PRMT-7/PRMT7 activates HLH-30/TFEB to guard plasma membrane integrity compromised by bacterial pore-forming toxins.

Bacterial pore-forming toxins (PFTs) that disrupt host plasma membrane integrity (PMI) significantly contribute to the virulence of various pathogens. However, how host cells protect PMI in response to PFT perforation in vivo remains obscure. Previously, we demonstrated that the HLH-30/TFEB-dependent intrinsic cellular defense (INCED) is elicited by PFT to maintain PMI in Caenorhabditis elegans intestinal epithelium. Yet, the molecular mechanism for the full activation of HLH-30/TFEB by PFT remains elusive. Here, we reveal that PRMT-7 (protein arginine methyltransferase-7) is indispensable to the nuclear transactivation of HLH-30 elicited by PFTs. We demonstrate that PRMT-7 participates in the methylation of HLH-30 on its RAG complex binding domain to facilitate its nuclear localization and activation. Moreover, we showed that PRMT7 is evolutionarily conserved to regulate TFEB cellular localization and repair plasma damage caused by PFTs in human intestinal cells. Together, our observations not only unveil a novel PRMT-7/PRMT7-dependent post-translational regulation of HLH-30/TFEB but also shed insight on the evolutionarily conserved mechanism of the INCED against PFT in metazoans.

Decreasing the incidence of central line-associated bloodstream infection in a medical intensive care unit: a best practice implementation project.

INTRODUCTION AND OBJECTIVES: Bloodstream infections are common in critically ill patients using central venous access devices (CVAD) in intensive care units (ICU). This project aimed to decrease the incidence of central line-associated bloodstream infections (CLABSI) by using evidence-based strategies. METHODS: The project applied the JBI audit and feedback methods. Thirty-two nurses and five resident physicians from the medical ICU of a medical center participated in the project. Preintervention compliance was measured for the 11 key evidence-based criteria (six audit criteria of central venous catheter insertion and five audit criteria of dressing and catheter securement). Strategies were implemented to overcome the barriers identified in the baseline assessment. Impact evaluation and sustainability were conducted to change the CLABSI rate and the competence of healthcare professionals in providing CVAD care. The JBI Practical Application of Clinical Evidence System and Getting Research into Practice audit tools were used for the data collection, analysis, and implementation planning. RESULTS: Barriers included insufficient knowledge among nurses and physicians, poor compliance with the standard CVAD insertion procedure by physicians, inadequate cooperation among the CVAD care team members, and lack of CVAD-related equipment. The strategies included education and training in CVAD care, the establishment of a team resource management program, and the provision of appropriate equipment. Following project implementation, the CLABSI rate decreased from 8.38 to 3.9 BSIs/1000 CVAD-days. CONCLUSIONS: The project successfully decreased the CLABSI rate and increased the competence of healthcare professionals. Implementation of best practices in clinical care should focus on leadership, team resource management, education, monitoring, and innovation.

Host CDK-1 and formin mediate microvillar effacement induced by enterohemorrhagic Escherichia coli.

Enterohemorrhagic Escherichia coli (EHEC) induces changes to the intestinal cell cytoskeleton and formation of attaching and effacing lesions, characterized by the effacement of microvilli and then formation of actin pedestals to which the bacteria are tightly attached. Here, we use a Caenorhabditis elegans model of EHEC infection to show that microvillar effacement is mediated by a signalling pathway including mitotic cyclin-dependent kinase 1 (CDK1) and diaphanous-related formin 1 (CYK1). Similar observations are also made using EHEC-infected human intestinal cells in vitro. Our results support the use of C. elegans as a host model for studying attaching and effacing lesions in vivo, and reveal that the CDK1-formin signal axis is necessary for EHEC-induced microvillar effacement.

Positive psychological changes after breast cancer diagnosis and treatment: The role of trait resilience and coping styles.

Purpose: This study aimed to examine the relationships among trait resilience, coping styles, and perceived positive psychological changes in women's lives after breast cancer diagnosis and treatment.Design: The study adopted a cross-sectional design.Sample/Method: A total of 201 participants diagnosed with stage I-IV breast cancer were recruited. The average time since diagnosis was 39.14 months. Four rating scales were used to assess the participants' trait resilience, coping styles, perceived growth, and health-related quality of life. These are the Connor-Davidson Resilience Scale (CD-RISC), the Mini-Mental Adaptation to Cancer Scale (Mini-MAC), the Chinese Posttraumatic Growth Inventory (PTGI), and the Functional Assessment of Cancer Therapy Scale-Breast (FACT-B).Findings: Hierarchical analysis showed that trait resilience significantly predicted high levels of perceived growth and health-related quality of life. This effect was moderated by Positive-Acceptance coping. The study also found that Negative-Affect coping had a direct effect on lowering health-related quality of life but had no influence on perceived growth.Conclusions: These findings highlight the facilitating effect of trait resilience and Positive-Acceptance coping on the psychological well-being and perceived growth among breast cancer outpatients.Implications: Trait resilience may be a protective, even facilitating factor of cancer adaptation. The knowledge that trait resilience offers a way to enhance wellness after cancer diagnosis and treatments may be useful in a clinical setting.

3D porous calcium-alginate scaffolds cell culture system improved human osteoblast cell clusters for cell therapy.

Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine. Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge. A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters. The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability. This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation. The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection. The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects.

Insulin-loaded hydroxyapatite combined with macrophage activity to deliver insulin for diabetes mellitus.

We aimed to develop a diabetes mellitus (DM) treatment that could be administered by intramuscular (IM) injection and it lasted for more than 3 days. The objective was to load insulin into the lattice space of hydroxyapatite (HAP) to prevent its release based on a concentration gradient or detachment from the surface, with insulin release being aided by cellular activity. To avoid insulin denaturation during the synthesis of insulin-loaded HAP (insHAP), we developed a single-step insHAP synthesis method by the hydrolysis of brushite. X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) results suggested that insulin could be loaded into the HAP crystal lattice. After IM administration in rats with DM, the synthesized insHAP is thought to be engulfed by macrophages, escape from lysosome/endosome hybrids following disruption by osmotic pressure, and pumped into the extracellular space before entering the blood stream by diffusion. In rats with DM, the normal blood glucose level was maintained for 4 days after a single IM injection of the synthesized insHAP particles. Thus, insHAP may provide a breakthrough in insulin delivery for DM treatment, and may also be used to deliver fluorescent proteins, antibodies, and anticancer drugs.

Sequela of preterm versus term infants born to mothers on a methadone maintenance program: differential course of neonatal abstinence syndrome.

OBJECTIVE: We determined the effect of preterm delivery on the course of neonatal abstinence syndrome (NAS) in infants born to mothers participating in a methadone maintenance program. STUDY DESIGN: A retrospective cohort study was conducted in which infant and maternal data were collected from the medical records of 53 preterm and 66 term infants. Infants were selected from all infants admitted to Thomas Jefferson University hospital born between 1998 and 2002 whose mothers were enrolled in the methadone maintenance program. All infants were managed by a standard protocol utilizing the Neonatal Abstinence Scoring System (NASS) and neonatal opiate solution (NOS). Preterm and term infants were compared. RESULTS: Preterm infants had shorter lengths of stay, treatment courses and required less medication than did term infants during the same time period. CONCLUSION: These data indicate that following exposure to maternal methadone, preterm infants have a different neonatal course than do infants born at term.