Metaproteomic Analysis of an Oral Squamous Cell Carcinoma Dataset Suggests Diagnostic Potential of the Mycobiome.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, with an estimated 5-year survival rate of only 40-50%, largely due to late detection and diagnosis. Emerging evidence suggests that the human microbiome may be implicated in OSCC, with oral microbiome studies putatively identifying relevant bacterial species. As the impact of other microbial organisms, such as fungi and viruses, has largely been neglected, a bioinformatic approach utilizing the Trans-Proteomic Pipeline (TPP) and the R statistical programming language was implemented here to investigate not only bacteria, but also viruses and fungi in the context of a publicly available, OSCC, mass spectrometry (MS) dataset. Overall viral, bacterial, and fungal composition was inferred in control and OSCC patient tissue from protein data, with a range of proteins observed to be differentially enriched between healthy and OSCC conditions, of which the fungal protein profile presented as the best potential discriminator of OSCC within the analysed dataset. While the current project sheds new light on the fungal and viral spheres of the oral microbiome in cancer in silico, further research will be required to validate these findings in an experimental setting.

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.

Bioinformatic Analysis to Investigate Metaproteome Composition Using Trans-Proteomic Pipeline.

With evidence emerging that the microbiome has a role in the onset of many human diseases, including cancer, analyzing these microbial communities and their proteins (i.e., the metaproteome) has become a powerful research tool. The Trans-Proteomic Pipeline (TPP) is a free, comprehensive software suite that facilitates the analysis of mass spectrometry (MS) data. By utilizing available microbial proteomes, TPP can identify microbial proteins and species, with an acceptable peptide false-discovery rate (FDR). An application to a publicly available oral cancer dataset is presented as an example to identify the viral metaproteome on the oral cancer invasive tumor front. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Collection of data and resources Basic Protocol 2: Analysis of MS data using TPP Basic Protocol 3: Analysis of TPP output using R in RStudio.

The Prevent Alcohol and Risk-Related Trauma in Youth (P.A.R.T.Y) program: An interactive injury prevention initiative in South-Western Sydney.

BACKGROUND: The Prevent Alcohol and Risk Related Trauma in Youth (P.A.R.T.Y) program is an interactive injury prevention intervention, specifically designed for "at risk" youths aged 15 to 19 years. Emerging evidence has highlighted its positive impact on altering student attitudes towards risk-taking behaviour across several Australian and international settings. This study aims to describe the risk-taking behaviours of youths in South-Western and Greater Western Sydney, and assess the effectiveness of the Liverpool P.A.R.T.Y program to alter attitudes towards risk-taking. METHODS: From 2015 to 2020, schools and youth organisations across South-Western and Greater Western Sydney were invited to participate in the Liverpool Hospital P.A.R.T.Y program. Youths aged 15 to 19 years were selected to attend by their respective teachers based on eligibility criteria. Knowledge and attitudes towards risk-taking behaviours were measured using surveys across three time points (pre-program, immediately post-program, 3-to-6 months post-program). RESULTS: A total of 2544 participants from 50 schools and youth organisations attended the Liverpool Hospital P.A.R.T.Y program. There were 130 participants who did not record a response to a single question across all three time points and were omitted from analysis. Of the remaining 2414 participants, 49% were male, and 41% had access to a provisional driver's license or learner's permit. There were significant changes in knowledge and attitudes to risk-taking behaviours from pre-to immediately-post-program. A separate analysis across all three time points was conducted in response to a poor 3-to-6-month follow-up rate (25%). There was decay in improvements across all six questions, with the largest change seen in perceived likelihood of injury when engaging in physically risk-taking activities (52.2% to 36.9%, OR 0.44, 95% CI 0.33 - 0.60, p < 0.001). CONCLUSION: This study demonstrated significant changes in participant attitudes towards risk-taking behaviours and their consequences, immediately after participating in the Liverpool Hospital P.A.R.T.Y program. However, the poor response rates at later follow-up highlight the need for ongoing engagement of the South-Western and Greater Western Sydney youths, to ensure these improvements are sustained.

Does delirium prevention reduce risk of in-patient falls among older adults? A systematic review and trial sequential meta-analysis.

OBJECTIVES: To determine whether delirium prevention interventions reduce the risk of falls among older hospitalised patients. METHODS: A systematic search of health-care databases was undertaken. Given the frequency of small sample sized trials, a trial sequential meta-analysis was conducted to present estimate summary effects to date. A Bayesian approach was used to estimate the posterior probability of the delirium prevention interventions reducing falls risk by various clinically relevant levels. RESULTS: Five randomised controlled trials were included in our final meta-analysis. There was a 43% reduction in the risk of falls among participants in the delirium prevention intervention arm, compared to the control; however, confidence intervals were wide (RE RR = 0.57, 95% CI 0.32; 1.00, p = 0.05). This result was found to be statistically significant, according to traditional significance levels (z > 1.96) and the more conservative trial sequential analysis monitoring boundaries. The posterior probabilities of the delirium prevention intervention reducing the risk of falls by 10%, 20% and 30% were 0.86, 0.63 and 0.29 respectively. CONCLUSIONS: The results of this systematic review and trial sequential meta-analysis suggest that delirium prevention trials may reduce the risk of in-hospital falls among older patients by 43%. However, despite significant risk reduction found upon meta-analysis, the variation among study populations and intervention components raised questions around its application in clinical practice. Further research is required to investigate what the necessary components of a multifactorial intervention are to reduce both delirium and fall incidence among older adult in-patients.

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.

Proliferation and Apoptosis Pathways and Factors in Oral Squamous Cell Carcinoma.

Oral cancer is the most common form of head and neck squamous cell carcinoma (HNSCC) and most frequently presents as oral squamous cell carcinoma (OSCC), which is associated with an alarmingly high mortality rate. Internationally, a plethora of research to further our understanding of the molecular pathways related to oral cancer is performed. This research is of value for early diagnosis, prognosis, and the investigation of new drugs that can ameliorate the harmful effects of oral cancer and provide optimal patient outcomes with minimal long-term complications. Two pathways on which the progression of OSCC depends on are those of proliferation and apoptosis, which overlap at many junctions. Herein, we aim to review these pathways and factors related to OSCC progression. Publicly available search engines, PubMed and Google Scholar, were used with the following keywords to identify relevant literature: oral cancer, proliferation, proliferation factors, genes, mutations, and tumor suppressor. We anticipate that the use of information provided through this review will further progress translational cancer research work in the field of oral cancer.

Feasibility, Acceptability, and Psychosocial Outcomes of a Mindfulness-Based Interactive e-Book for Young People with Cancer.

Purpose: Receiving a cancer diagnosis for young people is likely to adversely impact the individual's quality of life. Mindfulness-based interventions (MBIs) are an emerging strategy used to improve psychosocial well-being. However, challenges have been reported in relation to adherence and accessibility of face-to-face mindfulness programs among young people. This study examined the feasibility and acceptability of a mindfulness-based interactive e-Book to improve psychosocial well-being of young people with cancer. Methods: Concurrent mixed methods approach with a pre-intervention-post-intervention survey and semistructured interviews evaluated the feasibility and acceptability of a MBI delivered over a 6-week period, and its effect on psychosocial well-being of young people with cancer 15 to 24 years of age. Results: Of the 31 young people, both survivors and on active treatment, enrolled in the study, 20 (64.5%) completed the post-intervention survey. Textual data and interviews (n = 3) revealed that young people enjoyed the intervention and found it useful and easy to navigate, but wanted more attention paid to cancer-specific stressors, as well as opportunities for face-to-face or online interactions. Psychosocial well-being measures demonstrated a statistically significant decrease in depressive symptoms (2.35 to 1.25, p = 0.03) and psychological distress (23.63 to 19.79, p = 0.03), along with nonsignificant increases in mindfulness (20.05 to 22.9, p = 0.08) and quality of life (62.0 to 69.1, p = 0.13). Conclusion: Young people found the self-help MBI, delivered in an interactive e-Book platform, useful and acceptable. There were psychosocial benefits, although recruitment and retention were study challenges and can be improved in future research.

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.

Silk fibroin photo-lyogels containing microchannels as a biomaterial platform for in situ tissue engineering.

The biophysical properties of biomaterials are key to directing the biological responses and biomaterial integration and function in in situ tissue engineering approaches. We present silk photo-lyogels, a biomaterial format fabricated using a new combinatorial approach involving photo-initiated crosslinking of silk fibroin via di-tyrosine bonds followed by lyophilization to generate 3D, porous lyogels showing physical properties distinct to those of lyophilized silk sponges or silk hydrogels. This fabrication approach allowed introduction of microchannels into 3D constructs via biofabrication approaches involving silk crosslinking around an array of 3D printed photocurable resin pillars to generate parallel channels or around a 3D printed sacrificial thermosensitive gel to generate interconnected channels in a rapid manner and without the need for chemical modification of silk fibroin. The presence of interconnected microchannels significantly improved migration of endothelial cells into 3D photo-lyogels in vitro, and tissue infiltration, photo-lyogel integration, and vascularization when implanted in vivo in a mouse subcutaneous model. Taken together, these findings demonstrate the feasibility and utility of a new combinatorial fabrication approach for generation of silk biomaterials that support cell interactions and implant integration for in situ tissue engineering approaches.

Trends of skin cancer mortality after transplantation in the United States: 1987 to 2013.

BACKGROUND: Solid organ transplant recipients are at increased risk of skin cancer, but population-based mortality data are limited. OBJECTIVE: Mortality and predictors of skin cancer death posttransplantation were investigated. METHODS: All US organ transplant recipients between 1987 and 2013, identified through the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, were included. Mortality and hazard ratios (HR) were calculated for the overall population and patient subgroups. RESULTS: The overall mortality was 5308 per 100,000 person-years and the skin cancer-specific mortality was 35.27 per 100,000 person-years. Risk factors associated with skin cancer death included thoracic versus abdominal transplantation (HR 2.90, 95% confidence interval [CI] 2.52-3.34), age over 50 years (HR 2.86, CI 2.43-3.38), white race (HR 6.29, CI 4.63-8.53), and male sex (HR 1.85, CI 1.57-2.19). Mortality was highest for malignant melanoma (mortality of 11.48), followed by squamous cell carcinoma (mortality of 4.94) and Merkel cell carcinoma (mortality of 4.59). LIMITATIONS: Limitations of this study included potential underreporting and misclassification of death from skin cancer in the data set. CONCLUSION: Mortality from posttransplantation skin cancer is reported. Older patients, male patients, white patients, and thoracic transplant recipients had increased mortality from skin cancer.

Clinician vs Self-ratings of Hirsutism in Patients With Polycystic Ovarian Syndrome: Associations With Quality of Life and Depression.

IMPORTANCE: Qualitative evidence suggests that hirsutism inflicts significant negative impacts on quality of life and may be associated with depression. Quantitative research is essential to determine best practices in caring for hirsute patients. OBJECTIVE: To quantify quality-of-life impact of hirsutism and evaluate how the degree of hirsutism (as assessed by patients and clinicians) is associated with quality of life and depressive symptoms. DESIGN, SETTING, PARTICIPANTS: This study included 229 patients aged 14 to 52 years consecutively recruited from a polycystic ovarian syndrome (PCOS) clinic between May 18, 2006, and October 25, 2012, who met the Rotterdam PCOS criteria. Data analysis was completed July 2015, and alterations were completed in response to reviewer comments in January 2016. MAIN OUTCOMES AND MEASURES: Clinicians and patients rated degree of hirsutism using the modified Ferriman-Gallwey (mFG) instrument, a visual scoring method assessing androgen-dependent hair growth in 9 body areas. Hirsutism-related quality of life was assessed using the Skindex-16, a validated quality of life instrument for skin disorders. Depressive symptoms were assessed using the Beck Depression Inventory-Fast screen. RESULTS: Overall, 229 patients aged 14 to 52 years who met the Rotterdam criteria for polycystic ovarian syndrome rated themselves and were rated by clinicians for hirsutism. Total mean self-rated mFG score for patients was 13.3 out of a total 36 possible points; total mean clinician-rated mFG score for patients was 8.63 (P < .001); self-ratings for hirsutism were higher for all body areas except thigh. Hirsutism had a significant negative effect on quality of life; the mean (SD) Skindex-16 score for the emotion domain was 73.9 (29.8) and 44.3 (33.7) for the function domain. Higher degrees of hirsutism (determined by both patients and clinicians) were moderately associated with more negative quality-of-life impact; however, self-ratings (r = 0.19-0.46) were more strongly associated than clinician ratings (r = 0.14-0.32)(P < .05 for all). Only self-ratings of hirsutism were significantly associated with risk of depression (r = 0.14; P < .05). CONCLUSIONS AND RELEVANCE: There is notable discordance in the perception of hirsutism between patients and clinicians; patients view their hirsutism as more severe than clinicians do. Quality-of-life impacts of hirsutism are consistent with that reported for other serious skin conditions. This negative impact is only partially associated with the degree of hirsutism, with self-ratings being more highly associated with quality of life impact than clinician ratings. These results support guidelines recommending that treatment be guided largely by patient distress with hair growth and subjective perceptions as opposed to clinician judgment of degree. Patient self-rating is critical information for patient-centered care for hirsute patients.

Cutaneous granulomas in the setting of primary immunodeficiency: a report of four cases and review of the literature.

IMPORTANCE: Cutaneous granulomas without an identifiable infectious etiology are a rare manifestation of primary immunodeficiency (ID). These cutaneous lesions can be misdiagnosed, often as sarcoidosis, when the skin findings precede the diagnosis of immunodeficiency. OBJECTIVE: We present four cases from our institution and review the literature in order to emphasize the clinical relevance of this association, discuss the histologic and immunohistochemical features, and explore possible pathogenic mechanisms of granuloma formation. EVIDENCE REVIEW: We retrospectively reviewed case reports of all patients presenting with cutaneous granulomas in the setting of primary immunodeficiency. Cases with insufficient information to confirm an immunodeficiency state were excluded. Four patients from our clinic were included, for 54 total cases. FINDINGS: The majority of cutaneous granulomas are seen in three types of immunodeficiencies: ataxia-telangiectasia, severe combined immunodeficiency, and combined variable immunodeficiency. Twenty-six percent of patients developed cutaneous granulomas prior to their immunodeficiency diagnosis. Histologically, various granulomatous patterns have been described. Immunohistochemistry revealed a CD4+/CD8+ lymphocyte ratio of less than or equal to 1 in our four patients, which may help differentiate cutaneous granulomas in primary ID from sarcoidal granulomas that typically show a CD4+ predominance. CONCLUSIONS AND RELEVANCE: Cutaneous granulomas are a rare manifestation of primary ID and occur predominantly in immunodeficiencies that affect T and B cell compartments.

Self-reported pigmentary phenotypes and race are significant but incomplete predictors of Fitzpatrick skin phototype in an ethnically diverse population.

BACKGROUND: Fitzpatrick skin phototype (FSPT) is the most common method used to assess sunburn risk and is an independent predictor of skin cancer risk. Because of a conventional assumption that FSPT is predictable based on pigmentary phenotypes, physicians frequently estimate FSPT based on patient appearance. OBJECTIVE: We sought to determine the degree to which self-reported race and pigmentary phenotypes are predictive of FSPT in a large, ethnically diverse population. METHODS: A cross-sectional survey collected responses from 3386 individuals regarding self-reported FSPT, pigmentary phenotypes, race, age, and sex. Univariate and multivariate logistic regression analyses were performed to determine variables that significantly predict FSPT. RESULTS: Race, sex, skin color, eye color, and hair color are significant but weak independent predictors of FSPT (P<.0001). A multivariate model constructed using all independent predictors of FSPT only accurately predicted FSPT to within 1 point on the Fitzpatrick scale with 92% accuracy (weighted kappa statistic 0.53). LIMITATIONS: Our study enriched for responses from ethnic minorities and does not fully represent the demographics of the US population. CONCLUSIONS: Patient self-reported race and pigmentary phenotypes are inaccurate predictors of sun sensitivity as defined by FSPT. There are limitations to using patient-reported race and appearance in predicting individual sunburn risk.

A primer on the current state of microarray technologies.

DNA microarray technology has been used for genome-wide gene expression studies that incorporate molecular genetics and computer science analyses on massive levels. The availability of microarrays permit the simultaneous analysis of tens of thousands of genes for the purposes of gene discovery, disease diagnosis, improved drug development, and therapeutics tailored to specific disease processes. In this chapter, we provide an overview on the current state of common microarray technologies and platforms. Since many genes contribute to normal functioning, research efforts are moving from the search for a disease-specific gene to the understanding of the biochemical and molecular functioning of a variety of genes whose disrupted interaction in complicated networks can lead to a disease state. The field of microarrays has evolved over the past decade and is now standardized with a high level of quality control, while providing a relatively inexpensive and reliable alternative to studying various aspects of gene expression.