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This study aimed to identify risk factors for involuntary referral by police to emergency room (ER) psychiatric services for community-based patients with a mental illness via a generalized estimating equation (GEE) analysis. The analysis was based on data from the Management Information System of Psychiatric Care (MISPC) system for patients with a severe mental illness in Taipei, Taiwan and registered referral records of the police. Data on 6378 patients aged ≥20 years were used in this study, including 164 patients who were involuntarily referred to the ER by the police and 6214 patients who were not during the period of January 1, 2018 to December 31, 2020. GEEs were utilized to explore possible risk factors of repeated involuntary referral to ER psychiatric services for patients with a severe mental illness. The logistic regressions indicated that patients defined as "severe" according to the Mental Health Act of Taiwan (crude odds ratio (OR): 3.840, 95 % confidence interval (CI): 2.407-6.126), with a disability (crude OR: 3.567, 95 % CI: 1.339-9.501), with two or more family members with a psychiatric disorder (crude OR: 1.598, 95 % CI: 1.002-2.548), with a history of a suicide attempt (crude OR: 25.582, 95 % CI: 17.608-37.167), and with a history of domestic violence (crude OR: 16.141, 95 % CI: 11.539-22.579) were positively associated with involuntary referral to ER psychiatric services. However, age (crude OR: 0.971, 95 % CI: 0.960-0.983) and the MISPC score (crude OR: 0.834, 95 % CI: 0.800-0.869) were inversely associated with involuntary referral to ER psychiatric services. After adjusting for demographics and potential confounders, we found that patients defined as "severe" (Exp (ß): 3.236), with a disability (Exp (ß): 3.715), with a history of a suicide attempt (Exp (ß): 8.706), and with a history of domestic violence (Exp (ß): 8.826), as well as age (Exp (ß): 0.986) and the MISPC score (Exp (ß): 0.902) remained significantly associated with repeated involuntary referral to ER psychiatric services. In conclusion, community-based mentally ill patients with a history of a suicide attempt, with a history of domestic violence, with a severe illness, and with a profound level of disability were highly associated with involuntary referral to ER psychiatric services. We suggest that community mental health case managers identify significant factors associated with involuntary referral to ER psychiatric services to accordingly arrange case management plans.
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Serviços de Emergência Psiquiátrica , Transtornos Mentais , Humanos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Polícia , Encaminhamento e Consulta , Fatores de Risco , AdultoRESUMO
We report on the development of a high-resolution and highly efficient beamline for soft X-ray resonant inelastic X-ray scattering (RIXS) located at the Taiwan Photon Source. This beamline adopts an optical design that uses an active grating monochromator (AGM) and an active grating spectrometer (AGS) to implement the energy compensation principle of grating dispersion. Active gratings are utilized to diminish defocus, coma and higher-order aberrations, as well as to decrease the slope errors caused by thermal deformation and optical polishing. The AGS is mounted on a rotatable granite platform to enable momentum-resolved RIXS measurements with scattering angles over a wide range. Several high-precision instruments developed in-house for this beamline are described briefly. The best energy resolution obtained from this AGM-AGS beamline was 12.4â meV at 530â eV, achieving a resolving power of 4.2 × 104, while the bandwidth of the incident soft X-rays was kept at 0.5â eV. To demonstrate the scientific impact of high-resolution RIXS, we present an example of momentum-resolved RIXS measurements on a high-temperature superconducting cuprate, i.e. La2-xSrxCuO4. The measurements reveal the A1g buckling phonons in superconducting cuprates, opening a new opportunity to investigate the coupling between these phonons and charge-density waves.
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Virtual photons can mediate interaction between atoms, resulting in an energy shift known as a collective Lamb shift. Observing the collective Lamb shift is challenging, since it can be obscured by radiative decay and direct atom-atom interactions. Here, we place two superconducting qubits in a transmission line terminated by a mirror, which suppresses decay. We measure a collective Lamb shift reaching 0.8% of the qubit transition frequency and twice the transition linewidth. We also show that the qubits can interact via the transmission line even if one of them does not decay into it.
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Growing evidence indicates that resistin-an obesity-related cytokine-is upregulated in breast cancer patients, yet its impact on breast cancer behavior remains to be ascertained. Similarly, Toll-like receptor 4 (TLR4) has been implicated in breast cancer progression, however, its clinically relevant endogenous ligand remains elusive. In this study, we observed that high serum resistin levels in breast cancer patients positively correlated with tumor stage, size and lymph node metastasis. These findings were replicated in animal models of breast cancer tumorigenesis and metastasis. Resistin was found to promote epithelial-mesenchymal transition and stemness in breast cancer cells-mechanisms critical to tumorigenesis and metastasis-through a TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/signal transducer and activator of transcription 3 (STAT3) signaling pathway and negated by TLR4-specific antibody and antagonist. These findings provide clear evidence that resistin is a clinically relevant endogenous ligand for TLR4, which promotes tumor progression via TLR4/NF-κB/STAT3 signaling, providing insights into a novel therapeutic target in breast cancer.
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Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal , Células-Tronco Neoplásicas/patologia , Resistina/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Mama/patologia , Neoplasias da Mama/sangue , Carcinogênese/patologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , NF-kappa B , Estadiamento de Neoplasias , Resistina/sangue , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-ZebraRESUMO
Our systematic review and meta-analysis of observational studies indicated that the use of antipsychotics was associated with a nearly 1.5-fold increase in the risk of fracture. First-generation antipsychotics (FGAs) appeared to carry a higher risk of fracture than second-generation antipsychotics (SGAs). INTRODUCTION: The risk of fractures associated with the use of antipsychotic medications has inconsistent evidence between different drug classes. A systematic review and meta-analysis was conducted to evaluate whether there is an association between the use of antipsychotic drugs and fractures. METHODS: Searches were conducted through the PubMed and EMBASE databases to identify observational studies that had reported a quantitative estimate of the association between use of antipsychotics and fractures. The summary risk was derived from random effects meta-analysis. RESULTS: The search yielded 19 observational studies (n = 544,811 participants) with 80,835 fracture cases. Compared with nonuse, use of FGAs was associated with a significantly higher risk for hip fractures (OR 1.67, 95% CI, 1.45-1.93), and use of second generation antipsychotics (SGAs) was associated with an attenuated but still significant risk for hip fractures (OR 1.33, 95% CI, 1.11-1.58). The risk of fractures associated with individual classes of antipsychotic users was heterogeneous, and odds ratios ranged from 1.24 to 2.01. Chlorpromazine was associated with the highest risk (OR 2.01, 95% CI 1.43-2.83), while Risperidone was associated with the lowest risk of fracture (OR 1.24, 95% CI 0.95-1.83). CONCLUSIONS: FGA users were at a higher risk of hip fracture than SGA users. Both FGAs and SGAs were associated with an increased risk of fractures, especially among the older population. Therefore, the benefit of the off-label use of antipsychotics in elderly patients should be weighed against any risks for fracture.
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Antipsicóticos/efeitos adversos , Fraturas por Osteoporose/induzido quimicamente , Fraturas do Fêmur/induzido quimicamente , Fraturas do Quadril/induzido quimicamente , Humanos , Medição de Risco/métodosRESUMO
BACKGROUND: Despite the huge and growing global burden of hepatocellular carcinoma (HCC), high-quality population-based studies of HCC prevalence and outcomes are scarce. PURPOSE: To analyze trends and predictors of hospital resource utilization and mortality rates in a population of patients who had received HCC surgery. PATIENTS AND MATERIALS: This population-based patient cohort study retrospectively analyzed 23,107 patients who had received surgical treatment for HCC from 1998 to 2009. RESULTS: The prevalence rate of surgical treatment in HCC patients significantly increased by 167.4% from 4.857 per 100,000 persons in 1998 to 12.989 per 100,000 persons in 2009 (P < 0.001). Age, gender, Deyo-Charlson co-morbidity index score, hospital volume, surgeon volume, digestive system disease, hepatitis type and liver cirrhosis were significantly associated with HCC surgical outcomes (P < 0.05). Over the 12-year period analyzed, the estimated mean hospital treatment cost increased 9.4% whereas mean length of stay (LOS) decreased 25.3%. The estimated mean overall survival time after HCC surgery was 40.9 months (SD 1.2 months), and the overall in-hospital 1-, 3-, and 5-year survival rates were 97.2%, 79.9%, 61.1%, and 54.6%, respectively. CONCLUSIONS: These population-based data reveal that the prevalence of HCC has increased, especially in older patients. Additionally, hospital treatment costs for HCC have increased despite decreases in LOS. These analytical results should be applicable to most countries with relatively small populations. Additionally, healthcare providers and patients should recognize that attributes of both the patient and the hospital may affect outcomes.
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Carcinoma Hepatocelular/cirurgia , Recursos em Saúde/estatística & dados numéricos , Hepatectomia/tendências , Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/epidemiologia , Estudos de Coortes , Comorbidade , Intervalo Livre de Doença , Feminino , Hepatectomia/economia , Hepatectomia/estatística & dados numéricos , Hepatite B Crônica/epidemiologia , Hepatite C Crônica/epidemiologia , Custos Hospitalares/tendências , Mortalidade Hospitalar , Humanos , Tempo de Internação/tendências , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Taiwan/epidemiologia , Resultado do Tratamento , Adulto JovemRESUMO
The design, construction and commissioning of a beamline and spectrometer for inelastic soft X-ray scattering at high resolution in a highly efficient system are presented. Based on the energy-compensation principle of grating dispersion, the design of the monochromator-spectrometer system greatly enhances the efficiency of measurement of inelastic soft X-rays scattering. Comprising two bendable gratings, the set-up effectively diminishes the defocus and coma aberrations. At commissioning, this system showed results of spin-flip, d-d and charge-transfer excitations of NiO. These results are consistent with published results but exhibit improved spectral resolution and increased efficiency of measurement. The best energy resolution of the set-up in terms of full width at half-maximum is 108â meV at an incident photon energy tuned about the Ni L3-edge.
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Y-box binding protein-1 (YB-1) is highly expressed in tumors and it participates in various cellular processes. Previous studies indicated that YB-1 binds to mispaired DNA and interacts with several mismatch repair (MMR)-related factors. However, its role in the MMR system remains undefined. Here, we found that YB-1 represses mutS homolog 6 (MSH6)-containing MMR complex formation and reduces MutSα mismatch binding activity by disrupting interactions among MMR-related factors. In an effort to elucidate how YB-1 exerts this inhibitory effect, we have identified two functional proliferating cell nuclear antigen (PCNA)-interacting protein (PIP)-boxes that mediate YB-1/PCNA interaction and locate within the C-terminal region of YB-1. This interaction is critical for the regulatory role of YB-1 in repressing MutSα mismatch binding activity, disrupting MutSα/PCNA/G/T heteroduplex ternary complex formation and inhibiting in vitro MMR activity. The differential regulation of 3' and 5' nick-directed MMR activity by YB-1 was also observed. Moreover, YB-1 overexpression is associated with the alteration of microsatellite pattern and the enhancement of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced and spontaneous mutations. Furthermore, upregulation of other PIP-box-containing proteins, such as myeloid cell leukemia-1 (Mcl-1) and inhibitor of growth protein 1b (ING1b), has no impact on MMR complex formation and mutation accumulation, thus revealing the significant effect of YB-1 on regulating the MMR system. In conclusion, our study suggests that YB-1 functions as a PCNA-interacting factor to exert its regulatory role on the MMR process and involves in the induction of genome instability, which may partially account for the oncogenic potential of YB-1.
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Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/metabolismo , Proteína 2 Homóloga a MutS/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteína 1 de Ligação a Y-Box/metabolismo , Sítios de Ligação , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Metilnitronitrosoguanidina/farmacologia , Instabilidade de Microssatélites , Mutação , Antígeno Nuclear de Célula em Proliferação/química , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Proteína 1 de Ligação a Y-Box/química , Proteína 1 de Ligação a Y-Box/genéticaRESUMO
Effects of mulberry leaf-related extracts (MLREs) on hydrogen peroxide-induced DNA damage in human lymphocytes and on inflammatory signaling pathways in human aortic endothelial cells (HAECs) were studied. The tested MLREs were rich in flavonols, especially bombyx faces tea (BT) in quercetin and kaempferol. Polyphenols, flavonoids, and anthocyanidin also abounded in BT. The best trolox equivalent antioxidant capacity (TEAC) was generated from the acidic methanolic extracts of BT. Acidic methanolic and water extracts of mulberry leaf tea (MT), mulberry leaf (M), and BT significantly inhibited DNA oxidative damage to lymphocytes based on the comet assay as compared to the H2O2-treated group. TNF- α -induced monocyte-endothelial cell adhesion was significantly suppressed by MLREs. Additionally, nuclear factor kappa B (NF- κ B) expression was significantly reduced by BT and MT. Significant reductions were also observed in both NF- κ B and activator protein (AP)-1 DNA binding by MLREs. Significant increases in peroxisome proliferator-activated receptor (PPAR) α and γ DNA binding by MLREs were also detected in M and MT extracts, but no evidence for PPAR α DNA binding in 50 µ g/mL MT extract was found. Apparently, MLREs can provide distinct cytoprotective mechanisms that may contribute to its putative beneficial effects on suppressing endothelial responses to cytokines during inflammation.
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Cancer stem cells are refractory to conventional therapy, which result to cancer metastasis and chemo-radioresistance. Grp78 is known to have important roles in cytoprotection and tumorigenesis in several cancers. We therefore examined whether Grp78 can serve as a therapeutic target for refractory stemness phenotype of head and neck cancer (HNC). Six HNC cell lines were used. Fluorescence-activated cell sorting (FACS) analysis was used to sort CD24(-)CD44(+) and Grp78(+) cells. The small interfering RNA (siRNA) knockdown and cDNA transfection were applied to examine the effects of Grp78 on cellular function. Western blot and confocol microscopy were used to determine the effects of downstream protein expressions. Xenografted mouse tumors and immunohistochemistry were used to validate the results. We found that Grp78 regulated the conversion of CD24(-)CD44(+) cells, a characteristic of HNC stem cells. The CD24(-)CD44(+)Grp78(+) cells showed superior chemo-radioresistance and invasion ability compared with CD24(-)CD44(+), Grp78(+) or the parental cells. Silencing Grp78 increased chemo-radiosensitivity, inhibited cell invasion, reverse epithelial-mesenchymal transition, suppressed cancer stemness, withdrew CD24(-)CD44(+) cell conversion and induced differentiated phenotype. Study in xenografted mice further showed that CD24(-)CD44(+)Grp78(+) cells exhibited highest tumorigenesis, compared with CD24(-)CD44(+) CD24(+)CD44(+) or the parental cells. Grp78 knockdown dramatically restrained tumor growth along with the inhibition of stem cell regulatory proteins Oct-4 and Slug. Grp78 may serve as a molecular target that can be further developed for eradication of refractory HNC with stemness phenotype.
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Neoplasias de Cabeça e Pescoço/terapia , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Células-Tronco Neoplásicas/patologia , Animais , Antígeno CD24/biossíntese , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Chaperona BiP do Retículo Endoplasmático , Transição Epitelial-Mesenquimal , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Proteínas de Choque Térmico/deficiência , Humanos , Receptores de Hialuronatos/biossíntese , Camundongos , Terapia de Alvo Molecular , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Fenótipo , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Distribuição Aleatória , Transfecção , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Cyclotron harmonic interactions are a key physics issue of critical importance to the generation of terahertz radiation via the electron cyclotron maser instability for practical magnetic field strengths. We present an inherent mechanism, as well as a deciding factor, which governs the competition between low- and high-harmonic interactions. Multimode simulations reveal the physical process in which a significant advantage develops for the lower-harmonic interaction, which eventually dominates in the fully nonlinear stage. The results also suggest a start-up scenario for persistent higher-harmonic operation.
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Chronic hepatitis C virus (HCV) infection is associated with chronic inflammation of liver, which leads to the development of cirrhosis and hepatocellular carcinoma (HCC). Because of severe side effects and only a 50-70% cure rate in genotype 1 HCV-infected patients upon current standard treatment with pegylated interferon-α plus ribavirin, new therapeutic regimens are still needed. San-Huang-Xie-Xin-Tang (SHXT) is a transitional Chinese herbal formula, composed of Rhei rhizoma, Scutellaria radix and Coptidis rhizome, and possesses anti-inflammatory effect. Here, we describe a (+)-catechin-containing fraction extracted from SHXT, referred as SHXT-frC, exhibited effective inhibition of HCV replication, with selectivity index value (SI; CC50 /EC50) of 84, and displayed synergistic anti-HCV effects when combined with interferon-α, HCV protease inhibitor telaprevir or polymerase inhibitor 2'-C-methylcytidine. The activation of factor-κB (NF-κB) and cyclooxygenase-2 (COX-2) signalling pathway has particular relevance to HCV-associated HCC. SHXT-frC treatment also caused a concentration-dependent decrease in the induction of COX-2 and NF-κB expression caused by either HCV replication or HCV NS5A protein. Collectively, SHXT-frC could be an adjuvant treatment for patients with HCV-induced liver diseases.