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This study investigated sex differences perceived relocation stress and glycemic control among older adults with type 2 diabetes in long-term care facilities. A cross-sectional correlation design was used to recruit 120 residents during their first year after moving into the facilities in southern Taiwan. The results showed that almost two-thirds of the participants (64.2%) were women. The mean age was 79.62 (SD = 1.71). Older women with diabetes were reported to have significantly lower levels of education and poor glycemic control but higher levels of perceived relocation stress than men; however, functional independence was significantly higher in men. Although perceived relocation stress significantly predicted HbA1c levels in both women and men, length of stay was also significant in predicting HbA1c levels in women. These findings indicate the need for effective physical and psychological measures to improve glycemic control during the first year of stay in long-term care facilities.
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Diabetes Mellitus Tipo 2 , Controle Glicêmico , Estresse Psicológico , Humanos , Feminino , Masculino , Idoso , Estudos Transversais , Controle Glicêmico/métodos , Controle Glicêmico/psicologia , Taiwan , Diabetes Mellitus Tipo 2/psicologia , Diabetes Mellitus Tipo 2/terapia , Estresse Psicológico/psicologia , Idoso de 80 Anos ou mais , Fatores Sexuais , Assistência de Longa Duração/métodos , Assistência de Longa Duração/psicologia , Assistência de Longa Duração/normas , Assistência de Longa Duração/estatística & dados numéricos , Hemoglobinas Glicadas/análise , Glicemia/análiseRESUMO
BACKGROUND: Acute kidney injury (AKI) is a severe complication of coronavirus disease 2019 (COVID-19) and is associated with a higher risk of mortality. Understanding the risk factors contributing to COVID-19-related AKI and mortality before vaccination is important for the initiation of preventative measures and early treatment strategies. METHODS: This study included patients aged ≥18 years diagnosed with COVID-19 through polymerase chain reaction from May 2020 to July 2021, admitted in three local hospitals in Taiwan, with an extended follow-up until June 30, 2022. A median follow-up period of 250 days was used to assess AKI development and mortality. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. Multivariate Cox regression analysis of AKI and mortality-related risk factors was performed. RESULTS: Of the 720 hospitalized patients with COVID-19, 90 (22%) developed AKI. Moreover, 80%, 10.1%, and 8.9% of the patients had stage 1, 2, and 3 AKI, respectively. Patients with stage 1-3 AKI had significantly lower survival rates than those without AKI (p = 0.0012). The mean duration of post-admission AKI occurrence was 9.50 ± 11.32 days. Older age, hypoalbuminemia, and higher D-dimer and ferritin levels were associated with COVID-19 mortality. In COVID-19 AKI, in addition to older age and high D-dimer and ferritin levels, chronic kidney disease emerged as an independent risk factor. CONCLUSION: COVID-19-related AKI develops early, exhibits a temporal association with respiratory failure, and is linked to an unfavorable prognosis. The mortality rate increased according to the AKI stage (p = 0.0012). Age; albumin, D-dimer, and ferritin levels; and the underlying chronic kidney disease status upon admission are crucial factors for predicting AKI development, which increases the mortality risk. Monitoring the renal function not only within 10 days of COVID-19 onset, but also within one month after the disease onset.
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Cepharanthine (CEP), a bioactive compound derived from Stephania Cephalantha Hayata, is cytotoxic to various malignancies. However, the underlying mechanism of gastric cancer is unknown. CEP inhibited the cellular activity of gastric cancer AGS, HGC27 and MFC cell lines in this study. CEP-induced apoptosis reduced Bcl-2 expression and increased cleaved caspase 3, cleaved caspase 9, Bax, and Bad expression. CEP caused a G2 cell cycle arrest and reduced cyclin D1 and cyclin-dependent kinases 2 (CDK2) expression. Meanwhile, it increased oxidative stress, decreased mitochondrial membrane potential, and enhanced reactive oxygen species (ROS) accumulation in gastric cancer cell lines. Mechanistically, CEP inhibited Kelch-like ECH-associated protein (Keap1) expression while activating NF-E2 related factor 2 (Nrf2) nuclear translocations, increasing transcription of Nrf2 target genes quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HMOX1), and glutamate-cysteine ligase modifier subunit (GCLM). Furthermore, a combined analysis of targeted energy metabolism and RNA sequencing revealed that CEP could alter the levels of metabolic substances such as D (+) - Glucose, D-Fructose 6-phosphate, citric acid, succinic acid, and pyruvic acid, thereby altering energy metabolism in AGS cells. In addition, CEP significantly inhibited tumor growth in MFC BALB/c nude mice in vivo, consistent with the in vitro findings. Overall, CEP can induce oxidative stress by regulating Nrf2/Keap1 and alter energy metabolism, resulting in anti-gastric cancer effects. Our findings suggest a potential application of CEP in gastric cancer treatment.
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Introduction: Diabetic foot self-management intervention programs have been proven to positively influence individuals' behaviors in preventing diabetic foot ulcers. Using digital technologies to deliver programs can facilitate compliance with diabetes self-management programs. However, few studies have focused on the effects of such digital programs on improving the self-efficacy and behaviors of older adults with type 2 diabetes in the community. Aim: To evaluate the effects of a digital foot self-management program on self-efficacy, self-care behavior, and Hemoglobin A1c levels. Design: A single-blinded, randomized controlled trial was conducted. Methods: The intervention program comprised a 4-week digital foot care program with one face-to-face education session, phone calls once weekly, and LINE messages (social media) three times per research nurse and a follow-up of three months. Patients in the control group received routine care. Results: A total of 100 participants (n = 50 in the control and n = 50 in the intervention groups) completed the study with a mean age of 67.55 (SD = 11.17). The results showed significant improvements in self-efficacy (F = 2187.24, p < 0.01) and self-care behavior (F = 614.71, p < 0.01) in foot care between the groups. The Hemoglobin A1c levels showed a 0.41% reduction over time in the experimental group (t = -3.759; p < 0.01), whereas the control group showed a 0.06% reduction (t = -0.797, p > 0.05). Conclusion: The newly developed digital foot self-management program was effective in community-dwelling older adult patients with type 2 diabetes.
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BACKGROUND: Motivation is an important factor in disease management for diabetic patients. However, motivational strengthening interventions have been inadequately effective in effecting behavior change in this group. PURPOSE: This study was designed to investigate the effect of a motivational interview intervention on self-efficacy, self-care behavior, and blood sugar control in patients with type 2 diabetes. METHODS: The target population comprised patients with type 2 diabetes in two medical wards of a regional hospital in the southern Taiwan. The 112 participants were randomly assigned to the experimental group (n = 56) and control group (n = 56). Over a three month period, the experimental group received 6 motivational interview sessions of 50 minutes each in addition to usual diabetes care, while the control group received usual diabetes care on the ward. Both groups completed the demographic questionnaire, Chinese version of Diabetes Self-Efficacy Scale, Diabetes Self-Care Behavior Scale, glycosylated hemoglobin level pre-test, and 3 months post-test survey. The results were analyzed using SPSS 22.0 for Windows. RESULTS: A total of 55 patients in the experimental group and 52 patients in the control group completed the study. After analysis, significant inter-group differences in self-efficacy and self-care behavior were found between the experimental group and the control group at pre-test and three-month post-test (p < .001). For the experimental group, the three-month post-test score and glycated hemoglobin value were higher than at pre-test. The three-month post-test value was significantly lower (p < .001) than the pre-test value, and the change effect in the experimental group was better than that in the control group. There was a significant difference in the stages of change between pre-test and post-test (χ2 = 43.89, p < .001), and the change effect in the experimental group was better than that in the control group. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The proposed motivational interview intervention can help patients with type 2 diabetes admitted to medical wards improve their self-efficacy, self-care behavior, and glycated hemoglobin values. In the future, nursing education should improve the teaching of motivational interview skills to allow nurses to conduct effective interviews quickly during treatment, increase their patients' motivation to self-control blood sugar, and enable patients to learn blood sugar control skills before discharge to achieve effective blood sugar control.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Controle Glicêmico , Autoeficácia , Glicemia , Hemoglobinas GlicadasRESUMO
OBJECTIVES: Studies have identified many nursing interventions that can prevent delirium and fall accidents in clinical patients, detect and treat delirium early to prevent functional decline in the patient, shorten hospitalization duration, and lower the death rate. This study aimed to explore delirium care by intensive care unit (ICU) nurses in a medical center of southern Taiwan. METHODS: This study conducted 3 semistructured focus group interviews, each for a single medical ICU, involving groups of 6 to 8 nurses each. The nurses were recruited through purposive sampling. This research was approved by an institutional review board in the medical center of southern Taiwan from March 31, 2020, to January 30, 2021. The co-principal investigator described the purpose and process of this study to the participants before they provided their written informed consents. The interviews were conducted in the meeting room and were audiotape recorded. The recordings were transcribed and subject to content analysis to identify the themes of delirium care. RESULTS: For nursing interventions of delirium, satisfying the patient's physical needs: comfort care, massages, and early rehabilitation; and psychological care: being presence, communication, and ensuring familial support were included. In terms of environmental interventions for delirium, providing reorientation, music, light, belongings with sentimental value, and audiovisual equipment were included. However, according to the recruited medical ICU nurses, these nonpharmacological interventions, although effective, do not have long-lasting effects. Finally, nurses reported themselves as having been attacked by patients with delirium. Thus, they all agreed that restraining patients with delirium may be necessary, but restraining is a double-edged sword for ICU delirium patients. CONCLUSIONS: Research team suggests for future studies to extend their evidence-based findings of physical, psychological, and environmental care for ICU delirium patients toward integrating the efforts of various health care professionals.
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Delírio , Humanos , Grupos Focais , Taiwan , Delírio/diagnóstico , Unidades de Terapia Intensiva , Cuidados CríticosRESUMO
Retinoic-acid-receptor-related orphan receptor γ (RORγ) is a major transcription factor for proinflammatory IL-17A production. Here, we revealed that the RORγ deficiency protects mice from STZ-induced Type 1 diabetes (T1D) through inhibiting IL-17A production, leading to improved pancreatic islet ß cell function, thereby uncovering a potential novel therapeutic target for treating T1D. We further identified a novel RORγ inverse agonist, ginseng-derived panaxadiol, which selectively inhibits RORγ transcriptional activity with a distinct cofactor recruitment profile from known RORγ ligands. Structural and functional studies of receptor-ligand interactions reveal the molecular basis for a unique binding mode for panaxadiol in the RORγ ligand-binding pocket. Despite its inverse agonist activity, panaxadiol induced the C-terminal AF-2 helix of RORγ to adopt a canonical active conformation. Interestingly, panaxadiol ameliorates mice from STZ-induced T1D through inhibiting IL-17A production in a RORγ-dependent manner. This study demonstrates a novel regulatory function of RORγ with linkage of the IL-17A pathway in pancreatic ß cells, and provides a valuable molecule for further investigating RORγ functions in treating T1D.
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Diabetes Mellitus Tipo 1 , Panax , Animais , Camundongos , Interleucina-17/metabolismo , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Ligantes , Agonismo Inverso de Drogas , Panax/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/agonistasRESUMO
BACKGROUND: The aim of the current study was to develop and validate a Perceived Relocation Stress Scale. METHODS: A cross-sectional research design was used. A total of 175 older adults residing in long-term care facilities in Southern Taiwan for at least 1 y were recruited. An exploratory factor analysis was performed to examine item convergent and discriminant validity. Concurrent validity was checked using the Depression Anxiety and Stress scale. The reliability was analyzed using Cronbach's alpha and intraclass correlation coefficients. RESULTS: The face and content validity of the scale were verified by adequately measuring the scale items. Factor analysis consisted of four components (challenge/chance, positive appraisal, threat, loss), with a total variance of 67.35%. The content validity was determined by an expert panel to systematically examine the relevance of all items. The results of item convergent and discriminant validity supported the constructs of the scale. The alpha coefficient for the overall scale was .958, indicating good internal consistency reliability. CONCLUSIONS: The Perceived Relocation Stress Scale is a reliable and valid measurement to assess the stress perceived by older individuals being transferred to a long-term care facility.
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Instalações de Saúde , Assistência de Longa Duração , Humanos , Idoso , Taiwan , Reprodutibilidade dos Testes , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
Materials and Methods: Three hundred sixty (n = 360) broiler chickens were equally divided into control (C) and thiram (T) groups. Furthermore, the C and T groups were dividedinto 8-, 9-, 11-, and 13-day-old chickens. Results: Clinically, it was observed that broiler chickens of group T had abnormal posture, gait, and lameness, and histopathological results revealed dead and abnormal chondrocytes of T group on day 6. Real-time qPCR results showed that HDAC1, MTA1, H4, and PCNA genes were significantly expressed (P < 0.05). HDAC1 was upregulated on days 1, 2, 4, and 6 (P < 0.01); MTA1 was upregulated on days 1 and 2 (P < 0.01); H4 was upregulated on days 2 and 4 (P < 0.01), and PCNA was downregulated on days 1, 2, and 4 (P < 0.01). Furthermore, IHC results of HDAC1 protein were significantly (P < 0.01) expressed in proliferative zone of day 1 and hypertrophic zone of day 6. MTA1 protein was significantly (P < 0.01) expressed on days 1, 2, and 6 in all zones, except prehypertrophic zone of day 2. Conclusion: In conclusion, the mRNA expressions of HDAC1, MTA1, H4, and PCNA were differentially expressed in the chondrocytes of thiram-induced TD chickens. HDAC1 and MTA1 protein expression found involved and responsible in the abnormal chondrocytes' proliferation of broiler chicken.
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Osteocondrodisplasias , Doenças das Aves Domésticas , Animais , Proliferação de Células/genética , Galinhas/genética , Lâmina de Crescimento/metabolismo , Osteocondrodisplasias/induzido quimicamente , Osteocondrodisplasias/genética , Doenças das Aves Domésticas/induzido quimicamente , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/patologia , Antígeno Nuclear de Célula em Proliferação/genética , Tiram/toxicidade , Tíbia/patologiaRESUMO
BACKGROUND: Literature on the spirituality of cancer patients has been mainly focused on the experiences of western patients. Few studies explore the experience of Asian cancer patients, while no spiritual study on cancer patients has been conducted in Vietnam. PURPOSE: The purpose of this study was to survey the spiritual distress of cancer patients at two general hospitals in northern Vietnam. METHODS: This was a quantitative survey with a cross-sectional design. This study used purposive sampling with a fitting the inclusion criteria, alongside the Spiritual Distress Scale-Vietnam version (SDS-V). The data was collected by an investigator in two general hospitals in northern Vietnam. The study received approval from two research councils. RESULTS: The results demonstrated that the demographics of cancer patients in the study reflected the national data of Vietnam. Regarding the four exploratory dimensions, more than 50% of cancer patients expressed feeling hardship and sorrow, most did not feel loneliness, most patients reported a good relationship with others and God, while the majority of were afraid to discuss death. CONCLUSIONS: Due to impact of aging and poverty on the sample patients, further studies into the interconnectivity between economics and the spiritual health status of patients is recommended. Additionally, since the 132 Vietnamese cancer patients reported a positive relationship with others and God, healthcare professionals should study effective strategies to apply the above strengths in easing hardships for future cancer patients.
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Neoplasias , Terapias Espirituais , Estudos Transversais , Humanos , Espiritualidade , VietnãRESUMO
The nuclear receptor farnesoid-X-receptor (FXR) plays an essential role in bile acid, glucose, and lipid homeostasis. In the last two decades, several diseases, such as obesity, type 2 diabetes, nonalcoholic fatty liver disease, cholestasis, and chronic inflammatory diseases of the liver and intestine, have been revealed to be associated with alterations in FXR functions. FXR has become a promising therapeutic drug target, particularly for enterohepatic diseases. Despite the large number of FXR modulators reported, only obeticholic acid (OCA) has been approved for primary biliary cholangitis (PBC) therapy as FXR modulator. In this review, we summarize the structure and function of FXR, the development of FXR modulators, and the structure-activity relationships of FXR modulators. Based on the structural analysis, we discuss potential strategies for developing future therapeutic FXR modulators to overcome current limitations, providing new perspectives for enterohepatic and metabolic diseases treatment.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Biologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Desenvolvimento de Medicamentos , Fibrose , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismoRESUMO
Pathogenicity of tibial dyschondroplasia (TD) in broiler chickens is not detected yet. Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway-related genes were investigated in thiram induced TD chickens. Real-time qPCR and immunohistochemical (IHC) technique were used to observe the expression changes of STAT3 and SOSC3 gene on days 1, 2, 4, 6 after feeding 100 mg·kg-1 thiram. Morphological, pathological, and histological results of this study suggested that chondrocyte cells were observed more damaged on day 6 than day 1, 2, and 4. Therefore, Lameness and damaged chondrocytes gradually increased from day 1 to 6. The mRNA expression level of STAT3 was observed insignificant (P > 0.05) in thiram induced TD chickens' group of day 1. However, on days 2, 4, and 6, the expression was significant (P < 0.05). SOCS3 increased in thiram group on days 1, 2 and 6, decreased on day 4 (P < 0.05). The p-STAT3 and SOCS3 protein's protein localization was evaluated in the control and thiram-induced TD broiler chickens through IHC, suggesting that SOSC3 protein was observed significantly higher on days 1, 2, and 6 and down-regulated on day 4. p-STAT3 protein on thiram induced group was observed significantly upregulated on days 4 and 6. In conclusion, the differential expression of STAT3 and SOCS3 showed that the JAK-STAT signaling pathway might play an important role in regulating an abnormal proliferation, differentiation, or apoptosis of chondrocytes in TD at an early stage.
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Galinhas/genética , Janus Quinases/metabolismo , Osteocondrodisplasias/veterinária , Doenças das Aves Domésticas/genética , Fator de Transcrição STAT3/genética , Proteína 3 Supressora da Sinalização de Citocinas/genética , Tíbia/metabolismo , Animais , Apoptose , Condrócitos/metabolismo , Regulação para Baixo , Lâmina de Crescimento , Osteocondrodisplasias/induzido quimicamente , Osteocondrodisplasias/enzimologia , Osteocondrodisplasias/genética , Doenças das Aves Domésticas/enzimologia , RNA Mensageiro , Transdução de Sinais , TiramRESUMO
BACKGROUND: Relocating from home to a long-term facility is frequently a stressful event for older persons with diabetes. Therefore, it is important that nurses have available an intervention program that effectively reduces relocation anxiety and promotes adaptation in this population. PURPOSE: To evaluate the effectiveness of a mindfulness-based intervention in reducing relocation anxiety and promoting adaptation in older persons with diabetes. METHODS: Four long-term care facilities in Kaohsiung City were selected as the study sites. Residents of these facilities who had diabetes and who had moved in within the previous year were recruited as participants using a simple random-sampling method. The experimental group (n = 34) received a 9-week mindfulness-based intervention and the control group (n = 32) received routine diabetes care and maintained their normal daily routine. Outcome measurements included a demographic datasheet, the Taiwanese version of the State Anxiety Inventory, and the individual mental factors subscale of the elderly adaptation problem scale. These measures were administered at baseline and upon completion of the intervention. RESULTS: Thirty participants in each group completed the study. The mean differences between the baseline and post-test scores in the experimental group for relocation anxiety (t = 5.15, p < .01) and adaptation (t = -5.57, p < .01) were both significant. Among the participants who tested positive for relocation anxiety at pretest (a mean score > 30.13; 83.3% of the participants), those in the experimental group reported a more significant decrease (p < .05) in relocation anxiety at posttest than their control group peers. Among the participants who tested as having poor adaptation pretest (a mean scores < 45.62; 71.7% of the participants), those in the experimental group reported a more significant improvement (p < .05) in adaptation at posttest than their control group peers. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The results indicate that the 9-week intervention has the potential to help older people with diabetes improve their relocation anxiety and adaptation. This study may be used as a reference to improve emotional distress among residents of long-term care facilities.
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Adaptação Psicológica , Ansiedade/psicologia , Diabetes Mellitus/psicologia , Atenção Plena , Características de Residência , Idoso , Diabetes Mellitus/epidemiologia , Humanos , Avaliação de Programas e Projetos de Saúde , Instituições Residenciais , Taiwan/epidemiologiaRESUMO
AIMS: The aim of this study was to determine physical, behavioural and psychosocial effects of a newly developed mindfulness programme for older adults with type 2 diabetes relocating to long-term care facility. BACKGROUND: Taiwan is viewed as an "aged society" with significant proportion of the population living in a long-term care facility. Approximately one third of residents living in long-term care facilities have been diagnosed with type 2 diabetes, and disruption to management of their glycaemic levels is at risk for up to one year after relocating to a long-term care facility. DESIGN: A cluster randomised controlled trial was used to examine the effects of a newly developed mindfulness programme on outcomes of glycaemic levels, relocation stress and depression. METHODS: A total of 140 participants were recruited from six long-term care facilities in Southern Taiwan. A mindfulness programme was delivered over 9 weeks and consisted of meditations, education and exercise techniques that were delivered by a Registered Nurse trained in mindfulness strategies. Participants in the control group received routine care as provided in the facilities, including routine check-ups at diabetes clinics as necessary. Data were analysed by Johnson-Neyman technique and generalised estimating equations. RESULTS: In total, 120 residents completed the study. The majority of patients were female (64.8%), and 83.5% of the sample were financially supported by their children. The results showed significant improvements in glycated haemoglobin (HbA1c), relocation stress (Wald χ2 = 78.91) and depression (Wald χ2 = 45.70) between groups. In the intervention group, the mean of HbA1c levels showed 16.4% reduction (Mean differences = 1.3; SD = 0.3). However, there were no significant differences in relocation stress and depression within groups. CONCLUSION: The results provided positive effects of the mindfulness programme for older people with diabetes moving into long-term care facilities. The programme will assist in future planning for diabetes care in long-term care facilities. IMPLICATIONS FOR PRACTICE: To incorporate the mindfulness program into existing diabetes education programs for older people living in LTCFs. Further investigation on the sustainability of the mindfulness program is warranted.
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Depressão/psicologia , Diabetes Mellitus Tipo 2/terapia , Controle Glicêmico/psicologia , Assistência de Longa Duração , Atenção Plena , Transferência de Pacientes , Idoso , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , TaiwanRESUMO
BACKGROUND: The gap between the expectation and the development of role competency is a dilemma that nurse practitioners (NPs) face in clinical settings. PURPOSE: This study was designed to explore the perceived importance and actual practice of the role competencies of NPs and to compare the differences between the ideal and practical domains as well as related factors. METHODS: This cross-sectional design study used Q-sort to collect data. A 56-item "Nurse Practitioner Role Capacity Questionnaire" was used as the research tool. Two questionnaires: Perceptions of Important Role Competencies and Actual Execution of Role Competencies were distributed to NPs twice, at times that were 2 weeks apart. A total of 40 participants were recruited, including 21(52.5%) internal medicine NPs and 19 (47.5%) surgical medicine NPs. RESULTS: The significant differences that were identified in this study between the perceived importance and actual practice of role competencies were, by domain: medical assistance (t = -5.62, p < .001), clinical research (t = 4.14, p < .001), professional consultation (t = 2.29, p = .027), and direct care (t = 2.21, p = .033). The correlative factors for these differences were: education level (t = -2.17, p = .036) and membership in the Nurse Practitioner Association (t = -2.36, p = .017). NPs with higher levels of education and with membership in the Nurse Practitioner Association earned higher scores for self-expectation in important clinical competency. CONCLUSIONS: NPs face discrepancies in their role expectations, in important part due to their role as providers of medical assistance in clinical practical settings. NPs need to learn and demonstrate the roles and functions of advanced nursing practice to enhance nursing professionalism profoundly.
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Competência Clínica , Profissionais de Enfermagem/psicologia , Papel do Profissional de Enfermagem/psicologia , Estudos Transversais , Humanos , Q-Sort , Inquéritos e QuestionáriosRESUMO
Novel kojic acid derivatives (KADs) with the potential ability to inhibit tyrosinase were synthesized and were further identified by Q-Exactive, IR and NMR. Among these compounds, KAD2 showed the best inhibitory effects on diphenolase activity and monophenolase activity, with IC50 of 7.50⯵M and 20.51⯵M, respectively. The anti-melanogenic activity of KAD2 was further confirmed by assessing the inhibition of melanin content and intracellular tyrosinase activity in B16F10 cells and zebrafish model. It demonstrated that KAD2 suppressed the expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase related protein-1 and 2 (TRP-1 and TRP-2) in a concentration-dependent manner. Furthermore, KAD2 dose-dependently suppressed the expression of the phosphorylation of protein kinase A (PKA) and cAMP-response element binding protein (CREB) and rescued the phosphorylation of Akt. Additionally, KAD2 could inhibit body pigmentation in zebrafish. Taken together, our findings elucidated that KAD2 has significant anti-melanogenic activity via CREB and Akt pathway-mediated suppression the expression of MITF and TYR family proteins in B16F10 cells. It could provide new insight into the development of novel anti-melanogenic agents to apply in the fields of food sciences, agriculture, cosmetics and medicine.
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Melaninas/biossíntese , Melanoma Experimental/metabolismo , Pironas/farmacologia , Peixe-Zebra/metabolismo , Agaricales/enzimologia , Animais , Forma Celular/efeitos dos fármacos , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Pigmentação/efeitos dos fármacos , Pironas/síntese química , Pironas/químicaRESUMO
The synthesis of L-ascorbyl flurbiprofenate was achieved by esterification and transesterification in nonaqueous organic medium with Novozym 435 lipase as biocatalyst. The conversion was greatly influenced by the kinds of organic solvents, speed of agitation, catalyst loading amount, reaction time, and molar ratio of acyl donor to L-ascorbic acid. A series of solvents were investigated, and tert-butanol was found to be the most suitable from the standpoint of the substrate solubility and the conversion for both the esterification and transesterification. When flurbiprofen was used as acyl donor, 61.0% of L-ascorbic acid was converted against 46.4% in the presence of flurbiprofen methyl ester. The optimal conversion of L-ascorbic acid was obtained when the initial molar ratio of acyl donor to ascorbic acid was 5 : 1. kinetics parameters were solved by Lineweaver-Burk equation under nonsubstrate inhibition condition. Since transesterification has lower conversion, from the standpoint of productivity and the amount of steps required, esterification is a better method compared to transesterification.
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Ácido Ascórbico/química , Flurbiprofeno/química , Lipase/química , Enzimas Imobilizadas , Esterificação , Proteínas FúngicasRESUMO
Crocodile choline, an active compound isolated from Crocodylus siamensis, was found to exert potent anti-cancer activities against human gastric cancer cells in vitro and in vivo. Our study revealed that crocodile choline led to cell cycle arrest at the G2/M phase through attenuating the expressions of cyclins, Cyclin B1, and CDK-1. Furthermore, crocodile choline accelerated apoptosis through the mitochondrial apoptotic pathway with the decrease in mitochondrial membrane potential, the increase in reactive oxygen species production and Bax/Bcl-2 ratio, and the activation of caspase-3 along with the release of cytochrome c. In addition, this study, for the first time, shows that Notch pathway is remarkably deregulated by crocodile choline. The combination of crocodile choline and Notch1 short interfering RNA led to dramatically increased cytotoxicity than observed with either agent alone. Notch1 short interfering RNA sensitized and potentiated the capability of crocodile choline to suppress the cell progression and invasion of gastric cancer. Taken together, these data suggested that crocodile choline was a potent progression inhibitor of gastric cancer cells, which was correlated with mitochondrial apoptotic pathway and Notch pathway. Combining Notch1 inhibitors with crocodile choline might represent a novel approach for gastric cancer.
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Apoptose/efeitos dos fármacos , Colina/administração & dosagem , Receptor Notch1/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Jacarés e Crocodilos/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Proteína Quinase CDC2 , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Ciclina B1/biossíntese , Quinases Ciclina-Dependentes/biossíntese , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/biossínteseRESUMO
Apoptosis, programmed cell death under physiological or pathological conditions, plays a critical role in the tissue homeostasis of eukaryotes. It is desirable to prevent the occurrence and metastasis of cancer through inducing apoptosis. Our previous study demonstrated that apoptosis could be induced by extract from crocodile in human cholangiocarcinoma. ESC-3, a novel cytotoxic compound isolated from the extract induced apoptosis in Mz-ChA-1 cells via the mitochondria-dependent pathway in a dose-dependent manner. In this study, ESC-3 significantly inhibited the proliferation of A2780 cells and arrested the cells at G2/M phase. After exposure to ESC-3, A2780 cells displayed typical morphological changes and the ability of colony-forming was remarkably inhibited. ESC-3 could significantly upregulate the expression of Bax proteins while Bcl-2 protein remained unchanged, resulting in the elevation of Bax/Bcl-2 ratio, which usually could induce apoptosis. The critical protein of Wnt signaling (ß-catenin) was significantly downregulated, whereas Hes1, the downstream protein of Notch signaling, was remarkably attenuated through upregulating the expression of P53. In addition, xenograft models demonstrated that ESC-3 effectively suppressed the growth of OvCa tumors (T/C=42%). Western blot analysis of PCNA and VEGF confirmed that ESC-3 could inhibit the growth and metastasis of OvCa tumors. In conclusion, apoptosis could be induced by ESC-3 through Wnt/ß-catenin and Notch signaling in vitro and in vivo, and might have therapeutic potential for the treatment of human OvCa.
Assuntos
Carcinoma/tratamento farmacológico , Proteínas de Neoplasias/biossíntese , Neoplasias Ovarianas/tratamento farmacológico , Extratos de Tecidos/administração & dosagem , Jacarés e Crocodilos , Animais , Apoptose/efeitos dos fármacos , Carcinoma/genética , Carcinoma/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Receptores Notch/efeitos dos fármacos , Extratos de Tecidos/química , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
OBJECTIVE: The objective was to compare the effectiveness between a systematic assessment tool and a traditional assessment tool for discharge planning. METHODS: This research adopted a two-group comparison study design, and convenience sampling was adopted to recruit patients requiring discharge-planning services at eight wards in a regional teaching hospital in Southern Taiwan. The postdischarge care requirements of two groups of patients were evaluated using a traditional assessment tool and a systematic assessment tool in different implementation periods, respectively. Sixty-eight patients were matched with similar age and with similar activity in daily living index scores to compare the effectiveness of the tools. RESULTS: The systematic assessment tool exhibited higher assessment integrity and placement appropriateness, as well as lower rates of rehospitalization or mortality within discharge 14 days. The two groups exhibited no significant difference in inappropriate hospital days, primary decision-makers' satisfaction, and proportion of referral professionals who meet patient care requirements. However, the differences in three items of satisfaction exhibited moderate-to-large effect sizes, which may be of clinical importance. CONCLUSIONS: To meet the needs of primary decision-makers in a family, enhance their satisfaction, and provide effective discharge-planning services, clinicians should adopt the systematic assessment tool to assess the postdischarge care requirements of a patient, and the hospital should provide relevant facilities to assist in implementing all plans.