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Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients.
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Fosfoglicerato Desidrogenase , Neoplasias Gástricas , Humanos , Fosfoglicerato Desidrogenase/genética , Fosfoglicerato Desidrogenase/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Linhagem Celular Tumoral , Glutamina/metabolismo , NutrientesRESUMO
BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Gencitabina , Capecitabina/efeitos adversos , Desoxicitidina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pancreáticas/patologia , Adenocarcinoma/induzido quimicamenteRESUMO
Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2. First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.
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Decreased medial cheek fat volume during aging leads to loss of a youthful facial shape. Increasing facial volume by methods such as adipose-derived stem cell (ASC) injection can produce facial rejuvenation. High-intensity focused ultrasound (HIFU) can increase adipogenesis in subcutaneous fat by modulating cilia on ASCs, which is accompanied by increased HSP70 and decreased NF-κB expression. Thus, we evaluated the effect of HIFU on increasing facial adipogenesis in swine (n = 2) via modulation of ASC cilia. Expression of CD166, an ASC marker, differed by subcutaneous adipose tissue location. CD166 expression in the zygomatic arch (ZA) was significantly higher than that in the subcutaneous adipose tissue in the mandible or lateral temporal areas. HIFU was applied only on the right side of the face, which was compared with the left side, where HIFU was not applied, as a control. HIFU produced a significant increase in HSP70 expression, decreased expression of NF-κB and a cilia disassembly factor (AURKA), and increased expression of a cilia increasing factor (ARL13B) and PPARG and CEBPA, which are the main regulators of adipogenesis. All of these changes were most prominent at the ZA. Facial adipose tissue thickness was also increased by HIFU. Adipose tissue volume, evaluated by magnetic resonance imaging, was increased by HIFU, most prominently in the ZA. In conclusion, HIFU increased ASC marker expression, accompanied by increased HSP70 and decreased NF-κB expression. Additionally, changes in cilia disassembly and length and expression of adipogenesis were observed. These results suggest that HIFU could be used to increase facial volume by modulating adipogenesis.
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Adipogenia , Animais , Suínos , Cílios/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Face , Gordura Subcutânea/citologia , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Adipócitos/citologia , NF-kappa B/metabolismoRESUMO
Patients with pediatric B-cell acute lymphoblastic leukemia (B-ALL) have a high survival rate, yet the prognosis of adults and patients with relapsed/refractory disease is relatively poor. Therefore, it is imperative to develop new therapeutic strategies. Here, we screened 100 plant extracts from South Korean Flora and investigated their anti-leukemic effect using CCRF-SB cells as a B-ALL model. The top cytotoxic extract identified in this screening was the Idesia polycarpa Maxim. branch (IMB), which efficiently inhibited the survival and proliferation of CCRF-SB cells, while having minimal to no impact on normal murine bone marrow cells. Mechanistically, the IMB-induced proapoptotic effect involves the increase of caspase 3/7 activity, which was shown to be associated with the disruption of the mitochondrial membrane potential (MMP) through the reduction in antiapoptotic Bcl-2 family expression. IMB also promoted the differentiation of CCRF-SB cells via the upregulation of the expression of differentiation-related genes, PAX5 and IKZF1. Given that resistance to glucocorticoid (GC) is often found in patients with relapsed/refractory ALL, we investigated whether IMB could restore GC sensitivity. IMB synergized GC to enhance apoptotic rate by increasing GC receptor expression and downmodulating mTOR and MAPK signals in CCRF-SB B-ALL cells. These results suggest that IMB has the potential to be a novel candidate for the treatment of B-ALL.
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Industry 4.0 requires high-speed data exchange that includes fast, reliable, low-latency, and cost-effective data transmissions. As visible light communication (VLC) can provide reliable, low-latency, and secure connections that do not penetrate walls and are immune to electromagnetic interference; it can be considered a solution for Industry 4.0. The non-orthogonal multiple access (NOMA) technique can achieve high spectral efficiency using the same frequency and time resources for multiple users. It means that smaller amounts of resources will be used compared with orthogonal multiple access (OMA). Therefore, handling multiple data transmissions with VLC-NOMA can be easier for factory automation than OMA. However, as the transmit power is split, the reliability is reduced. Therefore, this study proposed a deep neural network (DNN)-based power-allocation algorithm (DBPA) to improve the reliability of the system. Further, to schedule multiple nodes in VLC-NOMA system, a priority-based user-pairing (PBUP) scheme is proposed. The proposed techniques in VLC-NOMA system were evaluated in terms of the factory automation scenario and showed that it improves reliability and reduces missed deadlines.
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Luz , Alocação de Recursos , Reprodutibilidade dos Testes , Automação , AlgoritmosRESUMO
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) poses an increasing clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype. METHODS: We recruited 125 Korean patients (83 with biopsy-proven NAFLD and 42 without NAFLD) and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed single nucleotide polymorphisms. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean individuals with NAFLD was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models. RESULTS: The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in patients with NAFLD homozygous for the non-reference allele of rs2291702, compared to no-NAFLD individuals with the same genotype (p = 4.79 × 10-6). This change was replicated in an additional 162 individuals, yielding a combined p value of 8.05 × 10-8 from a total of 245 patients with NAFLD and 42 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing endoplasmic reticulum stress, and exacerbated NAFLD diet-induced liver fibrosis in mice, while overexpression of AGXT2 attenuated liver fibrosis and steatosis. CONCLUSIONS: We identified a new molecular role for AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD. LAY SUMMARY: Elucidating causal genes for non-alcoholic fatty liver disease (NAFLD) has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 Korean individuals (83 with NAFLD and 42 without NAFLD), we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of causal genes that act on the basis of genotype.
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Programas de Rastreamento/métodos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Transaminases/farmacologia , Adulto , Idoso , Antifibróticos/farmacologia , Antifibróticos/uso terapêutico , Feminino , Estudo de Associação Genômica Ampla/métodos , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Humanos , Fígado/patologia , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , República da Coreia/epidemiologia , Transaminases/uso terapêuticoRESUMO
Adhesion of carbon nanotube (CNT) onto a cathode substrate is very crucial for field electron emitters that are operating under high electric fields. As a supporting precursor of CNT field emitters, we adopted silicon carbide (SiC) nano-particle fillers with Ni particles and then enhanced interfacial reactions onto Kovar-alloy substrates through the optimized wet pulverization process of SiC aggregates for reliable field electron emitters. As-purchased SiC aggregates were efficiently pulverized from 20 to less than 1 micro-meter in a median value (D50). CNT pastes for field emitters were distinctively formulated by a mixing process of the pulverized SiC aggregates and pre-dispersed CNTs. X-ray photoelectron spectroscopy studies showed that the optimally pulverized SiC-CNT paste-emitter had a stronger Si 2p3/2 signal in the Ni2Si phase than the as-purchased one. The Si 2p3/2 signal would represent interfacial reaction of the SiC nano-particle onto Ni from the CNT paste and the Kovar substrate, forming the supporting layer for CNT emitters. The optimal paste-emitter even in a vacuum-sealed tube exhibited a highly reliable field emission current with a high current density of 100 mA cm-2 for over 50 h along with good reproducibility. The enhanced interfacial reaction of SiC filler onto the metal substrates could lead to highly reliable field electron emitters for vacuum electronic devices.
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BACKGROUND: Mutations in ADCK4 (aarF domain containing kinase 4) generally manifest as steroid-resistant nephrotic syndrome and induce coenzyme Q10 (CoQ10) deficiency. However, the molecular mechanisms underlying steroid-resistant nephrotic syndrome resulting from ADCK4 mutations are not well understood, largely because the function of ADCK4 remains unknown. METHODS: To elucidate the ADCK4's function in podocytes, we generated a podocyte-specific, Adck4-knockout mouse model and a human podocyte cell line featuring knockout of ADCK4. These knockout mice and podocytes were then treated with 2,4-dihydroxybenzoic acid (2,4-diHB), a CoQ10 precursor analogue, or with a vehicle only. We also performed proteomic mass spectrometry analysis to further elucidate ADCK4's function. RESULTS: Absence of Adck4 in mouse podocytes caused FSGS and albuminuria, recapitulating features of nephrotic syndrome caused by ADCK4 mutations. In vitro studies revealed that ADCK4-knockout podocytes had significantly reduced CoQ10 concentration, respiratory chain activity, and mitochondrial potential, and subsequently displayed an increase in the number of dysmorphic mitochondria. However, treatment of 3-month-old knockout mice or ADCK4-knockout cells with 2,4-diHB prevented the development of renal dysfunction and reversed mitochondrial dysfunction in podocytes. Moreover, ADCK4 interacted with mitochondrial proteins such as COQ5, as well as cytoplasmic proteins such as myosin and heat shock proteins. Thus, ADCK4 knockout decreased the COQ complex level, but overexpression of ADCK4 in ADCK4-knockout podocytes transfected with wild-type ADCK4 rescued the COQ5 level. CONCLUSIONS: Our study shows that ADCK4 is required for CoQ10 biosynthesis and mitochondrial function in podocytes, and suggests that ADCK4 in podocytes stabilizes proteins in complex Q in podocytes. Our study also suggests a potential treatment strategy for nephrotic syndrome resulting from ADCK4 mutations.
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Hidroxibenzoatos/farmacologia , Proteínas Quinases/fisiologia , Ubiquinona/análogos & derivados , Animais , Estabilidade Enzimática , Glomerulosclerose Segmentar e Focal/etiologia , Células HEK293 , Humanos , Metiltransferases/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/fisiologia , Proteínas Mitocondriais/metabolismo , Podócitos/enzimologia , Ubiquinona/metabolismoRESUMO
Non-orthogonal multiple access (NOMA) has a key feature that the cell-center user (CCU) has prior information about the messages of the cell-edge user (CEU) in the same user-pair. It means that CCU can be used for retransmission when the CEU requests retransmission. As ultra-reliability and low-latency communication (URLLC) requires high-reliability constraints (e.g., 99.999%), using CCU for retransmission can be useful to satisfy the reliability constraint. In this study, to ensure the reliability of CEU, cooperative retransmission (CR) scheme for downlink NOMA systems is proposed. And the CR scheme is evaluated with Block error rate (BLER) considering reliability and with packet loss rate (PLR) in terms of reliability and latency constraints. And the evaluation results showed that the proposed CR scheme can satisfy the target BLER for URLLC low SNR compared to the conventional retransmission scheme, and showed the improved PLR compared to the conventional retransmission scheme in low SNRs.
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Noma , Comunicação , Redes de Comunicação de Computadores , Humanos , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
The use of porous three-dimensional (3D) composite scaffolds has attracted great attention in bone tissue engineering applications because they closely simulate the major features of the natural extracellular matrix (ECM) of bone. This study aimed to prepare biomimetic composite scaffolds via a simple 3D printing of gelatin/hyaluronic acid (HA)/hydroxyapatite (HAp) and subsequent biomineralization for improved bone tissue regeneration. The resulting scaffolds exhibited uniform structure and homogeneous pore distribution. In addition, the microstructures of the composite scaffolds showed an ECM-mimetic structure with a wrinkled internal surface and a porous hierarchical architecture. The results of bioactivity assays proved that the morphological characteristics and biomineralization of the composite scaffolds influenced cell proliferation and osteogenic differentiation. In particular, the biomineralized gelatin/HA/HAp composite scaffolds with double-layer staggered orthogonal (GEHA20-ZZS) and double-layer alternative structure (GEHA20-45S) showed higher bioactivity than other scaffolds. According to these results, biomineralization has a great influence on the biological activity of cells. Hence, the biomineralized composite scaffolds can be used as new bone scaffolds in bone regeneration.
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Regeneração Óssea , Durapatita , Gelatina , Ácido Hialurônico , Impressão Tridimensional , Engenharia Tecidual , Alicerces Teciduais , Biomineralização , Diferenciação Celular , Fenômenos Químicos , Durapatita/química , Módulo de Elasticidade , Gelatina/química , Análise Espectral , Alicerces Teciduais/química , ViscosidadeRESUMO
Cancer is heterogeneous among patients, requiring a thorough understanding of molecular subtypes and the establishment of therapeutic strategies based on its behavior. Gastric cancer (GC) is adenocarcinoma with marked heterogeneity leading to different prognoses. As an effort, we previously identified a stem-like subtype, which is prone to metastasis, with the worst prognosis. Here, we propose FNBP1 as a key to high-level cell motility, present only in aggressive GC cells. FNBP1 is also up-regulated in both the GS subtype from the TCGA project and the EMT subtype from the ACRG study, which include high portions of diffuse histologic type. Ablation of FNBP1 in the EMT-type GC cell line brought changes in the cell periphery in transcriptomic analysis. Indeed, loss of FNBP1 resulted in the loss of invasive ability, especially in a three-dimensional culture system. Live imaging indicated active movement of actin in FNBP1-overexpressed cells cultured in an extracellular matrix dome. To find the transcription factor which drives FNBP1 expression in an EMT-type GC cell line, the FNBP1 promoter region and DNA binding motifs were analyzed. Interestingly, the Sp1 motif was abundant in the promoter, and pharmacological inhibition and knockdown of Sp1 down-regulated FNBP1 promoter activity and the transcription level, respectively. Taken together, our results propose Sp1-driven FNBP1 as a key molecule explaining aggressiveness in EMT-type GC cells.
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Transição Epitelial-Mesenquimal/genética , Proteínas de Ligação a Ácido Graxo/genética , Regulação Neoplásica da Expressão Gênica , Fator de Transcrição Sp1/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Matriz Extracelular , Proteínas de Ligação a Ácido Graxo/metabolismo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica , Motivos de Nucleotídeos , Neoplasias Gástricas/patologiaRESUMO
An optical see-through (OST) display is affected more severely by ambient light than any other type of displays when placed in an outdoor environment with bright illuminance because of its transparency and thus, its inherent color distortion can worsen. It is hard to directly apply existing gamut mapping methods to an OST display because of its morphological gamut characteristic and the effect of ambient light. In this paper, we propose a new robust gamut mapping method which works against bright ambient light. The process is divided into two steps: lightness mapping (LM) and chroma reproduction. LM aligns the lightness level of sRGB gamut with OST gamut and partitions the region of OST gamut based on the relative size of the sRGB gamut and its lightness value. The second step (chroma reproduction) determines an appropriate chroma reproduction method (gamut compression or extension) and a proper direction for gamut mapping based on the characteristics of each region in order to minimize the effects of ambient light. The quality of color reproduction is qualitatively and quantitatively evaluated based on accurate measurements of the displayed colors. It has been experimentally confirmed that the proposed gamut mapping method can reduce color distortion more than the existing parametric gamut mapping algorithms.
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BACKGROUND: Early diagnosis of severe acute pancreatitis (AP) is important to reduce morbidity and mortality. We investigated the association between the triglyceride and glucose index (TyG index) and the prognosis of severe AP (SAP). METHODS: The TyG index was calculated as: ln [fasting triglycerides (mg/dL) x fasting plasma glucose (mg/dL)]/2. Multivariable logistic regression analyses were used to investigate the independent association between the TyG index and the severity of AP. RESULTS: In this study, 373 patients with AP were recruited from three hospitals. The TyG index was higher in the SAP group than in the non-SAP group. Further, the TyG index was higher than in patients admitted to an intensive care unit and those who died of AP. The TyG index was an independent predictive factor for SAP (odds ratio 7.14, 95% confidence interval 2.80-18.19). The area under the curve increased significantly, from 0.738 to 0.830, after adding the TyG index to a predictive SAP model. CONCLUSIONS: Our findings suggest that the TyG index is an independent prognostic factor in patients with AP and could be used as a simple prognostic indicator for SAP.
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Glicemia , Pancreatite , Triglicerídeos , Biomarcadores/sangue , Diagnóstico Precoce , Glucose , Humanos , Pancreatite/diagnóstico , Prognóstico , Triglicerídeos/sangueRESUMO
Oxidative stress and adipogenesis play key roles in the pathogenesis of Graves' orbitopathy (GO). In this study, the therapeutic effects of caffeine on the reduction of oxidative stress and adipogenesis were evaluated in primary cultured GO orbital fibroblasts in vitro. Orbital fibroblasts were cultured from orbital connective tissues obtained from individuals with GO. Intracellular reactive oxygen species (ROS) levels induced by hydrogen peroxide or cigarette smoke extract and the expression of anti-oxidative enzymes were measured after caffeine treatment. After adipogenic differentiation and caffeine treatment, cells were stained with Oil Red O and the levels of peroxisome proliferator activator γ (PPARγ), C/EBPα, and C/EBPß were determined by western blot analysis. Hydrogen peroxide and cigarette smoke extract increased the levels of intracellular ROS and anti-oxidative enzymes, which decreased in a dose-dependent manner upon pretreatment with caffeine in GO orbital fibroblasts. Oil Red-O staining results revealed a decrease in lipid droplets; furthermore, PPARγ, C/EBPα, and C/EBPß protein expression levels were inhibited upon treatment with caffeine during adipocyte differentiation. In conclusion, caffeine decreased oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. These findings may contribute to the development of new types of caffeine-containing pharmacological agents for use in the management of GO.
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Adipogenia/efeitos dos fármacos , Antioxidantes/farmacologia , Cafeína/farmacologia , Fibroblastos/efeitos dos fármacos , Oftalmopatia de Graves/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Adulto , Western Blotting , Proteína alfa Estimuladora de Ligação a CCAAT/efeitos dos fármacos , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/efeitos dos fármacos , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Estudos de Casos e Controles , Sobrevivência Celular , Feminino , Fibroblastos/metabolismo , Heme Oxigenase-1/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Oxidantes/farmacologia , PPAR gama/efeitos dos fármacos , PPAR gama/metabolismo , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Fumaça , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1/efeitos dos fármacos , Superóxido Dismutase-1/metabolismo , Tiorredoxinas/efeitos dos fármacos , Tiorredoxinas/metabolismo , Produtos do TabacoRESUMO
OBJECTIVE: In this multicentre open-label trial, we compared behavioural and neuropsychiatric symptoms in Parkinson's disease (PD) patients with impulse control disorders (ICD) treated with dopamine agonists before and 12 weeks after substituting dopamine agonists with an equivalent dose of levodopa/carbidopa slow-release formulation. METHODS: Baseline characteristics of 50 PD patients with ICD were compared with those of 60 medicated and 40 drug-naive PD control groups. Neuropsychiatric trait changes in the PD-ICD group were investigated 12 weeks after the intervention. ICD behaviours were assessed via modified Minnesota Impulsive Disorders Interview (mMIDI), whereas parkinsonian severity and neuropsychiatric characters were systematically assessed with the Unified PD Rating Scale (UPDRS) and a predefined neuropsychological assessment battery. RESULTS: At baseline, ICD patients showed higher scores in the Neuropsychiatric Inventory and anxiety, anger and obsessive-compulsive traits compared with both PD control groups. In contrast, the three PD groups showed indifference in the impulsivity scales. At 12 weeks post intervention, ICD behaviours significantly improved (p<0.001, Δ modified MIDI score=â5.27 ± 5.75) along with the UPDRS II daily activity scores (p=0.02, Δ=â2.07 ± 4.53). Behavioural disinhibition tended to improve (p=0.06), although no significant changes were observed in the Neuropsychiatric Inventory and personality trait scores. Dopamine agonist withdrawal syndrome developed in 5.3% of the PD-ICD group. CONCLUSIONS: This study provides class IV evidence suggesting that switching from dopamine agonists to levodopa/carbidopa slow-release formulations alleviated ICD behaviours in PD patients leading to improvement in daily activities whereas neuropsychiatric traits associated with ICD persisted after the 12-week therapy. TRIAL REGISTRATION NUMBER: NCT01683253.
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Antiparkinsonianos/uso terapêutico , Carbidopa/uso terapêutico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/tratamento farmacológico , Agonistas de Dopamina/uso terapêutico , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos Disruptivos, de Controle do Impulso e da Conduta/etiologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Combinação de Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Pramipexol/uso terapêuticoRESUMO
INTRODUCTION: Impulse control disorder (ICD) in Parkinson's disease (PD) is a critical nonmotor symptom with personality or neuropsychiatric traits contributing to ICD. OBJECTIVE: This study aimed to identify predictive traits for persistent or paradoxical aggravation of ICD after dopamine agonist substitution therapy for ICD in PD. METHODS: We conducted a case-control study using a database of a multicenter intervention trial for ICD in PD. The poor-outcome group was defined by showing paradoxical increases in ICD behaviors after the substitution of dopamine agonists with levodopa. We analyzed the pre-intervention personality traits associated with the poor outcome and also evaluated the risk traits for refractory ICD using a receiver-operating characteristic (ROC) curve analysis. RESULTS: The poor-outcome group showed higher levels of anger expression (p =0.007) and obsessive-compulsive traits (p =0.009) compared with the good-outcome group at the pre-intervention state. In the ROC curve analysis, the Obsessive-Compulsive Inventory showed the highest area under the curve with 80.0% sensitivity and 74.3% specificity in discriminating against the poor-outcome group. CONCLUSIONS: Our results suggest that assessment of obsessive compulsiveness may be useful for predicting the refractoriness of ICD behaviors in planning an interventional treatment for ICD in PD.
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Transtornos Disruptivos, de Controle do Impulso e da Conduta/tratamento farmacológico , Transtornos Disruptivos, de Controle do Impulso e da Conduta/psicologia , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Ira , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Estudos de Casos e Controles , Comportamento Compulsivo/psicologia , Transtornos Disruptivos, de Controle do Impulso e da Conduta/complicações , Transtornos Disruptivos, de Controle do Impulso e da Conduta/diagnóstico , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Feminino , Humanos , Levodopa/efeitos adversos , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Comportamento Obsessivo/psicologia , Doença de Parkinson/tratamento farmacológico , Fatores de Risco , Sensibilidade e Especificidade , Falha de TratamentoRESUMO
BACKGROUND AND AIM: Predicting severe pancreatitis is important for early aggressive management of patients with acute pancreatitis (AP). Despite the established role of diabetes mellitus (DM) in the risk of AP, the impact of DM on the clinical outcome in AP has not been fully elucidated. The objective of this study was to assess the risk of mortality and severity in AP among patients with type-2 DM. METHODS: Patients diagnosed with first attacks of AP were enrolled from January 2013 to June 2015. RESULTS: A total of 201 patients (63.2% male, mean age, 59.4 y) with AP were included. Etiologies included gallstones (51.2%), alcohol (37.3%), hypertriglyceridemia (2%), and idiopathic causes (9.5%). There were 54 AP patients (26.9%) with type-2 DM. Severity indices in AP, such as Atlanta Classification (severe), Ranson score, and Bedside Index of Severity in Acute Pancreatitis, were higher in subjects with DM than those without DM. Prevalence of intensive care unit admission and mortality were higher in AP patients with DM compared with those without DM. The association between DM and increased risk of mortality in AP remained statistically significant even after adjustments for confounding factors and Atlanta Classification (odds ratio, 7.76, 95% confidence interval, 1.26-47.63, P=0.027). CONCLUSIONS: Type-2 DM was associated with severity and increased mortality in patients with AP. Our findings provide evidence of the potential role of DM in the pathogenesis and management of severe AP.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Unidades de Terapia Intensiva/estatística & dados numéricos , Pancreatite/epidemiologia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/etiologia , Pancreatite/mortalidade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) predict severity in various diseases. In this study, we evaluated the value of NLR and PLR as prognostic factors in acute pancreatitis (AP). METHODS: Patients with AP were prospectively enrolled from March 2014 to September 2016 at Yonsei University Wonju College of Medicine. NLR and PLR were obtained at admission and were compared with other known prognostic scoring systems. RESULTS: A total of 243 patients were enrolled with an etiology of gallstone (n = 134) or alcohol (n = 109). NLR (17.7 ± 18.3 vs. 8.8 ± 8.4, P < 0.001) and PLR (344.1 ± 282.6 vs. 177.8 ± 150.1, P < 0.001) were significantly higher in the gallstone AP group than in the alcoholic AP group. For gallstone AP, NLR and PLR were significantly higher in severe AP, whereas high NLR and PLR were not related to severe AP in alcoholic AP. For the gallstone AP group, NLR and PLR demonstrated a predictive value significantly superior to C-reactive protein (CRP), whereas NLR, PLR, and CRP were not significant predictors for alcoholic AP. CONCLUSION: Our study demonstrated that NLR and PLR can predict the severity of AP, but only in gallstone AP.