Pinitol suppresses tumor necrosis factor-α-induced invasion of prostate cancer LNCaP cells by inhibiting nuclear factor-κB-Mediated matrix Metalloproteinase-9 expression

Purpose: To investigate the mechanism by which pinitol inhibits tumor necrosis factor-α (TNF-α)- induced expression of matrix metalloproteinase-9 (MMP-9) and invasion of prostate cancer LNCaP cells.Methods: Reverse transcription-polymerase chain reaction (RT-PCR) together with Western blot analysis was used to analyze the expression of MMP-9 and nuclear factor-κB (NF-κB) subunits, p65 and p50, in TNF-α- treated LNCaP cells, while 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay,  flow cytometry, and DNA fragmentation were used to evaluate cell viability and apoptosis. MMP-9 activity and invasion were measured by gelatin zymography and matrigel invasion assay, respectively. DNA-binding activity of NF-κB and AP-1 was determined by electrophoretic mobility shift assay and luciferase activity.Results: MMP-9 activity significantly increased in response to TNF-α; however, pinitol reduced TNF-α- induced MMP-9 activity without cytotoxicity. Matrigel invasion assay showed that pinitol reduced TNF-α-induced invasion of prostate cancer LNCaP cells. Further, it  downregulated the expression of MMP-9 gene induced by TNF-α-treatment. Pinitol suppressed TNF-α-induced NF-κB activity by  suppressing nuclear translocation of the NF-κB subunits, p65 and p50.Conclusion: The results indicate that pinitol is a potential anti-invasive agent and acts by suppressing TNF-α-induced cancer cell invasion and specifically inhibiting NF-κB as well as downstream target genes such as MMP-9

Sexual behaviour, sexually transmitted infections and attitudes to chlamydia testing among a unique national sample of young Australians: Baseline data from a randomised controlled trial

Background: Chlamydia infection is the most common notifiable sexually transmitted infection (STI) in Australia and mostly affects young people (15 - 25 years). This paper presents baseline data from a randomised controlled trial that aimed to increase chlamydia testing among sexually active young people. The objectives were to identify associations between sexual behaviour, substance use and STI history and explore attitudes to chlamydia testing. Methods: This study was conducted in cyberspace. Study recruitment, allocation, delivery of interventions and baseline and follow up data collection all took place online. Participants were 16 - 25 years old and resided in Australia. Substance use correlates of sexual activity; predictors of history of STIs; barriers to and facilitators of chlamydia testing were analysed. Results: Of 856 participants (79.1% female), 704 had experienced penetrative intercourse. Sexually active participants were more likely to smoke regularly or daily, to drink alcohol, or to have binge drunk or used marijuana or other illicit substances recently. Risk factors for having a history of any STI were 3 or more sexual partners ever, 6 or more partners in the past 12 months, condom non-use and being 20 years or older. Almost all sexually active participants said that they would have a chlamydia test if their doctor recommended it. Conclusions: Sexually active young people are at risk of STIs and may engage in substance use risk behaviours. Where one health risk behaviour is identified, it is important to seek information about others. Chlamydia testing can be facilitated by doctors and nurses recommending it. Primary care providers have a useful role in chlamydia control. © 2014 Kang et al.; licensee BioMed Central Ltd

Adolescents' self-efficacy and digital health literacy: a cross-sectional mixed methods study.

BACKGROUND: The internet and social media are increasingly popular sources of health information for adolescents. Using online health information requires digital health literacy, consisting of literacy, analytical skills and personal capabilities such as self-efficacy. Appraising trustworthiness and relevance of online health information requires critical health literacy to discriminate between sources, critically analyse meaning and relevance, and use information for personal health. Adolescents with poor digital health literacy risk using misinformation, with potential negative health outcomes. We aimed to understand adolescents' contemporary digital health literacy and compared self-efficacy with capability. METHODS: Adolescents (12-17 years) completed an eHEALS self-report digital health literacy measure, a practical search task using a think-aloud protocol and an interview to capture perceived and actual digital health literacy. eHEALS scores were generated using descriptive statistics, search tasks were analysed using an observation checklist and interviews were thematically analysed based on Social Cognitive Theory, focussing on self-efficacy. RESULTS: Twenty-one participants generally had high self-efficacy using online health information but perceived their digital health literacy to be higher than demonstrated. They accessed online health information unintentionally on social media and intentionally via search engines. They appraised information medium, source and content using general internet searching heuristics taught at school. Information on social media was considered less trustworthy than websites, but participants used similar appraisal strategies for both; some search/appraisal heuristics were insufficiently nuanced for digital health information, sometimes resulting in misplaced trust or diminished self-efficacy. Participants felt anxious or relieved after finding online health information, depending on content, understanding and satisfaction. They did not act on information without parental and/or health professional advice. They rarely discussed findings with health professionals but would welcome discussions and learning how to find and appraise online health information. CONCLUSIONS: Whilst adolescents possess many important digital health literacy skills and generally feel self-efficacious in using them, their critical health literacy needs improving. Adolescents desire increased digital health literacy so they can confidently appraise health information they find online and on social media. Co-designed educational interventions with adolescents and health providers are required

Response to imatinib rechallenge in a patient with a recurrent gastrointestinal stromal tumor after adjuvant therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Adjuvant imatinib improves recurrence-free survival of patients following resection of primary KIT-positive gastrointestinal stromal tumors. However, it is unknown whether patients who previously received adjuvant imatinib therapy will respond to imatinib rechallenge as treatment for recurrent disease. Here we present the first report documenting the benefits of imatinib rechallenge in a patient previously exposed to imatinib during adjuvant treatment.</p> <p>Case presentation</p> <p>A 51-year-old Asian woman with a wedge-resected primary gastric gastrointestinal stromal tumor at high risk of relapse underwent two years of adjuvant treatment with imatinib. Only 10 months after the completion of adjuvant imatinib treatment, a computed tomography scan revealed gastrointestinal stromal tumor recurrence in this patient, with multiple peritoneal nodules in the upper abdomen being detected. Our patient was rechallenged with imatinib 400 mg/day and had a partial response after one month of treatment. Imatinib rechallenge was well tolerated by our patient; the only adverse events she experienced were grade 1 edema, anemia and fatigue. Our patient maintained a partial response two years and six months after the imatinib rechallenge. However, computed tomography scans three months later showed that our patient had disease progression.</p> <p>Conclusions</p> <p>This case report demonstrates that a patient with a gastrointestinal stromal tumor who had previously received adjuvant imatinib therapy responded to imatinib rechallenge as treatment for her recurrent disease. These results indicate that imatinib sensitivity can be maintained in a patient with previous exposure to adjuvant imatinib therapy.</p

Preoperative bowel stimulation prior to ileostomy closure to restore bowel function more quickly and improve postoperative outcomes: a systematic review

Aim Closure of a diverting ileostomy following restorative surgery is often associated with significant short‐term morbidity and variable long‐term bowel function. The aim of this systematic review was to investigate if preoperative stimulation of the defunctioned bowel restores bowel function more quickly after ileostomy closure and improves postoperative outcomes when compared with standard preoperative care. Method MEDLINE, Embase, CENTRAL, Google Scholar and ClinicalTrials.gov were searched for studies evaluating preoperative bowel stimulation in patients with a temporary ileostomy after low anterior resection or ileal pouch–anal anastomosis, regardless of their design, publication type or language. Study selection, data extraction and study assessment were performed by one reviewer and verified by another. Study results were synthesized narratively. The GRADE approach was used to assess the quality of evidence. Results Eight studies involving a total of 267 participants were included. The studies had a moderate to high risk of bias and were of varying methodological quality. Preoperative stimulation of the defunctioned bowel reduced the time to postoperative restoration of bowel function and the length of hospital stay when compared with standard preoperative care. Other functional outcomes and postoperative complication rates were similar to those of standard preoperative care. The overall quality of evidence was very low. Conclusion Despite these promising early results, there is insufficient high‐quality evidence to recommend routine implementation of preoperative bowel stimulation in clinical practice. Nevertheless, there is no evidence suggesting that the intervention worsens outcomes or is unsafe, paving the way for rigorous assessment of effectiveness, acceptability and cost‐effectiveness within the context of well‐designed clinical trials

Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth

Cell size is believed to influence cell growth and metabolism. Consistently, several studies have revealed that large cells have lower mass accumulation rates per unit mass (i.e., growth efficiency) than intermediate-sized cells in the same population. Sizedependent growth is commonly attributed to transport limitations, such as increased diffusion timescales and decreased surface-to-volume ratio. However, separating cell size- and cell cycle-dependent growth is challenging. To address this, we monitored growth efficiency of pseudodiploid mouse lymphocytic leukemia cells during normal proliferation and polyploidization. This was enabled by the development of large-channel suspended microchannel resonators that allow us to monitor buoyant mass of single cells ranging from 40 pg (small pseudodiploid cell) to over 4,000 pg, with a resolution ranging from ∼1% to ∼0.05%. We find that cell growth efficiency increases, plateaus, and then decreases as cell cycle proceeds. This growth behavior repeats with every endomitotic cycle as cells grow into polyploidy. Overall, growth efficiency changes 33% throughout the cell cycle. In contrast, increasing cell mass by over 100-fold during polyploidization did not change growth efficiency, indicating exponential growth. Consistently, growth efficiency remained constant when cell cycle was arrested in G2. Thus, cell cycle is a primary determinant of growth efficiency. As growth remains exponential over large size scales, our work finds no evidence for transport limitations that would decrease growth efficiency

Mammalian cell growth dynamics in mitosis

The extent and dynamics of animal cell biomass accumulation during mitosis are unknown, primarily because growth has not been quantified with sufficient precision and temporal resolution. Using the suspended microchannel resonator and protein synthesis assays, we quantify mass accumulation and translation rates between mitotic stages on a single-cell level. For various animal cell types, growth rates in prophase are commensurate with or higher than interphase growth rates. Growth is only stopped as cells approach metaphase-to-anaphase transition and growth resumes in late cytokinesis. Mitotic arrests stop growth independently of arresting mechanism. For mouse lymphoblast cells, growth in prophase is promoted by CDK1 through increased phosphorylation of 4E-BP1 and cap-dependent protein synthesis. Inhibition of CDK1-driven mitotic translation reduces daughter cell growth. Overall, our measurements counter the traditional dogma that growth during mitosis is negligible and provide insight into antimitotic cancer chemotherapies

A healthy lifestyle text message intervention for adolescents: protocol for the Health4Me randomized controlled trial.

BACKGROUND: Adolescence presents a window of opportunity to establish good nutrition and physical activity behaviours to carry throughout the life course. Adolescents are at risk of developing cardiovascular and other chronic diseases due to poor the complex interplay of physical and mental health lifestyle risk factors. Text messaging is adolescents main form of everyday communication and text message programs offer a potential solution for support and improvement of lifestyle health behaviours. The primary aim of this study is to determine effectiveness of the Health4Me text message program to improve adolescent's physical activity or nutrition behaviours among adolescents over 6-months, compared to usual care. METHODS: Health4Me is a virtual, two-arm, single-blind randomised controlled trial, delivering a 6-month healthy lifestyle text message program with optional health counselling. Recruitment will be through digital advertising and primary care services. In total, 330 adolescents will be randomised 1:1 to intervention or control (usual care) groups. The intervention group will receive 4-5 text messages per week for 6-months. All text messages have been co-designed with adolescents. Messages promote a healthy lifestyle by providing practical information, health tips, motivation and support for behaviour change for physical activity, nutrition, mental health, body image, popular digital media and climate and planetary health. Virtual assessments will occur at baseline and 6-months assessing physical health (physical activity, nutrition, body mass index, sleep), mental health (quality of life, self-efficacy, psychological distress, anxiety, depression, eating disorder risk) and lifestyle outcomes (food insecurity and eHealth literacy). DISCUSSION: This study will determine the effectiveness of a 6-month healthy lifestyle text message intervention to improve physical activity and nutrition outcomes in adolescents. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ANZCTR) ACTRN12622000949785 , Date registered: 05/07/2022

School-based HPV vaccination positively impacts parents’ attitudes toward adolescent vaccination

Introduction This qualitative study aimed to explore parental attitudes, knowledge and decision-making about HPV vaccination for adolescents in the context of a gender-neutral school-based Australian National Immunisation Program (NIP). Methods Semi-structured interviews with parents of adolescents eligible for HPV vaccination were undertaken as part of an evaluation of a cluster-randomised controlled trial of a complex intervention in 40 schools (2013–2015). In this qualitative study, we purposively recruited a nested sample of parents from 11 schools across two Australian jurisdictions. Interviews explored parent knowledge and understanding of the HPV vaccine program; HPV vaccination decision-making; their adolescent’s knowledge about HPV vaccination; and their adolescent’s understanding about HPV vaccination, sexual awareness and behaviour. Transcripts were analysed using inductive and deductive thematic analysis. Results Parents’ of 22 adolescents had positive attitudes towards the program; the school-based delivery platform was the key driver shaping acceptance of and decision-making about HPV vaccination. They had difficulty recalling, or did not read, HPV vaccination information sent home. Some adolescents were involved in discussions about vaccination, with parents’ responsible for ultimate vaccine decision-making. All parents supported in-school education for adolescents about HPV and HPV vaccination. Parents’ knowledge about HPV vaccination was limited to cervical cancer and was largely absent regarding vaccination in males. Conclusions Parents’ positive attitudes towards the NIP and inclusion of the HPV vaccine is central to their vaccine decision-making and acceptance. More intensive communication strategies including school education opportunities are required to improve parents’ knowledge of HPV-related disease and to promote vaccine decision-making with adolescents