Identification of the human Cytochrome P450 enzymes (P450s) responsible for metabolizing infigratinib to its pharmacologically active Metabolites, BHS697, and CQM157, and assessment of their in vitro inhibition of P450s and UDP-glucuronosyltransferases (UGTs).

Infigratinib, an oral FGFR inhibitor for advanced cholangiocarcinoma, yielded two active metabolites, BHS697 and CQM157, with similar receptor affinity. Our study characterized P450s that are responsible for the metabolism of infigratinib to its two major active metabolites, BHS697 and CQM157. In vitro inhibition of P450s and UGTs by infigratinib, BHS697 or CQM157 was further investigated. The unbound apparent Km values for metabolism of infigratinib to BHS697 by HLM, human recombinant CYP2C8, CYP2C19, CYP2D6 and CYP3A4 enzymes are 4.47, 0.65, 2.50, 30.6 and 2.08 µM, while Vmax values are 90.0 pmol/min/mg protein, 0.13, 0.027, 0.81, and 0.56 pmol/min/pmol protein, respectively. The unbound apparent Km value for metabolism of infigratinib to CQM157 by HLM is 0.049 µM, while the Vmax value is 0.32 pmol/min/mg protein respectively. In HLM, infigratinib displayed moderate inhibition of CYP3A4 and CYP2C19 and weak or negligible inhibition of other P450 isoforms. BHS697 exhibited weak inhibition of CYP2B6, CYP2C9, CYP2C19 and CYP3A4, and no inhibition of CYP2C8 and CYP2D6. CQM157 moderately inhibited CYP2C9 and CYP3A4, and weakly or negligibly inhibited other P450 isoforms. Regarding UGTs, infigratinib moderately inhibited UGT1A4 and weakly inhibited UGT1A1, respectively. BHS697 weakly inhibited UGT1A1. In contrast, CQM157 moderately inhibited both UGT1A1 and UGT1A4. Our findings provide novel insights into the metabolism of and potential DDIs implicating infigratinib.

Assessment of Illness Severity in Adults Hospitalized With Acute Respiratory Tract Infection due to Influenza, Respiratory Syncytial Virus, or Human Metapneumovirus.

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs). METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. RESULTS: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms. CONCLUSIONS: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.

Evaluation in a porcine wound model and long-term clinical assessment of an autologous heterogeneous skin construct used to close full-thickness wounds.

Acute and chronic wounds involving deeper layers of the skin are often not adequately healed by dressings alone and require therapies such as skin grafting, skin substitutes, or growth factors. Here we report the development of an autologous heterogeneous skin construct (AHSC) that aids wound closure. AHSC is manufactured from a piece of healthy full-thickness skin. The manufacturing process creates multicellular segments, which contain endogenous skin cell populations present within hair follicles. These segments are physically optimized for engraftment within the wound bed. The ability of AHSC to facilitate closure of full thickness wounds of the skin was evaluated in a swine model and clinically in 4 patients with wounds of different etiologies. Transcriptional analysis demonstrated high concordance of gene expression between AHSC and native tissues for extracellular matrix and stem cell gene expression panels. Swine wounds demonstrated complete wound epithelialization and mature stable skin by 4 months, with hair follicle development in AHSC-treated wounds evident by 15 weeks. Biomechanical, histomorphological, and compositional analysis of the resultant swine and human skin wound biopsies demonstrated the presence of epidermal and dermal architecture with follicular and glandular structures that are similar to native skin. These data suggest that treatment with AHSC can facilitate wound closure.

Are There Differences in Opioid Prescriptions to Urban and Rural Patients by Oral and Maxillofacial Surgeons in Massachusetts From 2011 to 2021?

PURPOSE: Oral-maxillofacial surgeons (OMSs) are frequent prescribers of opioid analgesics. It remains unclear if prescription patterns differ for urban versus rural patients, given potential differences in access to and delivery of care. This study aimed to characterize urban-rural differences in opioid analgesic prescriptions to patients in Massachusetts by OMSs from 2011 to 2021. METHODS: This retrospective cohort study used the Massachusetts Prescription Monitoring Program database to identify Schedule II and III opioid prescriptions by providers with specialty of oral and maxillofacial surgery from 2011 to 2021. The primary predictor variable was patient geography (urban/rural) and secondary predictor was year (2011-2021). The primary outcome variable was milligram morphine equivalent (MME) per prescription. Secondary outcome variables were days' supply per prescription and number of prescriptions received per patient. Descriptive and linear regression statistics were performed to analyze differences in prescriptions to urban and rural patients each year and throughout the study period. RESULTS: The study data, which includes OMS opioid prescriptions (n = 1,057,412) in Massachusetts from 2011 to 2021, ranged annually between 63,678 and 116,000 prescriptions to between 58,000 and 100,000 unique patients. The cohorts each year ranged between 48 and 56% female with mean ages between 37 and 44 years. There were no differences in the mean number of patients per provider in urban and rural populations in any year. The study sample had a large majority of urban patients (>98%). MME per prescription, days' supply per prescription, and prescriptions received per patient were all generally similar between urban and rural patients each year, with the largest MME per prescription difference in 2019 (87.3 for rural to 73.9 for urban patients, P < .01). From 2011 to 2021, all patients had a steady decrease in MME per prescription (ß = -6.64, 95% confidence interval: -6.81, -6.48; R2 = 0.39) and day's supply per prescription (ß = -0.1, 95% confidence interval: -0.1, -0.09; R2 = 0.37). CONCLUSION: In Massachusetts, there were similar opioid prescribing patterns by oral and maxillofacial surgeons to urban and rural patients from 2011 to 2021. There has also been a steady decrease in the duration and total dosage of opioid prescriptions to all patients. These results are consistent with multiple statewide policies over the last several years aimed at curbing opioid overprescribing.

Do Race and Ethnicity Affect the Age When Third Molars are Extracted?

PURPOSE: Socioeconomic and racial statuses are barriers to dental and medical healthcare in America leading to poor health outcomes. Delayed management of third molars may increase the risk of complications. There have been no large-scale studies examining the role race and ethnicity have on timing of third molar extraction. The purpose of this study is to explore the associations of race and ethnicity on age of third molar extractions and complications. MATERIALS AND METHODS: This retrospective cohort study composed of patients who underwent third molar extraction at Boston Children's Hospital from April 2011 to March 2021. Patients self-identified race as White, Black/African American, Asian, Native American/Pacific Islander, other, and prefer not to answer. Patients identified ethnicity as Hispanic or non-Hispanic. Subjects with incomplete medical records were excluded. Primary predictor variables were race and ethnicity. The primary outcome variable was the age of third molar extractions and the secondary outcome variable was postoperative complications. Descriptive, univariate, and multivariate statistics were conducted. P < .05 was considered statistically significant. Covariates included gender, insurance type, interpreter requirements, and preoperative symptoms. RESULTS: This study included 3,933 patients after exclusion criteria were applied. The mean age was 18.6 ± 2.49 years. When third molars were removed, White patients were older than the non-White population (18.8 vs 18.2 years, P < .001). Black or African American patients were younger than all other races (18.1 vs 18.7 years, P < .001). Hispanics were younger compared to non-Hispanics (18.1 vs 18.7 years, P < .001). Patients with preoperative symptoms removed their wisdom teeth at an older age compared to those who were asymptomatic (19.0 vs 18.5 years, P < .001). Black patients experienced more preoperative symptoms than other races (46.2% vs 29.2%, P < .001). White patients experienced the most postoperative complications (7.7% vs 5.0%, P = .003), while Black or African American patients experienced less postoperative complications (2.7% vs 7.5%, P < .001). CONCLUSION: This study provides no evidence that patients from historically under-represented racial and ethnic groups had inadequate access for removal of their third molars. Patients from these communities experienced a lower rate of complications after third molar extractions confirming quality of care was not compromised for these patients.

Comparative assessment of reported symptoms of influenza, respiratory syncytial virus, and human metapneumovirus infection during hospitalization and post-discharge assessed by Respiratory Intensity and Impact Questionnaire.

BACKGROUND: The hospitalized acute respiratory tract infection (HARTI) study used the Respiratory Intensity and Impact Questionnaire (RiiQ™) Symptom Scale, derived from FluiiQ™, to assess and compare the burden of respiratory infection symptoms for patients with influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) infection, with or without core risk factors (CRF) (age ≥65; chronic heart, renal, obstructive pulmonary disease; asthma). METHODS: This was a prospective cohort study in adult patients hospitalized with acute respiratory tract infection (40 centers, 12 countries) during two consecutive influenza/RSV/hMPV seasons (2017-2019). The RiiQ™ Symptom Scale and EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) were assessed by interview at two timepoints during hospitalization and at 1, 2, and 3 months post-discharge. RESULTS: Mean lower respiratory tract (LRT) symptom scores were higher for RSV and hMPV participants compared to influenza at 48 h after enrollment/early discharge (p = 0.001) and 3 months post-discharge (p = 0.007). This was driven by LRT symptoms, including shortness of breath (SOB) (p < 0.01) and wheezing (p < 0.01) during hospitalization, and SOB (p < 0.05) and cough (p < 0.05) post-discharge. Participants with CRF reported more moderate-to-severe SOB (p < 0.05) and wheezing (p < 0.05) compared to CRF(-) participants post-discharge. EQ-5D-5L scores were moderately associated with RiiQ™ LRT and systemic symptoms domains. CONCLUSIONS: Results from the HARTI study suggest that in the study population, LRT symptoms were more severe for RSV and hMPV groups and for patients with CRF. RiiQ™ Symptom Scale scores shows a moderate association with EQ-5D-5L indicating that the RiiQ™ may provide useful insights and offer advantages over other measures for use in interventional RSV adult clinical studies.

The feasibility and acceptability of mobile application-based assessment of suicidality using self-report components of a novel tool, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

The aim of this study was to assess the validity of a mobile application-based self-report questionnaire in the assessment of suicidality. We developed a program for the administration of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT). We invited university students and trainees enrolled in a study of addictions to complete this component of the SIBAT using the program on their mobile devices or personal computer. 196 participants completed all required modules of the SIBAT, with 97 using their mobile device and 99 using their personal computer. Rates of completed questionnaires between the two groups were compared, as were the responses to the items and the total scores. There was a significant difference between proportions of scale completion in both groups, with a greater number of participants who used a personal computer to complete the scale not responding to all questions compared to participants who used a mobile device to complete the scale. Data collected via mobile device showed good concurrent validity with data collected via personal computer. A trend toward greater disclosure of suicidality was observed in the mobile device group however, replication of these findings using larger sample sizes is needed.

Internal consistency and concurrent validity of self-report components of a new instrument for the assessment of suicidality, the Suicide Ideation and Behavior Assessment Tool (SIBAT).

This study aimed to assess the internal consistency of self-report components of the Suicide Ideation and Behavior Assessment Tool (SIBAT) and validate it with relevant elements of the Mini International Neuropsychiatric Interview (MINI). The SIBAT is a newly developed instrument for the evaluation of suicidality. In this study, we invited university students and trainees participating in a study of addictions to complete the self-report component of the SIBAT as an add-on study. We evaluated the internal consistency of the self-report component of the SIBAT and validated it against the suicidality component of the MINI. Data were analysed using both complete case analysis and multiple imputation. SIBAT data were collected for 394 participants, 314 of whom had also completed the MINI. The internal consistency of modules 2, 3, and 5 of the SIBAT was high. Each item from module 5 had a statistically significant association with the corresponding item from the MINI. The sum of scores from modules 2 and 3 had a moderate correlation with the assessment of suicide risk determined by the MINI, and a strong correlation with the total score of SIBAT module 5. The completion median time of modules 2, 3 and 5 was 14.3 min.

Mobile App-Based Self-Report Questionnaires for the Assessment and Monitoring of Bipolar Disorder: Systematic Review.

BACKGROUND: Bipolar disorder is a chronic, progressive illness characterized by recurrent episodes of mania and depression. Self-report scales have historically played a significant role in the monitoring of bipolar symptoms. However, these tools rely on episodic memory, which can be unreliable and do not allow the clinician to monitor brief episodic symptoms or the course of symptoms over shorter periods of time. Mobile app-based questionnaires have been suggested as a tool to improve monitoring of patients with bipolar disorder. OBJECTIVE: This paper aims to determine the feasibility and validity of mobile app-based self-report questionnaires. METHODS: We performed a systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, PsycInfo, Web of Science, Ovid MEDLINE, and EMBASE databases were searched for papers published in English that assessed adherence to and the validity of mobile app-based self-report questionnaires. Relevant studies published from database creation to May 22, 2020, were identified, and results examining the validity of and rates of adherence to app-based self-report questionnaires are reported. RESULTS: A total of 13 records were identified for inclusion in this review. Of these studies, 4 assessed the concurrent validity of mobile app-based self-report tools, with the majority of findings indicating significant associations between data collected using these tools and the Young Mania Rating Scale, Hamilton Depression Rating Scale-17, or Montgomery-Åsberg Depression Rating Scale (P<.001 to P=.24). Three studies comparing the variability or range of symptoms between patients with bipolar disorder and healthy controls suggested that these data are capable of differentiating between known groups. Two studies demonstrated statistically significant associations between data collected via mobile app-based self-report tools and instruments assessing other clinically important factors. Adherence rates varied across the studies examined. However, good adherence rates (>70%) were observed in all but 1 study using a once-daily assessment. There was a wide range of adherence rates observed in studies using twice-daily assessments (42%-95%). CONCLUSIONS: These findings suggest that mobile app-based self-report tools are valid in the assessment of symptoms of mania and depression in euthymic patients with bipolar disorder. Data collected using these tools appear to differ between patients with bipolar disorder and healthy controls and are significantly associated with other clinically important measures. It is unclear at this time whether these tools can be used to detect acute episodes of mania or depression in patients with bipolar disorder. Adherence data indicate that patients with bipolar disorder show good adherence to self-report assessments administered daily for the duration of the study periods evaluated.

Student nurses' ethical views on responses to the severe acute respiratory syndrome outbreak.

BACKGROUND: Fifteen years have passed since the outbreak of severe acute respiratory syndrome in Hong Kong. At that time, there were reports of heroic acts among professionals who cared for these patients, whose bravery and professionalism were highly praised. However, there are concerns about changes in new generation of nursing professionals. OBJECTIVE: We aimed to examine the attitude of nursing students, should they be faced with severe acute respiratory syndrome patients during their future work. RESEARCH DESIGN: A questionnaire survey was carried out to examine the attitude among final-year nursing students to three ethical areas, namely, duty of care, resource allocation, and collateral damage. ETHICAL CONSIDERATIONS: This study was carried out in accordance with the requirements and recommendations of the Central Research and Ethics Committee, School of Health Sciences at Caritas Institute of Higher Education. FINDINGS: Complete responses from 102 subjects were analyzed. The overwhelming majority (96.1%) did not agree to participate in the intubation of severe acute respiratory syndrome patients if protective measures, that is, N95 mask and gown, were not available. If there were insufficient N95 masks for all the medical, nursing, and allied health workers in the hospital (resource allocation), 37.3% felt that the distribution of N95 masks should be by casting lot, while the rest disagreed. When asked about collateral damage, more than three-quarters (77.5%) said that severe acute respiratory syndrome patients should be admitted to intensive care unit. There was sex difference in nursing students' attitude toward severe acute respiratory syndrome care during pregnancy and influence of age in understanding intensive care unit care for these patients. Interestingly, 94.1% felt that there should be a separate intensive care unit for severe acute respiratory syndrome patients. CONCLUSION: As infection control practice and isolation facilities improved over the years, relevant knowledge and nursing ethical issues related to infectious diseases should become part of nursing education and training programs, especially in preparation for outbreaks of infectious diseases or distress.

Evaluation of General and Tailor Made Force Fields via X-ray Thermal Diffuse Scattering Using Molecular Dynamics and Monte Carlo Simulations of Crystalline Aspirin.

We have performed a comparison of the experimental thermal diffuse scattering (TDS) from crystalline Aspirin (form I) to that calculated from molecular dynamics (MD) simulations based on a variety of general force fields and a tailor-made force field (TMFF). A comparison is also made with Monte Carlo (MC) simulations which use a "harmonic network" approach to describe the intermolecular interactions. These comparisons were based on the hypothesis that TDS could be a useful experimental data in validation of such simulation parameter sets, especially when calculations of dynamical properties (e.g., thermodynamic free energies) from molecular crystals are concerned. Currently such a validation of force field parameters against experimental data is often limited to calculation of specific physical properties, e.g., absolute lattice energies usually at 0 K or heat capacity measurements. TDS harvested from in-house or synchrotron experiments comprises highly detailed structural information representative of the dynamical motions of the crystal lattice. Thus, TDS is a well-suited experimental data-driven means of cross validating theoretical approaches targeted at understanding dynamical properties of crystals. We found from the results of our investigation that the TMFF and COMPASS (from the commercial software "Materials Studio") parameter sets gave the best agreement with experiment. From our homologous MC simulation analysis we are able to show that force constants associated with the molecular torsion angles are likely to be a strong contributing factor for the apparent reason why these aforementioned force fields performed better.

Universal Health Coverage through Community Nursing Services: China vs. Hong Kong.

OBJECTIVE:: this article looks at how the development of community nursing services in China and Hong Kong can enhance universal health coverage. METHODS:: literature and data review have been utilized in this study. RESULTS:: nursing services have evolved much since the beginning of the nursing profession. The development of community nursing services has expanded the scope of nursing services to those in need of, not just hospital-level nursing care, but more holistic care to improve health and quality of life. CONCLUSION:: despite the one-country-two-systems governance and the difference in population and geography, Hong Kong and China both face the aging population and its complications. Community nursing services help to pave the road to Universal Health Coverage. OBJETIVO:: este artigo analisa a forma como o desenvolvimento de serviços de enfermagem comunitários na China e Hong Kong pode melhorar a cobertura universal de saúde. MÉTODOS:: literatura e revisão de dados foram utilizados neste estudo. RESULTADOS:: serviços de enfermagem têm evoluído muito desde o início da profissão de enfermagem. O desenvolvimento dos serviços de enfermagem da comunidade ampliou o escopo dos serviços de enfermagem, para aqueles que precisam não apenas de cuidados de enfermagem de nível de hospital, mas cuidados mais holísticos para melhorar a saúde e qualidade de vida. CONCLUSÃO:: apesar de ser "um-país-dois-sistemas" de governo, e as diferenças de população e geografia, Hong Kong e China enfrentam o envelhecimento da população e suas complicações. Os serviços de enfermagem da comunidade ajudam a pavimentar o caminho para a cobertura de saúde universal. OBJETIVO:: este artículo analiza cómo el desarrollo de los servicios de enfermería comunitaria en China y Hong Kong pueden expandir la cobertura universal de salud. MÉTODOS:: revisión de datos y literatura han sido utilizados en este estudio. RESULTADOS:: los servicios de enfermería han evolucionado mucho desde el comienzo de la profesión. El desarrollo de los servicios de enfermería comunitaria han ampliado el alcance de los servicios de enfermería a las personas que necesitan, no sólo en cuidados de enfermería en el hospital, sino también en una atención más integral para mejorar la salud y calidad de vida. CONCLUSIÓN:: a pesar del tipo de gobierno "un país, dos sistemas" y las diferencias de población y geografía, Hong Kong y China se enfrentan al envejecimiento de la población y sus complicaciones. Los servicios de enfermería comunitaria ayudan a allanar el camino hacia la cobertura universal de salud.

Universal Health Coverage through Community Nursing Services: China vs. Hong Kong / Cobertura Universal de Saúde através dos serviços de enfermagem comunitários: China vs. Hong Kong / Cobertura Universal de Salud a través de Servicios Comunitarios de Enfermería: China versus Hong Kong

ABSTRACT Objective: this article looks at how the development of community nursing services in China and Hong Kong can enhance universal health coverage. Methods: literature and data review have been utilized in this study. Results: nursing services have evolved much since the beginning of the nursing profession. The development of community nursing services has expanded the scope of nursing services to those in need of, not just hospital-level nursing care, but more holistic care to improve health and quality of life. Conclusion: despite the one-country-two-systems governance and the difference in population and geography, Hong Kong and China both face the aging population and its complications. Community nursing services help to pave the road to Universal Health Coverage.

RESUMO Objetivo: este artigo analisa a forma como o desenvolvimento de serviços de enfermagem comunitários na China e Hong Kong pode melhorar a cobertura universal de saúde. Métodos: literatura e revisão de dados foram utilizados neste estudo. Resultados: serviços de enfermagem têm evoluído muito desde o início da profissão de enfermagem. O desenvolvimento dos serviços de enfermagem da comunidade ampliou o escopo dos serviços de enfermagem, para aqueles que precisam não apenas de cuidados de enfermagem de nível de hospital, mas cuidados mais holísticos para melhorar a saúde e qualidade de vida. Conclusão: apesar de ser “um-país-dois-sistemas” de governo, e as diferenças de população e geografia, Hong Kong e China enfrentam o envelhecimento da população e suas complicações. Os serviços de enfermagem da comunidade ajudam a pavimentar o caminho para a cobertura de saúde universal.

RESUMEN Objetivo: este artículo analiza cómo el desarrollo de los servicios de enfermería comunitaria en China y Hong Kong pueden expandir la cobertura universal de salud. Métodos: revisión de datos y literatura han sido utilizados en este estudio. Resultados: los servicios de enfermería han evolucionado mucho desde el comienzo de la profesión. El desarrollo de los servicios de enfermería comunitaria han ampliado el alcance de los servicios de enfermería a las personas que necesitan, no sólo en cuidados de enfermería en el hospital, sino también en una atención más integral para mejorar la salud y calidad de vida. Conclusión: a pesar del tipo de gobierno “un país, dos sistemas” y las diferencias de población y geografía, Hong Kong y China se enfrentan al envejecimiento de la población y sus complicaciones. Los servicios de enfermería comunitaria ayudan a allanar el camino hacia la cobertura universal de salud.

Isoprenyl caffeate, a major compound in manuka propolis, is a quorum-sensing inhibitor in Chromobacterium violaceum.

The emergence of antibiotic-resistant bacterial pathogens, especially Gram-negative bacteria, has driven investigations into suppressing bacterial virulence via quorum sensing (QS) inhibition strategies instead of bactericidal and bacteriostatic approaches. Here, we investigated several bee products for potential compound(s) that exhibit significant QS inhibitory (QSI) properties at the phenotypic and molecular levels in Chromobacterium violaceum ATCC 12472 as a model organism. Manuka propolis produced the strongest violacein inhibition on C. violaceum lawn agar, while bee pollen had no detectable QSI activity and honey had bactericidal activity. Fractionated manuka propolis (pooled fraction 5 or PF5) exhibited the largest violacein inhibition zone (24.5 ± 2.5 mm) at 1 mg dry weight per disc. In C. violaceum liquid cultures, at least 450 µg/ml of manuka propolis PF5 completely inhibited violacein production. Gene expression studies of the vioABCDE operon, involved in violacein biosynthesis, showed significant (≥two-fold) down-regulation of vioA, vioD and vioE in response to manuka propolis PF5. A potential QSI compound identified in manuka propolis PF5 is a hydroxycinnamic acid-derivative, isoprenyl caffeate, with a [M-H] of 247. Complete violacein inhibition in C. violaceum liquid cultures was achieved with at least 50 µg/ml of commercial isoprenyl caffeate. In silico docking experiments suggest that isoprenyl caffeate may act as an inhibitor of the violacein biosynthetic pathway by acting as a competitor for the FAD-binding pockets of VioD and VioA. Further studies on these compounds are warranted toward the development of anti-pathogenic drugs as adjuvants to conventional antibiotic treatments, especially in antibiotic-resistant bacterial infections.

Disease activity assessment in ankylosing spondylitis in a Chinese cohort: BASDAI or ASDAS?

Recently, the Ankylosing Spondylitis Disease Activity Score (ASDAS), a new index, has been shown to be validated and highly discriminatory in assessing ankylosing spondylitis (AS) disease activity. This study is to evaluate the performance of ASDAS in a local Chinese cohort of AS in a cross-sectional setting and to compare it with the existing instrument, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Consecutive patients with AS were recruited from a local rheumatology clinic. Data, including BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Visual Analogue Scale (VAS) for spinal pain, and patient and physician global assessments were gathered during clinic visit. Inflammatory markers, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and high-sensitivity (hs)-CRP were collected. ASDAS was calculated accordingly. The discriminatory capacity of BASDAI and ASDAS was compared by: (1) standardized mean difference statistics, (2) R (2) in linear regressions, and (3) area under receiver operating characteristic curve (AUC) in logistic regression models. Both ASDAS and BASDAI showed satisfactory predictive value on disease activity with reference to patient and physician global assessment. R (2) in linear regression models ranged from 0.6-0.7. Both indices also demonstrated good discriminatory capacity as evidenced by a relatively high AUC (> 0.8) under the logistic regression models using either patient or physician global assessment score ≥4 and <4 as cut off of high and low disease activity status, respectively. Although we could not demonstrate significant differences in the performance between them, subgroup analysis suggested better discriminatory ability of ASDAS in the high inflammatory marker subgroup. ASDAS and BASDAI showed similarly good performance in a cross-sectional setting in a local Chinese AS cohort. ASDAS performed better in subgroup with raised inflammatory markers.