout has been highlighted as a promising functional material rich in bioactive compounds called isothiocyanates (ITCs) and it can be grown in very short periods in controlled indoor farms. However, because ITCs content depends on multiple factors such as cultivar, germination time and myrosinase activity, those variables need to be controlled during germination or extraction to produce functional materials enriched in ITCs. Sulforaphene (SFEN), an ITC found primarily in radishes (Raphanus sativus L.), exerts beneficial effects on obesity. However, the optimal germination and extraction conditions for radish sprout (RSP) to increase SFEN content remain unascertained, and the extract's anti-obesity effect has yet to be evaluated. RESULTS: The present study found that the SFEN content was highest in purple radish sprout (PRSP) among the six cultivars investigated. Optimal SFEN content occurred after 2 days of PRSP germination (2 days PRSP). To maximize the dry matter yield, total ITCs and SFEN contents in RSP extract, we found the optimal conditions for extracting PRSP [27.5 °C, 60 min, 1:75.52 solute/solvent (w/v), no ascorbic acid] using response surface methodology. Consistent with high SFEN content, 2 days PRSP extract significantly outperformed 3 days or 4 days PRSP extract in inhibiting lipid accumulation in 3T3-L1 cells. Moreover, 2 days PRSP extract suppressed adipogenesis and lipogenesis-related protein expression. CONCLUSION: Regarding the cultivar, germination time and extraction conditions, optimally produced PRSP extract contains high SFEN content and exerts anti-obesity effects. Thus, we suggest PRSP extract as a potent functional material for obesity prevention. © 2024 Society of Chemical Industry.


Subject(s)
Germination , Isothiocyanates , Plant Extracts , Raphanus , Raphanus/chemistry , Raphanus/growth & development , Raphanus/metabolism , Germination/drug effects , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Isothiocyanates/pharmacology , Isothiocyanates/isolation & purification , Isothiocyanates/chemistry , Isothiocyanates/analysis , Mice , Animals , 3T3-L1 Cells , Sulfoxides
12.
J Foot Ankle Surg ; 63(2): 127-131, 2024.
Article in English | MEDLINE | ID: mdl-37898330

ABSTRACT

The anterior inferior tibiofibular ligament (AITFL) avulsion fracture accompanying an ankle fracture can compromise ankle stability, necessitating accurate evaluation and a clear understanding of its pathophysiology.. The aim of this study was to investigate the association between AITFL avulsion fracture and Lauge-Hansen, Wagstaffe classification. A retro-prospective study was conducted at a university-affiliated tertiary care medical center. We selected 128 patients who underwent surgery at our institution between January 2013 and July 2017 and analyzed the association between AITFL avulsion fracture and the foot position. According to the modified Wagstaffe classification system, there were 39 cases of type II, followed by 9 cases of type III and 8 cases of type IV. Of the7 pronation-abduction fractures, 3 were AITFL avulsion fracture (43%), while of the 21 pronation-external rotation fractures, 9 were AITFL avulsion fracture (43%). Of the 95 supination-external rotation fractures, there were 56 cases (59%) of AITFL avulsion fractures. Of the pronation fractures, 0% were fibular avulsion fractures and 43% were tibial avulsion fractures. Of the supination fractures, 44% were fibular avulsion fractures and 16% were tibial avulsion fracture. The difference in the ratio of fibular to tibial avulsion fractures between pronation and supination fractures was significant (p < .001). These results suggest that tibial avulsion fractures of type IV in the modified Wagstaffe classification and pronation fractures occur due to collision with the anterolateral corners of the distal bone when the talus externally rotates. Moreover, in cases of pronation fractures, a new type of AITFL avulsion fracture has been observed.


Subject(s)
Ankle Fractures , Fractures, Avulsion , Lateral Ligament, Ankle , Tibial Fractures , Humans , Ankle Fractures/complications , Ankle Fractures/diagnostic imaging , Ankle Fractures/surgery , Fractures, Avulsion/complications , Fractures, Avulsion/diagnostic imaging , Fractures, Avulsion/surgery , Lateral Ligament, Ankle/surgery , Prospective Studies , Retrospective Studies , Fracture Fixation, Internal/methods
13.
J Minim Access Surg ; 20(2): 222-224, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37148105

ABSTRACT

ABSTRACT: If the cause of the bile leakage after hepaticojejunostomy is accidental non-anastomosis of one bile duct, it is unlikely that the leakage will resolve spontaneously, and reoperation may be necessary. However, if the patient has contraindications to surgery, other treatments should be considered. In this case report, we describe a new percutaneous tract creation between the isolated right bile duct and Roux-en-Y afferent jejunal loop in a patient who underwent hepaticojejunostomy, and the right bile duct was accidentally not anastomosed with the jejunal loop.

14.
Ann Surg Oncol ; 30(5): 2916-2925, 2023 May.
Article in English | MEDLINE | ID: mdl-36637642

ABSTRACT

BACKGROUND: A stepwise surgical approach with hemithyroidectomy and completion thyroidectomy was used to achieve definite characterization of follicular thyroid carcinoma (FTC). Choosing appropriate candidates for completion thyroidectomy has been controversial. OBJECTIVE: The aim of this study was to clarify the selection criteria for completion thyroidectomy using telomerase reverse transcriptase (TERT) promoter mutation. METHODS: A total of 87 FTC patients who had information about TERT promoter mutation from August 1995 to November 2020 were investigated. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each of the World Health Organization (WHO) 2017 classifications were calculated. RESULTS: Of the 87 patients, 8 (9.2%) had initial distant metastasis and 15 (17.2%) had persistent disease or developed structural recurrence. The threshold diameter for initial distant metastasis, disease recurrence, and cancer-specific death was 2 cm in minimally invasive FTC (MI-FTC) with mutant TERT (M-TERT) and in encapsulated angioinvasive FTC (EA-FTC) with M-TERT, while that in MI-FTC with wild-type TERT (WT-TERT) and EA-FTC with WT-TERT was 4 cm. The cumulative risk of initial distant metastasis, disease recurrence, and cancer-specific death according to primary tumor size in each WHO 2017 classification was significantly different only in patients with WT-TERT (p = 0.001, p = 0.019, and p = 0.005, respectively). CONCLUSIONS: The data suggest 2 cm as a critical threshold diameter for performance of completion thyroidectomy in MI-FTC with M-TERT and EA-FTC with M-TERT. TERT promoter mutational status can help select candidates for completion thyroidectomy.


Subject(s)
Adenocarcinoma, Follicular , Neoplasms, Glandular and Epithelial , Telomerase , Thyroid Neoplasms , Humans , Thyroidectomy , Thyroid Neoplasms/genetics , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Patient Selection , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/surgery , Adenocarcinoma, Follicular/genetics , Adenocarcinoma, Follicular/surgery , Adenocarcinoma, Follicular/pathology , Mutation , Neoplasms, Glandular and Epithelial/surgery , Telomerase/genetics
15.
Eur J Neurol ; 30(2): 344-352, 2023 02.
Article in English | MEDLINE | ID: mdl-36288409

ABSTRACT

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.


Subject(s)
Hypotension, Orthostatic , Parkinson Disease , REM Sleep Behavior Disorder , Humans , Parkinson Disease/diagnostic imaging , Parkinson Disease/genetics , 3-Iodobenzylguanidine , Dopamine Plasma Membrane Transport Proteins/genetics , Glucosylceramidase/genetics , Tomography, Emission-Computed, Single-Photon/methods , Positron-Emission Tomography , Tropanes , Radionuclide Imaging , Mutation
16.
Eur J Neurol ; 30(8): 2583-2586, 2023 08.
Article in English | MEDLINE | ID: mdl-37170789

ABSTRACT

BACKGROUND AND PURPOSE: Mutations in the gene encoding valosin-containing protein (VCP) are related to myriad medical conditions, including familial amyotrophic lateral sclerosis, inclusion body myopathy, and frontotemporal dementia. There are several reports of a link between these mutations and early onset Parkinson disease (PD). CASE DESCRIPTION: We report a 53-year-old PD patient with VCP mutation who later developed motor complications, thus receiving subthalamic nucleus deep brain stimulation (DBS) at the age of 56 years. However, myopathy emerged 1.5 years after surgery. CONCLUSIONS: With the phenotype variability of VCP, DBS should be carefully evaluated, considering the possible unfavorable long-term outcomes due to other symptoms of this mutation.


Subject(s)
Deep Brain Stimulation , Frontotemporal Dementia , Muscular Diseases , Osteitis Deformans , Parkinson Disease , Humans , Valosin Containing Protein/genetics , Parkinson Disease/genetics , Parkinson Disease/therapy , Mutation , Frontotemporal Dementia/genetics , Frontotemporal Dementia/therapy , Cell Cycle Proteins/genetics , Osteitis Deformans/genetics
17.
Acta Oncol ; 62(8): 880-888, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37656769

ABSTRACT

BACKGROUND: Lymphedema is a chronic, debilitating disease that often requires life-long management. Predicting clinical manifestations and prognosis is crucial in clinical practice because the treatment of lymphedema should be individualized for best clinical outcome. The aim of this study is to explore the location and severity of lymphedema secondary to inguinal and/or iliac lymph node dissection (LND) in patients with melanoma. METHODS: Patients with melanoma who received LND at a single tertiary medical center between 1 January 2010 and 31 September 2022 were retrospectively reviewed. Patient who received inguinal LND only were designate as the inguinal group while those who received both ilioinguinal LND were included in the ilioinguinal group. Volumetric measurement was used to objectify the severity and location of lymphedema. Clinical data was acquired for 12-15 months of follow-up. RESULTS: Among 81 patients, 43 (53%) had developed lymphedema in the lower extremities at an average of 33 days after the surgery. Initially, patients manifested with medial thigh lymphedema in the inguinal group while patients were presented with whole leg lymphedema in the ilioinguinal group. Lower leg volume of the ilioinguinal group was significantly higher than the inguinal group. After more than 12 months of lymphedema treatment, upper leg volume was higher in the ilioinguinal group than the inguinal group (12.7% vs 5.4%, p < 0.05). CONCLUSION: Lymphedema developed in early post-op period. The ilioinguinal group presented with a larger volume of lymphedema in the distal area of the legs. Even after sufficient treatment, predominant lymphedema remained in the proximal leg for the ilioinguinal group. Patients with both inguinal and iliac LND were associated with more severe lymphedema. Based on the dissection sites, the clinical manifestations and prognosis of leg lymphedema can vary widely. Thus, clinicians should consider the dissection site when approaching melanoma patients with lymphedema.


Subject(s)
Lymphedema , Melanoma , Skin Neoplasms , Humans , Skin Neoplasms/surgery , Skin Neoplasms/pathology , Retrospective Studies , Lymphatic Metastasis , Melanoma/complications , Melanoma/surgery , Melanoma/pathology , Lymph Node Excision/adverse effects , Lower Extremity , Lymphedema/etiology
18.
Cell Mol Life Sci ; 79(4): 211, 2022 Mar 27.
Article in English | MEDLINE | ID: mdl-35344108

ABSTRACT

Taste stem/progenitor cells from posterior mouse tongues have been used to generate taste bud organoids. However, the inaccessible location of taste receptor cells is observed in conventional organoids. In this study, we established a suspension-culture method to fine-tune taste bud organoids by apicobasal polarity alteration to form the accessible localization of taste receptor cells. Compared to conventional Matrigel-embedded organoids, suspension-cultured organoids showed comparable differentiation and renewal rates to those of taste buds in vivo and exhibited functional taste receptor cells and cycling progenitor cells. Accessible taste receptor cells enabled the direct application of calcium imaging to evaluate the taste response. Moreover, suspension-cultured organoids can be genetically altered. Suspension-cultured taste bud organoids harmoniously integrated with the recipient lingual epithelium, maintaining the taste receptor cells and gustatory innervation capacity. We propose that suspension-cultured organoids may provide an efficient model for taste research, including taste bud development, regeneration, and transplantation.


Subject(s)
Taste Buds , Animals , Epithelium/physiology , Mice , Organoids , Taste/physiology , Taste Buds/physiology , Tongue/innervation
19.
BMC Musculoskelet Disord ; 24(1): 201, 2023 Mar 17.
Article in English | MEDLINE | ID: mdl-36932406

ABSTRACT

BACKGROUND: Capsular contracture is a well-known etiology in the primary stiff shoulder; thus capsular contracture and resultant decreased joint volume could lead to postoperative stiffness, which is a commonly reported morbidity after arthroscopic rotator cuff repair (ARCR). The purpose of this study was (1) to quantify the joint volume (total joint volume and each quadrant compartmental volume) using computed tomography arthrography (CTA) and (2) to demonstrate the relationship between joint volume and postoperative range of motion (ROM) after ARCR. MATERIALS AND METHODS: Eighty-three patients (60 ± 5.11 years, men = 26, women = 57) who had undergone ARCR between January 2015 to December 2020 due to small to medium full-thickness tear and followed by CTA 6 months postoperatively were retrospectively reviewed. An image reconstruction program (3D Slicer, version 4.11.2 software) was used to calculate the joint volume (total joint volume and quadrant compartment joint volumes; anteroinferior, anterosuperior, posterosuperior and posteroinferior). For shoulder ROM, data including scaption (Sc), external rotation on side (ERs), external rotation at 90° (ER90), and internal rotation on back (IRb) were collected 6 months postoperatively. An evaluation of the correlation between joint volume and each shoulder motion was performed. RESULTS: There were moderate correlations between the total joint volume and each motion (Sc: Pearson coefficient, 0.32, p = 0.0047; ERs: Pearson coefficient, 0.24, p = 0.0296; ER90: Pearson coefficient, 0.33, p = 0.0023; IRb: Pearson coefficient, 0.23, p = 0.0336). Among the quadrant compartments, the anteroinferior (Sc: Pearson coefficient, 0.26, p = 0.0199; ERs: Pearson coefficient, 0.23, p = 0.0336; ER90: Pearson coefficient, 0.25, p = 0.0246; IRb: Pearson coefficient, 0.26, p = 0.0168) and posterosuperior (Sc: Pearson coefficient, 0.24, p = 0.029; ER90: Pearson coefficient, 0.29, p = 0.008; IRb: Pearson coefficient, 0.22, p = 0.0491) and posteroinferior (Sc: Pearson coefficient, 0.30, p = 0.0064; ER90: Pearson coefficient, 0.29, p = 0.0072) showed moderate correlations with each shoulder motion. CONCLUSION: Total joint volume, anteroinferior compartment joint volume, posterosuperior compartment joint volume and posteroinferior compartment joint volume were related to postoperative ROM after ARCR. Perioperative methods to increase the joint volume, especially the anteroinferior, posterosuperior and posteroinferior parts of the capsule may prevent postoperative stiffness after ARCR. LEVEL OF EVIDENCE: Level III; Retrospective Case-Control Study.


Subject(s)
Contracture , Rotator Cuff Injuries , Shoulder Joint , Male , Humans , Female , Rotator Cuff/diagnostic imaging , Rotator Cuff/surgery , Retrospective Studies , Rotator Cuff Injuries/diagnostic imaging , Rotator Cuff Injuries/surgery , Shoulder Joint/diagnostic imaging , Shoulder Joint/surgery , Case-Control Studies , Treatment Outcome , Arthroscopy/adverse effects , Arthroscopy/methods , Range of Motion, Articular
20.
Int Endod J ; 56(12): 1550-1558, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37787769

ABSTRACT

AIM: Limiting the incidence of resorption associated with delayed replantation of avulsed teeth is critical for long-term tooth survival. In this study, we assessed whether icariin, a natural product with anti-osteoclastic properties, could reduce root resorption in a rat model of tooth replantation. METHODOLOGY: Cytocompatibility of icariin (10, 20, 40 and 80 µM) was evaluated by CCK-8 proliferation assay in vitro, and an osteoclastogenesis assay was performed to evaluate the effect of icariin on the differentiation of rat bone marrow macrophages and human peripheral blood monocytes into tartrate-resistant acid phosphatase-stained (TRAP+ ) multinucleated giant cells (MNGCs). Differentiation of human periodontal ligament stem cells (hPDLSCs) treated with icariin (10 µM) was also evaluated at 5, 10 and 21 days of osteogenic induction. The first maxillary molars of five-week-old male Sprague-Dawley rats were extracted, denuded of PDL, then treated either with neutralized collagen solution (Carrier control) or icariin in collagen (3 µg/µL) before replantation into their sockets. The animals were euthanized 2 weeks post-surgery for micro-computed tomography (micro-CT) imaging and histological analyses. RESULTS: Icariin was cytocompatible and significantly reduced the differentiation of TRAP+ MNGCs in a dose-dependent manner compared to the control. Moreover, icariin enhanced alkaline phosphatase activity, expression of osteogenic marker genes and proteins, and calcium deposition in hPDLSCs. Micro-CT imaging of the replanted samples demonstrated a significantly higher volume of remaining roots in the icariin-treated group than in the control group. Histological analysis revealed a marked number of resorptive lacunae with TRAP activity in the control group, whereas icariin-treated samples showed signs of functional healing and reduced osteoclastic activity. CONCLUSIONS: Icariin was biocompatible and demonstrated potent anti-osteoclastic and pro-osteogenic properties that reduced resorption and promoted functional healing of denuded roots in a rat maxillary first molar model of replantation. These findings indicate that root surface treatment with icariin may be a clinically relevant and practical method for improving the retention and survival of teeth with compromised PDL after delayed replantation following traumatic avulsion.


Subject(s)
Root Resorption , Tooth Avulsion , Humans , Rats , Male , Animals , Rats, Sprague-Dawley , X-Ray Microtomography , Root Resorption/prevention & control , Periodontal Ligament , Collagen , Tooth Replantation/methods
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