Systemic inflammatory response syndrome triggered by blood-borne pathogens induces prolonged dendritic cell paralysis and immunosuppression.

Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3-4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor ß partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS.

Targeted Isolation of Antibiofilm Compounds from Halophytic Endophyte Bacillus velezensis 7NPB-3B Using LC-HR-MS-Based Metabolomics.

The discovery of new natural products has become more challenging because of the re-isolation of compounds and the lack of new sources. Microbes dwelling in extreme conditions of high salinity and temperature are huge prospects for interesting natural metabolites. In this study, the endophytic bacteria Bacillus velezensis 7NPB-3B isolated from the halophyte Salicornia brachiata was screened for its biofilm inhibition against methicillin-resistant Staphylococcus aureus (MRSA). The fractionation of the crude extract was guided by bioassay and LC-HRMS-based metabolomics using multivariate analysis. The 37 fractions obtained by high-throughput chromatography were dereplicated using an in-house MS-Excel macro coupled with the Dictionary of Natural Products database. Successive bioactivity-guided separation yielded one novel compound (1), a diketopiperazine (m/z 469.258 [M - H]-) with an attached saturated decanoic acid chain, and four known compounds (2-5). The compounds were identified based on 1D- and 2D-NMR and mass spectrometry. Compounds 1 and 5 exhibited excellent biofilm inhibition properties of >90% against the MRSA pathogen at minimum inhibition concentrations of 25 and 35 µg/mL, respectively. The investigation resulted in the isolation of a novel diketopiperazine from a bacterial endophyte of an untapped plant using an omics approach.

Australian dental school academics' perceptions of gerodontology education in the undergraduate curriculum.

INTRODUCTION: Australia's rapidly growing population of dentate, frail, care-dependent older people require graduates skilled in managing the health needs of this patient group. The perceptions of academics teaching gerodontology may inform future dental curricula recommendations. This study explored the perceptions of gerodontology education amongst Australian dental school academics. MATERIALS AND METHODS: All nine Australian dental schools providing entry-to-practice dentistry programs were invited to participate in semi-structured interviews. Academics from six dentistry programs took part, and the data were analysed using a thematic approach. RESULTS: The three main themes identified from interviews included 'clinical exposure', 'organisational levers', and 'sociological barriers'. The attitudes of students, as well as society and health professionals, were seen as strongly influential in preparing the workforce for managing the oral health of older people. The themes inter-linked with a knock-on effect where societal attitudes and organisational levers impact on the ability to successfully support students' preparation for gerodontology practice. Limited resources were barriers to achieving ideal learning and teaching and continued upon graduation as oral health care for older people was perceived as undervalued and under-resourced. CONCLUSION: There has been a continued cycle of failure in healthcare schemes and advocacy for the improvement of oral health for older people which has contributed to the inadequate preparation of dental graduates for managing frail and care-dependent older people. Organisational, societal, and political change is needed to support the education of dental students in this area to ensure graduate dentists are competent to manage the oral care needs of this growing population.

Using a novel ambulatory monitoring system to support patient safety on an acute infectious disease ward during an unfolding pandemic.

AIM: To gain staff feedback on the implementation and impact of a novel ambulatory monitoring system to support coronavirus patient management on an isolation ward. DESIGN: Qualitative service evaluation. METHODS: Semi-structured interviews were conducted with 15 multidisciplinary isolation ward staff in the United Kingdom between July 2020 and May 2021. Interviews were audio-recorded, transcribed and analysed using thematic analysis. FINDINGS: Adopting Innovation to Assist Patient Safety was identified as the overriding theme. Three interlinked sub-themes represent facets of how the system supported patient safety. Patient Selection was developed throughout the pandemic, as clinical staff became more confident in choosing which patients would benefit most. Trust In the System described how nurses coped with discrepancies between the ambulatory system and ward observation machines. Finally, Resource Management examined how, once trust was built, staff perceived the ambulatory system assisted with caseload management. This supported efficient personal protective equipment resource use by reducing the number of isolation room entries. Despite these reported benefits, face-to-face contact was still highly valued, despite the risk of coronavirus exposure. CONCLUSION: Hospital wards should consider using ambulatory monitoring systems to support caseload management and patient safety. Patients in isolation rooms or at high risk of deterioration may particularly benefit from this additional monitoring. However, these systems should be seen as an adjunct to nursing care, not a replacement. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses valued ambulatory monitoring as a means of ensuring the safety of patients at risk of deterioration and prioritizing their workload. IMPACT: The findings of this research will be useful to all those developing or considering implementation of ambulatory monitoring systems in hospital wards. REPORTING METHOD: This manuscript follows the Consolidated criteria for Reporting Qualitative Research (COREQ) guidelines with inclusion of relevant SQUIRE guidelines for reporting quality improvement. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Use of Multivariate Analysis to Unravel the Differences between Two Chamomile Varieties and Their Anticancer and Antioxidant Activities.

BACKGROUND: Plants from the Asteraceae family were commonly used to treat various diseases. The metabolomic profile of this family consisted of bioactive flavonoids and other phenolics. Chamomile is a member of the Asteraceae family. Jordanian and European chamomile are two varieties of Matricaria chamomilla (German chamomile), which were grown under different environmental conditions, were studied. Many examples of plant varieties with significant distinction in the secondary metabolite they afford have been described in the literature. Multivariate statistical analysis was employed to measure the depth of this variation in two chamomile varieties. METHODS: From both types, crude extracts were prepared using solvents of different polarities and tested for their biological activity. The semipolar fraction of the European variety showed anticancer and antioxidant activity. Meanwhile, the semipolar fraction of the Jordanian type exhibited only antioxidant activity. Both extracts were fractionated, and then the biological activity was again assayed. RESULTS: European and Jordanian chamomile fractions produced dicaffeoylquinic acid isomers exhibiting antioxidant capability. Additionally, Z-glucoferulic acid was produced from the European chamomile, demonstrating antioxidant activity. The European samples afforded two major compounds, chrysosplenetin and apigenin, that displayed anticancer activity. CONCLUSIONS: Different environmental conditions between Jordanian and European chamomile affected the type of isolated compounds. Structure elucidation was performed with HPLC-MS coupled with dereplication techniques and 2D NMR experiments.

A systems approach to the perceptions of the integration of public health into pharmacy practice: A qualitative study.

Background: Pharmacists, as health professionals, are ideally positioned to support the health and wellbeing of populations, in addition to their role of providing individualised health care. Objective: The aim of this study was to explore current opinion on the contribution of pharmacists to public health and how this may be enhanced to positively impact public health indicators. Methods: A total of 24 pharmacists from Australia, United Kingdom, Canada and the United States of America, and Australian public health professionals and consumers participated in semi-structured interviews between January and October 2021. Interpretive thematic analysis was applied with coding of transcripts using the constant comparison method. Themes were developed and named in accordance with Bronfenbrenner's ecological theory of development. Results: Pharmacists contribute to public health and have important roles in health education and illness prevention services. Strong enablers in community pharmacy include trust by consumers and ease of accessibility to pharmacists. Pharmacists are viewed as leaders in communities and contribute to the health system broadly in areas such as medication policy and public health organisations.Participants suggested that pharmacist contributions to public health are often unrecognized by the pharmacy profession, health professionals and consumers, and could be developed to allow effective contributions. Strategies to improve pharmacist contributions included clarifying public health-related terminology, increased development of pharmacy roles and reform for community pharmacies to participate in health prevention and promotion services. Integration of public health in pharmacy education, professional development, and recognition of pharmacy roles across all system levels were also identified as important. Conclusions: The study indicated that pharmacists currently contribute to the improvement of public health. However, development strategies are required for this to be more effective in integrating public health approaches into their professional practice to be recognized for their public health-related roles.

A comparative evaluation of quality and depth of learning by trainee doctors in regional, rural, and remote locations.

BACKGROUND: An equitable supply and distribution of medical practitioners for all the population is an important issue, especially in Australia where 28% of the population live in rural and remote areas. Research identified that training in rural/remote locations is a predictor for the uptake of rural practice, but training must provide comparable learning and clinical experiences, irrespective of location. Evidence shows GPs in rural and remote areas are more likely to be engaged in complex care. However, the quality of GP registrar education has not been systematically evaluated. This timely study evaluates GP registrar learning and clinical training experiences in regional, rural, and remote locations in Australia using assessment items and independent evaluation. METHODS: The research team retrospectively analysed GP trainee formative clinical assessment reports compiled by experienced medical educators during real-time patient consultations. Written reports were assessed using Bloom's taxonomy classified into low and high cognitive level thinking. Regional, rural, and remotely located trainees were compared using Pearson chi-squared test and Fisher's exact test (for 2 × 2 comparisons) to calculate associations between categorical proportions of learning setting and 'complexity'. RESULTS: 1650 reports (57% regional, 15% rural and 29% remote) were analysed, revealing a statistically significant association between learner setting and complexity of clinical reasoning. Remote trainees were required to use a high level of clinical reasoning in managing a higher proportion of their patient visits. Remotely trained GPs managed significantly more cases with high clinical complexity and saw a higher proportion of chronic and complex cases and fewer simple cases. CONCLUSIONS: This retrospective study showed GP trainees in all locations experienced comparable learning experiences and depth of training. However, learning in rural and remote locations had equal or more opportunities for seeing higher complexity patients and the necessity to apply greater levels of clinical reasoning to manage each case. This evidence supports learning in rural and remote locations is of a similar standard of learning as for regional trainees and in several areas required a superior level of thinking. Training needs to seriously consider utilising rural and remote clinical placements as exceptional locations for developing and honing medical expertise.

Effects of candidates' demographics and evaluation of the virtual Multiple Mini Interview (vMMI) as a tool for selection into paediatric training in Queensland.

INTRODUCTION: The Queensland Basic Paediatric Training Network (QBPTN) is responsible for the selection of candidates into paediatric training in Queensland. The COVID-19 pandemic necessitated interviews to be conducted 'virtually' as virtual Multiple-Mini-Interviews (vMMI). The study aimed to describe the demographic characteristics of candidates applying for selection into paediatric training in Queensland, and to explore their perspectives and experiences with the vMMI selection tool. METHODOLOGY: The demographic characteristics of candidates and their vMMI outcomes were collected and analysed with a mixed methods approach. The qualitative component was comprised of seven semi-structured interviews with consenting candidates. RESULTS: Seventy-one shortlisted candidates took part in vMMI and 41 were offered training positions. The demographic characteristics of candidates at various stages of selection were similar. The mean vMMI scores were not statistically different between candidates from the Modified Monash Model 1 (MMM1) location and others [mean (SD): 43.5 (5.1) versus 41.7 (6.7), respectively, p = 0.26]. However, there was a statistically significant difference (p value 0.03) between being offered and not offered a training position for candidates from MMM2 and above. The analysis of the semi-structured interviews suggested that candidate experiences of the vMMI were influenced by the quality of the management of the technology used. Flexibility, convenience, and reduced stress were the main factors that influenced candidates' acceptance of vMMI. Perceptions of the vMMI process focused on the need to build rapport and facilitate communication with the interviewers. DISCUSSION: vMMI is a viable alternative to face-to-face (FTF) MMI. The vMMI experience can be improved by facilitating enhanced interviewer training, by making provision for adequate candidate preparation and by having contingency plans in place for unexpected technical challenges. Given government priorities in Australia, the impact of candidates' geographical location on the vMMI outcome for candidates from MMM >1 location needs to be further explored.

Readiness to enter the workforce: perceptions of health professions students at a regional Australian university.

BACKGROUND: Perceived readiness for practice can help mitigate the stress and uncertainty associated with transitioning from university into the workforce. This study aimed to identify factors influencing the readiness for clinical practice among final-year medical, dental, and pharmacy students at an Australian regional university. METHODS: The study utilised a sequential explanatory mixed-methods approach with surveys administered for the quantitative phase and interviews/focus groups for the qualitative phase. Descriptive statistics and inductive thematic analysis were utilised for the quantitative and qualitative data, respectively. Triangulation of findings from both phases facilitated in-depth understanding of the factors that influenced participants' self-perceived readiness for clinical practice. RESULTS: From the three disciplines, 132 students completed the survey and 14 participated in the focus groups and interviews. Students felt most prepared in their patient-centred capabilities, core skills, and advanced consultation skills, and least prepared in their system-related capabilities and clinical care skills. Themes identified as essential enablers and confidence builders in relation to workforce readiness in all three disciplines were: gained knowledge and skills, value of clinical placement experiences, support from peers, family and staff. However, students felt their work-readiness was impaired by heavy academic workloads and poor knowledge of health care systems, which affected skills development. Participants suggested additional support in health care system and clinical governance, mental healthcare, and induction to placement sites to further improve their work readiness. CONCLUSIONS: The findings of this study suggest that improving work-readiness of healthcare students requires alignment of learning needs to real-world practice opportunities, ensuring support systems are appropriate, and early familiarisation with the healthcare system.

The Use of Wearable Pulse Oximeters in the Prompt Detection of Hypoxemia and During Movement: Diagnostic Accuracy Study.

BACKGROUND: Commercially available wearable (ambulatory) pulse oximeters have been recommended as a method for managing patients at risk of physiological deterioration, such as active patients with COVID-19 disease receiving care in hospital isolation rooms; however, their reliability in usual hospital settings is not known. OBJECTIVE: We report the performance of wearable pulse oximeters in a simulated clinical setting when challenged by motion and low levels of arterial blood oxygen saturation (SaO2). METHODS: The performance of 1 wrist-worn (Wavelet) and 3 finger-worn (CheckMe O2+, AP-20, and WristOx2 3150) wearable, wireless transmission-mode pulse oximeters was evaluated. For this, 7 motion tasks were performed: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia exposure followed, in which inspired gases were adjusted to achieve decreasing SaO2 levels at 100%, 95%, 90%, 87%, 85%, 83%, and 80%. Peripheral oxygen saturation (SpO2) estimates were compared with simultaneous SaO2 samples to calculate the root-mean-square error (RMSE). The area under the receiver operating characteristic curve was used to analyze the detection of hypoxemia (ie, SaO2<90%). RESULTS: SpO2 estimates matching 215 SaO2 samples in both study phases, from 33 participants, were analyzed. Tapping, rubbing, turning pages, and using a tablet degraded SpO2 estimation (RMSE>4% for at least 1 device). All finger-worn pulse oximeters detected hypoxemia, with an overall sensitivity of ≥0.87 and specificity of ≥0.80, comparable to that of the Philips MX450 pulse oximeter. CONCLUSIONS: The SpO2 accuracy of wearable finger-worn pulse oximeters was within that required by the International Organization for Standardization guidelines. Performance was degraded by motion, but all pulse oximeters could detect hypoxemia. Our findings support the use of wearable, wireless transmission-mode pulse oximeters to detect the onset of clinical deterioration in hospital settings. TRIAL REGISTRATION: ISRCTN Registry 61535692; http://www.isrctn.com/ISRCTN61535692. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2019-034404.

Metabolomic Profiling of Malaysian and New Zealand Honey Using Concatenated NMR and HRMS Datasets.

This study aims to compare the metabolomic profiles of Malaysian and New Zealand honey while determining their anti-oncogenic activity for potential prophylactic functions. Metabolomics tools including multivariate analysis were applied on concatenated LC-HRMS and NMR datasets to afford an intensive chemical profile of honey samples and have a snapshot of the bioactive metabolites in the respective collections. Malaysian samples were found to have higher sugar and polyphenolic content, while New Zealand samples afforded higher concentration of low molecular weight (MW) lipids. However, New Zealand honey collected from the northern islands had higher concentration of acetylated saccharides, while those from the southern islands yielded higher low MW phenolic metabolites that were comparable to Malaysian honey. Mild anti-oncogenic compounds against breast cancer cell line ZR75 were putatively identified in Malaysian honey that included earlier described antioxidants such as gingerdiol, 2-hexylphenol-O-ß-D-xylopyranoside, plastoquinone, tropine isovalerate, plumerinine, and 3,5-(12-phenyl-8-dodecenyl)resorcinol, along with several phenolic esters and lignans.

Experiences of current vital signs monitoring practices and views of wearable monitoring: A qualitative study in patients and nurses.

AIMS: To understand current experiences of vital signs monitoring of patients and clinical staff on a surgical ward, and views on the introduction of wearable ambulatory monitoring into the general ward environment. DESIGN: Qualitative study. METHODS: Semi-structured interviews using topic guides were conducted with 15 patients and 15 nurses on a surgical ward between July 2018 and August 2019. The concept of ambulatory wearable devices for clinical monitoring was introduced at the end of the interview. RESULTS: Three interconnected themes were identified. Vital sign data as evidence for escalation, examined nurses' use of data to support escalation of care and the implications for patients perceived to be deteriorating who have not reached the threshold for escalation. The second theme, Trustworthiness of vital sign data, described nurses' practice of using manual measurements to recheck or confirm automated vital signs readings when concerned. The final theme, finding a balance between continuous and intermittent monitoring, both patients and nurses agreed that although continuous monitoring may improve safety and reassurance, these needed to be balanced with multiple limitations. Factors to be considered included noise pollution, comfort, and impact on patient mobility and independence. Introduction of the concept of ambulatory wearable devices was viewed positively by both groups as offering solutions to some of the issues identified with traditional monitoring. However, most agreed that this would not be suitable for all patients and should not replace direct nurse/patient contact. CONCLUSION: Both patients and staff identified the benefits of continuous monitoring to improve patient safety but, due to limitations, use should be carefully considered and patient-centred. IMPACT: Feedback from nurses and patients suggests there is scope for ambulatory monitoring systems to be integrated into the hospital environment; however, both groups emphasized these should not add more noise to the ward nor replace direct nursing contact.

A Real-Time Wearable System for Monitoring Vital Signs of COVID-19 Patients in a Hospital Setting.

The challenges presented by the Coronavirus disease 2019 (COVID-19) pandemic to the National Health Service (NHS) in the United Kingdom (UK) led to a rapid adaptation of infection disease protocols in-hospital. In this paper we report on the optimisation of our wearable ambulatory monitoring system (AMS) to monitor COVID-19 patients on isolation wards. A wearable chest patch (VitalPatch®, VitalConnect, United States of America, USA) and finger-worn pulse oximeter (WristOx2® 3150, Nonin, USA) were used to estimate and transmit continuous Heart Rate (HR), Respiratory Rate (RR), and peripheral blood Oxygen Saturation (SpO2) data from ambulatory patients on these isolation wards to nurse bays remote from these patients, with a view to minimising the risk of infection for nursing staff. Our virtual High-Dependency Unit (vHDU) system used a secure web-based architecture and protocols (HTTPS and encrypted WebSockets) to transmit the vital-sign data in real time from wireless Android tablet devices, operating as patient data collection devices by the bedside in the isolation rooms, into the clinician dashboard interface available remotely via any modern web-browser. Fault-tolerant software strategies were used to reconnect the wearables automatically, avoiding the need for nurses to enter the isolation ward to re-set the patient monitoring equipment. The remote dashboard also displayed the vital-sign observations recorded by the nurses, using a separate electronic observation system, allowing them to review both sources of vital-sign data in one integrated chart. System usage was found to follow the trend of the number of local COVID-19 infections during the first wave of the pandemic in the UK (March to June 2020), with almost half of the patients on the isolation ward monitored with wearables during the peak of hospital admissions in the local area. Patients were monitored for a median of 31.5 [8.8, 75.4] hours, representing 88.1 [62.5, 94.5]% of the median time they were registered in the system. This indicates the system was being used in the isolation ward during this period. An updated version of the system has now also been used throughout the second and third waves of the pandemic in the UK.

A Chest Patch for Continuous Vital Sign Monitoring: Clinical Validation Study During Movement and Controlled Hypoxia.

BACKGROUND: The standard of care in general wards includes periodic manual measurements, with the data entered into track-and-trigger charts, either on paper or electronically. Wearable devices may support health care staff, improve patient safety, and promote early deterioration detection in the interval between periodic measurements. However, regulatory standards for ambulatory cardiac monitors estimating heart rate (HR) and respiratory rate (RR) do not specify performance criteria during patient movement or clinical conditions in which the patient's oxygen saturation varies. Therefore, further validation is required before clinical implementation and deployment of any wearable system that provides continuous vital sign measurements. OBJECTIVE: The objective of this study is to determine the agreement between a chest-worn patch (VitalPatch) and a gold standard reference device for HR and RR measurements during movement and gradual desaturation (modeling a hypoxic episode) in a controlled environment. METHODS: After the VitalPatch and gold standard devices (Philips MX450) were applied, participants performed different movements in seven consecutive stages: at rest, sit-to-stand, tapping, rubbing, drinking, turning pages, and using a tablet. Hypoxia was then induced, and the participants' oxygen saturation gradually reduced to 80% in a controlled environment. The primary outcome measure was accuracy, defined as the mean absolute error (MAE) of the VitalPatch estimates when compared with HR and RR gold standards (3-lead electrocardiography and capnography, respectively). We defined these as clinically acceptable if the rates were within 5 beats per minute for HR and 3 respirations per minute (rpm) for RR. RESULTS: Complete data sets were acquired for 29 participants. In the movement phase, the HR estimates were within prespecified limits for all movements. For RR, estimates were also within the acceptable range, with the exception of the sit-to-stand and turning page movements, showing an MAE of 3.05 (95% CI 2.48-3.58) rpm and 3.45 (95% CI 2.71-4.11) rpm, respectively. For the hypoxia phase, both HR and RR estimates were within limits, with an overall MAE of 0.72 (95% CI 0.66-0.78) beats per minute and 1.89 (95% CI 1.75-2.03) rpm, respectively. There were no significant differences in the accuracy of HR and RR estimations between normoxia (≥90%), mild (89.9%-85%), and severe hypoxia (<85%). CONCLUSIONS: The VitalPatch was highly accurate throughout both the movement and hypoxia phases of the study, except for RR estimation during the two types of movements. This study demonstrated that VitalPatch can be safely tested in clinical environments to support earlier detection of cardiorespiratory deterioration. TRIAL REGISTRATION: ISRCTN Registry ISRCTN61535692; https://www.isrctn.com/ISRCTN61535692.

Prospective observational study to examine health-related quality of life and develop models to predict long-term patient-reported outcomes 6 months after hospital discharge with blunt thoracic injuries.

OBJECTIVE: This study aimed to examine the long-term outcomes and health-related quality of life in patients with blunt thoracic injuries over 6 months from hospital discharge and develop models to predict long-term patient-reported outcomes. DESIGN: A prospective observational study using longitudinal survey design. SETTING: The study recruitment was undertaken at 12 UK hospitals which represented diverse geographical locations and covered urban, suburban and rural areas across England and Wales. PARTICIPANTS: 337 patients admitted to hospital with blunt thoracic injuries were recruited between June 2018-October 2020. METHODS: Participants completed a bank of two quality of life surveys (Short Form-12 (SF-12) and EuroQol 5-Dimensions 5-Levels) and two pain questionnaires (Brief Pain Inventory and painDETECT Questionnaire) at four time points over the first 6 months after discharge from hospital. A total of 211 (63%) participants completed the outcomes data at 6 months after hospital discharge. OUTCOMES MEASURES: Three outcomes were measured using pre-existing and validated patient-reported outcome measures. Outcomes included: Poor physical function (SF-12 Physical Component Score); chronic pain (Brief Pain Inventory Pain Severity Score); and neuropathic pain (painDETECT Questionnaire). RESULTS: Despite a trend towards improving physical functional and pain at 6 months, outcomes did not return to participants perceived baseline level of function. At 6 months after hospital discharge, 37% (n=77) of participants reported poor physical function; 36.5% (n=77) reported a chronic pain state; and 22% (n=47) reported pain with a neuropathic component. Predictive models were developed for each outcome highlighting important data collection requirements for predicting long-term outcomes in this population. Model diagnostics including calibration and discrimination statistics suggested good model fit in this development cohort. CONCLUSIONS: This study identified the recovery trajectories for patients with blunt thoracic injuries over the first 6 months after hospital discharge and present prognostic models for three important outcomes which after external validation could be used as clinical risk stratification scores.

Protocol for a systematic review assessing ambulatory vital sign monitoring impact on deterioration detection and related clinical outcomes in hospitalised patients.

INTRODUCTION: Ambulatory monitoring systems (AMS) can facilitate early detection of clinical deterioration, and have the potential to improve hospitalised patient outcomes. The objective of this systematic review is to assess the impact of vital signs monitoring on detection of deterioration and related outcomes in hospitalised patients using AMS, in comparison with standard care. METHODS AND ANALYSIS: A systematic search was conducted on 27 August 2020 in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, CENTRAL and Health Technology Assessment databases, as well as grey literature. Search results will be reviewed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis checklist for systematic reviews. Studies comparing the use of ambulatory monitoring devices against standard care for deterioration detection and related clinical outcomes in hospitalised patients will be included and further clinical and other outcomes will also be explored. Deterioration-related outcomes may include (but not limited to) unplanned intensive care admissions, rapid response team activation and unscheduled emergency interventions, as defined by the included studies. Two reviewers will independently extract study data and assess the quality and risk of bias of included studies. Where possible, a meta-analysis will be conducted and quantitative results presented. Alternatively, a narrative synthesis will be reported. ETHICS AND DISSEMINATION: Ethical approval is not required for this study as no primary data will be collected. This study is part of our virtual High Dependency Unit project and will be disseminated through peer-reviewed publications, public and scientific conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020188633.

Gerodontology in the dental school curriculum: A scoping review.

OBJECTIVE: To explore the current status of gerodontology in the undergraduate dental curriculum. BACKGROUND: Internationally, there is recognition for the need to include gerodontology in dental education due to accelerating numbers of older dentate people. There is wide variation in the content and method of delivery of gerodontology in undergraduate curricula of dental schools. METHODS: A scoping review framework was chosen to identify existing gaps and key concepts in the research on current undergraduate gerodontology education. Arksey and O'Malley's framework was used with the qualitative data analysis software NVivo to identify comparable information on geriatric dental education. RESULTS: Five themes were highlighted in the studies including (1) gerodontology curriculum content, (2) attitudes, skills and knowledge of undergraduate dental students, (3) didactic teaching, (4) elective and compulsory teaching, and (5) extra-mural learning. The review found large variations in methodologies, presentation of data and findings. All studies emphasised a need for greater inclusion of gerodontology content in the undergraduate dental curriculum. CONCLUSION: The review found limited research reporting on the educational outcomes of gerodontology in dental curricula with a lack of comprehensive information to inform gerodontology content in dental schools. This review has highlighted the need for national and international guidelines to ensure mandatory inclusion of sufficient and specific gerodontology training to prepare graduates for a growing dentate frail and care-dependent population.

Exploring the Chemical Space of Macro- and Micro-Algae Using Comparative Metabolomics.

With more than 156,000 described species, eukaryotic algae (both macro- and micro-algae) are a rich source of biological diversity, however their chemical diversity remains largely unexplored. Specialised metabolites with promising biological activities have been widely reported for seaweeds, and more recently extracts from microalgae have exhibited activity in anticancer, antimicrobial, and antioxidant screens. However, we are still missing critical information on the distinction of chemical profiles between macro- and microalgae, as well as the chemical space these metabolites cover. This study has used an untargeted comparative metabolomics approach to explore the chemical diversity of seven seaweeds and 36 microalgal strains. A total of 1390 liquid chromatography-mass spectrometry (LC-MS) features were detected, representing small organic algal metabolites, with no overlap between the seaweeds and microalgae. An in-depth analysis of four Dunaliella tertiolecta strains shows that environmental factors may play a larger role than phylogeny when classifying their metabolomic profiles.

Regulation of Bcl-XL by non-canonical NF-κB in the context of CD40-induced drug resistance in CLL.

In chronic lymphocytic leukemia (CLL), the lymph node (LN) microenvironment delivers critical survival signals by inducing the expression of anti-apoptotic Bcl-2 members Bcl-XL, Bfl-1, and Mcl-1, resulting in apoptosis blockade. We determined previously that resistance against various drugs, among which is the clinically applied BH3 mimetic venetoclax, is dominated by upregulation of the anti-apoptotic regulator Bcl-XL. Direct clinical targeting of Bcl-XL by, e.g., Navitoclax is however not desirable due to induction of thrombocytopenia. Since the actual regulation of Bcl-XL in CLL in the context of the LN microenvironment is not well elucidated, we investigated various candidate LN signals to drive Bcl-XL expression. We found a dominance for NF-κB signaling upon CD40 stimulation, which results in activation of both the canonical and non-canonical NF-κB signaling pathways. We demonstrate that expression of Bcl-XL is first induced by the canonical NF-κB pathway, and subsequently boosted and continued via non-canonical NF-κB signaling through stabilization of NIK. NF-κB subunits p65 and p52 can both bind to the Bcl-XL promoter and activate transcription upon CD40 stimulation. Moreover, canonical NF-κB signaling was correlated with Bfl-1 expression, whereas Mcl-1 in contrast, was not transcriptionally regulated by NF-κB. Finally, we applied a novel compound targeting NIK to selectively inhibit the non-canonical NF-κB pathway and showed that venetoclax-resistant CLL cells were sensitized to venetoclax. In conclusion, protective signals from the CLL microenvironment can be tipped towards apoptosis sensitivity by interfering with non-canonical NF-κB signaling.