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1.
Hepatology ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33942350

RESUMO

BACKGROUND & AIMS: Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various biliary tract cancer (BTC) subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH & RESULTS: Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose (DDD) was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Analyses accounted for competing risk of cardiovascular deaths, landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI, 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI, 0.48 to 0.59) and 0.42 (95% CI, 0.31 to 0.58) for ≤1 and >1 maximum DDD, respectively, and showed a dose-response trend (p < 0.001; nonusers as a reference). Cancer-specific mortality was lower with postdiagnosis aspirin use in patients with all major BTC subtypes. CONCLUSIONS: The nationwide study revealed that postdiagnosis aspirin use was associated with improved BTC-specific mortality of various subtypes. The findings suggest that additional randomized trials are required to investigate aspirin's efficacy in BTC.

2.
Sci Rep ; 11(1): 9346, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931661

RESUMO

This study determines the effect of the configuration of the magnetic field on the movement of gas bubbles that evolve from platinum electrodes. Oxygen and hydrogen bubbles respectively evolve from the surface of the anode and cathode and behave differently in the presence of a magnetic field due to their paramagnetic and diamagnetic characteristics. A magnetic field perpendicular to the surface of the horizontal electrode causes the bubbles to revolve. Oxygen and hydrogen bubbles revolve in opposite directions to create a swirling flow and spread the bubbles between the electrodes, which increases conductivity and the effectiveness of electrolysis. For vertical electrodes under the influence of a parallel magnetic field, a horizontal Lorentz force effectively detaches the bubbles and increases the conductivity and the effectiveness of electrolysis. However, if the layout of the electrodes and magnetic field results in upward or downward Lorentz forces that counter the buoyancy force, a sluggish flow in the duct inhibits the movement of the bubbles and decreases the conductivity and the charging performance. The results in this study determine the optimal layout for an electrode and a magnetic field to increase the conductivity and the effectiveness of water electrolysis, which is applicable to various fields including energy conversion, biotechnology, and magnetohydrodynamic thruster used in seawater.

3.
Nutrients ; 13(4)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805038

RESUMO

Primary congenital hypothyroidism is a disease associated with low serum thyroxine and elevated thyroid-stimulating hormone (TSH) levels. The processes of screening and treating congenital hypothyroidism, in order to prevent neurodevelopmental impairment (NDI) in newborns, have been well investigated. Unlike term infants, very preterm infants (VPIs) may experience low thyroxine with normal TSH levels (<10.0 µIU/mL) during long-stay hospitalization. In the current literature, thyroxine treatment has been evaluated only for TSH-elevated VPIs. However, the long-term impact of low thyroxine levels in certain VPIs with normal TSH levels deserves more research. Since July 2007, VPIs of this study unit received screenings at 1 month postnatal age (PNA) for serum TSH levels and total thyroxine (TT4), in addition to two national TSH screenings scheduled at 3-5 days PNA and at term equivalent age. This study aimed to establish the correlation between postnatal 1-month-old TT4 concentration and long-term NDI at 24 months corrected age among VPIs with serial normal TSH levels. VPIs born in August 2007-July 2016 were enrolled. Perinatal demography, hospitalization morbidities, and thyroid function profiles were analyzed, and we excluded those with congenital anomalies, brain injuries, elevated TSH levels, or a history of thyroxine treatments. In total, 334 VPIs were analyzed and 302 (90.4%) VPIs were followed-up. The postnatal TT4 concentration was not associated with NDI after multivariate adjustment (odd ratios 1.131, 95% confidence interval 0.969-1.32). To attribute the NDI of TSH-normal VPIs to a single postnatal TT4 concentration measurement may require more research.

4.
ACS Nano ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33729770

RESUMO

Although colloidal lead halide perovskite quantum dots (PQDs) exhibit desirable emitter characteristics with high quantum yields and narrow bandwidths, instability has limited their applications in devices. In this paper, we describe spray-synthesized CsPbI3 PQD quantum emitters displaying strong photon antibunching and high brightness at room temperature and stable performance under continuous excitation with a high-intensity laser for more than 24 h. Our PQDs provided high single-photon emission rates, exceeding 9 × 106 count/s, after excluding multiexciton emissions and strong photon antibunching, as confirmed by low values of the second-order correlation function g(2)(0) (reaching 0.021 and 0.061 for the best and average PQD performance, respectively). With such high brightness and stability, we applied our PQDs as quantum random number generators, which demonstrably passed all of the National Institute of Standards and Technology's randomness tests. Intriguingly, all of the PQDs exhibited self-healing behavior and restored their PL intensities to greater than half of their initial values after excitation at extremely high intensity. Half of the PQDs even recovered almost all of their initial PL intensity. The robust properties of these spray-synthesized PQDs resulted from high crystallinity and good ligand encapsulation. Our results suggest that spray-synthesized PQDs have great potential for use in future quantum technologies (e.g., quantum communication, quantum cryptography, and quantum computing).

5.
Cell Signal ; 81: 109930, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33515696

RESUMO

MicroRNA-27 is a critical non-coding metabolic gene that is often aberrantly overexpressed in non-alcoholic fatty livers (NAFLD). However, the pathogenic role of miR-27 in NAFLD remains unknown. In this study, we attempted to identify the mechanism by which miR-27 was regulated in the context of insulin resistance, a predisposed metabolic disorder in NAFLD. Our data from cell culture and animal studies showed that insulin, CREB, and Hippo signalings coordinately regulated miR-27. First, miR-27 was upregulated in palmitate-treated cells and high fat diet-fed mouse livers, which exhibited insulin resistance and CREB overexpression. Second, miR-27 peaked in the mouse liver at the post-absorptive phase when CREB activity was increased. Also, miR-27 was increased rapidly in cell lines when CREB was deactivated by insulin treatment. Third, miR-27 was decreased in cultured cells when CREB was downregulated by siRNA or metformin treatment. In contrast, Forskolin-mediated activation of CREB promoted miR-27 expression. Fourth, Hippo signaling repressed miR-27 in a CREB-independent manner: miR-27 was reduced in cells at full confluence but was inhibited in cells transfected with siRNA against Lats2 and Nf2, which were two positive regulators of Hippo signaling. Lastly, bioinformatics and luciferase assay showed that miR-27 inhibited Akt phosphorylation by targeting Pdpk1 and Pik3r1. Overexpression of miR-27 impaired Akt phosphorylation in cell lines and primary mouse hepatocytes upon insulin stimulation. In conclusion, our data suggest that insulin, CREB, and Hippo signalings contribute to aberrant miR-27 overexpression and eventually lead to insulin resistance in NAFLD.

6.
Mil Med ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410872

RESUMO

INTRODUCTION: Fecal immunochemical testing (FIT) is the most commonly used colorectal cancer (CRC) screening tool worldwide and accounts for 10% of all CRC screening in the United States. Potential vulnerabilities for patients enrolled to facilities within the military health system have recently come to light requiring reassessment of best practices. We studied the impact of a process improvement initiative designed to improve the safety and quality of care for patients after a positive screening FIT given previously published reports of poor organization performance. METHODS: During a time of increased utilization of nonendoscopic means of screening, we assessed rates of colonoscopy completion and time to colonoscopy after positive FIT after a multi-faceted process improvement initiative was implemented, compared against an institutional control period. The interventions included mandatory indication labeling at the time of order entry, as well as utilization of subspecialty nurse navigators to facilitate rapid follow-up even the absence of a referral from primary care. RESULTS: Preintervention, 34.8% of patients did not have appropriate follow-up of a positive FIT. Those that did had a variable and prolonged wait time of 140.1 ± 115.9 days. Postintervention, a standardized order mandating test indication labeling allowed for proactive gastroenterology involvement. Colonoscopy follow-up rate increased to 91.9% with an average interval of 21.9 ± 12.3 days. CONCLUSION: The addition of indication labels and patient navigation after positive screening FIT was associated with 57.1% absolute increase in timely diagnostic colonoscopy. Similar highly reliable systems-based solutions should be adopted for CRC screening, and further implementation for other preventative screening interventions should be pursued.

7.
Oncogenesis ; 9(12): 104, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33281189

RESUMO

Human HLTF participates in the lesion-bypass mechanism through the fork reversal structure, known as template switching of post-replication repair. However, the mechanism by which HLTF promotes the replication progression and fork stability of damaged forks remains unclear. Here, we identify a novel protein-protein interaction between HLTF and PARP1. The depletion of HLTF and PARP1 increases chromosome breaks, further reduces the length of replication tracks, and concomitantly increases the number of stalled forks after methyl methanesulfonate treatment according to a DNA fiber analysis. The progression of replication also depends on BARD1 in the presence of MMS treatment. By combining 5-ethynyl-2'-deoxyuridine with a proximity ligation assay, we revealed that the HLTF, PARP1, and BRCA1/BARD1/RAD51 proteins were initially recruited to damaged forks. However, prolonged stalling of damaged forks results in fork collapse. HLTF and PCNA dissociate from the collapsed forks, with increased accumulation of PARP1 and BRCA1/BARD1/RAD51 at the collapsed forks. Our results reveal that HLTF together with PARP1 and BARD1 participates in the stabilization of damaged forks, and the PARP1-BARD1 interaction is further involved in the repair of collapse forks.

8.
Adv Sci (Weinh) ; 7(19): 2001467, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33042758

RESUMO

Extracellular particles (EPs) including extracellular vesicles (EVs) and exomeres play significant roles in diseases and therapeutic applications. However, their spatiotemporal dynamics in vivo have remained largely unresolved in detail due to the lack of a suitable method. Therefore, a bioluminescence resonance energy transfer (BRET)-based reporter, PalmGRET, is created to enable pan-EP labeling ranging from exomeres (<50 nm) to small (<200 nm) and medium and large (>200 nm) EVs. PalmGRET emits robust, sustained signals and allows the visualization, tracking, and quantification of the EPs from whole animal to nanoscopic resolutions under different imaging modalities, including bioluminescence, BRET, and fluorescence. Using PalmGRET, it is shown that EPs released by lung metastatic hepatocellular carcinoma (HCC) exhibit lung tropism with varying distributions to other major organs in immunocompetent mice. It is further demonstrated that gene knockdown of lung-tropic membrane proteins, solute carrier organic anion transporter family member 2A1, alanine aminopeptidase/Cd13, and chloride intracellular channel 1 decreases HCC-EP distribution to the lungs and yields distinct biodistribution profiles. It is anticipated that EP-specific imaging, quantitative assays, and detailed in vivo characterization are a starting point for more accurate and comprehensive in vivo models of EP biology and therapeutic design.

9.
Medicine (Baltimore) ; 99(41): e22504, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031288

RESUMO

In clinical trials of tofacitinib for rheumatoid arthritis (RA), Japanese and Korean patients had higher incidence of herpes zoster (HZ) than subjects from elsewhere; however, post-market data from Asia are lacking. Hence, we investigated the incidence of HZ and its risk factors in Taiwanese RA patients receiving tofacitinib. At a medical center in Taichung, Taiwan, we enrolled patients with active RA treated with tofacitinib between January 4, 2015 and December 9, 2017, following unsuccessful methotrexate therapy and no tofacitinib exposure RA patients as a control group. Demographic characteristics, interferon-gamma levels, and lymphocyte counts were compared. Among 125 tofacitinib-treated RA patients, 7 developed HZ, an incidence rate of 3.6/100 person-years. Patients with HZ had shorter disease duration than those without, but higher frequency of prior HZ. Baseline interferon-gamma levels and HLA-DR activated T cell counts were positively correlated and significantly lower in patients with HZ than without. Strikingly, 5/7 HZ cases occurred within 4 months of starting tofacitinib therapy. Incidence of HZ in tofacitinib-treated Taiwanese RA patients is lower than rates in Japan or Korea, and commensurate with the global average. HZ may occur soon after commencing tofacitinib therapy. The role of interferon-gamma and activated T cells in tofacitinib-related HZ deserves further investigation.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Herpes Zoster/epidemiologia , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Linfócitos T , Idoso , Artrite Reumatoide/sangue , Estudos de Casos e Controles , Feminino , Humanos , Incidência , Interferon gama/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia
10.
Nutrients ; 12(8)2020 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-32722642

RESUMO

Human milk (HM) must be accurately fortified for extremely low birth weight (ELBW) preterm infants with human milk fortifiers (HMFs). Powdered HMF has some limitations in terms of sterilization and accuracy. A concentrated preterm formula (CPF) may serve as a safe liquid HMF to facilitate growth. Hence, we launched a quality improvement project for fortification accuracy of minute volume HM. A CPF, Similac Special Care 30 (SSC30), was newly introduced as an HMF when daily feeding reached 100 cm3/kg. CPF + HM (1:2 volume ratio), CPF + HM (1:1 volume ratio), and powdered HMF + HM (1 packet in 25 cm3) represented three fortification stages. Fortification shifted to powdered HMF while tolerable feeding reached 25 cm3/meal. The outcome was compared before (Period-I, January 2015 to June 2016, n = 37) and after the new implement (Period-II, July 2016 to December 2017, n = 36). Compared with the Period-I group, the Period-II group had significantly higher daily enteral milk intake in the first 4 weeks of life, and higher percentages of fortification in the HM-fed infants in the first 8 weeks after birth. The Period-II group also significantly increased in body weight growth in terms of z-score at term equivalent age (p = 0.04) and had better language and motor performance at 24 months old (p = 0.048 and p = 0.032, respectively). Using the liquid CPF as a strategical alternative fortification of HM might be beneficial for extremely preterm infants in terms of growth as well as neurodevelopment.

11.
Support Care Cancer ; 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32720008

RESUMO

PURPOSE: To examine the effects of emotional distress, illness perception, and mental adjustment on return to work (RTW) among patients with head and neck cancer (HNC) and identify factors associated with RTW. METHODS: A cross-sectional study with convenience sampling was conducted in Taiwan. Structured questionnaires were used to collect data on RTW status and to explore possible factors related to RTW. RTW status was assessed by a single question. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, illness perception was assessed by the Brief Illness Perception Questionnaire, and mental adjustment was assessed using the Mini-mental Adjustment to Cancer Scale. Sociodemographic and disease background data were also collected and analyzed. Factors related to RTW were identified by multivariate logistic regression. RESULTS: A total of 150 patients with HNC were recruited into the study. Of them, 58 (38.7%) returned to work after treatment. Compared to those who did not RTW, patients who did RTW had lower levels of emotional distress (anxiety and depression), better illness perception (cognitive illness representations and illness comprehensibility), and better mental adjustment (hopelessness and helplessness, anxious preoccupation, avoidance, and fatalism). Multivariable analysis indicated that anxiety (OR = 0.863, p < 0.05), avoidance (OR = 1.280, p < 0.001), cognitive illness representations (OR = 0.891, p < 0.01), illness comprehensibility (OR = 1.271, p < 0.05), higher education level (OR = 3.048-3.609, p < 0.05), married status (OR = 5.220, p < 0.05), tumor site in oral cavity (OR = 5.057, p < 0.05), and no reconstruction (OR = 3.415, p < 0.05) were significantly associated with RTW. CONCLUSION: The issue of RTW among patients with HNC is related to multidimensional factors, including sociodemographic, psychological, and disease-related situations. We suggest that programs for emotional rehabilitation and occupational counseling need to be developed to assist patients with HNC to RTW at an early stage.

12.
Eur J Cancer Care (Engl) ; 29(4): e13243, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32510671

RESUMO

OBJECTIVE: Head and neck cancer (HNC) patients suffer from symptoms and fear of recurrence (FoR), which both affect their quality of life (QoL). Based on a self-regulation model, the purpose of the study was to examine patients' FoR as a mediator of the relation between symptoms and QoL, and to identify which symptoms may trigger FoR. METHODS: A cross-sectional study was conducted, using convenience sampling. Structured questionnaires were used to collect data at a medical centre in Northern Taiwan. The analytic methods included descriptive statistics, structural equation modelling and linear regression. RESULTS: A total of 103 participants were recruited. Patients experienced a medium level of symptom severity and QoL but a moderate to high level of FoR. Symptom severity, FoR and QoL were significantly correlated. FoR was a significant partial mediator between symptom severity and QoL. The significant factors of the overall FoR and the subscale of health worry were "pain in general" and "pain in the mouth, throat or neck." "Pain in general" was a significant factor for the subscale of cancer worry. CONCLUSIONS: This theory-driven study supports a mediation model of FoR among HNC patients and provides a more comprehensive understanding of the antecedents and consequences of FoR.

13.
Aliment Pharmacol Ther ; 52(4): 682-691, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32573827

RESUMO

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations. AIMS: To explore genetic variants associated with chronic HBV infection. METHODS: The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole-genome genotyping by Axiom-Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method. RESULTS: Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10-35 ) was significantly associated with HBV chronicity (Pcorrected  < 8.6 × 10-8 ). Imputation analyses showed that HLA-DPA1*02:02 and HLA-DPB1*05:01 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09-1.89) and 1.61 (1.29-2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA-DRB1*13:02, HLA-DQA1* 01:02 and HLA-DQB1*06:09 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17-0.58), 0.70 (0.56-0.87) and 0.33 (0.18-0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein. CONCLUSIONS: HLA class II variants are relevant for chronicity after HBV acquisition.


Assuntos
Genes MHC da Classe II/genética , Estudo de Associação Genômica Ampla , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Bancos de Espécimes Biológicos/estatística & dados numéricos , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Taiwan/epidemiologia
14.
Genome Res ; 30(3): 375-391, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127416

RESUMO

Circular RNAs (circRNAs), a class of long noncoding RNAs, are known to be enriched in mammalian neural tissues. Although a wide range of dysregulation of gene expression in autism spectrum disorder (ASD) have been reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in postmortem brains from individuals with ASD and controls and identified 60 circRNAs and three coregulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This reflects the previous observation that ASD-derived organoids show overproduction of inhibitory neurons. We further confirmed that some ASD risk genes (NLGN1, STAG1, HSD11B1, VIP, and UBA6) were regulated by an up-regulated circRNA (circARID1A) via sponging a down-regulated microRNA (miR-204-3p) in human neuronal cells. Particularly, alteration of NLGN1 expression is known to affect the dynamic processes of memory consolidation and strengthening. To the best of our knowledge, this is the first systems-level view of circRNA regulatory networks in ASD cortex samples. We provided a rich set of ASD-associated circRNA candidates and the corresponding circRNA-microRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology.

15.
Semin Arthritis Rheum ; 50(3): 451-457, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32115237

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease that develops mainly in women of reproductive age. We aimed to explore the risk of pregnancy complications in Asian patients with SLE. METHODS: From January 2005 to December 2014, we conducted a nationwide case-control study, using Taiwan's National Health Insurance Research Database. Obstetric complications and perinatal outcomes in SLE patients were compared with those without SLE. RESULTS: 2059 SLE offspring and 8236 age-matched, maternal healthy controls were enrolled. We found increased obstetric and perinatal complications in SLE population compared with healthy controls. SLE patients exhibited increased risk of preeclampsia/eclampsia (8.98% vs.1.98%, odds ratio [OR]: 3.87, 95% confidence interval [95% CI]: 3.08-4.87, p<0.0001). Their offspring tended to have lower Apgar scores (<7) at both 1 min (10.7% vs. 2.58%, p<0.0001) and 5 min (4.25% vs. 1.17%, p<0.0001), as well as higher rates of intrauterine growth restriction (IUGR, 9.91% vs. 4.12%, OR: 2.24, 95% CI: 1.85-2.71, p<0.0001), preterm birth (23.70% vs 7.56%, OR: 3.00, 95% CI: 2.61-3.45, p<0.0001), and stillbirth (4.23% vs. 0.87%, OR: 3.59, 95% CI: 2.54-5.06, p<0.0001). The risks of preterm birth and stillbirth were markedly increased in SLE patients with concomitant preeclampsia/eclampsia or IUGR. Preterm birth of SLE patients was 1~4 gestational weeks earlier than that of healthy controls and the peak occurrence of stillbirth in SLE population was at 20~30 gestational weeks. CONCLUSIONS: Asian SLE patients exhibited increased risks of maternal complications and adverse birth outcomes. Frequent antenatal visits before 20 gestational weeks are recommended in high-risk SLE patients.

16.
Heliyon ; 6(3): e03538, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32181403

RESUMO

Pharmacokinetic studies of maxacalcitol in healthy Taiwanese subjects have been conducted. This study to compare the pharmacokinetic properties of maxacalcitol in healthy Taiwanese and Japanese subjects. Healthy male Taiwanese subjects (n = 24) and healthy male Japanese subjects (n = 24) were enrolled in separate single-center and received a single intravenous dose of 1.25, 2.5 and 5 µg maxacalcitol. Male subjects were exclusively employed in the study due to the first administration of maxacalcitol to Taiwanese. Serum samples were collected for up to 72 h for pharmacokinetic analysis, and safety was assessed. Exposures to maxacalcitol as mean C5 and AUCinf appeared to increase with increase of doses in Taiwanese subjects (C5: 74.0, 159, and 321 pg/mL; AUCinf: 473, 763, and 1460 hï½¥pg/mL) and Japanese subjects (C5: 92.9, 174, and 346 pg/mL; AUCinf: 312, 588, and 1040 hï½¥pg/mL). After single bolus IV administration, linearity in maxacalcitol exposure was shown over the dose range of 1.25-5 µg in both Taiwanese and Japanese male healthy subjects. C5 of maxacalcitol was slightly lower (85%) in Taiwanese compared with that in Japanese and AUCinf of maxacalcitol in Taiwanese subjects was contrarily 15.0 (41.6%) higher than that in Japanese subjects, resulted in not much difference in pharmacokinetics of maxacalcitol between Taiwanese and Japanese. Moreover, maxacalcitol was well tolerated in both healthy Taiwanese and Japanese subjects.

17.
Sci Rep ; 10(1): 4072, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139769

RESUMO

No standard treatment for Bacille Calmette-Guérin (BCG)-associated osteomyelitis, a rare but serious complication of the BCG vaccine, has been established. This study explored the short- and long-term outcomes of surgical intervention for BCG-associated osteomyelitis. Four patients with BCG osteomyelitis aged 9-21 months when diagnosed and treated at the Department of Orthopedics, Kaohsiung Veterans General Hospital, Taiwan, between January 2001 and April 2019 were analysed. Radiography revealed osteolytic lesions of the involved sites. Magnetic resonance imaging revealed physeal involvement in three patients. Debridement was performed for all four patients. One patient then underwent additional arthroscopy because of suspect intra-articular involvement. Specimens obtained intraoperatively were sent for pathology, culture, and to the national reference mycobacterial laboratory for BCG detection using polymerase chain reaction. All four patients had positive results for Mycobacterium bovis and satisfactory short-term results. Functional monitoring using QuickDASH or the Lower Extremity Functional Scale revealed excellent long-term outcomes despite tiny limb length discrepancy observed during follow-up in two patients. Prompt diagnosis plus proper intervention is required to prevent further major complications of BCG osteomyelitis. Minimally invasive debridement led to positive clinical outcomes and is therefore recommended.


Assuntos
Vacina BCG/efeitos adversos , Imunocompetência , Imagem por Ressonância Magnética/métodos , Osteomielite/etiologia , Vacinação/efeitos adversos , Antituberculosos/uso terapêutico , Vacina BCG/administração & dosagem , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Osteomielite/tratamento farmacológico , Osteomielite/patologia , Taiwan
18.
Sci Rep ; 10(1): 2838, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071352

RESUMO

A major obstacle to nanodrugs-mediated cancer therapy is their rapid uptake by the reticuloendothelial system that decreases the systemic exposure of the nanodrugs to tumors and also increases toxicities. Intralipid has been shown to reduce nano-oxaliplatin-mediated toxicity while improving bioavailability. Here, we have found that Intralipid reduces the cytotoxicity of paclitaxel for human monocytic cells, but not for breast, lung, or pancreatic cancer cells. Intralipid also promotes the polarization of macrophages to the anti-cancer M1-like phenotype. Using a xenograft breast cancer mouse model, we have found that Intralipid pre-treatment significantly increases the amount of paclitaxel reaching the tumor and promotes tumor apoptosis. The combination of Intralipid with half the standard clinical dose of Abraxane reduces the tumor growth rate as effectively as the standard clinical dose. Our findings suggest that pre-treatment of Intralipid has the potential to be a powerful agent to enhance the tumor cytotoxic effects of Abraxane and to reduce its off-target toxicities.


Assuntos
Paclitaxel Ligado a Albumina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Imunidade Inata/efeitos dos fármacos , Fosfolipídeos/farmacologia , Óleo de Soja/farmacologia , Animais , Antineoplásicos , Apoptose/efeitos dos fármacos , Disponibilidade Biológica , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Emulsões/farmacologia , Feminino , Xenoenxertos , Humanos , Camundongos , Nanopartículas/química , Oxaliplatina/farmacologia , Paclitaxel/química , Paclitaxel/farmacologia , Fosfolipídeos/imunologia , Óleo de Soja/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Support Care Cancer ; 28(7): 3323-3330, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31758322

RESUMO

Oncology outpatient care centers generally subjugate patients' psychosocial needs to their physical care requirements. Consequently, the patients' self-management (SM) ability and utilization of social resources are essential in regulating their psychological distress (anxiety and depression). The study aims were (1) to examine the prevalence and severity of psychological distress in female cancer patients in outpatient settings in Taiwan and (2) to identify the major factors of psychological distress. Female cancer patients were recruited from oncology outpatient settings in Taiwan. Patients completed the questionnaires of anxiety, depression, social support, and utilization of social resources, and SM ability. In total, 116 patients were included. A total of 17.2% and 21.6% of the patients were at risk of anxiety and depression, respectively. Patients' mean anxiety and depression scores were 4.2 (SD = 4.1) and 4.1 (SD = 4.0), respectively. The patients' physical function, attendance of social support groups, degree of social support, and SM ability had a significant effect on their anxiety and depression. Patients' anxiety was intensified by the presence of comorbidity. Health professionals in oncology outpatient care centers should assess the patients' physical function, comorbidity, SM ability, and social support/engagement in order to reduce their psychological distress and devise appropriate follow-up interventions.


Assuntos
Neoplasias/psicologia , Autogestão/psicologia , Apoio Social , Estresse Psicológico/psicologia , Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Recursos em Saúde , Humanos , Pessoa de Meia-Idade , Neoplasias/terapia , Pacientes Ambulatoriais , Taiwan
20.
Mol Cancer Ther ; 19(1): 52-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31562255

RESUMO

The tumor microenvironment (TME) is a key determinant of metastatic efficiency. We performed a quantitative high-throughput screen (qHTS) of diverse medicinal chemistry tractable scaffolds (44,420 compounds) and pharmacologically active small molecules (386 compounds) using a layered organotypic, robust assay representing the ovarian cancer metastatic TME. This 3D model contains primary human mesothelial cells, fibroblasts, and extracellular matrix, to which fluorescently labeled ovarian cancer cells are added. Initially, 100 compounds inhibiting ovarian cancer adhesion/invasion to the 3D model in a dose-dependent manner were identified. Of those, eight compounds were confirmed active in five high-grade serous ovarian cancer cell lines and were further validated in secondary in vitro and in vivo biological assays. Two tyrosine kinase inhibitors, PP-121 and milciclib, and a previously unreported compound, NCGC00117362, were selected because they had potency at 1 µmol/L in vitro Specifically, NCGC00117362 and PP-121 inhibited ovarian cancer adhesion, invasion, and proliferation, whereas milciclib inhibited ovarian cancer invasion and proliferation. Using in situ kinase profiling and immunoblotting, we found that milciclib targeted Cdk2 and Cdk6, and PP-121 targeted mTOR. In vivo, all three compounds prevented ovarian cancer adhesion/invasion and metastasis, prolonged survival, and reduced omental tumor growth in an intervention study. To evaluate the clinical potential of NCGC00117362, structure-activity relationship studies were performed. Four close analogues of NCGC00117362 efficiently inhibited cancer aggressiveness in vitro and metastasis in vivo Collectively, these data show that a complex 3D culture of the TME is effective in qHTS. The three compounds identified have promise as therapeutics for prevention and treatment of ovarian cancer metastasis.

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