RESUMO
BACKGROUND AND AIMS: Risk stratification for patients with a higher risk of hepatocellular carcinoma (HCC) is crucial. We aimed to investigate the role of the Fibrosis-4 (FIB-4) index in predicting chronic hepatitis C (CHC)-related HCC. METHODS: A retrospective cohort study consecutively included treatment-naive CHC patients receiving longitudinal follow-up at the National Taiwan University Hospital from 1986 to 2014. The clinical data were collected and traced for HCC development. Multivariable Cox proportional hazard regression analysis was used to investigate the predictors for HCC. RESULTS: A total of 1285 patients in the ERADICATE-C cohort were included. The median age was 54, 56% were females, and 933 had HCV viremia. There were 33%, 38%, and 29% of patients having FIB-4 index <1.45, 1.45-3.25, and ≥3.25, respectively. After a median of 9-year follow-up, 186 patients developed HCC. Multivariable analysis revealed that older age, AFP≥20 ng/mL, cirrhosis, and a higher FIB-4 index were independent predictors for HCC. Compared with patients with FIB-4 index <1.45, those with FIB-4 1.45-3.25 had a 5.51-fold risk (95% confidence interval [CI]: 2.65-11.46), and those with FIB-4 ≥ 3.25 had 7.45-fold risk (95% CI: 3.46-16.05) of HCC. In CHC patients without viremia, FIB-4 index 1.45-3.25 and FIB-4 ≥ 3.25 increased 6.78-fold and 16.77-fold risk of HCC, respectively, compared with those with FIB-4 < 1.45. CONCLUSION: The baseline FIB-4 index can stratify the risks of HCC in untreated CHC patients, even those without viremia. The FIB-4 index should thus be included in the management of CHC.
RESUMO
Focusing on health professionals' tweets regarding COVID-19, this study examines whether and how those tweets are unique based on their identity as health experts. The data revealed that the infusion of health communication with political opinions, whether pro- or against certain political parties or health policies, reflects values and may deviate from the original purpose of health communication. In addition, sentiment analysis countered the intuitive thought that health experts merely fulfill their role as neutral encyclopedias without excessively carrying sentiment. We conclude by reflecting on the meaning of health communication in relation to the political stances of professionals.
Assuntos
COVID-19 , Comunicação em Saúde , Mídias Sociais , Humanos , Pandemias , Pessoal de SaúdeRESUMO
BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder that primarily causes symmetrical polyarthritis and bone deformity. In RA patients, sight-threatening inflammatory eye complications would be expected. OBJECTIVE: The objective of the study is to ascertain the macular retinal vessel density changes in RA patients and controls using optical coherence tomography angiography (OCTA), and to investigate the association between disease and microvascular density alterations. METHODS: A total of 12 RA patients (24 eyes) and 12 age- and gender-matched control participants (24 eyes) were recruited to the study. We used the Early Treatment Diabetic Retinopathy Study partitioning, hemispheric quadrants and annular partitioning to segment each image into different subregions. The vascular density of superficial retina layer, deep retina layer and conjunctival capillary plexus was quantitatively measured by OCTA and compared with the control group. Correlation analysis was used to explore the relationship between STMI and conjunctival capillaries densities. RESULTS: In the superficial retinal layer, the vascular density of S, I, L, SL, SR, IL and C1-C5 were significantly decreased in the RA group compared with the control group (P<0.05). For the deep retinal layer, the vascular density of S, SL, SR, IL, C1, C2 and C4 also decreased in RA group. A significant positive correlation was indicated between conjunctival vascular and STMI densities (r = 0.713, P<0.05). CONCLUSION: OCTA results suggest that RA patients present with a reduced macular retinal vascular density. These subtle alterations of ocular microcirculation may precede severe eye involvements and may be a potential biomarker for early distinguishing abnormal eyes from healthy eyes.
Assuntos
Artrite Reumatoide , Tomografia de Coerência Óptica , Humanos , Feminino , Angiofluoresceinografia/métodos , Tomografia de Coerência Óptica/métodos , Retina/diagnóstico por imagem , Microvasos/diagnóstico por imagem , Artrite Reumatoide/diagnóstico por imagemRESUMO
Psychological stress is widely acknowledged as a major contributor to immunosuppression, rendering individuals more susceptible to various diseases. The complex interplay between the nervous, endocrine, and immune systems underlies stress-induced immunosuppression. However, the underlying mechanisms of psychological-stress-induced immunosuppression remain unclear. In this study, we utilized a restraint stress mouse model known for its suitability in investigating physiological regulations during psychological stress. Comparing it with cold exposure, we observed markedly elevated levels of stress hormones corticosterone and cortisol in the plasma of mice subjected to restraint stress. Furthermore, restraint-stress-induced immunosuppression differed from the intravenous immunoglobulin-like immunosuppression observed in cold exposure, with restraint stress leading to increased macrophage cell death in the spleen. Suppression of pyroptosis through treatments of inflammasome inhibitors markedly ameliorated restraint-stress-induced spleen infiltration and pyroptosis cell death of macrophages in mice. These findings suggest that the macrophage pyroptosis associated with restraint stress may contribute to its immunosuppressive effects. These insights have implications for the development of treatments targeting stress-induced immunosuppression, emphasizing the need for further investigation into the underlying mechanisms.
Assuntos
Terapia de Imunossupressão , Piroptose , Animais , Camundongos , Morte Celular , Macrófagos , Restrição FísicaRESUMO
Immune checkpoint inhibitors are groundbreaking resources for cancer therapy. However, only a few patients with hepatocellular carcinoma (HCC) have shown positive responses to anti-PD-1 therapy. Neoantigens are sequence-altered proteins resulting from somatic mutations in cancer. This study identified the neoantigens of Hep-55.1C and Dt81 Hepa1-6 HCCs by comparing their whole exome sequences with those of a normal C57BL/6 mouse liver. Immunogenic long peptides were pooled as peptide vaccines. The vaccination elicited tumor-reactive immune responses in C57BL/6 mice, as demonstrated by IFN-γ ELISPOT and an in vitro killing assay of splenocytes. In the treatment of three mouse HCC models, combined neoantigen vaccination and anti-PD-1 resulted in more significant tumor regression than monotherapies. Flow cytometry of the tumor-infiltrating lymphocytes showed decreased Treg cells and monocytic myeloid-derived suppressor cells, increased CD8+ T cells, enhanced granzyme B expression, and reduced exhaustion-related markers PD-1 and Lag-3 on CD8+ T cells in the combination group. These findings provide a strong rationale for conducting clinical studies of using neoantigen vaccination in combination with anti-PD-1 to treat patients with HCC.
Assuntos
Vacinas Anticâncer , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Linfócitos T CD8-Positivos , Camundongos Endogâmicos C57BL , Vacinas Anticâncer/farmacologiaRESUMO
Introduction: During the COVID-19 pandemic, many employees were encouraged to temporarily work from home as an attempt to decrease social contact with others. However, the employees' quality of life (QoL) may have been threatened by this mode of working. This study, therefore, aims to explore the employees' QoL given the new mode of working from home (WFH) as a result of the pandemic vs. working in the office (WIO), the amount of social contact that they were exposed to, and the ratio of face-to-face contact that they had. Methods: A total of 803 WFH employees and 588 WIO employees' QoL was assessed during the same time period using the WHOQOL-BREF, which contains four domains: physical health, psychological health, social relationship, and the environment. We then divided the participants into 16 groups in accordance with the levels of work mode, social contact quantity, and face-to-face contact ratio-forming a case-control study. A differential item functioning (DIF) analysis was used to analyze the responses on the WHOQOL-BREF under the 4-dimensional rating scale model fitting. Results: The results indicated that WFH employees' QoL was superior to that of WIO employees. The relationship between the WFH mode and the employees' QoL was specifically moderated by the amount of social contact and the ratio of face-to-face contact that was experienced. The results further demonstrated that the increased amount of non-face-to-face contact was better for WFH employees' QoL than that of WIO employees. Discussion: In conclusion, the WFH mode was practical during the COVID-19 pandemic, as our findings indicated that WFH employees' QoL was better than WIO employees' QoL. However, maintaining social connections is equally important as this allows employees to perform better at their jobs and maintain such performance. The employees with a higher number of social support had a better QoL. Additionally, the facets detected as DIF items provided implications for the QoL with regard to the research methodology and insight into factors affecting the employees' QoL.
RESUMO
The efficacy of treatment for advanced hepatocellular carcinoma (HCC) has remained limited. Polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded RNA that serves as a viral mimic and induces an immune response. Intratumoral (IT) poly-ICLC injections can induce an autovaccination effect and prime the immune system, whereas intramuscular (IM) injection of poly-ICLC can attract and maintain tumor-specific cytotoxic T lymphocytes in tumors. We found that IT injection of poly-ICLC upregulated the expression of CD83 and CD86 on conventional type 1 dendritic cells in tumors. Combination therapy with IT followed by IM injections of poly-ICLC significantly inhibited tumor growth and increased the tumor-infiltrating CD8+ T cells in two syngeneic mouse models of HCC. Depletion of CD8+ T cells attenuated the antitumor effect. An IFN-γ enzyme-linked immunospot of purified tumoral CD8+ T cells revealed a significant proportion of tumor-specific T cells. Finally, the sequential poly-ICLC therapy induced abscopal effects in two dual-tumor models. This study provides evidence that the sequential poly-ICLC therapy significantly increased infiltration of tumor-specific CD8+ T cells in the tumors and induced CD8+ T cell-dependent inhibition of tumor growth, as well as abscopal effects.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carboximetilcelulose Sódica , Linfócitos T CD8-Positivos , Neoplasias Hepáticas/terapia , Poli I-C , Polilisina , VacinaçãoRESUMO
BACKGROUND: Liver transplantation (LT) is the treatment of choice for patients with hepatocellular carcinoma (HCC). Recurrence of HCC after LT occurs in 10% to 20% of cases. Preclinical studies to evaluate immune checkpoint inhibitors in conjunction with immunosuppressant treatment in transplant recipients have been lacking. Here, we evaluated the efficacy, safety, and mechanism of programmed cell death-1 (PD1) blockade under tacrolimus treatment in transplant recipients. METHODS: We used a murine allogeneic skin transplantation model and murine syngeneic subcutaneous and orthotopic HCC models and measured the tumor volume and the change in tumor-infiltrating lymphocytes under PD1 blockade and tacrolimus treatment. RESULTS: Tacrolimus treatment prolonged allograft survival in the allogeneic transplantation model and enhanced tumor growth in both subcutaneous and orthotopic HCC models. PD1 blockade suppressed tumor growth and lung metastasis in correlation with the number of infiltrating CD8 + T cells. Under tacrolimus treatment, PD1 blockade still resulted in an antitumor effect accompanied by a significant increase in tumor-infiltrating CD8 + T cells, natural killer cells, dendritic cells, and natural killer T cells. Tacrolimus treatment rescued the acceleration of transplant rejection induced by PD1 blockade in the allogeneic transplantation model. CONCLUSIONS: Our data suggest that treatment with high-dose tacrolimus in conjunction with PD1 blockade has an antitumor effect and reduces transplant rejection in mouse models of allograft skin transplantation and HCC. Thus, these results suggest that a clinical trial of PD1 inhibitors for HCC in LT merits consideration.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Tacrolimo/farmacologia , Neoplasias Hepáticas/patologia , Imunoterapia , Imunossupressores/farmacologia , Linfócitos T CD8-PositivosRESUMO
Studies have suggested that maternal autoimmune diseases are associated with an increased risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, research on the association of paternal autoimmune diseases with ADHD and ASD risk has remained inconclusive. Using the Taiwan National Health Insurance Research Database, we selected 708,517 family triads (father-mother-child) between 2001 and 2008 and followed them until the end of 2011. Parental autoimmune diseases as well as ADHD and ASD in children were identified during the study period. Increased ADHD risk in children in terms of hazard ratios (HRs) and 95% confidence intervals (CIs) was associated with prenatal exposure to paternal autoimmune diseases, including Sjögren's syndrome (HR: 8.41, 95% CI: 2.72-26.05), psoriasis (HR: 1.95, 95% CI: 1.05-3.63), and ankylosing spondylitis (HR: 2.02, 95% CI: 1.29-2.15), as well as maternal autoimmune diseases, such as systemic lupus erythematosus (HR: 1.53, 95% CI: 1.09-2.15), type 1 diabetes mellitus (HR: 1.55, 95% CI: 1.02-2.36), inflammatory bowel disease (HR: 2.37, 95% CI: 1.59-3.52), psoriasis (HR: 1.70, 95% CI: 1.00-2.87), and ankylosing spondylitis (HR: 2.07, 95% CI: 1.11-3.86). However, ASD was only associated with paternal inflammatory bowel disease (HR: 3.08, 95% CI: 1.15-8.28) and ankylosing spondylitis (HR: 2.65, 95% CI: 1.10-6.39). Both paternal and maternal autoimmune diseases were associated with increased likelihood of ADHD in children. However, only paternal autoimmune diseases were related to offspring ASD risk. The precise pathomechanism underlying the correlation between parental autoimmunity and child neurodevelopment requires further investigation.
Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Doenças Autoimunes , Doenças Inflamatórias Intestinais , Psoríase , Espondilite Anquilosante , Feminino , Gravidez , Humanos , Estudos de Coortes , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/complicações , Espondilite Anquilosante/complicações , Fatores de Risco , Pais , Doenças Autoimunes/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Psoríase/complicações , Doenças Inflamatórias Intestinais/complicaçõesRESUMO
Motion is a typical reaction among animals and humans trying to reach better conditions in a changing world. This aspect has been studied intensively in social dilemmas where competing players' individual and collective interests are in conflict. Starting from the traditional public goods game model, where players are locally fixed and unconditional cooperators or defectors are present, we introduce two additional strategies through which agents can change their positions of dependence on the local cooperation level. More importantly, these so-called sophisticated players should bear an extra cost to maintain their permanent capacity to evaluate their neighborhood and react accordingly. Hence, four strategies compete, and the most successful one can be imitated by its neighbors. Crucially, the introduction of costly movement has a highly biased consequence on the competing main strategies. In the majority of parameter space, it is harmful to defectors and provides a significantly higher cooperation level when the population is rare. At an intermediate population density, which would be otherwise optimal for a system of immobile players, the presence of mobile actors could be detrimental if the interaction pattern changes slightly, thereby blocking the optimal percolation of information flow. In this parameter space, sophisticated cooperators can also show the co-called Moor effect by first avoiding the harmful vicinity of defectors; they subsequently transform into an immobile cooperator state. Hence, paradoxically, the additional cost of movement could be advantageous to reach a higher general income, especially for a rare population when subgroups would be isolated otherwise.
Assuntos
Comportamento Cooperativo , Teoria dos Jogos , Animais , Evolução Biológica , HumanosRESUMO
BACKGROUND: Using a 10 week nationwide online survey performed during a time period containing the time ahead, the start, and the peak of a COVID-19 outbreak in Taiwan, we investigated aspects that could affect participants' vaccination intentions. METHODS: From March to May 2021, we surveyed 1,773 people in Taiwan, aged from 20 to 75 years, to determine potential acceptance rates and factors influencing the acceptance of a COVID-19 vaccine. We used an ordinal logistic regression with a backward selection method to identify factors that affected vaccination intention. RESULTS: Several factors could increase individuals' vaccination intentions including: being male, older, with an openness personality, having a better quality of life in the physical health domain, having better knowledge and personal health behavior, having more trust in the government, and being worried about misinformation. Perceived risks played a crucial role in the vaccine decision-making process. When the pandemic intensified, people's vaccination intentions increased significantly. CONCLUSION: The findings of the present study could highlight individuals' vaccination attitudes and provide governments with an empirical and dynamic base to design tailored strategies to increase vaccination rates.
Assuntos
COVID-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Surtos de Doenças/prevenção & controle , Feminino , Humanos , Masculino , Qualidade de Vida , Taiwan/epidemiologia , Vacinação , Hesitação VacinalRESUMO
The rise of the Big Data paradigm has made it more feasible to track how personal networks evolve on social media, where auto-generated contact records and fine-grained temporal data sequences help capture how and when interpersonal ties and contacts change their roles. Using a sample of matched survey data and social media records, we investigated the mechanisms by which indirect contacts ("degree-2 alters") transform into direct contacts ("degree-1 alters") from a Facebook user's (ego's) point of view. To highlight the temporal sequences, we assigned different roles to the same alters depending on how each of them is connected with ego at different periods of time. Multilevel event history analyses pinpoint several online actions and network features of ego, degree-1 alters, and degree-2 alters, as the key factors that contribute to the transformation from indirect contacts into direct contacts.
L"essor du paradigme du Big Data a rendu plus réalisable le suivi de l"évolution des réseaux personnels sur les médias sociaux, où les enregistrements de contacts générés automatiquement et les séquences de données temporelles à grain fin permettent de saisir comment et quand les liens interpersonnels et les contacts changent de rôle. À l"aide d"un échantillon de données d"enquête et d"enregistrements de médias sociaux appariés, nous avons étudié les mécanismes par lesquels les contacts indirects ("altérations de degré 2â³) se transforment en contacts directs ("altérations de degré 1â³) du point de vue d"un utilisateur de Facebook (ego). Pour mettre en évidence les séquences temporelles, nous avons attribué des rôles différents aux mêmes alters en fonction de la façon dont chacun d"entre eux est connecté avec ego à différentes périodes de temps. Les analyses multiniveaux de l"historique des événements mettent en évidence plusieurs actions en ligne et caractéristiques du réseau d"ego, des alters de degré 1 et des alters de degré 2, comme étant les facteurs clés qui contribuent à la transformation des contacts indirects en contacts directs.
Assuntos
Mídias Sociais , Apoio Social , Big Data , Humanos , Inquéritos e QuestionáriosRESUMO
The accuracy of expansion microscopy (ExM) depends on the structural preservation of samples embedded in a hydrogel. However, it has been unknown to what extent gel embedding alters the molecular positions of individual labeled sites. Here, we quantified the accuracy of gel embedding by using stochastic optical reconstruction microscopy (STORM) to image DNA origami with well-defined structures. We found that embedding in hydrogels based on polyacrylamide, the most widely used chemistry in ExM, resulted in random displacements of labeled sites with a standard deviation of ~ 16 nm. In contrast, we found that embedding in tetra-gel, a hydrogel that does not depend on free-radical chain-growth polymerization, preserved labeled sites with a standard deviation of less than 5 nm. By combining tetra-gel ExM with STORM, we were able to resolve 11-nm structural features without the loss in accuracy seen with polyacrylamide gels. Our study thus provides direct measurements of the single-molecule distortions resulting from hydrogel embedding, and presents a way to improve super-resolution microscopy through combination with tetra-gel ExM.
Assuntos
Géis/química , Microscopia de Fluorescência , Imagem Óptica , Resinas Acrílicas/química , DNA/química , Conformação de Ácido NucleicoRESUMO
Sophisticated axolotl limb regeneration is a highly orchestrated process that requires highly regulated gene expression and epigenetic modification patterns at precise positions and timings. We previously demonstrated two waves of post-amputation expression of a nerve-mediated repressive epigenetic modulator, histone deacetylase 1 (HDAC1), at the wound healing (3 days post-amputation; 3 dpa) and blastema formation (8 dpa onward) stages in juvenile axolotls. Limb regeneration was profoundly inhibited by local injection of an HDAC inhibitor, MS-275, at the amputation sites. To explore the transcriptional response of post-amputation axolotl limb regeneration in a tissue-specific and time course-dependent manner after MS-275 treatment, we performed transcriptome sequencing of the epidermis and soft tissue (ST) at 0, 3, and 8 dpa with and without MS-275 treatment. Gene Ontology (GO) enrichment analysis of each coregulated gene cluster revealed a complex array of functional pathways in both the epidermis and ST. In particular, HDAC activities were required to inhibit the premature elevation of genes related to tissue development, differentiation, and morphogenesis. Further validation by Q-PCR in independent animals demonstrated that the expression of 5 out of 6 development- and regeneration-relevant genes that should only be elevated at the blastema stage was indeed prematurely upregulated at the wound healing stage when HDAC1 activity was inhibited. WNT pathway-associated genes were also prematurely activated under HDAC1 inhibition. Applying a WNT inhibitor to MS-275-treated amputated limbs partially rescued HDAC1 inhibition, resulting in blastema formation defects. We propose that post-amputation HDAC1 expression is at least partially responsible for pacing the expression timing of morphogenic genes to facilitate proper limb regeneration.
RESUMO
SUMMARY: Axolotl limb regeneration is a fascinating characteristic that has attracted attention for several decades. Our previous studies on axolotl limb regeneration indicated that the satellite cells in the remnant muscles move distally into the blastema to regenerate new muscles that are separated by a gap from remnant muscles. Thereafter, the regenerative muscle fibers start to reconnect with remnant ones. In this study, the reconnection at the individual muscle fiber level was elucidated to test the hypothesis that this reconnection happens synchronously among involved muscles. Three pairs of EGFP+ mid-bud stage blastemas were transplanted onto freshly amputated stumps of RFP+ axolotls at the same thigh position to generate double fluorescence chimeric regenerative hindlimbs. These regenerative limbs were harvested very late far beyond they had reached the late differentiation stage. Fluorescence imaging of these limbs in cross sections revealed that in the proximal remnant part of the muscle fiber, reconnection occurred at a different pace among the muscles. In the major thigh muscle gracilis, the reconnection started from the periphery before it was completed. Furthermore, RFP+ muscle fibers contributed to muscle regeneration in the distal regenerative parts. Intriguingly, this red cell contribution was limited to ventral superficial muscles of the calf. This kind of double fluorescence chimeric limb regeneration model may help increase the understanding of the patterning of axolotl limb regeneration in late stages.
RESUMEN: La regeneración del miembro de Axolotl es una característica fascinante que ha llamado la atención durante varias décadas. Nuestros estudios previos sobre la regeneración del miembro del Axolotl indicaron que las células satélite en los músculos remanentes se mueven distalmente hacia el blastema para regenerar nuevos músculos que están separados por una brecha de músculos remanentes. A partir de entonces, las fibras musculares regenerativas comienzan a reconectarse con las restantes. En este estudio, se aclaró la reconexión a nivel de fibra muscular individual para probar la hipótesis de que esta reconexión ocurre sincrónicamente entre los músculos involucrados. Se trasplantaron tres pares de blastemas EGFP+ en la etapa de yema media en tocones recién amputados de axolotls RFP+ en la misma posición del muslo para generar miembros posteriores regenerativos quiméricos de fluorescencia doble. Estos miembros regenerativos se cosecharon muy tarde mucho más allá de haber alcanzado la etapa de diferenciación tardía. Las imágenes de fluorescencia de estos miembros en secciones transversales revelaron que en la parte remanente proximal de la fibra muscular, la reconexión se produjo a un ritmo diferente entre los músculos. En el músculo grácil, la reconexión comenzó desde la periferia antes de completarse. Además, las fibras musculares RFP+ contribuyeron a la regeneración muscular en las partes regenerativas distales. Curiosamente, esta contribución de glóbulos rojos se limitó a los músculos superficiales ventrales de la pantorrilla. Este tipo de modelo de regeneración quimérica de doble fluorescencia del miembro puede ayudar a aumentar la comprensión del patrón de la regeneración del miembro del Axolotl en etapas tardías.
Assuntos
Animais , Regeneração/fisiologia , Extremidades/fisiologia , Ambystoma mexicanum/fisiologia , Animais Geneticamente Modificados , Transplante de Células , FluorescênciaRESUMO
PURPOSE/BACKGROUND: The increased risk of type 2 diabetes mellitus (T2DM) among users of antidepressants (ADs) might be mediated by depression. We investigated whether ADs are associated with increased risk of T2DM in patients with depression. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of ADs and the risk of T2DM is examined. METHODS/PROCEDURES: We conducted a retrospective nested case-control study using data from Taiwan's National Health Insurance Research Database between 2000 and 2013. A total of 3038 patients with depression, 1519 cases of T2DM, and 1519 controls matched for age, sex, and index date, were included. Exposure to ADs was categorized by type and SERT. The association between AD exposure and T2DM development was assessed using conditional logistic regression analysis. FINDINGS/RESULTS: No association between T2DM development and selective serotonin reuptake inhibitors (adjusted odds ratio [AOR], 1.01; 95% confidence interval [CI], 0.87-1.19; P = 0.962), serotonin-norepinephrine reuptake inhibitors (AOR, 1.13; 95% CI, 0.94-1.37; P = 1.196), tricyclic antidepressants (AOR, 1.01; 95% CI, 0.85-1.21; P = 0.906), or others (AOR, 0.88; 95% CI, 0.75-1.03; P = 0.104) was found. Alternatively, no association between individual ADs and potency of affinity to SERT and the risk of T2DM was found. IMPLICATIONS/CONCLUSIONS: No association between ADs and increase risk of T2DM was found in patients with depression. However, regular metabolic evaluations are recommended for patients with depression regularly taking ADs.
Assuntos
Antidepressivos/efeitos adversos , Diabetes Mellitus Tipo 2/induzido quimicamente , Antidepressivos/farmacologia , Estudos de Casos e Controles , Bases de Dados Factuais , Depressão/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligação Proteica/efeitos dos fármacos , Estudos Retrospectivos , Fatores de Risco , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismoRESUMO
BACKGROUND: Young individuals with attention-deficit hyperactivity disorder (ADHD) may have an elevated risk of influenza because of the difficulty in complying with the behavioral procedures that help protect against influenza. Moreover, the effects of sufficient methylphenidate treatment on influenza have received little attention. OBJECTIVE: This study evaluated the association between ADHD medication usage and influenza and assessed the effect of duration of ADHD treatment on the risk of influenza using a nationwide population-based database. METHODS: This study investigated methylphenidate usage and the risk of influenza among children and adolescents with ADHD. We identified 5259 young individuals aged less than 18 years who were diagnosed as having ADHD between 1996 and 2013 from the National Health Insurance Research Database of Taiwan, and we tested whether methylphenidate use affects influenza risk using Cox proportional hazard models. RESULTS: After controlling for confounding factors, the results indicated that influenza risk significantly reduced in the group of ADHD patients who were prescribed methylphenidate for 90 days and more (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.52-0.75, p<0.001), demonstrating a 38% reduction in the risk of influenza in this group. However, this was not observed in the group of ADHD patients who used methylphenidate for 1-90 days (HR: 0.69, 95% CI: 0.89-1.05, p=0.12). CONCLUSION: The lower incidence of influenza observed in the group prescribed with methylphenidate for a longer period highlights the importance of compliance to medication and psychoeducation with regard to ADHD management.
RESUMO
Glioblastoma multiforme is the most common and aggressive glial tumor with poor prognosis. Importantly, effective treatment options for glioblastoma are unmet needs. Obesity and low physical activity have been linked with a high risk of cancer, and exercise is related to delayed cancer development and progression. Epidemiological studies have revealed a correlation between exercise and the survival rate of patients with glioblastoma. Nevertheless, the mechanisms by which exercise exerts its anticancer effects in glioblastoma remain unclear. Here, we found that irisin, an exercise-induced myokine, induced G2 /M cell cycle arrest and increased p21 levels in glioblastoma cells, leading to the inhibition of cell proliferation. In addition, irisin inhibited glioblastoma cell invasion by upregulating TFPI-2 and even reversed the aggressive tumor phenotype promoted by co-cultivation with cancer-associated adipocytes. Furthermore, irisin retarded xenograft glioblastoma tumor growth, and radiolabeled irisin demonstrated specific tumor-targeting capability in vivo. Therefore, this study identified one potential molecular mechanism by which exercise prevents cancer progression via irisin. Intriguingly, irisin has the potential to be developed as a molecular imaging and therapeutic anticancer agent.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células , Exercício Físico , Fibronectinas/farmacologia , Glioma/tratamento farmacológico , Neuropeptídeos/farmacologia , Animais , Apoptose , Ciclo Celular , Movimento Celular , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Camundongos , Camundongos Nus , Invasividade Neoplásica , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Stannous oxide (SnO) nanowires were synthesized by a template and catalyst-free thermal oxidation process. After annealing a Sn nanowires-embedded anodic aluminum oxide (AAO) template in air, we obtained a large amount of SnO nanowires. SnO nanowires were first prepared by electrochemical deposition and an oxidization method based on an AAO template. The preparation of SnO nanowires used aluminum sheet (purity 99.999%) and then a two-step anodization procedure to obtain a raw alumina mold. Finally, transparent alumina molds (AAO template) were obtained by reaming, soaking with phosphoric acid for 20 min, and a stripping process. We got a pore size of < 20 nm on the transparent alumina mold. In order to meet electroplating needs, we produced a platinum film on the bottom surface of the AAO template by using a sputtering method as the electrode of electroplating deposition. The structure was characterized by X-ray diffraction (XRD). High resolution transmission electron microscopy (HRTEM) and field emission scanning electron microscopy (FESEM) with X-ray energy dispersive spectrometer (EDS) were used to observe the morphology. The EDS spectrum showed that components of the materials were Sn and O. FE-SEM results showed the synthesized SnO nanowires have an approximate length of ~10-20 µm with a highly aspect ratio of > 500. SnO nanowires with a Sn/O atomic ratio of ~1:1 were observed from EDS. The crystal structure of SnO nanowires showed that all the peaks within the spectrum lead to SnO with a tetragonal structure. This study may lead to the use of the 1D structure nanowires into electronic nanodevices and/or sensors, thus leading to nano-based functional structures.