Conectar
by Shota Moriya, Hiromi Kazama, Hirotsugu Hino, Naoharu Takano, Masaki Hiramoto, Shin Aizawa, Keisuke Miyazawa
We previously reported that macrolide antibiotics, such as clarithromycin (CAM), blocked autophagy flux, and simultaneous proteasome and autophagy inhibition by bortezomib (BTZ) plus CAM resulted in enhanced apoptosis induction in multiple myeloma (MM) cells via increased endoplasmic reticulum (ER) stress loading. However, in actual therapeutic settings, cell adhesion-mediated drug resistance between bone marrow stromal cells (BMSC) and MM cells has been known to be a barrier to treatment. To investigate whether CAM could enhance BTZ-induced cytotoxicity in MM cells under direct cell adhesion with BMSC, we established a co-culture system of EGFP-labeled MM cells with BMSC. The cytotoxic effect of BTZ on MM cells was diminished by its interaction with BMSC; however, the attenuated cytotoxicity was recovered by the co-administration of CAM, which upregulates ER stress loading and NOXA expression. Knockout of NOXA in MM cells canceled the enhanced cell death by CAM, indicating that NOXA is a key molecule for cell death induction by the co-administration of CAM. Since NOXA is degraded by autophagy as well as proteasomes, blocking autophagy with CAM resulted in the sustained upregulation of NOXA in MM cells co-cultured with BMSC in the presence of BTZ. Our data suggest that BMSC-associated BTZ resistance is mediated by the attenuation of ER stress loading. However, the addition of CAM overcomes BMSC-associated resistance via upregulation of NOXA by concomitantly blocking autophagy-mediated NOXA degradation and transcriptional activation of NOXA by ER stress loading.by Rashin Giti, Reza Jebal
ObjectivesThis study aimed to evaluate the color stability and translucency of various types of monolithic zirconia after immersion in chlorhexidine and Listerine mouthwashes.
Materials and methodsThis experimental study was performed on 36 disk-shaped specimens fabricated from low-translucent, high-translucent, and multilayered monolithic zirconia (n = 12 per group). Each group was equally divided and immersed in either 2% chlorhexidine (CHX) or Listerine mouthwash for 2 min daily over 7 days. Changes in color (ΔE) and the translucency parameter (ΔTP) were evaluated and compared. The data were analyzed with one-way ANOVA followed by Tukey’s post-hoc tests (α = 0.05).
ResultsChlorhexidine caused a significantly lower ΔE and a significantly higher ΔTP in multilayered zirconia compared to the low-translucency (ΔE: P = 0.0027, ΔTP: PPP = 0.0165). It also resulted in a significantly higher mean ΔTP in the multilayered zirconia group compared to the low-translucency (P = 0.0003) and high-translucency zirconia groups (P = 0.019).
ConclusionsIn both mouthwashes, multilayered monolithic zirconia exhibited the highest color stability among the tested materials; albeit with the most pronounced changes in translucency. Meanwhile, high-translucency monolithic zirconia was more prone to discoloration when exposed to both mouthwashes.
by Banghyun Lee, Suk-Joon Chang, Byung Su Kwon, Joo-Hyuk Son, Myong Cheol Lim, Yun Hwan Kim, Shin-Wha Lee, Chel Hun Choi, Kyung Jin Eoh, Jung-Yun Lee, Dong Hoon Suh, Yong Beom Kim
ObjectivesThis meta-analysis was undertaken to systematically evaluate the effects of poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy on the survival of newly diagnosed advanced epithelial ovarian cancer (EOC) patients.
Methods/MaterialsA systematic literature search revealed 3,227 studies. A subsequent selection process identified seven suitable randomized studies that assessed the survival outcomes in newly diagnosed advanced EOC patients administered PARPi (n = 1921; the PARPi group) or placebo (n = 1150; the placebo group). The survival outcomes were compared with respect to the PARPi treatment regardless of bevacizumab maintenance therapy. All adverse events ≥ grade 3 were analyzed. Review Manager Version 5.4.1 software was used for the meta-analysis.
ResultsThe two-year progression-free survival (PFS) was significantly better in the PARPi group than the placebo (Hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.41 to 0.68). Furthermore, patients in the PARPi group with the BRCA1/2 mutation (BRCAm), BRCA wild type, homologous-recombination deficiency (HRD), or HRD without BRCAm, but not with homologous-recombination proficiency had a significantly better two-year PFS than the patients in the placebo group. The five-year overall survival (OS) was comparable in the two groups, but patients in the PARPi group with BRCAm had a significantly better five-year OS than those in the placebo group (HR, 0.57; 95% CI, 0.44 to 0.74). In addition, the adverse event rate (≥ grade 3) was significantly higher in the PARPi group than in the placebo group (HR, 2.94; 95% CI, 1.13 to 7.63).
ConclusionsIn patients with newly diagnosed advanced EOC, PARPi maintenance therapy was significantly more effective in terms of survival than no PARPi treatment. However, the risk of serious adverse events was higher for patients who received PARPi maintenance therapy.
To describe Indonesian nurses' educational experience regarding care for people with intellectual disability and/or autism and to explore if these educational experiences are associated with their self-perceived confidence, comfort, knowledge and preparedness to care for these cohorts.
Cross-sectional descriptive survey.
A descriptive survey tool utilized in a study of Australian registered nurses was replicated and adapted for this study. Following descriptive analysis, chi-square analyses were undertaken to explore associations between educational experiences, and self-rated measures of confidence, comfort and knowledge to work with people with intellectual disability and/or autism. Although there was no end-user involvement in the design of the study, the concepts explored have all been raised by those with lived insights of intellectual disability and/or autism as being critical to their healthcare experiences.
There were 544 complete responses, and 51.7% were not exposed to any educational or clinical content relevant to caring for people with intellectual disability and/or autism. Moderate to low levels of self-perceived confidence, comfort, knowledge and preparedness to address healthcare needs of these cohorts were reported. Significant associations were identified between educational and clinical experiences during undergraduate training, and higher levels of self-perceived confidence, comfort and knowledge.
Mirroring international literature, the findings of this study highlight a large proportion of Indonesian nurses had little educational experience relevant to caring for people with intellectual disability and/or autism, and have relatively low levels of self-reported capability.
This study highlights gaps in the educational experiences, and self-perceived confidence, comfort, knowledge and preparedness of Indonesian nurses regarding caring for people with intellectual disability and/or autism. Given that internationally, people with intellectual disability and/or autism have disproportionately negative health outcomes and experiences, these findings have substantial implications for nursing curriculum, policy and professional development.
Inflammation is a key mediator in the development and progression of the atherosclerotic disease process as well as its resultant complications, like myocardial infarction (MI), stroke and cardiovascular (CV) death, and is emerging as a novel treatment target. Trials involving anti-inflammatory medications have demonstrated outcome benefit in patients with known CV disease. In this regard, colchicine appears to hold great promise. However, there are potential drawbacks to colchicine use, as some studies have identified an increased risk of infection, and a non-significant trend for increased all-cause mortality. Thus, a more thorough understanding of the underlying mechanism of action of colchicine is needed to enable a better patient selection for this novel CV therapy.
The primary objective of the Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE) trial is to assess the effect of colchicine on vascular inflammation in the carotid arteries and ascending aorta measured with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes who have experienced a recent vascular event (acute coronary syndrome (ACS)/MI, transient ischaemic attack (TIA) or stroke). Secondary objectives include determining colchicine’s effect on inflammatory biomarkers (high-sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6)). Additionally, we will assess if baseline inflammation imaging or biomarkers are associated with a treatment response to colchicine determined by imaging. Exploratory objectives will look at: (1) the difference in the inflammatory response to colchicine in patients with coronary events compared with patients with cerebral events; (2) the difference in the inflammatory response to colchicine in different vascular beds; (3) the relationship of FDG-PET imaging markers with serum biomarkers and (4) assessment of quality-of-life changes.
CADENCE is a multicentre, prospective, randomised, double-blinded, placebo-controlled study to determine the effect of colchicine on arterial inflammation as assessed with imaging and circulatory biomarkers, specifically carotid arteries and aortic FDG uptake as well as hs-CRP and IL-6 among others. Patients with T2DM or pre-diabetes who have recently experienced a CV event (within 30–120 days after an ACS (ie, ST-elevation MI (STEMI) or non-STEMI)) or TIA/stroke with documented large vessel atherosclerotic disease will be randomised to treatment with either colchicine 0.6 mg oral daily or placebo. Participants will undergo baseline clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan of the ascending aorta and left and right carotid arteries. Patients will undergo treatment for 6 months and have repeat clinical evaluation including EQ5D assessment, blood work for inflammatory markers and FDG PET/CT scan at the conclusion of the study. The primary outcome will be the change in the maximum target to background ratio (TBRmax) in the ascending aorta (or carotid arteries) from baseline to follow-up on FDG PET/CT imaging.
Colchicine is an exciting potential new therapy for CV risk reduction. However, its use is associated with side effects and greater understanding of its underlying mechanism of action is needed. Importantly, the current study will determine whether its anti-inflammatory action is an indirect systemic effect, or a more local plaque action that decreases inflammation. The results will also help identify patients who will benefit most from such therapy.
Cognitive dysfunction, a leading cause of mortality and morbidity in the USA and globally, has been shown to disproportionately affect the socioeconomically disadvantaged and those who identify as black or Hispanic/Latinx. Poor sleep is strongly associated with the development of vascular and metabolic diseases, which correlate with cognitive dysfunction. Therefore, sleep may contribute to observed disparities in cognitive disorders. The Epidemiologic Study of Disparities in Sleep and Cognition in Older Adults (DISCO) is a longitudinal, observational cohort study that focuses on gathering data to better understand racial/ethnic sleep disparities and illuminate the relationship among sleep, race and ethnicity and changes in cognitive function. This investigation may help inform targeted interventions to minimise disparities in cognitive health among ageing adults.
The DISCO study will examine up to 495 individuals aged 55 and older at two time points over 24 months. An equal number of black, white and Hispanic/Latinx individuals will be recruited using methods aimed for adults traditionally under-represented in research. Study procedures at each time point will include cognitive tests, gait speed measurement, wrist actigraphy, a type 2 home polysomnography and a clinical examination. Participants will also complete self-identified assessments and questionnaires on cognitive ability, sleep, medication use, quality of life, sociodemographic characteristics, diet, substance use, and psychological and social health.
This study was approved by the Northwestern University Feinberg School of Medicine Institutional Review Board. Deidentified datasets will be shared via the BioLINCC repository following the completion of the project. Biospecimen samples from the study that are not being analysed can be made available to qualified investigators on review and approval by study investigators. Requests that do not lead to participant burden or that conflict with the primary aims of the study will be reviewed by the study investigators.
by Je Sung You, Junho Cho, Hye Jung Shin, Jin Ho Beom
Acute myocardial infarction is an acute-stage disease that requires prompt diagnosis and treatment. Primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI) is a high-risk factor for post-contrast acute kidney injury (PC-AKI). This retrospective cohort study analyzed the data of 754 patients with STEMI who underwent pPCI and were integrated into the Fast Interrogation Rule for STEMI critical pathway program between 2015 and 2019. We aimed to determine the optimal cutoff baseline eGFR for identifying a high risk of PC-AKI after multivariable adjustment with statistically significant risk factors. We also compared the incidence rates of PC-AKI between the previous and current diagnostic criteria. The probability of PC-AKI increased when the baseline estimated glomerular filtration rate (eGFR) was ≤ 79mL/min/1.73 m2. The optimal cutoff baseline eGFR for high risk of PC-AKI was found to be an eGFR of ≤ 61 mL/min/1.73 m2 after multivariable adjustment. The current diagnostic criteria more accurately identified the patient group with impaired renal function. Our results have clinically significant implications for identifying patients at a high risk of developing PC-AKI, especially before and after the use of contrast agents in patients who require PCI for STEMI in the emergency department.Breast cancer survivors are increasing in South Korea, and resilience has become very important in their life.
This study aimed to examine the relationships among anxiety, depression, family support, problem-focused coping, emotion-focused coping, self-efficacy, and resilience, and the factors influencing the resilience of breast cancer survivors.
A cross-sectional descriptive design was employed. Participants were 153 breast cancer survivors after completion of treatment who were 5 years or less after diagnosis in South Korea. Measures were the general characteristics list, Korean version of Connor-Davidson Resilience Scale, Korean version of Hospital Anxiety and Depression Scale, family support scale, Korean version of Ways of Coping Checklist, and Self-Efficacy Scale.
The strongest predictor that influenced resilience was depression (β = −0.32), followed by family support (β = 0.23) and problem-focused coping (β = 0.15). Resilience levels in breast cancer survivors after completion of treatment were relatively low.
Interventions using problem-focused coping, including family members, could increase resilience, thus, moving away from focusing solely on the perspectives of cancer survivors when developing and implementing support interventions. Nurses should pay attention to influencing factors to help improve the resilience of breast cancer survivors during the extended survivorship phase.
To examine the relationship among eHealth literacy, empowerment and self-management and the mediating effects of empowerment in diabetic kidney disease (DKD) patients in the eHealthcare context.
Self-management is an essential aspect of healthcare in delaying disease progression for DKD. In the eHealthcare era, health services providing self-management are transforming. The ability and confidence of patients to use eHealth services is a critical issue that impacts the effectiveness of self-management, but little is known about the role of eHealth literacy and empowerment in self-management.
A cross-sectional study guided by the STROBE.
Overall, 127 Taiwanese patients were enrolled using convenience sampling. Data collection used structured questionnaires and chart reviews. Multiple regression was used to infer self-management predictors, and SPSS PROCESS macro and bootstrapping verified the mediating effects.
Empowerment and eHealth literacy both showed significant positive correlations with self-management. Empowerment was the main predictor of self-management and had a complete mediating effect between eHealth literacy and self-management.
Increasing patients' eHealth literacy can improve empowerment and prevent health inequality issues. Healthcare providers should consider improving patients' eHealth literacy to enhance their self-management.
Healthcare service systems need to create user-friendly eHealthcare environments, and healthcare professionals can provide multifaceted instructions that fit patients' eHealth literacy levels to enhance their motivation and confidence in disease care, thus cultivating positive self-management behaviours.
The popularity of eHealthcare services aimed at promoting self-management behaviours is increasing. However, the level of eHealth literacy is an essential factor that affects the effectiveness of self-management in the healthcare environment. In addition, empowerment is a major critical influence factor of self-management and a completely mediating variable between self-management and eHealth literacy. Consequently, healthcare providers should consider promoting patients' eHealth literacy to empower people using eHealthcare services for implementing self-management.
The Strengthening the Reporting of Observational Studies in cross-sectional studies (STROBE) checklist was used to ensure comprehensive reporting.
Patients were diagnosed with DKD in the study hospital. Physicians and case managers transferred patients to research assistants who screened them for the inclusion criteria and invited them to participate in this study if they met the requirements. After participants signed informed consent, the research nurse encouraged participants to respond to the research questionnaire face to face.
FreshRSS 