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

RESUMO

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.).


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Assistência ao Convalescente , Ponte de Artéria Coronária/efeitos adversos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Testes Diagnósticos de Rotina , Stents Farmacológicos/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Padrão de Cuidado , Resultado do Tratamento
2.
Nano Lett ; 24(6): 1891-1900, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38150559

RESUMO

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.
Hum Brain Mapp ; 45(2): e26619, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339822

RESUMO

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.


Assuntos
Memória de Curto Prazo , Dispositivos Eletrônicos Vestíveis , Humanos , Memória de Curto Prazo/fisiologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cognição/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia
4.
Small ; 20(24): e2306738, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38161257

RESUMO

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.


Assuntos
Receptores de Hialuronatos , Ácido Hialurônico , Imunoterapia , Células Matadoras Naturais , Células Matadoras Naturais/imunologia , Receptores de Hialuronatos/metabolismo , Animais , Humanos , Imunoterapia/métodos , Ácido Hialurônico/química , Linhagem Celular Tumoral , Ligantes , Camundongos , Polietilenoglicóis/química , Neoplasias/terapia , Neoplasias/imunologia
5.
Mamm Genome ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837040

RESUMO

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.

6.
Compr Psychiatry ; 129: 152447, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38134553

RESUMO

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.


Assuntos
Transtorno de Pânico , Realidade Virtual , Humanos , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/terapia , Agorafobia/diagnóstico , Agorafobia/terapia , Ansiedade/terapia , Transtornos de Ansiedade
7.
Lipids Health Dis ; 23(1): 165, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38835081

RESUMO

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.


Assuntos
Colesterol , Falência Renal Crônica , Triglicerídeos , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Colesterol/sangue , Fatores de Risco , Adulto , Triglicerídeos/sangue , HDL-Colesterol/sangue , Estudos Retrospectivos , Idoso , LDL-Colesterol/sangue , República da Coreia/epidemiologia , Modelos de Riscos Proporcionais
8.
J Shoulder Elbow Surg ; 33(8): 1724-1732, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38367925

RESUMO

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.


Assuntos
Artroscopia , Lesões de Bankart , Instabilidade Articular , Humanos , Artroscopia/métodos , Masculino , Estudos Retrospectivos , Feminino , Instabilidade Articular/cirurgia , Adulto , Lesões de Bankart/cirurgia , Recidiva , Articulação do Ombro/cirurgia , Adulto Jovem , Tomografia Computadorizada por Raios X
9.
J Sci Food Agric ; 104(9): 5010-5020, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38314949

RESUMO

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.


Assuntos
Germinação , Isotiocianatos , Extratos Vegetais , Raphanus , Raphanus/química , Raphanus/crescimento & desenvolvimento , Raphanus/metabolismo , Germinação/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Isotiocianatos/farmacologia , Isotiocianatos/isolamento & purificação , Isotiocianatos/química , Isotiocianatos/análise , Camundongos , Animais , Células 3T3-L1 , Sulfóxidos
10.
J Foot Ankle Surg ; 63(2): 127-131, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37898330

RESUMO

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.


Assuntos
Fraturas do Tornozelo , Fratura Avulsão , Ligamentos Laterais do Tornozelo , Fraturas da Tíbia , Humanos , Fraturas do Tornozelo/complicações , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Fratura Avulsão/complicações , Fratura Avulsão/diagnóstico por imagem , Fratura Avulsão/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Fixação Interna de Fraturas/métodos
11.
J Minim Access Surg ; 20(2): 222-224, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148105

RESUMO

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.

12.
Ann Surg Oncol ; 30(5): 2916-2925, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36637642

RESUMO

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.


Assuntos
Adenocarcinoma Folicular , Neoplasias Epiteliais e Glandulares , Telomerase , Neoplasias da Glândula Tireoide , Humanos , Tireoidectomia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Seleção de Pacientes , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/cirurgia , Adenocarcinoma Folicular/patologia , Mutação , Neoplasias Epiteliais e Glandulares/cirurgia , Telomerase/genética
13.
Eur J Neurol ; 30(2): 344-352, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36288409

RESUMO

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.


Assuntos
Hipotensão Ortostática , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Humanos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/genética , 3-Iodobenzilguanidina , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Glucosilceramidase/genética , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia por Emissão de Pósitrons , Tropanos , Cintilografia , Mutação
14.
Eur J Neurol ; 30(8): 2583-2586, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37170789

RESUMO

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.


Assuntos
Estimulação Encefálica Profunda , Demência Frontotemporal , Doenças Musculares , Osteíte Deformante , Doença de Parkinson , Humanos , Proteína com Valosina/genética , Doença de Parkinson/genética , Doença de Parkinson/terapia , Mutação , Demência Frontotemporal/genética , Demência Frontotemporal/terapia , Proteínas de Ciclo Celular/genética , Osteíte Deformante/genética
15.
Acta Oncol ; 62(8): 880-888, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37656769

RESUMO

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.


Assuntos
Linfedema , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Metástase Linfática , Melanoma/complicações , Melanoma/cirurgia , Melanoma/patologia , Excisão de Linfonodo/efeitos adversos , Extremidade Inferior , Linfedema/etiologia
16.
Cell Mol Life Sci ; 79(4): 211, 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35344108

RESUMO

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.


Assuntos
Papilas Gustativas , Animais , Epitélio/fisiologia , Camundongos , Organoides , Paladar/fisiologia , Papilas Gustativas/fisiologia , Língua/inervação
17.
BMC Musculoskelet Disord ; 24(1): 201, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932406

RESUMO

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.


Assuntos
Contratura , Lesões do Manguito Rotador , Articulação do Ombro , Masculino , Humanos , Feminino , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/cirurgia , Estudos Retrospectivos , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Estudos de Casos e Controles , Resultado do Tratamento , Artroscopia/efeitos adversos , Artroscopia/métodos , Amplitude de Movimento Articular
18.
Int Endod J ; 56(12): 1550-1558, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37787769

RESUMO

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.


Assuntos
Reabsorção da Raiz , Avulsão Dentária , Humanos , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Microtomografia por Raio-X , Reabsorção da Raiz/prevenção & controle , Ligamento Periodontal , Colágeno , Reimplante Dentário/métodos
19.
Am J Otolaryngol ; 44(1): 103683, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36323161

RESUMO

OBJECTIVES: Obstructive sleep apnea (OSA) is a sleep-related breathing disorder caused by repetitive obstruction of the upper airway; this impairs gaseous exchange, resulting in hypoxia, hypercapnia, and frequent arousals. Excessive daytime sleepiness (EDS) is a common daytime symptom of OSA. EDS manifests as fatigue and impaired attention, leading to poor performance at work and falling asleep while driving, which is a major socioeconomic problem. Therefore, it is important to properly treat EDS and accurately predict the response to treatment. However, few studies have compared OSA patients showing and not showing improvement in EDS. Therefore, this study aimed to objectively analyze and compare EDS improvement and non-improvement groups. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 57 OSA patients with EDS. Patients were divided into two groups according to the improvement in EDS after positive airway pressure (PAP) device treatment. We analyzed differences in clinical records including patients' age, sex, history of smoking, hypertension, diabetes, myocardial infarction, and cerebrovascular disease between the two groups. Systolic, diastolic blood pressure, blood test including blood glucose, total cholesterol, high- and low-density lipoprotein cholesterol, and triglyceride levels were also analyzed. Polysomnography (PSG) data, PAP device treatment compliance and scores of questionnaires related to various psychiatric symptoms, subjective sleep quality between the two groups were also analyzed. RESULTS: There was no statistically significant difference in age, gender, or past medical history between the two groups. Systolic and diastolic blood pressure, and blood test results, were also not significantly different. Among the questionnaires related to various psychiatric symptoms, the groups showed statistically significant differences in Social Avoidance and Distress Scale (SADS) and Fear of Negative Evaluation (FNE) scores (P = 0.001 and 0.020, respectively). The group differences in the scores on the other questionnaires were not significantly different. Among the PSG items, significant group differences were observed in the percentage of stage 2 non-REM sleep (N2%, P = 0.023), apnea index (AI, P = 0.005), apnea-hypopnea index (AHI, P = 0.023), and frequency of 3 % oxygen desaturation (ODI3, P = 0.001). No obesity-related parameters showed significant group differences. The percentage of days on which a PAP device was used (out of 90 days; PAP%) and percentage of days on which a PAP device was used for >4 h (Time4%) did not differ significantly. CONCLUSIONS: The SADS, FNE, AI, AHI, N2%, and ODI3 parameters differed significantly between the EDS improvement and non-improvement groups. These parameters may help clinicians treat and predict the prognosis of patients suffering with EDS.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Apneia Obstrutiva do Sono , Humanos , Estudos Retrospectivos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Distúrbios do Sono por Sonolência Excessiva/etiologia , Distúrbios do Sono por Sonolência Excessiva/terapia , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Polissonografia/métodos , Colesterol
20.
Medicina (Kaunas) ; 59(5)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37241228

RESUMO

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.


Assuntos
Neoplasias do Endométrio , Transição Epitelial-Mesenquimal , Feminino , Humanos , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Proliferação de Células , Movimento Celular , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/metabolismo
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