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Cough is a common symptom presenting in asthmatic children. In this investigation, an audio-based classification model is presented that can differentiate between healthy and asthmatic children, based on the combination of cough and vocalised /É:/ sounds. A Gaussian mixture model using mel-frequency cepstral coefficients and constant-Q cepstral coefficients was trained. When comparing the predicted labels with the clinician's diagnosis, this cough sound model reaches an overall accuracy of 95.3%. The vocalised /É:/ model reaches an accuracy of 72.2%, which is still significant because the dataset contains only 333 /É:/ sounds versus 2029 cough sounds.
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Tosse , Som , Criança , Tosse/diagnóstico , Humanos , Distribuição Normal , Espectrografia do SomRESUMO
BACKGROUND: Burnout causes personal suffering and adverse professional consequences. It is prevalent among medical students, although the relationship between burnout and lifestyle factors are understudied in Chinese medical students. Thus, this study aims to (i) estimate the prevalence of burnout among medical students in Hong Kong (HK) and (ii) delineate the relationship between burnout and various lifestyle factors. METHOD: 1,341 students were invited to complete a questionnaire from September to December 2017. Burnout was measured by the Maslach Burnout Inventory. Lifestyle factors including drinking habit, sleep habit and quality, and exercise level were assessed by validated instruments, including Alcohol Use Disorder Identification Test (AUDIT-C), Pittsburgh Sleep Quality Index (PSQI), and Godin-Shephard Leisure-Time Physical Activity (GSLTPA), respectively. Smoking status and use of self-medications were also inquired into, while demographic data was self-reported. Prevalence of burnout with confidence intervals was calculated. Difference in lifestyle and demographic data in students with or without burnout, were compared by t-test and Chi-square/Fisher's exact test. From this, all associations with significant p-value at p<0.1 were entered into the multiple logistic regression model. RESULTS: 731 students (55.6%) responded to the questionnaire. Prevalence of burnout was 27.9% (95%CI: 24.6%-31.5%). Only 3 students in the whole sample smoked; and 6.6% of students drank weekly but rarely drank more than 2 drinks per week. 6.3% and 2.3% self-medicated themselves with medications to improve their sleep and concentration, respectively. Using a multiple logistic regression model, only sleep quality and exercise level were significantly associated with the presence of burnout. CONCLUSION: Around a quarter of medical students in HK suffered from burnout. Burnout was found to be significantly associated with sleep quality and physical exercise. The study also highlighted that HK medical students lived very different lifestyles from those from other countries. More research is needed to design and establish the effectiveness of lifestyle interventional programs that enhance exercise level and sleep quality.
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Esgotamento Psicológico/epidemiologia , Educação de Graduação em Medicina , Estilo de Vida , Estudantes de Medicina/psicologia , Adolescente , Estudos Transversais , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Prevalência , Faculdades de Medicina , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common type of inflammatory arthritis in children. Treatment options have been expanded since the introduction of biologics, which are highly effective. The existing local JIA treatment guideline was published more than a decade ago, when use of biologics was not as common. In this article, we review the latest evidence on using biologics in three JIA subtypes: JIA of polyarticular course (pcJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA). Based on the latest information, an update on eligibility, response assessment, termination, and safety information for using biologics in these patients was performed. CONSENSUS PROCESS: The JIA Work Group, which consisted of nine paediatricians experienced in managing JIA, was convened in 2016. Publications before July 2017 were screened. Eligible articles were clinical trials, extension studies, systemic reviews, and recommendations from international societies and regulatory agencies about the use of biologics in pcJIA, ERA, and PsA. Evidence extraction, appraisal, and drafting of propositions were performed by two reviewers. Extracted evidence and drafted propositions were presented and discussed at the first two meetings. Overwhelming consensus was obtained at the final meeting in May 2018. Seven practice consensus statements were formulated. Regular review should be performed to keep the practice evidence-based and up-to-date.
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Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Antirreumáticos/efeitos adversos , Produtos Biológicos/efeitos adversos , Criança , Consenso , Humanos , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Postgraduate vocational training in family medicine (FM) is essential for physicians to build capacity and develop quality primary care. Inadequate standards in training and curriculum development can contribute to poor recruitment and retention of doctors in primary care. This study aimed to investigate: 1) the satisfaction level of doctors regarding vocational training in family medicine and associated demographics; and 2) the satisfaction level of doctors regarding their family medicine career and associated factors. METHOD: This is a cross sectional study of all family medicine physicians across all government-funded primary care clinics (GOPCs). The study questionnaire consisted of items from a standardized and validated physician survey named the Physician Worklife Survey (PWS) (Konrad et al., Med Care, 1999). We selected three scales (7 items) relating to global job satisfaction, global career satisfaction and global specialty (family medicine) satisfaction with additional items on training and demographics. All significant variables in bivariate analyses were further examined using stepwise logistic regression. RESULTS: Out of 424 eligible family medicine physicians, 368 physicians successfully completed the questionnaire. The response rate was 86.8%. Most participants were male (52.6%), were aged between 35 and 44 years (55.5%), were FM specialists (42.4%), graduated locally (86.2%), and had postgraduate qualifications. Eighty-two percent (82%) of participants were satisfied with their training. Having autonomy and protected time for training were associated with satisfaction with FM training. Satisfaction with family medicine as a career was correlated with physicians' satisfaction with their current job. Doctors who did not enroll in training (p < 0.001) and physicians who were older (p = 0.023) were significantly less satisfied. Stepwise multivariate regression showed that doctors who subjectively believed their training as "broad and in depth' had higher career satisfaction (p < 0.001). CONCLUSION: Overall, the satisfaction level of physicians on current family medicine training in Hong Kong was high. Having autonomy and protected time for training is associated with higher training satisfaction levels. Perceiving FM training as "broad and in-depth" is associated with higher family medicine career satisfaction.
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Medicina de Família e Comunidade/educação , Satisfação no Emprego , Educação Vocacional , Adulto , Estudos Transversais , Feminino , Clínicos Gerais/educação , Clínicos Gerais/psicologia , Clínicos Gerais/estatística & dados numéricos , Hong Kong , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This study aimed to assess the knowledge, attitudes and factors associated with promotion of umbilical cord blood (CB) donation by Chinese midwives to expectant mothers. DESIGN: An anonymous cross-sectional survey using self-administered questionnaires. SETTING: Hong Kong, China. PARTICIPANTS: One-hundred-and-forty-seven registered Chinese midwives were recruited by convenience sampling from government obstetric clinics and public and private hospitals. MEASUREMENTS AND FINDINGS: In addition to collecting demographic background information, the study examined the midwives' cord blood-related knowledge and perceptions as well as past-year practices and future intention of giving cord blood advice. Hong Kong midwives generally showed high levels of knowledge about the medical uses of cord blood but they were not as familiar with the administrative, legal and financial aspects of donation and storage. Only about 10% had received formal cord blood training and the majority felt that it should be integrated into midwifery program curricula. Although the midwives showed strong positive attitudes towards cord blood donation, only 10.9% consistently gave information and 7.5% consistently advised cord blood donation to expectant mothers in the preceding year while slightly higher percentages planned to do so in the future. In the multivariable models, higher educational attainment and hospital employment were the most consistent predictors of past-year practices of giving cord blood information and future intention to provide advice. Higher score in cord blood-related attitudes was significantly associated with giving past-year cord-blood advice, future intention to provide advice and future intention to recommend donation in the multivariable models. Key barriers to advising expectant mothers were the lack of a formal work protocol, lack of time in the clinic routine and fear of criticism by peers. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Increasing education, improving perceptions and changing workplace protocols will likely increase cord blood advising by Hong Kong midwives to their patients.
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Doadores de Sangue/psicologia , Sangue Fetal , Conhecimentos, Atitudes e Prática em Saúde , Enfermeiros Obstétricos/psicologia , Adulto , Feminino , Hong Kong , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , População UrbanaRESUMO
Onion (Allium cepa L.) and quercetin protect against oxidative damage and have positive effects on multiple functional parameters of spermatozoa, including viability and motility. However, the associated underlying mechanisms of action have not yet been identified. The aim of this study was to investigate the effect of onion peel extract (OPE) on voltage-gated proton (Hv1) channels, which play a critical role in rapid proton extrusion. This process underlies a wide range of physiological processes, particularly male fertility. The whole-cell patch-clamp technique was used to record the changes in Hv1 currents in HEK293 cells transiently transfected with human Hv1 (HVCN1). The effects of OPE on human sperm motility were also analyzed. OPE significantly activated the outward-rectifying proton currents in a concentration-dependent manner, with an EC50 value of 30 µg/mL. This effect was largely reversible upon washout. Moreover, OPE induced an increase in the proton current amplitude and decreased the time constant of activation at 0 mV from 4.9 ± 1.7 to 0.6 ± 0.1 sec (n = 6). In the presence of OPE, the half-activation voltage (V1/2 ) shifted in the negative direction, from 20.1 ± 5.8 to 5.2 ± 8.7 mV (n = 6), but the slope was not significantly altered. The OPE-induced current was profoundly inhibited by 10 µm Zn2+ , the most potent Hv1 channel inhibitor, and was also inhibited by treatment with GF109203X, a specific protein kinase C (PKC) inhibitor. Furthermore, sperm motility was significantly increased in the OPE-treated groups. OPE exhibits protective effects on sperm motility, at least partially via regulation of the proton channel. Moreover, similar effects were exerted by quercetin, the major flavonoid in OPE. These results suggest OPE, which is rich in the potent Hv1 channel activator quercetin, as a possible new candidate treatment for human infertility.
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Antioxidantes/farmacologia , Canais Iônicos/metabolismo , Cebolas/química , Extratos Vegetais/farmacologia , Proteína Quinase C/metabolismo , Inibidores Enzimáticos/farmacologia , Células HEK293 , Humanos , Indóis/farmacologia , Masculino , Maleimidas/farmacologia , Proteína Quinase C/antagonistas & inibidores , Quercetina/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacosRESUMO
The PIM kinase family (PIM1, 2 and 3) have a central role in integrating growth and survival signals, and are expressed in a wide range of solid and hematological malignancies. We now confirm that PIM2 is overexpressed in multiple myeloma (MM) patients, and within MM group it is overexpressed in the high-risk MF subset (activation of proto-oncogenes MAF/MAFB). This is consistent with our finding of PIM2's role in key signaling pathways (IL-6, CD28 activation) that confer chemotherapy resistance in MM cells. These studies have identified a novel PIM2-selective non-ATP competitive inhibitor (JP11646) that has a 4 to 760-fold greater suppression of MM proliferation and viability than ATP-competitive PIM inhibitors. This increased efficacy is due not only to the inhibition of PIM2 kinase activity, but also to a novel mechanism involving specific downregulation of PIM2 mRNA and protein expression not seen with the ATP competitive inhibitors. Treatment with JP11646 in xenogeneic myeloma murine models demonstrated significant reduction in tumor burden and increased median survival. Altogether our findings suggest the existence of previously unrecognized feedback loop(s) where PIM2 kinase activity regulates PIM2 gene expression in malignant cells, and that JP11646 represents a novel class of PIM2 inhibitors that interdicts this feedback.
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Antineoplásicos/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Humanos , Camundongos , NF-kappa B/fisiologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/fisiologiaRESUMO
A novel non-enzymatic photoelectrochemical (PEC) glucose sensor was first constructed based on the unique two-dimensional (2D) bismuth oxychloride-graphene nanohybrid sheets (BiOCl-G NHS). We have utilized a facile hydrothermal approach for the preparation of BiOCl-G NHS. Results from cyclic voltammetric and differential pulse voltammetric measurements revealed that the BiOCl-G NHS electrode is capable of generating photocurrent for glucose when its surface is irradiated with a light source (wavelength=365nm). The photocurrents produced for the presence of glucose at the bias potential of +0.50V showed a linear dependence on glucose concentration in the range between 0.5 and 10mM and had a detection limit of 0.22mM. The PEC detection of glucose at BiOCl-G NHS was not influenced by the presence of other common interfering species. The glucose levels, as determined by the BiOCl-G NHS sensor, agreed well with those obtained by the commercial glucometers. This novel non-enzymatic PEC glucose sensor exhibited good performances, such as a wider concentration range (500µM-10mM), high sensitivity (1.878µMmM-1cm-2 (500µM-2mM) and 127.2µMmM-1cm-2 (2mM-10mM)), good selectivity, reproducibility (RSD=2.4%) and applicability to real sample (human serum).
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Técnicas Biossensoriais/instrumentação , Bismuto/química , Glicemia/análise , Técnicas Eletroquímicas/instrumentação , Grafite/química , Nanoestruturas/química , Desenho de Equipamento , Humanos , Luz , Limite de Detecção , Nanoestruturas/ultraestrutura , Reprodutibilidade dos TestesRESUMO
In this work, an efficient photoelectrochemical (PEC) biosensing platform has been designed and developed based on graphene (G) through modifying it into an electroconductive polymer nanosponge (EPNS) and with the incorporation of titanium dioxide nanowires (TiO2 NW) (designated as TiO2 (G) NW@EPNS). Functioning as an efficient immobilization matrix for immobilization of the enzyme Cytochrome C (Cyt C), TiO2 (G) NW@EPNS delivers features for an efficient PEC biosensor, such as fast kinetics of direct electron transfer (DET) to the electrode and effective separation of photogenerated holes and electrons. TiO2 (G) NW@EPNS exhibited DET to the electrode with a highly heterogeneous electron transfer rate constant of 6.29±0.002s-1. The existence of TiO2, G and EPNS in conjunction facilitates DET between the electrode surface and the protein. The fabricated PEC nitrite ion (NO2-) biosensor showed superior analytical performances such as wide linear range (0.5-9000µM), lowest detection limit (0.225mM) and excellent specificity for NO2- in the presence other interferences at a very low bias potential (-0.11V). This study opens up the feasibility of fabricating a PEC biosensor for any analyte using a matrix comprising of G and a photoactive material and EPNS, because these components synergistically contribute to effective immobilization of on enzyme, DET to the electrode and simple read-out under the light.
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Técnicas Eletroquímicas/métodos , Grafite/química , Nanofios/química , Nitritos/análise , Titânio/química , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Citocromos c/química , Condutividade Elétrica , Técnicas Eletroquímicas/instrumentação , Enzimas Imobilizadas/química , Desenho de Equipamento , Modelos Moleculares , Nanofios/ultraestrutura , Processos Fotoquímicos , Polímeros/químicaRESUMO
INTRODUCTION: Patients with diabetes mellitus often delay insulin initiation and titration due to psychological factors. This phenomenon is known as 'psychological insulin resistance'. Tools that identify psychological insulin resistance are valuable for detecting its causes and can lead to appropriate counselling. The Insulin Treatment Appraisal Scale was initially developed for western populations and has been translated and validated to measure psychological insulin resistance in Taiwan (Chinese version of the Insulin Treatment Appraisal Scale, C-ITAS). The current study examined the prevalence of psychological insulin resistance and the validity of the C-ITAS in a local population. METHODS: This cross-sectional study involved 360 patients with diabetes mellitus from a government-funded general out-patient clinic who completed the C-ITAS questionnaire. The total C-ITAS score was compared for patients with psychological insulin resistance and those without, and the internal consistency and test-retest reliability of the C-ITAS were calculated. An exploratory factor analysis was used to identify factors within the C-ITAS. RESULTS: The prevalence of psychological insulin resistance was 44.9%. The internal consistency of the scale was high (Cronbach's alpha=0.78). The test-retest reliability was positive with all C-ITAS questions (0.294-0.725). The mean C-ITAS score was significantly higher among patients with psychological insulin resistance than those without (42.42 vs 35.78; P<0.001). The exploratory factor analysis, however, failed to identify the two clear factors identified in the original validation study. CONCLUSIONS: The C-ITAS appears to be a feasible and potentially useful tool for identifying psychological insulin resistance, but additional validation or translation is required before it can be widely used clinically.
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Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/psicologia , Insulina/uso terapêutico , Atenção Primária à Saúde , Idoso , Estudos Transversais , Feminino , Hong Kong , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Meropenem, a second carbapenem antimicrobial agent with a broad spectrum of activity, is used to treat sepsis and resistant-bacterial infections in veterinary medicine. The objective of this study was to identify the pharmacokinetics of meropenem in dogs receiving intermittent hemodialysis (IHD) and to determine the proper dosing in renal failure patients receiving IHD. Five healthy beagle dogs were given a single i.v. dose of 24 mg/kg of meropenem and received IHD. The blood flow rate, dialysate flow, and ultrafiltration rate were maintained at 40 mL/min, 300 mL/min, and 40 mL/h, respectively. Blood samples were collected for 24 h from the jugular vein and from the extracorporeal arterial and venous line. Urine samples and dialysate were also collected. The concentrations of meropenem were assayed using HPLC/MS/MS determination. The peak plasma concentration was 116 ± 37 µg/mL at 15 min. The systemic clearance was 347 ± 117 mL/h/kg, and the steady-state volume of distribution was 223 ± 67 mL/kg. Dialysis clearance was 71.1 ± 34.3 mL/h/kg, and the extraction ratio by hemodialysis was 0.455 ± 0.150. The half-life (T1/2 ) in dogs with IHD decreased compared with those without IHD, and the reduction in T1/2 was greater in renal failure patients than in normal patients. Sixty-nine percent and 21% of the administered drug were recovered by urine and dialysate in the unchanged form, respectively. In conclusion, additional dosing of 24 mg/kg of meropenem after dialysis could be necessary according to the residual renal function of the patient based on the simulated data.
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Antibacterianos/farmacocinética , Cães/sangue , Diálise Renal/veterinária , Tienamicinas/farmacocinética , Animais , Antibacterianos/administração & dosagem , Área Sob a Curva , Meia-Vida , Injeções Intra-Arteriais , Injeções Intravenosas , Masculino , Meropeném , Tienamicinas/administração & dosagemRESUMO
The fabrication of a highly sensitive electrochemical non-enzymatic glucose sensor based on copper nanoparticles (Cu NPs) dispersed in a graphene (G)-ferrocene (Fc) redox polymer multicomponent nanobead (MCNB) is reported. The preparation of MCNB involves three major steps, namely: i) the preparation of a poly(aniline-co-anthranilic acid)-grafted graphene (G-PANI(COOH), ii) the covalent linking of ferrocene to G-PANI(COOH) via a polyethylene imine (PEI), and iii) the electrodeposition of Cu NPs. The prepared MCNB (designated as G-PANI(COOH)-PEI-Fc/Cu-MCNB), contains a conductive G-PANI(COOH), electron mediating Fc, and electrocatalytic Cu NPs that make it suitable for ultrasensitive non-enzymatic electrochemical sensing. The morphology, structure, and electro activities of MCNB were characterized. Electrochemical measurements showed that the G-PANI(COOH)-PEI-Fc/Cu-MCNB/GCE modified electrode exhibited good electrocatalytic behavior towards the detection of glucose in a wide linear range (0.50 to 15mM), with a low detection limit (0.16mM) and high sensitivity (14.3µAmM(-1)cm(-2)). Besides, the G-PANI(COOH)-PEI-Fc/Cu-MCNB/GCE sensor electrode did not respond to the presence of electroactive interferrants (such as uric acid, ascorbic acid, and dopamine) and saccharides or carbohydrates (fructose, lactose, d-isoascorbic acid, and dextrin), demonstrating its selectivity towards glucose. The fabricated NEG sensor exhibited high precision for measuring glucose in serum samples, with an average RSD of 4.3% and results comparable to those of commercial glucose test strips. This reliability and stability of glucose sensing indicates that G-PANI(COOH)-PEI-Fc/Cu-MCNB/GCE would be a promising material for the non-enzymatic detection of glucose in physiological fluids.
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Compostos de Anilina/química , Técnicas Biossensoriais/instrumentação , Glicemia/análise , Cobre/química , Técnicas Eletroquímicas/instrumentação , Grafite/química , Nanocompostos/química , Desenho de Equipamento , Compostos Ferrosos/química , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Metalocenos , Nanocompostos/ultraestrutura , Oxirredução , Polietilenoimina/química , Reprodutibilidade dos TestesRESUMO
Herein, we fabricated a novel electrochemical-photoelectrochemical (PEC) dual-mode cholesterol biosensor based on graphene (G) sheets interconnected-graphene embedded titanium nanowires (TiO2(G)-NWs) 3D nanostacks (designated as G/Ti(G) 3DNS) by exploiting the beneficial characteristics of G and TiO2-NWs to achieve good selectivity and high sensitivity for cholesterol detection. The G/Ti(G) 3DNS was fabricated by the reaction between functionalized G and TiO2(G)-NWs. Cholesterol oxidase (ChOx) was subsequently immobilized in to G/Ti(G) 3DNS using chitosan (CS) as the binder and the dual mode G/Ti(G) 3DNS/CS/ChOx biosensor was fabricated. The electro-optical properties of the G/Ti(G) 3DNS/CS/ChOx bioelectrode were characterized by cyclic voltammetry and UV-vis diffuse reflection spectroscopy. The cyclic voltammetry of immobilized ChOx showed a pair of well-defined redox peaks indicating direct electron transfer (DET) of ChOx. The amperometric reduction peak current (at -0.05V) linearly increased with increase in cholesterol concentration. The G/Ti(G) 3DNS/CS/ChOx bioelectrode was selective to cholesterol with a remarkable sensitivity (3.82µA/cm(2)mM) and a lower detection limit (6µM). Also, G/Ti(G) 3DNS/CS/ChOx functioned as photoelectrode and exhibited selective detection of cholesterol under a low bias voltage and light irradiation. Kinetic parameters, reproducibility, repeatability, storage stability and effect of temperature and pH were evaluated. We envisage that G/Ti(G) 3DNS with its prospective characteristics, would be a promising material for wide range of biosensing applications.
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Técnicas Biossensoriais/instrumentação , Colesterol/sangue , Técnicas Eletroquímicas/instrumentação , Grafite/química , Nanoestruturas/química , Titânio/química , Humanos , Limite de Detecção , Nanoestruturas/ultraestrutura , Nanofios/química , Nanofios/ultraestruturaRESUMO
It is generally accepted that intracellular oxidative stress induced by proteasome inhibitors is a byproduct of endoplasmic reticulum (ER) stress. Here we report a mechanism underlying the ability of proteasome inhibitors bortezomib (BTZ) and carfilzomib (CFZ) to directly induce oxidative and ER stresses in multiple myeloma (MM) cells via transcriptional repression of a gene encoding mitochondrial thioredoxin reductase (TXNRD2). TXNRD2 is critical for maintenance of intracellular red-ox status and detoxification of reactive oxygen species. Depletion of TXNRD2 to the levels detected in BTZ- or CFZ-treated cells causes oxidative stress, ER stress and death similar to those induced by proteasome inhibitors. Reciprocally, restoration of near-wildtype TXNRD2 amounts in MM cells treated with proteasome inhibitors reduces oxidative stress, ER stress and cell death by ~46%, ~35% and ~50%, respectively, compared with cells with unrestored TXNRD2 levels. Moreover, cells from three MM cell lines selected for resistance to BTZ demonstrate elevated levels of TXNRD2, indirectly confirming its functional role in BTZ resistance. Accordingly, ectopic expression of TXNRD2 in MM cell xenografts in immunocompromised mice blunts therapeutic effects of BTZ. Our data identify TXNRD2 as a potentially clinically relevant target, inhibition of which is critical for proteasome inhibitor-dependent cytotoxicity, oxidative stress and ER stress.
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Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteassoma/uso terapêutico , Tiorredoxina Redutase 2/fisiologia , Animais , Apoptose/efeitos dos fármacos , Bortezomib/farmacologia , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Camundongos , Mieloma Múltiplo/enzimologia , Mieloma Múltiplo/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Super-Kamiokande (SK) can search for weakly interacting massive particles (WIMPs) by detecting neutrinos produced from WIMP annihilations occurring inside the Sun. In this analysis, we include neutrino events with interaction vertices in the detector in addition to upward-going muons produced in the surrounding rock. Compared to the previous result, which used the upward-going muons only, the signal acceptances for light (few-GeV/c^{2}-200-GeV/c^{2}) WIMPs are significantly increased. We fit 3903 days of SK data to search for the contribution of neutrinos from WIMP annihilation in the Sun. We found no significant excess over expected atmospheric-neutrino background and the result is interpreted in terms of upper limits on WIMP-nucleon elastic scattering cross sections under different assumptions about the annihilation channel. We set the current best limits on the spin-dependent WIMP-proton cross section for WIMP masses below 200 GeV/c^{2} (at 10 GeV/c^{2}, 1.49×10^{-39} cm^{2} for χχâbb[over ¯] and 1.31×10^{-40} cm^{2} for χχâτ^{+}τ^{-} annihilation channels), also ruling out some fraction of WIMP candidates with spin-independent coupling in the few-GeV/c^{2} mass range.
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We present the results of searches for nucleon decay via nâν[over ¯]π0 and pâν[over ¯]π+ using data from a combined 172.8 kt·yr exposure of Super-Kamiokande-I,-II, and-III. We set lower limits on the partial lifetime for each of these modes: τnâν[over ¯]π0>1.1×10(33) years and τpâν[over ¯]π+>3.9×10(32) years at a 90% confidence level.
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The trilepton nucleon decay modes pâe+νν and pâµ+νν violate |Δ(B-L)| by two units. Using data from a 273.4 kt yr exposure of Super-Kamiokande a search for these decays yields a fit consistent with no signal. Accordingly, lower limits on the partial lifetimes of τpâe+νν>1.7×10(32) years and τpâµ+νν>2.2×10(32) years at a 90% confidence level are obtained. These limits can constrain Grand Unified Theories which allow for such processes.
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We report an indication that the elastic scattering rate of solar B8 neutrinos with electrons in the Super-Kamiokande detector is larger when the neutrinos pass through Earth during nighttime. We determine the day-night asymmetry, defined as the difference of the average day rate and average night rate divided by the average of those two rates, to be [-3.2 ± 1.1(stat) ± 0.5(syst)]%, which deviates from zero by 2.7 σ. Since the elastic scattering process is mostly sensitive to electron-flavored solar neutrinos, a nonzero day-night asymmetry implies that the flavor oscillations of solar neutrinos are affected by the presence of matter within the neutrinos' flight path. Super-Kamiokande's day-night asymmetry is consistent with neutrino oscillations for 4 × 10(-5) eV(2) ≤ Δm 2(21) ≤ 7 × 10(-5) eV(2) and large mixing values of θ12, at the 68% C.L.
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Laser-assisted atom probe tomography has opened the way to three-dimensional visualization of nanostructures. However, many questions related to the laser-matter interaction remain unresolved. We demonstrate that the interface reaction can be activated by laser-assisted field evaporation and affects the quantification of the interfacial composition. At a vertical interface between Si and SiO2, a SiO2 molecule tends to combine with a Si atom and evaporate as a SiO molecule, reducing the evaporation field. The features of the reaction depend on the direction of the laser illumination and the inner structure of tip. A high concentration of SiO is observed at a vertical interface between Si and SiO2 when the Si column is positioned at the center of the tip, whereas no significant SiO is detected when the SiO2 layer is at the center. The difference in the interfacial compositions of two samples was due to preferential evaporation of the Si layer. This was explained using transmission electron microscopy observations before and after atom probe experiments.