CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia

Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL

Interprofessional team-based learning ::a qualitative study on the experiences of nursing and physiotherapy students

Traditional discipline-specific training has limitations in facilitating inter-professional communication and collaboration. To address this issue, two local universities in Hong Kong launched an interprofessional team-based learning program to allow the undergraduate healthcare students to formteams and experience collaborative problemsolving. This study aimed to evaluate the experiences of nursing and physiotherapy undergraduates following interprofessional learning activities. Twenty-seven 3rd-year nursing and physiotherapy undergraduates were recruited through purposive sampling. Semi-structured interviews were conducted, and written feedback was solicited until data saturation was achieved. An inductive thematic analysis was used for the data, and each theme was mutually exclusive. The findings revealed the positive experiences of the students with this interprofessional learning activity. Three main themes emerged: (1) the process of interprofessional learning; (2) profession-related outcomes of interprofessional learning; and (3) patient-related outcomes of interprofessional learning. The study indicated that interprofessional team-based learning activities enhanced learning experiences of the students through interactive learning with other healthcare students. Experiences of relationships that are trustful and complementary allow students to develop confidence in knowledge transfer and in interprofessional collaboration, as well as in providing a holistic patient-centered care. These findings substantiate the importance and value of interprofessional learning in healthcare education

Perceived Well-Being among Adults with Diabetes and Hypertension: A National Study

Perceived health and distresses are associated with the practice of lifestyle modifications, which increases the risk of diabetes and hypertension-related complications. This study aimed to define the characteristics and distribution of perceived health and distresses across the states between people with diabetes and hypertension. Data were derived from a national survey of US adults aged ≥18 years who were interviewed via phone call. Perceived health and distresses were assessed through corresponding questions. An amount of 333,316 respondents (43,911 with diabetes and 130,960 with hypertension) were included in the analysis; 61.8% of people with diabetes and 74.5% of people with hypertension reported having good or better health, while residents in the Southwest region perceived poor health statuses and more distresses. Education level (diabetes: odds ratio [OR] = 0.47–0.79, hypertension: OR = 0.42–0.76), employment status level (diabetes: OR = 1.40–2.22, hypertension: OR = 1.56–2.49), and household income (diabetes: OR = 0.22–0.65, hypertension: OR = 0.15–0.78) were significant factors associated with poorly perceived health among people with diabetes and hypertension, and the use of technology and strategies for policymakers are suggested to improve the perceived health status in this regard

Investigating the Interrelationships Among Mental Health, Substance Use Disorders, and Suicidal Ideation Among Lesbian, Gay, and Bisexual Adults in the United States: Population-Based Statewide Survey Study

BackgroundMental health disparities have been documented among lesbian, gay, and bisexual (LGB) adults in the United States. Substance use disorders and suicidal ideation have been identified as important health concerns for this population. However, the interrelationships among these factors are not well understood. ObjectiveThis study aims to investigate the interrelationships among mental health, substance use disorders, and suicidal ideation among LGB adults in the United States using a population-based statewide survey. MethodsOur study was an observational cross-sectional analysis, and the data for this study were collected from a sample of LGB adults who participated in the statewide survey. The survey collected information on mental health, substance use disorders, and suicidal ideation using validated measures. Descriptive statistics and inferential data analysis were conducted to explore the interrelationships among these factors. ResultsThe results showed that LGB adults who reported higher levels of depression and drug abuse and dependence also reported higher levels of suicidal tendency and mental illness. Inferential data analysis using χ2 tests revealed significant differences in depression score (χ22=458.241; P<.001), drug abuse and dependence score (χ22=226.946; P<.001), suicidal tendency score (χ22=67.795; P<.001), and mental illness score (χ22=363.722; P<.001) among the 3 sexual identity groups. Inferential data analysis showed significant associations between sexual identity and mental health outcomes, with bisexual individuals reporting the highest levels of depression, drug abuse and dependence, suicidal tendency, and mental illness. ConclusionsThis study provides important insights into the interrelationships among mental health, substance use disorders, and suicidal ideation among LGB adults in the United States. The findings underscore the need for targeted interventions and research aimed at addressing the mental health needs of sexual minority populations. Future research should aim to better understand the underlying mechanisms driving these disparities and develop culturally sensitive and tailored interventions that meet the unique needs of LGB individuals. Reducing stigma and discrimination against sexual minority populations is also crucial to improving their mental health outcomes

Hematopoietic Transcription Factor RUNX1 is Essential for Promoting Macrophage–Myofibroblast Transition in Non‐Small‐Cell Lung Carcinoma

Abstract Macrophage‐myofibroblast transition (MMT) is a newly discovered pathway for mass production of pro‐tumoral cancer‐associated fibroblasts (CAFs) in non‐small cell lung carcinoma (NSCLC) in a TGF‐β1/Smad3 dependent manner. Better understanding its regulatory signaling in tumor microenvironment (TME) may identify druggable target for the development of precision medicine. Here, by dissecting the transcriptome dynamics of tumor‐associated macrophage at single‐cell resolution, a crucial role of a hematopoietic transcription factor Runx1 in MMT formation is revealed. Surprisingly, integrative bioinformatic analysis uncovers Runx1 as a key regulator in the downstream of MMT‐specific TGF‐β1/Smad3 signaling. Stromal Runx1 level positively correlates with the MMT‐derived CAF abundance and mortality in NSCLC patients. Mechanistically, macrophage‐specific Runx1 promotes the transcription of genes related to CAF signatures in MMT cells at genomic level. Importantly, macrophage‐specific genetic deletion and systemic pharmacological inhibition of TGF‐β1/Smad3/Runx1 signaling effectively prevent MMT‐driven CAF and tumor formation in vitro and in vivo, representing a potential therapeutic target for clinical NSCLC

Comparison of clinical outcome and ease of handling in two double-bag systems in continuous ambulatory peritoneal dialysis: A prospective, randomized, controlled, multicenter study

Background: We performed a prospective, randomized, controlled, multicenter study on the use of two double-bag disconnect systems: Stay-Safe (SS; Fresenius Deutschland GmbH2) and Ultrabag (UB; Baxter Healthcare, Deerfield, IL) to assess the ease of handling, peritonitis rate, exit-site infection rate, and clinical outcome. Methods: We enrolled 110 new continuous ambulatory peritoneal dialysis (CAPD) patients; 55 patients were randomized to SS treatment, and 55 patients, to UB treatment. Results: Patients using the UB and SS systems were followed up for 946 and 846 patient-months, respectively. There were 21 episodes of peritonitis in 18 patients in the UB group and 23 episodes in 18 patients in the SS group. No significant difference was observed in peritonitis rates between the two systems, which were 45 and 36.8 patient-months per episode for the UB and SS groups, respectively. At 12 months, 82.1% of patients in the UB group and 72.1% in the SS group were free of peritonitis; at 18 months, 71.1% and 62.2% were free of peritonitis for the UB and SS groups, respectively (P = 0.559). Gram-positive organisms accounted for 28.6% of infections in the UB group and 39.1% in the SS group. Exit-site infection rates were one episode per 21 patient-months versus 19.2 patient-months in the UB and SS groups, respectively (P = 0.743). Patients perceived SS as easier to handle in 4 of the 13 steps immediately post-CAPD training. However, there was no significant difference in rankings between the two systems after 1 month of adaptation. Median training periods were 4 and 5 days for the SS and UB groups, respectively (P = 0.640). Conclusion: The two double-bag systems (UB and SS) have similar incidences of peritonitis and exit-site infection. Both systems showed comparably good clinical outcome. The SS system is easier to learn during the initial training period, but the difference is not significant after 1 month's adaptation. © 2002 by the National Kidney Foundation, Inc.Link_to_subscribed_fulltex

Probable Airborne Transmission of Burkholderia pseudomallei Causing an Urban Outbreak of Melioidosis during Typhoon Season in Hong Kong, China. <subtitle>Urban Outbreak of Melioidosis in Hong Kong</subtitle>

ABSTRACTBetween January 2015 and October 2022, 38 patients with culture-confirmed melioidosis were identified in the Kowloon West (KW) Region, Hong Kong. Notably, thirty of them were clustered in the Sham Shui Po (SSP) district, which covers an estimated area of 2.5 km2. Between August and October 2022, 18 patients were identified in this district after heavy rainfall and typhoons. The sudden upsurge in cases prompted an environmental investigation, which involved collecting 20 air samples and 72 soil samples from residential areas near the patients. A viable isolate of Burkholderia pseudomallei was obtained from an air sample collected at a building site five days after a typhoon. B. pseudomallei DNA was also detected in 21 soil samples collected from the building site and adjacent gardening areas using full-length 16S rRNA gene sequencing, suggesting that B. psuedomallei is widely distributed in the soil environment surrounding the district. Core genome-multilocus sequence typing showed that the air sample isolate was phylogenetically clustered with the outbreak isolates in KW Region. Multispectral satellite imagery revealed a continuous reduction in vegetation region in SSP district by 162,255 m2 from 2016 to 2022, supporting the hypothesis of inhalation of aerosols from the contaminated soil as the transmission route of melioidosis during extreme weather events. This is because the bacteria in unvegetated soil are more easily spread by winds. In consistent with inhalational melioidosis, 24 (63.2%) patients had pneumonia. Clinicians should be aware of melioidosis during typhoon season and initiate appropriate investigation and treatment for patients with compatible symptoms