The slow-release adiponectin analog ALY688-SR modifies early-stage disease development in the D2.mdx mouse model of Duchenne muscular dystrophy.

Fibrosis is associated with respiratory and limb muscle atrophy in Duchenne muscular dystrophy (DMD). Current standard of care partially delays the progression of this myopathy but there remains an unmet need to develop additional therapies. Adiponectin receptor agonism has emerged as a possible therapeutic target to lower inflammation and improve metabolism in mdx mouse models of DMD but the degree to which fibrosis and atrophy are prevented remain unknown. Here, we demonstrate that the recently developed slow-release peptidomimetic adiponectin analog, ALY688-SR, remodels the diaphragm of murine model of DMD on DBA background (D2.mdx) mice treated from days 7-28 of age during early stages of disease. ALY688-SR also lowered interleukin-6 (IL-6) mRNA but increased IL-6 and transforming growth factor-ß1 (TGF-ß1) protein contents in diaphragm, suggesting dynamic inflammatory remodeling. ALY688-SR alleviated mitochondrial redox stress by decreasing complex I-stimulated H2O2 emission. Treatment also attenuated fibrosis, fiber type-specific atrophy, and in vitro diaphragm force production in diaphragm suggesting a complex relationship between adiponectin receptor activity, muscle remodeling, and force-generating properties during the very early stages of disease progression in murine model of DMD on DBA background (D2.mdx) mice. In tibialis anterior, the modest fibrosis at this young age was not altered by treatment, and atrophy was not apparent at this young age. These results demonstrate that short-term treatment of ALY688-SR in young D2.mdx mice partially prevents fibrosis and fiber type-specific atrophy and lowers force production in the more disease-apparent diaphragm in relation to lower mitochondrial redox stress and heterogeneous responses in certain inflammatory markers. These diverse muscle responses to adiponectin receptor agonism in early stages of DMD serve as a foundation for further mechanistic investigations.NEW & NOTEWORTHY There are limited therapies for the treatment of Duchenne muscular dystrophy. As fibrosis involves an accumulation of collagen that replaces muscle fibers, antifibrotics may help preserve muscle function. We report that the novel adiponectin receptor agonist ALY688-SR prevents fibrosis in the diaphragm of D2.mdx mice with short-term treatment early in disease progression. These responses were related to altered inflammation and mitochondrial functions and serve as a foundation for the development of this class of therapy.

User evaluation of a mobile education application for the management of metabolic syndrome among cancer survivors.

OBJECTIVE: This study aimed to develop a smartphone education application for managing metabolic syndrome among cancer survivors and obtain user evaluation based on quantitative and qualitative data. METHODS: Ten cancer survivors and 10 oncology nurse specialists responded to a structured usability evaluation tool (Mobile Application Rating Scale: MARS). Quantitative data analysis was performed through descriptive statistics using SPSS version 25.0. We conducted semi-structured interviews of the cancer survivors and oncology nurse specialists. Qualitative data of interview responses were coded as the app's strengths and weaknesses, information, motivation, and behavioral change. RESULTS: The overall usability evaluation score of the app was 3.66 ± 0.39 for cancer survivors and 3.79 ± 0.20 for oncology nurse specialists. Both cancer survivors and oncology nurse specialists scored the area of functionality as the highest and engagement as the lowest. Additionally, the qualitative usability evaluation suggested that the app should be visually improved by including figures and tables to enhance readability and providing videos and more specific guidelines to directly elicit behavioral change. CONCLUSIONS: Metabolic syndrome in cancer survivors can be effectively managed by using the educational application developed in this study by improving the shortcomings of the app for cancer survivors.

Relationship Between Handgrip Strength and Metabolic Syndrome Among Middle-Aged and Elderly Cancer Survivors: A National Population Study.

BACKGROUND: The number of middle-aged and elderly cancer survivors is rising. Metabolic syndrome, which has been established as an important risk factor for mortality and cardiovascular disease, has also been linked to quality of life in middle-aged and elderly cancer survivors. Recent studies documented a relationship between handgrip strength and metabolic syndrome. OBJECTIVE: The aim of this study was to investigate the relationship between relative handgrip strength in middle-aged and elderly cancer survivors and metabolic syndrome in a national population-based sample from Korea. METHODS: This was a cross-sectional, secondary descriptive analysis of data from the sixth to seventh (2014-2018) Korea National Health and Nutrition Examination Survey (KNHANES VI-VII). A final total of 1096 cancer survivors aged 45 years and older were selected. RESULTS: Lower relative handgrip strength was linked to a higher risk of metabolic syndrome. For men, the adjusted odds ratio for having metabolic syndrome in individuals with a relative handgrip strength score of the 2 Quartile was 4.43 (95% confidence interval, 2.25-8.71) compared with the 4 Quartile (reference) ( P < .001), whereas for women, this was 3.67 (95% confidence interval, 2.06-6.53) ( P < .001). CONCLUSIONS: Lower relative handgrip strength is correlated with components of metabolic syndrome and is a risk factor for metabolic syndrome among middle-aged and elderly cancer survivors. IMPLICATIONS FOR PRACTICE: Physicians and nurses need to identify and monitor the handgrip strength for managing the risk of metabolic syndrome among middle-aged and elderly cancer survivors. Preventive and therapeutic programs that focus on handgrip strength should be developed to prevent metabolic syndrome during their rehabilitation.

Analysis of research on metabolic syndrome in cancer survivors using topic modeling and social network analysis.

This study aimed to identify the relationships between the keywords of research on metabolic syndrome in cancer survivors and the entire knowledge research structure, through topic extraction from a macro perspective. From six electronic databases, 918 studies published between 1996 and 2019 were identified and reviewed, and 365 were included. Keyword network analysis and topic modeling were applied to examine the studies. In keyword network analysis, "obesity," "treatment," "breast cancer," "body mass index," and "prostate cancer" were the major keywords, whereas "obesity" and "breast" were the dominant keywords and ranked high in frequency, degree centrality, and betweenness centrality. In topic modeling, five clustered topics emerged, namely metabolic syndrome component, post CTX(chemotherapy) sequence, prostate-specific antigen-sensitive plot, lifestyle formation, and insulin fluctuation. Topic 2, post CTX sequence, showed the highest salience in earlier studies, but this has decreased over time, and the themes of the studies have also broadened. This study may provide critical basic data for determining the changing trends of research on metabolic syndrome in cancer survivors and for predicting the direction of future research through the visualization of the effects and interactions between the major keywords in research on metabolic syndrome in cancer survivors.

Mitofusin-2 boosts innate immunity through the maintenance of aerobic glycolysis and activation of xenophagy in mice.

Mitochondrial function and innate immunity are intimately linked; however, the mechanisms how mitochondrion-shaping proteins regulate innate host defense remains largely unknown. Herein we show that mitofusin-2 (MFN2), a mitochondrial fusion protein, promotes innate host defense through the maintenance of aerobic glycolysis and xenophagy via hypoxia-inducible factor (HIF)-1α during intracellular bacterial infection. Myeloid-specific MFN2 deficiency in mice impaired the antimicrobial and inflammatory responses against mycobacterial and listerial infection. Mechanistically, MFN2 was required for the enhancement of inflammatory signaling through optimal induction of aerobic glycolysis via HIF-1α, which is activated by mitochondrial respiratory chain complex I and reactive oxygen species, in macrophages. MFN2 did not impact mitophagy during infection; however, it promoted xenophagy activation through HIF-1α. In addition, MFN2 interacted with the late endosomal protein Rab7, to facilitate xenophagy during mycobacterial infection. Our findings reveal the mechanistic regulations by which MFN2 tailors the innate host defense through coordinated control of immunometabolism and xenophagy via HIF-1α during bacterial infection.

Preparation and Evaluation of Intraperitoneal Long-Acting Oxaliplatin-Loaded Multi-Vesicular Liposomal Depot for Colorectal Cancer Treatment.

Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1-20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.

Oncology nurses' knowledge and awareness on metabolic syndrome in cancer survivors and the perceived barriers to the provision of related care: A mixed-method study.

OBJECTIVE: To identify oncology nurses' level of knowledge and awareness of metabolic syndrome (MetS) in cancer survivors and the perceived barriers to the provision of MetS-related care. METHODS: In this mixed-method study, 196 participants responded to a structured modified questionnaire that included items pertaining to MetS-related knowledge and awareness. Concurrently, 24 semi-structured interviews were conducted. A qualitative survey and quantitative interview were conducted between October 2018 and December 2018. RESULTS: While oncology nurses had a high level of knowledge of MetS in terms of its individual components, they failed to accurately differentiate MetS cases from non-MetS ones. Further, they showed a high level of awareness of MetS-related care for cancer survivors but did not apply their knowledge in clinical settings. In the qualitative survey, the nurses cited various factors pertaining to their perceived barriers to the provision of MetS-related care, including the fact that cancer survivors are distinguished by the specificity of the subject and inpatient environmental constraints. CONCLUSIONS: Oncology nurses had a high level of knowledge of MetS but failed to accurately identify MetS cases. Thus, their level of knowledge should be improved, and strategies are needed to overcome the perceived barriers to the provision of MetS-related care.

Cross-Sectional Study on Patient Safety Culture, Patient Safety Competency, and Adverse Events.

This study aims to examine the associations between nurses' perceptions of patient safety culture, patient safety competency, and adverse events. Using convenience sampling, we conducted a cross-sectional study from February to May 2018 in two university hospitals. Furthermore, we performed multiple logistic regression to examine associations between patient safety culture, patient safety competency, and adverse events. Higher mean scores for "communication openness" in patient safety culture were significantly correlated with lower rates for pressure ulcers and falls; furthermore, higher mean scores for "working in teams with other health professionals" in patient safety competency were significantly correlated with reductions in ventilator-associated pneumonia. We recommend that a well-structured hospital culture emphasizing patient safety and continuation of in-service education programs for nurses to provide high-quality, clinically safe care is required. Moreover, further research is required to identify interventions to improve patient safety culture and competency and reduce the occurrence of adverse events.

Locally Activating TrkB Receptor Generates Actin Waves and Specifies Axonal Fate.

Actin waves are filamentous actin (F-actin)-rich structures that initiate in the somato-neuritic area and move toward neurite ends. The upstream cues that initiate actin waves are poorly understood. Here, using an optogenetic approach (Opto-cytTrkB), we found that local activation of the TrkB receptor around the neurite end initiates actin waves and triggers neurite elongation. During actin wave generation, locally activated TrkB signaling in the distal neurite was functionally connected with preferentially localized Rac1 and its signaling pathways in the proximal region. Moreover, TrkB activity changed the location of ankyrinG--the master organizer of the axonal initial segment-and initiated the stimulated neurite to acquire axonal characteristics. Taken together, these findings suggest that local Opto-cytTrkB activation switches the fate from minor to major axonal neurite during neuronal polarization by generating actin waves.

Oxaliplatin-loaded chemically cross-linked hydrogels for prevention of postoperative abdominal adhesion and colorectal cancer therapy.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer among both men and women worldwide. New therapeutic strategies involving cytoreductive surgery and intra-peritoneal chemotherapy could lead to a definitive cure in some cases. However, postoperative intra-abdominal adhesion can cause further complications. In this study, hyaluronic acid (HA)- and carboxymethyl cellulose sodium (CMCNa)-based novel cross-linked hydrogels (HC hydrogels) were synthesized and fully characterized. We demonstrated that varied compositions of HA and CMCNa altered the microstructure, rheology, and degradation behavior of hydrogels. Pre-constructed hydrogels were further loaded with oxaliplatin to prevent intra-abdominal adhesion following chemotherapy. Sustained release of oxaliplatin was observed from hydrogels compared that from solutions, which release drugs through diffusion, following the Higuchi and Korsmeyer-Peppas models. Moreover, low adhesion scores in an in vivo SD rat model demonstrated inhibition of intra-peritoneal adhesion in response to HC hydrogels. Therefore, HC hydrogels offer a novel formulation strategy for providing an intra-abdominal anti-adhesion barrier after cytoreductive surgery and intra-peritoneal chemotherapy for CRC treatment.

Assessment of the awareness and knowledge of cancer survivors regarding the components of metabolic syndrome.

This study aimed to assess the prevalence of metabolic syndrome and the level of knowledge and awareness of its related conditions in a sample of cancer survivor patients. In this cross-sectional survey, a self-reported questionnaire was administered to outpatients aged >20 years with a diagnosis of cancer. This self-reported questionnaire on patient demographic characteristics, disease characteristics, and knowledge and awareness of metabolic syndrome was used as an instrument to assess patient's knowledge of metabolic syndrome. A total of 88 participants were included; of these 34.1% had metabolic syndrome, although only 6.8% of participants were diagnosed with metabolic syndrome. Over half of the participants had heard about metabolic syndrome; however, 70% of the participants did not know about the blood tests for the diagnosis of metabolic syndrome although they were aware of the physical measurements, such as weight, blood pressure, and waist circumference. The highest proportion of correct answers for questions about metabolic syndrome was related to stroke, while the lowest was about cholesterol levels. The proportions of correct answers for selected parameters were as follows: diabetes, 39.1%; adiposity, 47.2%; hypertension, 46.8%; cholesterol levels, 36.7%; arteriosclerosis, 45.5%; myocardial infarction, 37.8%; and stroke, 62.8%. The results suggest that the level of knowledge of metabolic syndrome among the cancer survivors in our sample was poor, although more than one-third of them had metabolic syndrome. Thus, it is essential to educate cancer survivors about metabolic syndrome and its related conditions to improve their overall health and quality of life.