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PURPOSE: Metabolic rewiring in malignant transformation is often accompanied by altered expression of metabolic isozymes. Phosphoenolpyruvate carboxykinase-2 (PCK2) catalyzes the rate-limiting step of gluconeogenesis and is the dominant isoform in many cancers including triple-negative breast cancer (TNBC). Our goal was to identify small molecule inhibitors of PCK2 enzyme activity. METHODS: We assessed the impact of PCK2 down regulation with shRNA on TNBC cell growth in vitro and used AtomNet® deep convolutional neural network software to identify potential small molecule inhibitors of PCK2-based structure. We iteratively tested candidate compounds in an in vitro PCK-2 enzyme assay. The impact of the top hit on metabolic flux and cell viability was also assessed. RESULTS: PCK2 downregulation decreased growth of BT-549 and MDA-MB-231 cells and reduced metabolic flux through pyruvate carboxylase. The first AtomNet® in silico structural screen of 7 million compounds yielded 86 structures that were tested in PCK2 enzyme assay in vitro. The top hit (IC50 = 2.4 µM) was used to refine a second round of in silico screen that yielded 82 candidates to be tested in vitro, which resulted in 45 molecules with inhibition > 20%. In the second in vitro screen we also included 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate, previously suggested to be PCK2 inhibitor based on structure, which emerged as the top hit. The specificity of this compound was tested in PCK1 and PCK2 enzymatic assays and showed IC50 of 500 nM and 3.5-27 nM for PCK1 and PCK2, respectively. CONCLUSION: 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate is a high affinity PCK2 enzyme inhibitor that also has significant growth inhibitory activity in breast cell lines in vitro and represents a potential therapeutic lead compound.
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Recent technological advances uncovered intricate biological processes underlying intratumor heterogeneity with clinical implications. These insights led to novel biomarkers for immunotherapies, justified serial tumour biopsies for therapeutic target profiling, inspired new treatment strategies, and ultimately might yield novel therapeutics that target clonal interdependence.
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Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Heterogeneidade GenéticaRESUMO
This study presents the trends of age-standardised incidence and mortality rates of common cancers in Brunei Darussalam from 2011 to 2020. All cancer cases diagnosed among Brunei Darussalam citizens and permanent residents in the period 2011 to 2020 were included in the study. De-identified data were provided by the CanReg5 based BDCR, Ministry of Health Brunei Darussalam. The annual age-standardised incidence and mortality rates per 100,000 persons were standardised by the direct method using the World Health Organization (WHO) world standard population distribution. Joinpoint regression analyses were used to study the incidence and mortality trends of cancer in Brunei Darussalam over the 2011-2020 period. Trends were expressed as average annual percent change (AAPC) over 2011 to 2020, or annual percent change (APC) for a given time period. There were a total of 6,495 new cancer cases diagnosed and 3,359 death cases recorded from 2011 to 2020, in Brunei Darussalam. The five common cancers for males were colorectal, lung and bronchus, prostate, liver, and non-Hodgkin lymphoma. Among females, the five most common cancers were breast, colorectal, lung and bronchus, corpus uteri and cervix uteri. The five leading cancer deaths for males were lung and bronchus, colorectal, liver, prostate, and stomach, while for females, the five leading cancer deaths were breast, lung and bronchus, colorectal, ovary, and cervix uteri. There was a significant increase in the incidence trend of corpus uteri (AAPC[Formula: see text]) and a significant decline in the incidence trend for cervical cancer (AAPC[Formula: see text]) from 2011 to 2020. There was a significant increase in the mortality trend of female breast cancer from 2011 to 2015 (APC[Formula: see text]), but the trend significantly declined from 2015 to 2020 (APC[Formula: see text]). We also found a significant decrease in mortality trends for stomach cancer (AAPC[Formula: see text]) from 2011 to 2020 for both genders combined. The burden of common cancers is expected to continue to grow with ageing population, effective public health interventions targeting high burden cancers and high-risk groups, and control of modifiable risk factors will continue to be the essential approaches in reducing cancer burden.
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Neoplasias Colorretais , Neoplasias Gástricas , Neoplasias do Colo do Útero , Humanos , Feminino , Masculino , Incidência , Brunei/epidemiologia , MortalidadeRESUMO
BACKGROUND: Although books and articles guiding the methods of sample size calculation for prevalence studies are available, we aim to guide, assist and report sample size calculation using the present calculators. RESULTS: We present and discuss four parameters (namely level of confidence, precision, variability of the data, and anticipated loss) required for sample size calculation for prevalence studies. Choosing correct parameters with proper understanding, and reporting issues are mainly discussed. We demonstrate the use of a purposely-designed calculators that assist users to make proper informed-decision and prepare appropriate report. CONCLUSION: Two calculators can be used with free software (Spreadsheet and RStudio) that benefit researchers with limited resources. It will, hopefully, minimize the errors in parameter selection, calculation, and reporting. The calculators are available at: ( https://sites.google.com/view/sr-ln/ssc ).
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Software , Estudos Transversais , Humanos , Tamanho da AmostraRESUMO
BACKGROUND: The older person is at greater risk of falls due to multiple intrinsic and extrinsic factors. This is compounded when the elderly is admitted to hospitals, as they are acutely ill and placed in an unfamiliar environment. Delirium and polypharmacy further complicate these problems. As falls reflect quality of care with potential for grave outcomes, this study aimed to identify the extent and risk of falls in public hospitals. METHODS: We conducted a nested case control study in 12 public hospitals in Malaysia. In the cohort section, we screened all inpatients 60 years of age and above daily until discharge, or the end of the study period. Daily, we identified those who fell, inclusive of near falls, in the preceding 24 h. Our enumerators interviewed patients on experience of fall, and supplemented data from the nurses and caregivers. For each case, ten controls were chosen. RESULTS: The incidence of falls/near falls was 1.0 per 1000 patient days (95% CI: 0.9, 1.1). Intrinsic risk factors found to be significant included patients who were not from a nursing home or not cared for by a domestic helper prior to admission, had prior history of indoor fall either in home or hospital, had four or more clinical diagnoses or exited from the bed on the weak side. Significant extrinsic factors were the absence of transfer bar in toilet, call bells, light switches or walking aids that were not within reach, as well as not having a walking aid. Non-sturdy chair was associated with lesser falls than when sturdy chairs with armrests were present. CONCLUSION: Querying patients for falls produced better results than incident reporting. Several intrinsic factors such as history of indoor or in-hospital fall, having four or more clinical diagnoses or exiting from weaker side and residence history may help to identify those at higher risk. Addressing significant extrinsic factors such as transfer bars and the identification of switches may help in reducing falls risk in hospitals. TRIAL REGISTRATION: This study was registered in National Medical Research Register of Malaysia ( NMRR-07-772-1044 ; date 26/05/2008) with Ethics Approval from Medical Research and Ethics Committee (MREC: MRG-07-LOI-HSR-1).
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Pacientes Internados , Idoso , Estudos de Casos e Controles , Humanos , Incidência , Malásia/epidemiologia , Fatores de RiscoRESUMO
BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality globally. This review aimed to summarise evidence on the key features, usability and benefits of CVD risk calculators using digital platforms for CVDs prevention and management in populations. METHODS: We used search engines and thematic analyses to conduct a scoping review. As the reporting guideline for this review, we used Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). RESULTS: A total of 17 studies meeting eligibility criteria were included in the analysis, from which about 70% of the studies have prognostic level I (n = 8) and level II (n = 4) evidence. The review found that various guidelines are recommending different algorithms for CVD risk prediction. The QRISK® was the most accurate CVD risk calculator for several study populations, whereas World Health Organization/International Society of Hypertension (WHO/ISH) risk scores were the least accurate. The key features of CVD risk calculators are variables, predictive accuracy, discrimination index, applicability, understandability, and cost-effectiveness. CONCLUSION: For the selected risk prediction tool, development and validation research must be done, which considers a mix of stroke-specific risk and CVD risk to establish its usability in the local community and advantages to the particular health-care environment. To get healthcare professionals more involved in preventing and treating CVDs, each healthcare setting should use an online CVD risk assessment tool that is more useful, accurate, and easy to use, based on the population and health system.
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Doenças Cardiovasculares , Hipertensão , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Atenção à Saúde , Humanos , Medição de Risco , Fatores de RiscoRESUMO
AIMS: This study investigated stress levels and coping strategies among working and nonworking women in the United Arab Emirates. BACKGROUND: Stress levels in working and nonworking women have previously been studied, but few studies used cortisol to measure stress or examined how coping strategies affect stress levels. METHODS: We employed a cross-sectional design with a convenience sample of women aged 20-65 years. Information on women's sociodemographic characteristics, perceived stress (using the Perceived Stress Scale) and coping strategies (using the Brief-COPE) was collected. Participants' morning (07:00-08:00) and evening (19:00-20:00) cortisol levels were measured using unstimulated saliva samples. RESULTS: In total, 417 working and 403 nonworking women participated in this study. More nonworking women reported high stress levels than working women (14.1% vs. 4.1%, p = .001). Working women reported more use of informational support and venting to cope with stress compared with nonworking women (94.0% vs. 88.1%, p = .001). More nonworking women had impaired morning (<0.094 mg/dl) and evening (>0.359 mg/dl) cortisol compared with working women (58.1% vs. 28.5% and 41.7% vs. 18.0%, respectively). Compared with working women, nonworking women had 3.25 (95%CI: 2.38, 4.47) and 3.78 (95%CI: 2.65, 5.43) times the odds of impaired morning and evening cortisol, respectively. CONCLUSION: Nonworking women exhibited higher levels of stress than working women. There is an urgent need to support nonworking women to manage stress through appropriate awareness campaigns and public health policies. IMPLICATIONS FOR MANAGEMENT: Policymakers and community leaders should consider the mental health of nonworking women as a priority in planning public health policies and programmes. Nurse managers must have a voice in reforming public health policy to support early assessment and management of stress among nonworking women.
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Adaptação Psicológica , Hidrocortisona , Feminino , Humanos , Estudos Transversais , Saúde Mental , Estresse Psicológico/complicaçõesRESUMO
AIMS: To assess the extent of posttraumatic stress disorder (PTSD) symptoms and severity, factors motivating work continuation, and factors influencing PTSD development among frontline nurses caring for patients with COVID-19. BACKGROUND: The COVID-19 pandemic has an emotional toll on nurses. Exposure to traumatic events associated with the pandemic places frontline nurses at risk for developing PTSD. DESIGN: Cross-sectional study. METHODS: Frontline nurses (n = 370) who cared for COVID-19 patients in three governmental hospitals in the United Arab Emirates were recruited from November 2020 to January 2021. The self-reported Posttraumatic Diagnostic Scale (PDS) was used to assess PTSD. The motivational factors for work continuation explored were: work-related factors (e.g., availability of personal protective equipment and management recognition), family support, and obligation to care. We used correlation and multiple regression analyses to investigate factors that influenced PDS score, including sociodemographic characteristics (e.g., gender, age, exercising status, and general health status), work factors (e.g., hospital type [COVID vs non-COVID], prior work experience, and encountering deaths), and factors motivating work continuation. The reporting of this study was consistent with STROBE guidelines. RESULTS: In total, 36.2% participants had a probable PTSD diagnosis (PDS score ≥28) with most reporting unwanted memories. Family support (95.9%) and management recognition (90.8%) were the most frequently reported motivating factors. Factors significantly associated with higher PDS score were smoking, lack of management recognition, not exercising, and encountering COVID-19 deaths; the correlation and regression coefficients (b) were significant (p < 0.05). CONCLUSIONS AND IMPLICATIONS FOR NURSING/HEALTH POLICY: Policy makers must expand healthcare policies to address frontline nurses' mental health as a priority during the pandemic. Nurse leaders must be involved in health policy development to protect nurses in anticipation of and during global health emergencies.
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COVID-19 , Enfermeiras e Enfermeiros , Transtornos de Estresse Pós-Traumáticos , COVID-19/epidemiologia , Estudos Transversais , Humanos , Enfermeiras e Enfermeiros/psicologia , Pandemias , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e QuestionáriosRESUMO
There are fewer eyespots on the forewings versus hindwings of nymphalids but the reasons for this uneven distribution remain unclear. One possibility is that, in many butterflies, the hindwing covers part of the ventral forewing at rest and there are fewer forewing sectors to display eyespots (covered eyespots are not continuously visible and are less likely to be under positive selection). A second explanation is that having fewer forewing eyespots confers a selective advantage against predators. We analysed wing overlap at rest in 275 nymphalid species with eyespots and found that many have exposed forewing sectors without eyespots: i.e. wing overlap does not constrain the forewing from having the same number or more eyespots than the hindwing. We performed two predation experiments with mantids to compare the relative fitness of and attack damage patterns on two forms of Bicyclus anynana butterflies, both with seven hindwing eyespots, but with two (in wild-type) or four (in Spotty) ventral forewing eyespots. Spotty experienced more intense predation on the forewings, were shorter-lived and laid fewer eggs. These results suggest that predation pressure limits forewing eyespot number in B. anynana. This may occur if attacks on forewing eyespots have more detrimental consequences for flight than attacks on hindwing eyespots.
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Borboletas , Animais , Pigmentação , Comportamento Predatório , Asas de AnimaisRESUMO
BACKGROUND: Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. It is the second leading cause of cancer death in men and women in Brunei Darussalam in 2017, posing a major burden on society. METHODS: This retrospective cohort study (n = 1035 patients diagnosed with CRC in Brunei Darussalam from 1st January 2002 until 31st December 2017) aims to compare the overall survival rates of CRC patients (2002-2017), to compare survival rates between two study periods (2002-2009 and 2010-2017) and to identify prognostic factors of CRC. Kaplan-Meier estimator and log-rank tests were performed to analyse the overall survival rates of CRC patients. Multiple Cox regression was performed to determine the prognostic factors of CRC with adjusted hazard ratios (Adj. HRs) reported. RESULTS: The 1-, 3- and 5-year survival rates of CRC patients are 78.6, 62.5, and 56.0% respectively from 2002 to 2017. The 1-, 3-, and 5-year survival rates of CRC patients for 2002-2009 are 82.2, 69.6, and 64.7%; 77.0, 59.1, and 51.3% for 2010-2017 respectively. A significant difference in CRC patients' survival rate was observed between the two study periods, age groups, ethnic groups, cancer stages, and sites of cancer (p < 0.05). The Adjusted Hazard Ratios (Adj. HRs) were significantly higher in the 2010-17 period (Adj. HR = 1.78, p < 0.001), older age group ( ≥ 60 years) (Adj. HR = 1.93, p = 0.005), distant cancer (Adj. HR = 4.69, p < 0.010), tumor at transverse colon and splenic flexure of colon (Adj. HR = 2.44, p = 0.009), and lower in the Chinese(Adj. HR = 0.63, p = 0.003). CONCLUSION: This study highlights the lower survival rates of CRC patients in 2010-2017, Malays, older patients, distant cancer, and tumors located at the latter half of the proximal colon (transverse colon), and predominantly LCRC (splenic flexure, descending colon, sigmoid colon, overlapping lesion colon and colon (NOS), as well as the rectosigmoid junction and rectum (NOS)). Age, ethnicity, cancer stage, and tumor location are significant prognostic factors for CRC. These findings underscore the importance of public health policies and programmes to enhance awareness on CRC from screening to developing strategies for early detection and management, to reduce CRC-associated mortality.
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Neoplasias do Colo/mortalidade , Neoplasias Retais/mortalidade , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Brunei/epidemiologia , Brunei/etnologia , Colo/patologia , Neoplasias do Colo/etnologia , Neoplasias do Colo/patologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Neoplasias Retais/etnologia , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: In keeping with nation-wide efforts to contain the spread of COVID-19, Universiti Brunei Darussalam (UBD) transformed fully its pedagogical delivery to online mode, where we investigated teaching and learning experiences, physical and mental health of undergraduate students and lecturers during the COVID-19 pandemic. METHODS: We conducted a cross-sectional study on undergraduate students and lecturers in a health science faculty using a self-developed pretested questionnaire through anonymous online data collection method. RESULTS: Fifty-six lecturers (100% response rate) and 279 students (93.3% response rate) participated. The positive experiences reported by students include becoming independent (72.8%) and adapting to online learning (67.4%), while lecturers learned new teaching techniques (50.0%) and became more innovative (50.0%) by learning new tools (48.2%). However, studying at home caused students to feel more distracted (72.0%) with a feeling of uncertainty towards examinations (66.7%), while lecturers felt that students' laboratory skills were compromised (44.6%). Even though online delivery of assessments enabled lecturers to explore all options (50.0%), they found it difficult to maintain appropriate questions (41.1%) and fair assessments (37.5%). Majority of students missed eating out (68.8%) and felt a lack of participation in extracurricular activities (64.9%), while lecturers reported more time for exercise (51.8%), despite having more screen time (50.0%) and computer-related physical stress (44.6%). In terms of mental health, increased stress in students was reported (64.9%), though they had more time for self-reflection (54.8%). Although lecturers reported a closer relationship with family (44.6%), they also felt more stressed due to deadlines, unexpected disruptions and higher workloads (44.6%) as well as concerns related to work, family and self (39.3%). CONCLUSION: In this abrupt shift to online teaching, students and lecturers in our study identified both positive and negative experiences including the impact on their physical and mental health. Our findings are important to provide the evidence for online pedagogical benefits and can serve to promote the enhancement and adaptation of digital technology in education. Our findings also aim to promote the importance of addressing physical and mental health issues of the university community's well-being through provision of emotional and mental health support and appropriate programs.
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COVID-19 , Pandemias , Estudos Transversais , Atenção à Saúde , Humanos , Saúde Mental , SARS-CoV-2 , EstudantesRESUMO
OBJECTIVE: Brief-COPE inventory is widely used to assess coping; however, validation evidence is absent and previous results were inconsistent. This study aimed to validate psychometric properties of this inventory to ensure culturally appropriate usage. METHODS: Preliminary validation study on 423 female nurses from the United Arab Emirates. Confirmatory factor analysis (CFA) with maximum likelihood estimation was computed to test four different previous models. Exploratory factor analysis (EFA) protocol was used to determine underlying domain structure of Brief-COPE in this population. RESULTS: The four previous models on CFA had inadequate fit indexes. Two-factor (22-items) second-order model that explained 37.0% of the total variance with Cronbach's alpha at 0.81 and 0.88, respectively, was suggested. CONCLUSION: This validation of Brief-COPE is timely considering nurses enduring different types of stressors. In addition, cultural diversity needs to be considered in coping research. Re-assessment of this exploratory structure is necessary to ensure accurate measurement of coping strategies.
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This is a cross-sectional study, using multivariate regression analysis, to explore the relationship of Islamic governance on psychosocial work stressors and work productivity in healthcare settings. The results revealed that Islamic governing components that are culturally assimilating were significantly related to positive aspects of psychosocial work stressors and increased productivity. Organisational goals that are re-directed towards the Maqasid, i.e. higher order of objectives in Islam, had direct benefits in reducing work-family conflict, promoting general health, increasing job satisfaction and improving commitment to work. Benefits, challenges and recommendations for future studies to expand the field of Islamic governance in organisational and cross-disciplinary healthcare research were discussed.
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Islamismo , Satisfação no Emprego , Estudos Transversais , Humanos , Inquéritos e QuestionáriosRESUMO
We report the transmission dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across different settings in Brunei. An initial cluster of SARS-CoV-2 cases arose from 19 persons who had attended the Tablighi Jama'at gathering in Malaysia, resulting in 52 locally transmitted cases. The highest nonprimary attack rates (14.8%) were observed from a subsequent religious gathering in Brunei and in households of attendees (10.6%). Household attack rates from symptomatic case-patients were higher (14.4%) than from asymptomatic (4.4%) or presymptomatic (6.1%) case-patients. Workplace and social settings had attack rates of <1%. Our analyses highlight that transmission of SARS-CoV-2 varies depending on environmental, behavioral, and host factors. We identify red flags for potential superspreading events, specifically densely populated gatherings with prolonged exposure in enclosed settings, persons with recent travel history to areas with active SARS-CoV-2 infections, and group behaviors. We propose differentiated testing strategies to account for differing transmission risk.
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Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Adulto , Idoso , Brunei/epidemiologia , COVID-19 , Teste para COVID-19 , Técnicas de Laboratório Clínico/estatística & dados numéricos , Análise por Conglomerados , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Feminino , Humanos , Malásia/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/transmissão , SARS-CoV-2 , Doença Relacionada a ViagensRESUMO
Case reports of patients with coronavirus disease-2019 (COVID-19) who have been discharged and subsequently report positive reverse transcription-polymerase chain reaction again (hereafter referred as "re-positive") do not fully describe the magnitude and significance of this issue. To determine the re-positive rate (proportion) and review probable causes and outcomes, we conduct a retrospective study of all 119 discharged patients in Brunei Darussalam up till April 23. Patients who were discharged are required to self-isolate at home for 14 days and undergo nasopharyngeal specimen collection postdischarge. Discharged patients found to be re-positive were readmitted. We reviewed the clinical and epidemiological records of all discharged patients and apply log-binomial models to obtain risk ratios for re-positive status. One in five recovered patients subsequently test positive again for severe acute respiratory syndrome coronavirus 2-this risk is more than six times higher in persons aged 60 years and above. The average Ct value of re-positive patients was lower predischarge compared with their readmission Ct value. Out of 111 close contacts tested, none were found to be positive as a result of exposure to a re-positive patient. Our findings support prolonged but intermittent viral shedding as the probable cause for this phenomenon. We did not observe infectivity potential in these patients.
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Teste Sorológico para COVID-19/estatística & dados numéricos , COVID-19/diagnóstico , Imunoensaio/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Brunei , COVID-19/imunologia , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , Estudos Retrospectivos , Fatores de Risco , Manejo de Espécimes , Fatores de Tempo , Eliminação de Partículas Virais , Adulto JovemRESUMO
Triple negative breast cancer (TNBC) is difficult to treat due to lack of druggable targets. We have found that treatment with the small molecule inhibitor KPT-9274 inhibits growth of TNBC cells and eventually leads to cell death. KPT-9274 is a dual specific inhibitor of PAK4 and Nicotinamide Phosphoribosyltransferase (NAMPT). The PAK4 protein kinase is often highly expressed in TNBC cells and has important roles in cell growth, survival, and migration. Previously we have found that inhibition of PAK4 leads to growth inhibition of TNBC cells both in vitro and in vivo. Likewise, NAMPT has been shown to be dysregulated in cancer due to its role in cell metabolism. In order to understand better how treating cells with KPT-9274 abrogates TNBC cell growth, we carried out an RNA sequencing of TNBC cells treated with KPT-9274. As a result, we identified Rictor as an important target that is inhibited in the KPT-9274 treated cells. Conversely, we found that Rictor is predicted to be activated when PAK4 is overexpressed in cells, which suggests a role for PAK4 in the regulation of Rictor. Rictor is a component of mTORC2, one of the complexes formed by the serine/threonine kinase mTOR. mTOR is important for the control of cell growth and metabolism. Our results suggest a new mechanism by which the KPT-9274 compound may block the growth of breast cancer cells, which is via inhibition of mTORC2 signaling. Consistent with this, sequencing analysis of PAK4 overexpressing cells indicates that PAK4 has a role in activation of the mTOR pathway.
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Acrilamidas/farmacologia , Aminopiridinas/farmacologia , Antineoplásicos/farmacologia , Citocinas/antagonistas & inibidores , Regulação para Baixo/efeitos dos fármacos , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Nicotinamida Fosforribosiltransferase/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Quinases Ativadas por p21/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Nicotinamida Fosforribosiltransferase/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Células Tumorais Cultivadas , Quinases Ativadas por p21/metabolismoRESUMO
AIMS: To compare morning and evening salivary melatonin levels, sleep quality and chronotype between nurses working fixed day shifts and those working rotating night shifts. BACKGROUND: Rotating night shift work is an inevitable part of nursing and is a major reason for disrupted sleep. DESIGN: Cross-sectional comparative design. PARTICIPANTS AND SETTINGS: We used cluster sampling to recruit 520 female nurses working fixed day and rotating night shifts in the United Arab Emirates. METHODS: Morning and evening melatonin were measured from corresponding saliva samples. The Pittsburgh Sleep Quality Index used to evaluate sleep quality and self-assessment of preferred circadian times was used to assess participants' chronotypes. Data were collected between October 2017-December 2018. RESULTS: Rotating night shift nurses had significantly lower evening melatonin compared with the fixed day shift group. No significant difference was found in sleep quality between the groups, although more participants in the rotating night shift group (N = 110, 42.31%) expressed better sleep quality than those in the fixed day group (N = 90, 36.00). Participants in the rotating night shift group expressed better subjective sleep, longer sleep duration, less disturbed sleep and better daily function (p > .05) than the fixed day group. Rotating night shift participants were more likely to have evening or intermediate chronotypes and more likely to report alignment of shift work to their chronotype compared with fixed day shift participants (p = .001). Longer shift duration, marital status and city location were associated with reduced evening melatonin among nurses on rotating night shifts. CONCLUSION: Rotating night shift nurses showed evidence of better sleep than those from the fixed day shift. Proper shift assignment, chronotype and alignment with shift work appeared to produce better sleep quality. IMPACT: Organizational policy must consider a novel model for work schedules that allow adequate off-duty days for sleep recovery among nurses.
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Melatonina , Enfermeiras e Enfermeiros , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Sono , Sonolência , Tolerância ao Trabalho ProgramadoRESUMO
Estrogen plays an important role in breast cancer development. While the mechanism of the estrogen effects is not fully elucidated, one possible route is by increasing the stem cell-like properties in the tumors. Tocopherols are known to reduce breast cancer development and progression. The aim of the present study is to investigate the effects of tocopherols on the regulation of breast cancer stemness mediated by estrogen. To determine the effects of tocopherols on estrogen-influenced breast cancer stem cells, the MCF-7 tumorsphere culture system, which enriches for mammary progenitor cells and putative breast cancer stem cells, was utilized. Treatment with estrogen resulted in an increase in the CD44+/CD24- subpopulation and aldehyde dehydrogenase activity in tumorspheres as well as the number and size of tumorspheres. Tocopherols inhibited the estrogen-induced expansion of the breast cancer stem population. Tocopherols decreased the levels of stem cell markers, including octamer-binding transcription factor 4 (OCT4), CD44 and SOX-2, as well as estrogen-related markers, such as trefoil factor (TFF)/pS2, cathepsin D, progesterone receptor and SERPINA1, in estrogen-stimulated tumorspheres. Overexpression of OCT4 increased CD44 and sex-determining region Y-box-2 levels and significantly increased cell invasion and expression of the invasion markers, matrix metalloproteinases, tissue inhibitors of metalloproteinase and urokinase plasminogen activator, and tocopherols inhibited these OCT4-mediated effects. These results suggest a potential inhibitory mechanism of tocopherols in estrogen-induced stemness and cell invasion in breast cancer.
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Neoplasias da Mama/tratamento farmacológico , Estrogênios/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Fator 3 de Transcrição de Octâmero/metabolismo , Tocoferóis/farmacologia , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle , Células-Tronco Neoplásicas/metabolismo , Receptores de Estrogênio/metabolismo , Tocoferóis/uso terapêuticoRESUMO
AIM: to explore high-dependency care nurses' experiences of their psychosocial work environment. METHODS: four focus groups were conducted with 23 emergency and critical care hospital nurses in Brunei. All sessions were recorded, transcribed verbatim and analysed using inductive-approach thematic analysis. FINDINGS: three major themes were identified. 'Specialisation/specific skills' explained a fundamental requirement for the high-dependency care nurses to work effectively and efficiently in their workplace. 'Task completion' narrated the pressure they experienced to complete their tasks within time constraints exacerbated by a reduced number of staff. 'Acknowledgement' signified their need for fair and adequate reward for their hard work through career progression and promotion. CONCLUSION: this study facilitates the design of future interventions and policies that promote a healthy psychosocial work environment by ensuring nurses working in these areas have the required specialisation skills, there is a balance of workload and nurse-to-patient ratios, and they are offered fairness and equity in career progression and promotion.
Assuntos
Atitude do Pessoal de Saúde , Enfermagem de Cuidados Críticos , Enfermagem em Emergência , Avaliação das Necessidades , Recursos Humanos de Enfermagem Hospitalar , Adulto , Brunei , Mobilidade Ocupacional , Competência Clínica , Feminino , Grupos Focais , Humanos , Masculino , Estresse Ocupacional , Carga de TrabalhoRESUMO
Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we - a group of scholars and practitioners from Africa, America, Asia and Europe - argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action.