Frailty and risk of subsequent fracture among older adults presenting to hospital with a minimal trauma fracture.

We investigated frailty and refracture risk among older adults with a minimal trauma fracture. After adjusting for age, sex, and site of initial fracture, increasing frailty was associated with an increased risk subsequent fracture. These results indicate the need to routinely screen for frailty following an initial fracture among older adults. INTRODUCTION: Minimal trauma fractures are common among older adults, and frailty increases risk of an initial minimal trauma fracture. This study was undertaken to estimate the risk of subsequent fracture based on frailty status at the time of an initial fracture. METHODS: The study population was older adults presenting to hospital, aged 60 years or more, with a minimal trauma fracture. Frailty was estimated using a cumulative deficit approach. The risk of subsequent fracture based on increasing cumulative frailty deficit item group, adjusted for sex, age, and site of initial fracture, was estimated using Cox's proportional hazard model. RESULTS: Between January 2014 and December 2020, 12,115 older adults presented to hospital (8371 women [69%]), with an initial minimal trauma fracture. The average age was 80 years (SD 9.5). Subsequent fractures identified during the follow-up period occurred in 1137 (9.4%) of study participants. The incidence of subsequent fracture ranged from 25.0 per 1000 older adults (95% confidence interval (CI) 22.4 to 27.8) among the lowest frailty deficit group (1 deficit item) to 31.8 per 1000 (95% CI 28.0 to 35.8) among the highest frailty deficit group (4 to 12 deficit items). After adjusting for age, sex, and site of initial fracture, an increasing number of frailty deficit items was associated with increased risk subsequent fracture (p-value for trend = 0.008). CONCLUSION: Our results indicate that following an initial minimal trauma fracture, frailty independently increases the risk of a subsequent fracture. Therefore, it is important at the time of an initial fracture that older women and men are screened for the presence of frailty, and models of care are implemented to reduce the risk of subsequent fracture among this vulnerable group of older adults.

Frailty among older surgical patients and risk of hospital acquired adverse events: The South-Western Sydney frailty and nurse sensitive indicators study.

BACKGROUND: While advances in healthcare mean people are living longer, increasing frailty is a potential consequence of this. The relationship between frailty among older surgical patients and hospital acquired adverse events has not been extensively explored. We sought to describe the relationship between increasing frailty among older surgical patients and the risk of hospital acquired adverse events. METHODS: We included consecutive surgical admissions among patients aged 70 years or more across the SWSLHD between January 2010 and December 2020. This study used routinely collected ICD-10-AM data, obtained from the government maintained Admitted Patient Data Collection. The relationships between cumulative frailty deficit items and risk of hospital acquired adverse events were assessed using Poisson regression modelling. This study followed the RECORD/STROBE guidelines. RESULTS: During the study period, 44,721 (57% women) older adults were admitted, and 41% (25,306) were planned surgical admissions. The risk of all adverse events increased with increasing number of frailty deficit items, the highest deficit items group (4-12 deficit items) compared with the lowest deficit items group (0 or 1 deficit item): falls adjusted rate ratio (adj RR) = 15.3, (95% confidence interval (CI) 12.1, 19.42); pressure injury adj RR = 21.3 (95% CI 12.53, 36.16); delirium adj RR = 40.9 (95% CI 31.21, 53.55); pneumonia adj RR = 16.5 (95% CI 12.74, 21.27); thromboembolism adj RR = 17.3 (95% CI 4.4, 11.92); and hospital mortality adj RR = 6.2 (95% CI 5.18, 7.37). CONCLUSION: The increase in number of cumulative frailty deficit items among older surgical patients was associated with a higher risk of adverse hospital events. The link offers an opportunity to clinical nursing professionals in the surgical setting, to develop and implement targeted models of care and ensure the best outcomes for frail older adults and their families.

A nurse-led intervention to reduce the incidence and duration of delirium among adults admitted to intensive care: A stepped-wedge cluster randomised trial.

BACKGROUND: Delirium is an acute change in behaviour, characterised by a fluctuating course, inattention, and disorganised thinking. For critically ill adults in the intensive care, the incidence of delirium has been reported to be at least 30% and is associated with both short-term and long-term complications, longer hospital stay, increased risk of mortality, and long-term cognitive problems. AIM: The objective of this study was to determine the effectiveness of a nurse-led delirium-prevention protocol in reducing the incidence and duration of delirium among adults admitted to intensive care. METHODS: A hybrid stepped-wedge cluster randomised controlled trial was conducted to assess the effectiveness of the implementation and dissemination of the nurse-led intervention to reduce the incidence and duration of delirium among adults admitted to the four adults intensive care units in the southwest of Sydney, Australia. RESULTS: Between May 2019 and February 2020, over a 10-month period, 2618 admissions, among 2566 patients, were included in the study. After an initial 3-month baseline period, each month there was a random crossover to the nurse-led intervention in one of the four intensive care units, and by the 7th month of the trial, all units were exposed to the intervention for at least 3 months. The incidence of acute delirium was observed to be 10.7% (95% confidence interval [CI] = 9.1-12.4%), compared to 14.1% (95% CI = 12.2-16.2%) during the preintervention (baseline) period (adjusted rate ratio [adjRR] = 0.78, 95% CI = 0.57-1.08, p = 0.134). The average delirium-free-days for these preintervention and postintervention periods were 4.1 days (95% CI = 3.9-4.3) and 4.4 days (95% CI = 4.2-4.5), respectively (adjusted difference = 0.24 days [95% CI = -0.12 to 0.60], p = 0.199). CONCLUSION: Following the introduction of a nurse-led, nonpharmacological intervention to reduce the burden of delirium, among adults admitted to intensive care, we observed no statistically significant decrease in the incidence of delirium or the duration of delirium.

Prevalence of SARS-CoV-2 antibodies among nurses: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: This systematic review and meta-analysis reports the seroprevalence of SARS-CoV-2 antibodies among nurses. BACKGROUND: With a growing body of literature reporting the positive serology for SARS-CoV-2 antibodies among healthcare workers, it remains unclear whether staff at the point of direct patient care are more prone to developing and transmitting the virus. Given nurses make up the majority of the global health workforce, outbreaks among these workers could severely undermine a health system's capability to manage the pandemic. We aimed to summarise and report the seroprevalence of SARS-CoV-2 antibodies among nurses globally. DESIGN: Systematic review and meta-analyses. METHODS: This systematic review was developed, undertaken and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We searched the electronic medical literature databases: MEDLINE; CINAHL; and EMBASE for studies reporting the seroprevalence of SARS-CoV-2 antibodies among nursing staff. Studies that reported nursing specific data were included in this review. Study quality was evaluated using the Joanna Briggs Institute checklist for studies reporting prevalence data. Studies were stratified according to the World Health Organisation region classifications, and results were presented using forest plots and summary prevalence and variance was estimated using a random effects model. RESULTS: Our electronic search identified 1687 potential studies, of which 1148 were screened for eligibility after duplicates were removed, and 51 of the studies were included in our meta-analysis. The overall seroprevalence of SARS-CoV-2 antibodies among nurses was estimated to be 8.1% (95% CI 6.9%-9.4%) among the 60,571 participants included in the studies. Seropositivity was highest in the African region (48.2%, 95% CI 39.2%-57.3%), followed by the European region (10.3%, 95% CI 8.0%-12.5%), the Region of the Americas (8.4%, 95% CI 6.0%-10.7%), the South-East Asia region (3.0%, 95% CI 0.00%-6.5%) and the Western Pacific region (0.5%, 95% CI 0.0%-1.0%). Pooled estimates were unable to be calculated in the Eastern Mediterranean region due to insufficient studies. CONCLUSION: The seroprevalence of SARS-CoV-2 antibodies among nurses is comparable to other healthcare workers, and possibly similar to the general population. Early adoption and adherence to personal protective equipment and social distancing measures could explain these similarities, meaning the majority of staff contracted the virus through community transmission and not in a healthcare setting. RELEVANCE TO CLINICAL PRACTICE: Fear and uncertainty have been features of this pandemic, including among nurses. This meta-analysis should provide some comfort to nurses that risks are similar to community exposure when adequate PPE is available and there is an adherence to infection control measures.

Synthesis of novel potent cytotoxicy podophyllotoxin-naphthoquinone compounds via microwave-assited multicomponent domino reactions.

A series of novel podophyllotoxin-naphthoquinone compounds 5a-p were synthesized in good yields using microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, aromatic benzaldehydes, tetronic acid and ammonium acetate. All the synthesized compounds were fully characterized by spectral data and evaluated for their cytotoxicity activities against KB, HepG2, Lu1, MCF7, and non-cancerous Hek-293 cell lines. Among 16 new compounds screened, compounds 5a, 5d, 5h, and 5k displayed high potent inhibitory activities with IC50 < 40 nM against HepG2 and SK-Lu-1 cell lines, and showed lower toxicity for non-cancerous Hek-293 cell line, demonstrating the potential importance of these compounds in the development of potential anticancer agents.

The efficacy and performance impact of Fostera PRRS in a Vietnamese commercial pig farm naturally challenged by a highly pathogenic PRRS virus.

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever, respiratory distress, and high mortality in pigs of all ages and has severely affected the Vietnam pork industry in recent years. The study was conducted to compare the efficacy, safety, and overall performance of a modified live PRRSV-2 vaccine (Fostera PRRS) to an existing PRRSV modified live vaccine on a farm with a recent history of HP-PRRSV-associated respiratory diseases. A total of 351 pigs were randomly allocated to three treatment groups: (i) vaccinated with Fostera PRRS at 1 day of age (n = 118), (ii) vaccinated with Fostera PRRS (n = 118) at 21 days of age, and (iii) vaccinated with Amervac PRRS (n = 115) at 21 days of age. The Fostera PRRS vaccinated pigs had milder clinical symptoms, lower levels of HP-PRRSV viremia, fewer pathological changes in the lung, and higher body weight gain at the end of the study compared with the Amervac PRRS group. Vaccination of pigs with Fostera PRRS at 1 day of age also significantly reduced viral loads in their blood (P < 0.05) and induced higher anti-PRRSV antibody titers (P < 0.01) compared with pigs vaccinated with Amervac PRRS at 21 days of age. Fostera PRRS vaccination at 1 day of age can be useful in protecting young piglets from early HP-PRRSV infection because the immunized pigs were marketed 20 days earlier than their peers immunized at 21-day old as they reached the target market weight earlier in this study.

Effects of inter-organism interactions in biofouling on microtopographic surfaces.

An extended model of the surface energetic attachment (SEA) model is introduced to study the fouling of marine organisms on microtopographic surfaces, taking into account the excluded volume interaction and the attraction between the organisms. It is shown that the excluded volume interaction leads to changes in the site-typed attachment probabilities which increase with the average spore density on the surface. As a result of these changes, the spore density map is flattened under very high density fouling. The attractive interaction on the other hand leads to aggregation of spores and the average aggregate size increased with the strength of attraction. The model can be mapped to a specific experiment to determine the attachment energy parameters. In contrast to various prior empirical approaches, the extended SEA model is rigorous from the statistical mechanics viewpoint, thus it provides a reliable tool for studying complex attachment behaviors of microorganisms on topographic surfaces.

Online Racial Discrimination, Suicidal Ideation, and Traumatic Stress in a National Sample of Black Adolescents.

Importance: Because of increased suicide rates among Black youth in the past 2 decades, there is a dire need for research on suicidal ideation and risk factors in this population. Objective: To examine the direct and indirect associations between online racial discrimination and suicidal ideation through posttraumatic stress disorder symptoms among Black adolescents living in the US, with consideration of potential differential associations by gender and age. Design, Setting, and Participants: This cross-sectional study used data drawn from the first wave of the National Survey of Critical Digital Literacy. Black adolescents aged 11 to 19 years were selected from a nationally representative probability-based sample. Data were collected from October 2020 to December 2020 and analyzed from August 2021 to October 2021. Main Outcomes and Measures: Hypotheses of the current study were formulated during research design and grounded in empirical literature. The individual online racial discrimination subscale (Online Victimization Scale), the UCLA Child/Adolescent posttraumatic stress disorder Reaction Index for DSM-5, and an item from the second edition of the Children's Depression Inventory were used to assess constructs. Mediation was assessed through mediation models with path analyses using structural equation modeling. Results: Among a total 525 participants, 265 were girls (50.5%) and 251 were boys (47.8%); the mean (SD) age was 14.8 (2.5) years. Findings from structural equation modeling analysis indicated that individual online racial discrimination was associated with posttraumatic stress disorder symptoms (ß = 0.49, SE = 0.06, P < .001), and posttraumatic stress disorder symptoms were associated with suicidal ideation (ß = 0.51, SE = 0.06, P < .001). Posttraumatic stress disorder was identified as a full mediator between online racial discrimination and suicide (ß = 0.25, SE = 0.04, P < .001). No differences by gender or age were found. Furthermore, no significant direct association between online racial discrimination and suicidal ideation was found. Conclusions and Relevance: This study found an association between individual online racial discrimination and posttraumatic stress disorder symptoms and between posttraumatic stress disorder symptoms and suicidal ideation. These risk factors are important to consider in continuing studies of the cause of suicidal ideation for Black adolescents in the US.

Linguistics-based formalization of the antibody language as a basis for antibody language models.

Apparent parallels between natural language and antibody sequences have led to a surge in deep language models applied to antibody sequences for predicting cognate antigen recognition. However, a linguistic formal definition of antibody language does not exist, and insight into how antibody language models capture antibody-specific binding features remains largely uninterpretable. Here we describe how a linguistic formalization of the antibody language, by characterizing its tokens and grammar, could address current challenges in antibody language model rule mining.

The Impact of Embryo Quality on Pregnancy Outcomes in Single Day 5 versus Day 6 Euploid Blastocyst Transfer: A Retrospective Cohort Study.

BACKGROUND: Selecting embryos with the highest implantation potential is crucial for in vitro fertilization (IVF) success. Both the timing of blastulation, day 5 (D5) or D6, and the embryo quality have been suggested as influential factors in determining the clinical outcome of single euploid blastocyst transfers. However, evidence supporting the superiority of D5 over D6 blastocysts remains inconclusive. The aim of this study was to compare clinical outcomes following the transfer of euploid blastocysts with different quality and timing of blastulation. MATERIALS AND METHODS: A retrospective cohort study was conducted at our Assisted Reproductive Center, analyzing the outcome of 774 transfers with D5 euploids and 155 transfers with D6 euploids performed between January 2019 and February 2022. RESULTS: The live birth rate was significantly lower in the euploid D6 group compared to the euploid D5 group (38.71vs. 55.04%, P=0.001). The outcome was significantly influenced by the quality of the embryos. Live birth rates were 62.14 and 53.61% following transfers of D5 and D6 excellent embryos respectively, 45.18 and 32.21% following transfer of D5 and D6 good embryos but only 28.64 and 19.32% following transfer of D5 and D6 fair embryos. The outcome difference was statistically significant across embryo quality categories (P=0.001). The adjusted risk ratios (RR) of clinical outcomes indicated that excellent euploid D5 embryos consistently outperformed other types of embryo quality. CONCLUSION: The timing of blastulation and embryo quality are crucial factors in determining the success of single euploid blastocyst transfers. Excellent euploid D5 transfers yielded superior clinical outcomes, providing valuable insights for IVF teams and patients when selecting embryos to be transferred.

Synthesis of new DOPO derivatives and investigation of their synergistic effect with APP-PEI on the flame retardancy of epoxy composite.

Epoxy resin has been extensively used in many industrial and daily applications due to its unique properties. However, the high flammability of epoxy has limited its further development. DOPO derivatives, which are organophosphorus compounds, are highly effective components of flame retardant epoxy composites due to their good compatibility with the resin and their lower toxicity compared to halogenated compounds. This study synthesized sixteen new DOPO derivatives, characterizing their chemical structures with NMR spectroscopy. The combination of synthesized DOPO derivatives and APP-PEI (ammonium polyphosphate-polyethyleneimine) has shown a synergistic effect on enhancing the flame retardancy of epoxy resin with the UL-94 V-0 rating and the LOI value of 28.6%. Moreover, the epoxy composites displayed relatively high mechanical performance with the impact strength of 26-28 kJ m-2.

An unsymmetrically π-extended porphyrin-based single-crystal field-effect transistor and its anisotropic carrier-transport behavior.

Anisotropic charge transport: Single-crystal organic field-effect transistor devices derived from aggregates of thiophene-appended porphyrins display very high mobility (0.27 cm(2) V(-1) s(-1)). This behavior is due to staircase stacking of the porphyrins with distances between layers of 3.17(7) Å. Furthermore, the charge-transport behavior is anisotropic owing to an anisotropic molecular arrangement in the single-crystal microplates.

The Impact of COVID-19 Pandemic on ESBL-Producing Enterobacterales Infections: A Scoping Review.

Several studies have reported an increased frequency of colonization and/or infection with antibiotic-resistant bacteria (ARB) during the COVID-19 pandemic. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) are a group of bacteria with intrinsic resistance to multiple antibiotics, including penicillins, cephalosporins, and monobactams. These pathogens are easy to spread and can cause difficult-to-treat infections. Here, we summarize the available evidence on the impact of the COVID-19 pandemic on infections caused by ESBL-PE. Using specific criteria and keywords, we searched PubMed, MEDLINE, and EMBASE for articles published up to 30 March 2023 on potential changes in the epidemiology of ESBL-E since the beginning of the COVID-19 pandemic. We identified eight studies that documented the impact of COVID-19 on ESBL-E. Five studies were focused on assessing the frequency of ESBL-PE in patient-derived specimens, and three studies investigated the epidemiological aspects of ESBL-PE infections in the context of the COVID-19 pandemic. Some of the studies that were focused on patient specimens reported a decrease in ESBL-PE positivity during the pandemic, whereas the three studies that involved patient data (1829 patients in total) reported a higher incidence of ESBL-PE infections in patients hospitalized for COVID-19 compared with those with other conditions. There are limited data on the real impact of the COVID-19 pandemic on the epidemiology of ESBL-PE infections; however, patient-derived data suggest that the pandemic has exacerbated the spread of these pathogens.

Prevalent Variants in the LDLR Gene Impair Responsiveness to Rosuvastatin among Family Members of Patients with Premature Myocardial Infarction.

BACKGROUND: Familial hypercholesterolemia (FH) is an inherited metabolic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-c) from birth. About 85% of all FH cases are caused by pathogenic variants in the LDLR gene. Individuals with FH have increased cardiovascular risk, including a high risk of premature myocardial infarction (PMI). METHODS: We conducted an opportunistic exome screening to identify variants in the LDLR gene among Vietnamese patients with PMI treated at a general hospital in southern Vietnam. A cascade testing for LDLR variants was conducted in their relatives within three generations, and the effects of the LDLR variant on the response to rosuvastatin treatment were also studied using a comparative before-and-after study design on those who were eligible. RESULTS: A total of 99 participants from the three generations of four PMI patients were recruited, mean age 37.3 ± 18.5 years, 56.6% males. Sanger sequencing revealed two variants in the LDLR gene: variant rs577934998 (c.664T>C), detected in 17 individuals within one family, and variant rs12710260 (c.1060+10G>C), found in 32 individuals (49.5%) in the other three families tested. Individuals harboring the variant c.664T>C had significantly higher baseline LDL-c and total cholesterol levels compared to those with variant c.1060+10G>C (classified as benign) or those without LDLR variants, and among the 47 patients subjected to a 3-month course of rosuvastatin therapy, those with variant c.664T>C had a significantly higher risk of not achieving the LDL-c target after the course of treatment compared to the c.1060+10G>C carriers. CONCLUSIONS: These findings provide evidence supporting the existence of pathogenic LDLR variants in Vietnamese patients with PMI and their relatives and may indicate the need for personalizing lipid-lowering therapies. Further studies are needed to delineate the extent and severity of the problem.

Clinical Features and the Outcome Evaluations of Keloid and Hypertrophic Scar Treatment with Triamcinolone Injection in Mekong Delta, Vietnam - A Cross-Sectional Study.

Background: Excessive scarring is a common problem that can have significant cosmetic and psychological consequences for patients. Intralesional injection therapy, such as the use of triamcinolone, has emerged as an effective treatment option for hypertrophic scars. The objective of this study was to describe the morphological features of hypertrophic scars, categorize them, and evaluate the efficacy of triamcinolone injection therapy in treating these scars. Materials and Methods: A cross-sectional descriptive study of 80 patients with hypertrophic scars treated with triamcinolone intralesional injection at Can Tho University of Medicine and Pharmacy Hospital from 5/2018 to 5/2021. Results: There were 80 patients in all, with a male/female ratio of 1/1.05 and a median age of 15-35. There were 129 scars in all, with scar age >1 year accounting for 83%, keloid scars accounting for 64%, and hypertrophic scars accounting for the remaining 36%. Scars are most commonly seen on the trunk, accounting for 53.5% of all scars, particularly on the anterior chest wall. When the source of scars was discovered, trauma and acne accounted for 24% and 23%, respectively, while the rest were predominantly spontaneous scars, accounting for 49%. Scarring and discomfort of mild to moderate severity were common clinical symptoms; scars larger than 5cm in size had more symptoms than scars smaller than 5cm. Prior to the therapy, the mean Vancouver Score Scale-VSS was 6.55±2.13. After 24 weeks of the therapy, 96.7% of patients had entirely improved itching symptoms, 75% had completely improved pain, and 25% still had minimal pain. After therapy, the mean Vancouver Score Scale-VSS was 2.55±1.81 (p<0.05). At week 24, 3.75% of patients experienced skin shrinkage, 3.75% experienced depigmentation, and 13.75% experienced vasodilation. Conclusion: Triamcinolone intralesional injection should be utilized as a first-line therapy for hypertrophic scarring.

Parent Perceptions of an Early Childhood System's Community Efforts: A Qualitative Analysis.

Understanding how parents, and other primary caregivers, perceive and experience early childhood programs and services is essential for identifying family-centered facilitators and barriers to service utilization. Therefore, this paper aims to explore parent knowledge of and experiences with community efforts of an early childhood system in Illinois: the All Our Kids Early Childhood Networks (AOK Networks). Our research team conducted focus group interviews with 20 parents across four Illinois counties. A semi-structured interview guide was used to examine parent perceptions of an early childhood system's community efforts in promoting the health and well-being of children aged from birth to five. Thematic network analysis was used to analyze all focus group data. Parents indicated three salient themes, including: (1) comprehensive information sharing practices, (2) diverse service engagement, and (3) barriers to service access. Overall, parents reported general satisfaction with the quality of available services and provided feedback regarding identified areas of need to increase the accessibility and utilization of local services. Engaging parents as partners is essential to the effective implementation of family-centered early childhood services. Families are the experts of their lived experiences, and incorporating their voices in program development and evaluation efforts works to increase positive child and family outcomes.

Co-encapsulated astaxanthin and kaempferol nanoparticles: fabrication, characterization, and their potential synergistic effects on treating non-alcoholic fatty liver disease.

Astaxanthin and kaempferol, renowned natural compounds, possess potent antioxidant properties and exhibit remarkable biological activities. However, their poor water solubility, low stability, and limited bioavailability are the primary bottlenecks that restrict their utilization in pharmaceuticals and functional foods. To overcome these drawbacks, this study aims to fabricate astaxanthin/kaempferol co-encapsulated nanoparticles and investigate their synergistic effects on reducing the risk of stress oxidation, chronic inflammation, and lipid accumulation in RAW264.7 and HepG2 cells. The synthesized astaxanthin/kaempferol nanoparticles exhibited well-defined spherical morphology with an average particle diameter ranging from 74 to 120 nm. These nanoparticles demonstrated excellent stability with the remaining astaxanthin content ranging from 82.5% to 92.1% after 6 months of storage at 4 °C. Nanoastaxanthin/kaempferol displayed high dispersibility and stability in aqueous solutions, resulting in a significant enhancement of their bioactivity. In vitro assessments on cell lines revealed that nanoastaxanthin/kaempferol enhanced the inhibition of H2O2-induced oxidative stress in HepG2 and LPS-induced NO production in RAW264.7 compared to nanoastaxanthin. Additionally, these nanoparticles reduced the expression of genes involved in inflammation (iNOS, IL-6 and TNF-α). Moreover, hepatocytes treated with nanoastaxanthin/kaempferol showed a reduction in lipid content compared to those treated with nanoastaxanthin, through enhanced regulation of lipid metabolism-related genes. Overall, these findings suggest that the successful fabrication of co-encapsulated nanoparticles containing astaxanthin and kaempferol holds promising therapeutic potential in the treatment of non-alcoholic fatty liver disease.

1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) induces phosphorylation of eukaryotic elongation factor-2 (eEF2): a cautionary note on the anticancer mechanism of an eEF2 kinase inhibitor.

Eukaryotic elongation factor-2 kinase (eEF2K) relays growth and stress signals to protein synthesis through phosphorylation and inactivation of eukaryotic elongation factor 2 (eEF2). 1-Benzyl-3-cetyl-2-methylimidazolium iodide (NH125) is a widely accepted inhibitor of mammalian eEF2K and an efficacious anti-proliferation agent against different cancer cells. It implied that eEF2K could be an efficacious anticancer target. However, eEF2K siRNA was ineffective against cancer cells including those sensitive to NH125. To test if pharmacological intervention differs from siRNA interference, we identified a highly selective small molecule eEF2K inhibitor A-484954. Like siRNA, A-484954 had little effect on cancer cell growth. We carefully examined the effect of NH125 and A-484954 on phosphorylation of eEF2, the known cellular substrate of eEF2K. Surprisingly, NH125 increased eEF2 phosphorylation, whereas A-484954 inhibited the phosphorylation as expected for an eEF2K inhibitor. Both A-484954 and eEF2K siRNA inhibited eEF2K and reduced eEF2 phosphorylation with little effect on cancer cell growth. These data demonstrated clearly that the anticancer activity of NH125 was more correlated with induction of eEF2 phosphorylation than inhibition of eEF2K. Actually, induction of eEF2 phosphorylation was reported to correlate with inhibition of cancer cell growth. We compared several known inducers of eEF2 phosphorylation including AMPK activators and an mTOR inhibitor. Interestingly, stronger induction of eEF2 phosphorylation correlated with more effective growth inhibition. We also explored signal transduction pathways leading to NH125-induced eEF2 phosphorylation. Preliminary data suggested that NH125-induced eEF2 phosphorylation was likely mediated through multiple pathways. These observations identified an opportunity for a new multipathway approach to anticancer therapies.

Tyrosinase inhibitors from the wood of Artocarpus heterophyllus.

From the methanolic-soluble extract of the wood of Artocarpus heterophyllus, four new flavones, artocarmins A-D (1-4), and three new chalcones, artocarmitins A-C (5-7), have been isolated together with 13 known compounds. Their structures were determined on the basis of the spectroscopic data. Compounds 1-4, 6, 7, 9-16, and 20 displayed significant tyrosinase inhibitory activity. The most active compound, morachalcone A (12) (IC50, 0.013 µM), was 3000 times more active as a tyrosinase inhibitor than a positive control, kojic acid (IC50, 44.6 µM).

An introduction to Bayes' theorem and examples of its application to a diagnostic test and a clinical trial.

BACKGROUND: The Bayesian approach to updating scientific knowledge involves using a probability distribution to describe a prior belief concerning an outcome of interest and combines this with some new information to create a posterior probability distribution to describe the updated current knowledge. AIM: To introduce the application of Bayes' theorem, using the conditional probability example of the Monty Hall problem and two examples of the clinical application of a Bayesian approach. DISCUSSION: Bayesian approaches enable the incorporation of prior knowledge into the interpretation of research findings and summaries of evidence to date. Bayesian approaches are being incorporated into most clinical trials. CONCLUSION: Bayesian approaches to interpreting the results of a diagnostic test and a clinical trial highlight the utility of these approaches to clinical nursing and the application of evidence-based practice. IMPLICATIONS FOR PRACTICE: Stimulation of an understanding and interest in the Bayesian approach among nurse researchers should lead to its wider application in nursing research.