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Microarray pathway analysis

Standard therapies used for the treatment of acute myeloid leukemia (AML) are cytotoxic agents that target rapidly proliferating cells. Unfortunately, this therapeutic approach has limited efficacy and significant toxicity and the majority of AML patients still die of their disease. In contrast to the poor prognosis of most AML patients, most individuals with a rare subtype of AML, acute promyelocytic leukemia, can be cured by differentiation therapy using regimens containing all-trans retinoic acid. GSK3 has been previously identified as a therapeutic target in AML where its inhibition can lead to the differentiation and growth arrest of leukemic cells. Unfortunately, existing GSK3 inhibitors lead to suboptimal differentiation activity making them less useful as clinical AML differentiation agents. Here, we describe the discovery of a novel GSK3 inhibitor, GS87. GS87 was discovered in efforts to optimize GSK3 inhibition for AML differentiation activity. Despite GS87's dramatic ability to induce AML differentiation, kinase profiling reveals its high specificity in targeting GSK3 as compared with other kinases. GS87 demonstrates high efficacy in a mouse AML model system and unlike current AML therapeutics, exhibits little effect on normal bone marrow cells. GS87 induces potent differentiation by more effectively activating GSK3-dependent signaling components including MAPK signaling as compared with other GSK3 inhibitors. GS87 is a novel GSK3 inhibitor with therapeutic potential as a differentiation agent for non-promyelocytic AML. Mol Cancer Ther; 15(7); 1485–94. ©2016 AACR.

Representative flow histograms showing CD11b staining of AML cells after GS87 treatment

Heatmap of Z-scores of genes that are significantly dysregulated

ATRA leads to marked induction of CD11b in Acute Promyelocytic Cells

GS87 does not lead to observable alterations in normal hematopoiesis

Heatmap of Z-scores of genes that are significantly dysregulated

Kinase profiling

Supplementary Figure Legends

GS87 does not significantly impact the viability of AML cells

Primer sequences

Microarray differential expression

Loneliness is a negative emotional feeling often experienced by older residents in long-term care facilities (LTCFs). Previous studies have shown that loneliness is related to depression, inferior quality of life, cardiovascular disease, and suicidal thoughts. Thus, it is important to understand older residents' viewpoints about loneliness to provide better care in the long-term care context. This study aimed to explore residents' perceptions of loneliness in LTCFs. For this qualitative research, data were collected from two LTCFs in northern Taiwan, and purposive sampling was used. In-depth interviews with 16 older residents were conducted using a semi-structured interview guide. Content analysis was performed to analyse the data. Four themes with nine subthemes were generated. The themes were: being cut off from continually meaningful relationships, experiencing tears of pain, feeling alone, and lacking a sense of belonging. The findings of this study can provide information for health care professionals to better understand older residents' views on loneliness and remind them to re-examine care protocols for psychological health care. Thus, this study found that in order to prevent or alleviate older residents' feelings of loneliness, the LTCFs should maintain continually meaningful relationships, accompany them, and give them a sense of belonging. The consolidated criteria for reporting qualitative research (COREQ) guidelines were used to report this study.

SummaryLoss of muscle stem cell (MuSC) self-renewal with aging reflects a combination of influences from the intracellular (e.g., post-transcriptional modifications) and extracellular (e.g., matrix stiffness) environment. Whereas conventional single cell analyses have revealed valuable insights into factors contributing to impaired self-renewal with age, most are limited by static measurements that fail to capture nonlinear dynamics. Using bioengineered matrices mimicking the stiffness of young and old muscle, we showed that while young MuSCs were unaffected by aged matrices, old MuSCs were phenotypically rejuvenated by young matrices. Dynamical modeling of RNA velocity vector fieldsin silicorevealed that soft matrices promoted a self-renewing state in old MuSCs by attenuating RNA decay. Vector field perturbations demonstrated that the effects of matrix stiffness on MuSC self-renewal could be circumvented by fine-tuning the expression of the RNA decay machinery. These results demonstrate that post-transcriptional dynamics dictate the negative effect of aged matrices on MuSC self-renewal.Graphical AbstractGraphical abstract description:The balance of self-renewal and differentiation in young muscle stem cells (MuSCs) is robust to perturbations of the biophysical microenvironment. In contrast, aged MuSCs are highly sensitive to extrinsic perturbations, and exposure to a youthful microenvironment rejuvenates the self-renewing potential of aged MuSCs by modulating post-transcriptional RNA dynamics.

Various individual characteristics may affect medication adherence; however, few studies have investigated the effect of interrelationships among these various individual characteristics on medication adherence. This cross-sectional study explored the interrelationships among risk factors for medication adherence and established a predictive model of low medication adherence among older adults with hypertension. Convenience sampling was used to recruit 300 older adults with hypertension. The following parameters were recorded: demographic and disease characteristics, health beliefs, self-efficacy, social support, and medication adherence of antihypertensive drugs. Classification and regression tree (CART) analysis was performed to develop a predictive model of low medication adherence. The CART model revealed that health belief, disease duration, self-efficacy, and social support interacted to contribute to various pathways of low medication adherence. The predicted accuracy of the model was validated with a low misclassification rate of 26%. The proposed classification model can help identify risk cases with low medication adherence. Suitable health education programs based on these risk factors to manage and improve medication adherence for older adults with hypertension could be considered.

Patients with coronavirus disease 2019 (COVID-19) has been isolated in hospital-managed isolation hotels under a policy of the Taiwan government. Centrally isolation patients are more likely to experience psychological symptoms. The purpose of the study was to investigate emotional disturbance during their isolation period and then pinpoint the factors during their isolation period associated with the emotional disturbance. We retrospectively analysed the medical charts of the patients confined to a Banqiao isolation hotel between May 28 and July 3, 2021. The 5-item brief symptom rating scale (BSRS-5) was used to evaluate emotional disturbance levels. Descriptive and logistic regression was used for the data analysis. In total, 197 complete medical records were reviewed, and of these 84 (42.6%) showed emotional disturbance. The majority of them reported only minor disturbance (n = 49, 58.3%). After controlling for confounding factors, being satisfied about medical information was the only protective factor associated with emotional disturbance (OR = 0.2, P = 0.018). Being a male patient (OR = 3.0, P = 0.005), worrying about stigmatization (OR = 2.2, P = 0.041) and being unable to contact family members (OR = 2.9, P = 0.018) increased the risk of experiencing emotional disturbance. Patients with clinical symptoms, namely sore throat (OR = 3.4, P = 0.013) and muscle aches (OR = 6.3, P = 0.005), were also found to be more likely to report emotional disturbance. Mental disturbance commonly occurs among patient with COVID-19 who are isolated in a hospital-managed hotel. Being a male patient, having symptoms, namely a sore throat and muscle pain, being unable to contact family and/or a failure to receive sufficient medical information were found to be associated with emotional disturbance. In order to help isolated patients, government officials should provide a clear rationale for isolation and recognize the patients' efforts to follow the government's policy, which will help to minimize social stigma.

Hyperpigmentation disorders are commonly encountered in dermatology clinics. The use of prescription-grade and over-the-counter topical lightening agents has increased in popularity, leading to a substantial growth of research over the past decade.We seek to review clinical studies evaluating the use of different Rx-grade and OTC ingredients in treating hyperpigmentation.A comprehensive search on PubMed was conducted to identify patient-based evidence on the most common ingredients used as topical lightening agents: arbutin, ascorbic acid, cysteamine, hydroquinone, kojic acid, niacinamide, retinoids, and triple-combination therapy. The topicals were classified as either prescription-grade or over-the-counter.Varying levels of evidence support the use of topicals in treating hyperpigmentation. There were more clinical trials examining Rx-grade products than OTC products. Mild but tolerated side effects are noted in many of these agents.Careful monitoring and adjustment of doses will be needed to maximize skin lightening benefits and minimize side effects.

Renal hypoxia has recently been implicated as a key contributor and indicator of various glomerular diseases. As such, monitoring changes in renal oxygenation in these disorders may provide an early diagnostic advantage that could prevent potential adverse outcomes. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is an emerging noninvasive technique for assessing renal oxygenation in glomerular disease. Although BOLD MRI has produced promising initial results for the use in certain renal pathologies, the use of BOLD imaging in glomerular diseases, including primary and secondary nephrotic and nephritic syndromes, is relatively unexplored. Early BOLD studies on primary nephrotic syndrome, nephrotic syndrome secondary to diabetes mellitus, and nephritic syndrome secondary to systemic lupus erythematosus have shown promising results to support its future clinical utility. In this review, we outline the advancements made in understanding the use of BOLD MRI for the assessment, diagnosis, and screening of these pathologies.

BACKGROUND: The emergency department (ED) help desk is an undergraduate‐run service learning program that screens ED patients for social needs, connects them to community resources, and follows‐up to promote connections with resources. Students accepted to the program participate in a didactic course on the fundamentals of social emergency medicine as well as available community resources. Students also receive training around interviewing patients and use of screening software. Students commit to at least three quarters of service, during which they attend weekly team meetings. METHODS: This qualitative study explores the impact of this service learning experience for students. Current and former students were identified by the director of the program. Purposive and snowball sampling was used to select a sample of participants that participated in a semistructured interview. Our codebook was developed inductively using thematic analysis. Themes were presented and discussed with the entire research team for further analysis and refinement. Data collection and analysis used a constant comparative approach, and data collection ceased when saturation was achieved. RESULTS: Study participants consisted of current and former ED help desk student volunteers (n = 21). All participants believed that the ED help desk service learning experience prepared them for future careers by providing an experience that filled a gap in their education. We identified four main themes: (1) participants’ perceived impact on patients, (2) learning from patients’ experiences and differences, (3) appreciating patients’ vulnerability and collaboratively addressing patients’ needs, and (4) learning to navigate patients’ social needs within the broader health care system. CONCLUSIONS: Our ED help desk service learning program offers a unique experience for students to learn about patients’ social needs, participate in meaningfully interactions with patients, and empower themselves and patients to work together as coproducers of patients’ care.

Loneliness has become one of the most common psychological problems experienced by older adults. Previous studies have indicated that loneliness is correlated with poor physical and psychological health outcomes; therefore, it is important to pay attention to people experiencing loneliness. However, there is a lack of information regarding the prevalence of loneliness, and its associated factors, among community-dwelling older adults in Indonesia, which this study aimed to understand. This study used a cross-sectional, descriptive, and correlational research design. Stratified random sampling was applied to 1360 participants, aged ≥ 60 years, in 15 community health centers in Kendari City, Indonesia. The following questionnaires were used to collect data, including demographic and characteristic information, Short Portable Mental Status Questionnaire, Multidimensional Scale of Perceived Social Support, Geriatric Depression Scale Short Form, and a single-item loneliness question. The prevalence of loneliness among older adults was 64.0%. The multivariate logistic regression showed that older adults who were female, lived with family, had fewer children, had a poor health status, had a poor oral status, had more chronic diseases, had no hearing problems, had poor cognitive function, and had depression had a higher chance of feeling lonely. Loneliness is a serious health issue among the older population in Indonesia. The government, social workers, and healthcare professionals should pay immediate attention to this psychological problem. The study also suggests that appropriate strategies for the prevention of loneliness should be developed in the near future.

Type-1 diabetes (T1D) is caused by immune-mediated destruction of insulin-producing beta-cells, resulting in insulin deficiency and hyperglycemia. Islet transplantation is a potential treatment for T1D, but clinical implementation is hampered by islet availability and poor islet survival post-transplantation. To overcome these issues, we developed an intravascular multiside hole catheter with an interior polydimethylsiloxane (PDMS) bioscaffold capable of housing a cellular cargo. We used computational fluid dynamics to determine an optimized catheter design, which we then fabricated. Using our hybrid PDMS bioscaffold-intravascular catheter, we demonstrated that this platform can successfully maintain

BACKGROUND Mortality rates from melanoma are higher among Hispanic populations than non-Hispanic White (NHW) populations. Interventions to improve sun safety are needed. The Reveal Imager is a camera that uses standard cross-polarized flash photography to record surface and subsurface skin conditions. OBJECTIVE This study aims to determine the intervention’s effectiveness in increasing awareness of sun damage and exposure reduction between Hispanic and NHW populations. METHODS A cohort of 322 participants, aged ≥18 years, were recruited from community events in 2018. Baseline information was collected on demographics, sun exposure, and perception of risk factors. A facial image was then captured using the Reveal Imager. The results were explained and counseling on sun safety was given, followed by filling out an immediate postimage survey. Chi-square tests, analysis of variance, Wilcoxon signed-rank test, McNemar tests, and multivariable logistic regression were used. RESULTS At follow-up, 125 of 141 (89%) Hispanic participants reported that viewing the UV photoaged image influenced intent-to-change sun protection behaviors, compared to 88 of 121 (73%) NHW participants (odds ratio 2.9, 95% CI 1.5-5.6). Of 141 Hispanic participants, 96 (68%) reported that they intended to increase sunscreen use, compared to only 41 of 121 (34%) NHW participants (P CONCLUSIONS We demonstrated an application of Reveal Imager for education and risk assessment. The Reveal Imager was especially helpful in motivating intention to change sun exposure among Hispanic populations.

Social media has become an important tool to facilitate global communication. Platforms such as Facebook, LinkedIn, Instagram, Snapchat, and Twitter have fundamentally altered the landscape by which individuals and organizations interact with one another. Social media affords individuals access to online medical information, facilitates communication amongst patients and clinicians, and allows photos and videos to be shared among patients and healthcare professionals. However, ethical dilemmas, ranging from maintaining patient privacy to disclosing conflicts of interest, arise from the expanded influence afforded to providers via social media and the lack of guidelines for its use in the professional context. This chapter explores ethical uses of social media for engaging patients, educating the public, and marketing dermatology practices.

This study empirically examines the effects of technological disruption on suppliers and customers in vertical production relationships. We use the introduction and passage of state blockchain laws to capture exogenous increases in firms’ ability to develop, adopt, and use smart-contract technology. In supply-chain pairs subjected to these technological shocks, we find that customers and suppliers experience asymmetric effects. Specifically, customer firms experience positive abnormal stock returns around law introductions, while suppliers have negative abnormal returns. After technological disruption, customers exhibit significantly more positive changes in operating performance, profit margins, and sales growth compared to their supplier counterparts. Also, compared to their in-state suppliers, shocked customers show significantly greater increases in their blockchain innovation activities, operating expenses, debt financing, and strategic alliance formation. We also find that those suppliers experiencing a law passage appear to pursue diversification strategies: they decrease their reliance on in-state customers and add more ties to out-of-state customers. Overall, our results suggest that smart-contract technology can have large effects on the balance of power between suppliers and customers, thereby fundamentally reshaping supply-chain relationships.

Background In intensive care units, patient death can have a negative psychological influence on the patient's nurse. However, how the frequency of events and factors contributed to acute stress among nurses remains unknown. Objective The objective of this study was to explore the prevalence of and the factors affecting acute stress disorder among intensive care unit nurses after their patient death. Methods Nurses from five adult intensive care units whose patient had died during the nurses' working shift were recruited from July 2018 to April 2019. Bryant's Acute Stress Disorder Scale, the Beck Anxiety Inventory, and the Beck Depression Inventory-II were used to measure acute stress, depression, and anxiety. Descriptive statistics, chi-square tests, independent sample t-tests, and stepwise logistic regression were used for data analysis. Results In total, 119 nurses were enrolled. Nearly one in three nurses (29.4%) had suffered from acute stress disorder after their patient had died. Nurses experienced a higher risk of acute stress disorder when their patients underwent cardiopulmonary resuscitation before death (odds ratio [OR] = 13.75, 95% confidence interval [CI]: 2.59–72.95), when their patients died unexpectedly (OR = 4.88, 95% CI: 1.16–20.56), and when they experienced verbal abuse from the patient family at the patient death (OR = 4.61, 95% CI: 1.18–18.05) compared with their counterparts. Conclusion Intensive care unit nurses often experience acute stress disorder after their patient death. The nurses of patients who underwent cardiopulmonary resuscitation before death and/or who died unexpectedly and/or nurses who were subjected to verbal abuse by the patient's family were at higher risk of acute stress disorder. A comprehensive program aimed at improving the knowledge, skills, and resilience of nurses is needed.