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Background and Objective: Migrant and refugee women, families, and their children can experience significant language, cultural, and psychosocial barriers to engage with child and family services. Integrated child and family health Hubs are increasingly promoted as a potential solution to address access barriers; however, there is scant literature on how to best implement them with migrant and refugee populations. Our aim was to explore with service providers and consumers the barriers, enablers, and experiences with Hubs and the resulting building blocks required for acceptable Hub implementation for migrant and refugee families., Design, Setting and Participants: This project was undertaken in Sydney, New South Wales, in communities characterised by cultural diversity. In this qualitative study, we used semi-structured interviews guided by the consolidated framework for implementation research, with service providers from health and social services (32 participants) and migrant and refugee parents (14 parents) of children who had accessed Hubs., Research and Discussion: Our initial qualitative data themes were developed into step-by-step building blocks, representing a way to address contextual determinants to establish and sustain a Hub that can support migrant and refugee families. These include the setting-up phase activities of buy-in and partnership development, which outlines mechanisms to foster collective action and collaboration between health and social services. Following this, our orientation model articulates the need to establish Hub coordination and navigation, activities that enhance a Hub's relevance for migrant and refugee families and ongoing integration mechanisms, such as engagement of same-language general practitioners. This is the first study to explore the building blocks required for acceptable Hub implementation to meet the needs of migrant and refugee families in the first 2000 days of a child's life-a critical time to optimise child development and health., Patient or Public Contribution: The research questions were developed based on qualitative research undertaken with Hub participants, community members, and service providers. The original investigator team had a consumer representative who has since relocated and consultation was undertaken with local Hub partner services. The researchers also consulted multicultural health services, including cultural support workers, to ensure research materials were culturally nuanced. Patients or participants have not directly been involved in the current study design., Clinical Trial Registration: This trial was registered with the Australian New Zealand Clinical Trials (ACTRN12621001088831)., (© 2025 The Author(s). Health Expectations published by John Wiley & Sons Ltd.)

Background: Although RANK-LRANK interaction is essential for osteoclastogenesis, the mechanisms by which cancer cells invade bone tissues and initiate osteolytic metastasis remain unclear. Here, we show that the hyperactivation of RelB fosters prostate cancer (PCa) osteolytic metastasis by coordinating interleukin-8 (IL-8) and calcium-binging protein A4 (S100A4)., Methods: The factors promoting PCa bone metastasis were investigated in sera from PCa patients and tumour tissues derived from nude mice using immunohistochemical analysis and enzyme-linked immunosorbent assays (ELISA). Cell mobility and mineralization were quantified using BioStation CT and Osteolmage assay. The relative cistrome was investigated in advanced PCa cells by standard transcriptional analyses, including the luciferase reporter response, site-directed mutagenesis, and chromatin immunoprecipitation (ChIP) assay. PCa cell-initiated tumour formation, expansion, and bone metastasis were validated in mice using multiple approaches, including orthotopic, intraskeletal, and caudal arterial implantation models., Results: IL-8 and S100A4 correlated with patient Gleason scores and bone metastasis. RelB upregulated IL-8, facilitating androgen receptor (AR)-independent growth. RelB-Sp1 interaction enhanced epithelial-mesenchymal transition (EMT) by activating Snail and Twist. RelB-NFAT1c super-enhancer upregulated S100A4 in the organization of the cytoskeleton and bone metastasis. The RelB-IL-8-S100A4 signalling axis was confirmed to promote osteolytic metastasis in nude mice., Conclusion: RelB-IL-8 reciprocally promoted EMT by activating inflammatory signalling and inactivating AR signalling. IL-8 is essential for provoking PCa metastasis but insufficient to drive bone metastasis. IL-8-S100A4 cooperation was necessary for metastatic cells to target the bone., Highlights: RelB activates inflammatory signalling by upregulating IL-8 and suppressing AR. RelB upregulates S100A4 by cooperating with NFATC1. IL-8 boosts EMT by activating Snail 1 and Twist 1, and S100A4 exacerbates osteolytic metastasis via calcium consumption. RelB harnesses IL-8 and S100A4 to drive PCa osteolytic metastasis., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Introduction: Pediatric head and neck (HN) trauma is an important contributor to pediatric morbidity, resulting in significant downstream consequences. Few studies provide epidemiological predictors of pediatric HN trauma on a national scale. The present study aims to identify risk factors of HN injury and mortality in the pediatric population., Methods: A retrospective cohort study was conducted for patients (age <18 years) using the US National Trauma Data Bank (NTDB 2007-2019). Demographic, injury, and physiologic outcome data were analyzed. HN injury was defined as a head or neck Abbreviated Injury Scale (AIS) >0. Logistic regression identified independent predictors of mortality following HN trauma., Results: Of the 1.42 million pediatric patients analyzed, 44.05% had HN injury. In patients aged 0-4, the most common mechanism was falls (47.67% in this age group) while in ages 14-17, motor vehicle/transport accidents (MVTs) were the most common mechanism (56.06%). Controlling for demographics, comorbidities, and injury severity, HN injury was associated with increased odds of mortality (OR 2.404, 95% CI 1.530-3.778). HN injury mortality was strongly predicted by firearm exposure (OR 11.28, 95% CI 6.074-20.95), age <4 (OR 1.179, 95% CI 1.071-1.299), and self-insured status (OR 1.977, 95% CI 1.811-2.157)., Conclusion: NTDB data demonstrate that the percentage of pediatric patients with HN trauma has decreased over the past 12 years although is associated with increased odds of mortality. Age and insurance status predicted mortality from HN trauma, with falls and MVTs being the most common mechanisms of injury. These data have implications for future public health efforts in this patient population., Level of Evidence: 3., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Lung diseases, including lung cancer, are rising causes of global mortality. Despite novel imaging technologies and the development of biomarker assays, the detection of lung cancer remains a significant challenge. However, the lung communicates directly with the external environment and releases aerosolized droplets during normal tidal respiration, which can be collected, stored and analzsed as exhaled breath condensate (EBC). A few studies have suggested that EBC contains extracellular vesicles (EVs) whose microRNA (miRNA) cargos may be useful for evaluating different lung conditions, but the cellular origin of these EVs remains unknown. In this study, we used nanoparticle tracking, transmission electron microscopy, Western blot analyses and super resolution nanoimaging (ONi) to detect and validate the identity of exhaled EVs (exh-EVs). Using our customizable antibody-purification assay, EV-CATCHER, we initially determined that exh-EVs can be selectively enriched from EBC using antibodies against three tetraspanins (CD9, CD63 and CD81). Using ONi we also revealed that some exh-EVs harbour lung-specific proteins expressed in bronchiolar Clara cells (Clara Cell Secretory Protein [CCSP]) and Alveolar Type II cells (Surfactant protein C [SFTPC]). When conducting miRNA next generation sequencing (NGS) of airway samples collected at five different anatomic levels (i.e., mouth rinse, mouth wash, bronchial brush, bronchoalveolar lavage [BAL] and EBC) from 18 subjects, we determined that miRNA profiles of exh-EVs clustered closely to those of BAL EVs but not to those of other airway samples. When comparing the miRNA profiles of EVs purified from matched BAL and EBC samples with our three tetraspanins EV-CATCHER assay, we captured significant miRNA expression differences associated with smoking, asthma and lung tumor status of our subjects, which were also reproducibly detected in EVs selectively purified with our anti-CCSP/SFTPC EV-CATCHER assay from the same samples, but that confirmed their lung tissue origin. Our findings underscore that enriching exh-EV subpopulations from EBC allows non-invasive sampling of EVs produced by lung tissues., (© 2024 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Objectives: To gather initial data on the effectiveness and tolerability of the addition of Ondansetron to bowel preparation regimens to justify a funded, larger, placebo-controlled study., Methods: Design, Setting, and Participants:: A total of 41 pediatric and young adult (age 2-22) patients participated in a single center, open label, parallel randomized trial, with simple randomization. All patients were recruited as outpatients, and all procedures occurred as outpatient procedures, with both recruitment and procedures occurring at a low-resource urban academic medical center in Brooklyn. Interventions and Outcome Measures:: The intervention studied was a single dose of oral-dissolving tablet Ondansetron provided before initiation of bowel preparation using a standardized prep of Polyethylene Glycol 3350 and Bisacodyl. There were 2 arms, a study arm using typical preparation (Polyethylene Glycol 3350 and Bisacodyl) and Ondansetron, and a control arm (Polyethylene Glycol 3350 and Bisacodyl). Patients received standard weight-based dosing. The primary outcome measure assessed was the Boston Bowel Preparation Scale (BBPS) to assess efficacy of preparation. Secondary objectives included evaluation of patient satisfaction via a survey answered by each patient. The questionnaire assessed the presence of the following symptoms during bowel prep: abdominal pain, nausea, bloating, vomiting, scale of ease/difficulty, and if the entire bowel prep was completed., Results: No benefit to BBPS from the addition of Ondansetron to bowel preparation was observed. Statistically significant improvement in reports of abdominal pain (35% decrease in Ondansetron arm) was noted with a P = 0.019. No statistically significant improvement was noted in other symptoms although all domains showed nonsignificant improvement in the Ondansetron arm., Conclusion: No benefit to efficacy of preparation as measured by the BBPS was observed. A single dose of Ondansetron before bowel preparation reduced reports of abdominal pain by 35%, with other symptomatic improvements suggesting possible improvements to be confirmed by a higher-powered study. Trial registration: NCT05439772., Competing Interests: The authors report no funding or conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Objective: To identify themes that contribute to the most positive and negative perspectives of cochlear implants (CIs) on Twitter., Study Design: A cross-sectional qualitative study., Setting: Social media (Twitter)., Methods: In this study, all English-language original tweets mentioning "cochlear implant" from 2019 to 2021 were collected from Twitter's Academic Research Database using a custom Python script. Sentiment analysis was performed using VADER, a sentiment analysis tool built to analyze the inherent positivity or negativity of social media posts. Tweets were quantitatively sorted by compound sentiment score (range -1 [most negative] to 1 [most positive]). Thematic analysis based on grounded theory was performed on the most positive, negative, and "liked" tweets., Results: Of the 19,376 tweets included, the average (standard deviation) compound sentiment score was 0.21 (0.46). A total of 10,375 (53.5%) tweets had a positive tone, 4965 (25.6%) were neutral and 4036 (20.8%) were negative. Of the 100 most negative tweets, the most prominent themes were media representation (21.9%), the controversy of CI within the Deaf community (19.8%), and unrelated to direct patient experience (16.7%). Of the 100 most positive tweets, the most prominent themes were tweets of happiness and support (25.0%), tweets unrelated to direct patient experience (18.0%), and tweets about hearing new sounds (10.0%)., Conclusion: While the majority of tweets on CI carried a positive tone, there are ongoing challenges with the stigma surrounding CI. Public perspectives of CI on social media may help clinicians counsel CI patients and elucidate issues that lead to newfound acceptance or ongoing stigma of CI in the general population., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Purpose: The purpose of the present study was to assess the overall clinical success rate of non-operative management for osteochondral lesions of the talus (OLT)., Methods: A literature search was conducted in the PubMed (MEDLINE), COCHRANE and EMBASE (Ovid) databases. Clinical success rates per separate study were calculated at the latest moment of follow-up and were defined as successful when a good or excellent clinical result at follow-up was reported in a qualitative manner or when a post-operative American Orthopaedic Foot and Ankle Society (AOFAS) score at or above 80 was reached. When clinical outcomes were based on other clinical scoring systems, outcomes reported as good or excellent were considered as clinical success. Studies methodologically eligible for a simplified pooling method were combined to calculate an overall pooled clinical success rate. Radiological changes over the course of conservative treatment were assessed either considering local OLT changes and/or overall ankle joint changes., Results: Thirty articles were included, including an overall of 868 patients. The median follow-up of the included studies was 37 months (range: 3-288 months). A simplified pooling method was possible among 16 studies and yielded an overall pooled clinical success rate of 45% (95% CI 40-50%). As assessed with plain radiographs, progression of ankle joint osteoarthritis was observed in of 9% (95% CI 6-14%) of the patients. As assessed through a Computed Tomography (CT) scan, focal OLT deterioration was observed in 11% (95% CI 7-18%) of the patients. As assessed with a Magnetic Resonance Imaging (MRI) scan, focal OLT deterioration was observed in 12% (95% CI 6-24%) of the patients. An unchanged lesion was detected on plain radiographs in 53% (48/91; CI 43-63%), 76% (99/131; 95% CI 68-82%) on a CT scan and on MRI in 84% (42/50; 95% CI 71-92%) of the patients., Conclusion: The current literature on non-operative management of OLTs is scarce and heterogeneous on indication and type of treatment. Promising clinical results are presented but need to interpreted with caution due to the heterogeneity in indication, duration and type of treatment. Further studies need to focus on specific types on conservative management, indications and its results., Level of Evidence: Systematic review, Level IV., (© 2023. The Author(s).)

To help health economic modelers respond to demands for greater use of complex systems models in public health. To propose identifiable features of such models and support researchers to plan public health modeling projects using these models. A working group of experts in complex systems modeling and economic evaluation was brought together to develop and jointly write guidance for the use of complex systems models for health economic analysis. The content of workshops was informed by a scoping review. A public health complex systems model for economic evaluation is defined as a quantitative, dynamic, non-linear model that incorporates feedback and interactions among model elements, in order to capture emergent outcomes and estimate health, economic and potentially other consequences to inform public policies. The guidance covers: when complex systems modeling is needed; principles for designing a complex systems model; and how to choose an appropriate modeling technique. This paper provides a definition to identify and characterize complex systems models for economic evaluations and proposes guidance on key aspects of the process for health economics analysis. This document will support the development of complex systems models, with impact on public health systems policy and decision making., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Mivavotinib (TAK-659), an orally administered, small-molecule, dual inhibitor of spleen tyrosine kinase and FMS-like tyrosine kinase 3 (SYK/FLT3), is under development for the treatment of patients with advanced malignancies. In this analysis, we evaluated the population pharmacokinetics (PK) of mivavotinib and its sources of variability (covariates) in adult patients with advanced solid tumors, or relapsed/refractory B-cell lymphomas or acute myeloid leukemia, using pooled data from 159 patients enrolled in 2 phase 1/2 clinical studies. A 2-compartment model with first-order linear elimination and a first-order absorption rate (and associated lag time) adequately described the PK of mivavotinib in this patient population. The population estimates of apparent clearance (CL/F) and apparent central compartment volume (V c /F) were 31.6 L/h and 893 L, respectively, resulting in a half-life of ≈20 hours. In the final model, creatinine clearance was included as a covariate of CL/F, and sex as a covariate of V c /F. Simulations showed that steady-state exposure to mivavotinib increased with decreasing renal function. Expanding eligibility by enrolling patients with moderate renal impairment in phase 1 increased the diversity of patients in early trials and allowed the model to inform dose adjustment in patients with moderate renal impairment in future trials. In addition, simulations showed median steady-state trough concentration of mivavotinib following 70 mg twice daily and 160 mg daily dosing to be commensurate with 100 ng/mL, the level leading to >90% FLT3 inhibition per ex vivo plasma immune assays and considered a potential exposure threshold required for FLT3-driven efficacy., (© 2022 Takeda Pharmaceutical Company and The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

With an ageing world population and ~20% of adults in Europe being affected by bone diseases, there is an urgent need to develop advanced regenerative approaches and biomaterials capable to facilitate tissue regeneration while providing an adequate microenvironment for cells to thrive. As the main components of bone are collagen and apatite mineral, scientists in the tissue engineering field have attempted in combining these materials by using different biomimetic approaches to favour bone repair. Still, an ideal bone analogue capable of mimicking the distinct properties (i.e., mechanical properties, degradation rate, porosity, etc.) of cancellous bone is to be developed. This review seeks to sum up the current understanding of bone tissue mineralisation and structure while providing a critical outlook on the existing biomimetic strategies of mineralising collagen for bone tissue engineering applications, highlighting where gaps in knowledge exist., (© 2022 The Authors. Biopolymers published by Wiley Periodicals LLC.)

Eosinophilic esophagitis (EoE), an eosinophil predominant, TH2-mediated condition increasing in prevalence in pediatric and adult populations, is typically treated with dietary manipulations to avoid triggering antigens. However, identifying specific dietary causes remains a persistent challenge, and restrictive diets are burdensome. Total dietary modification using amino acid-based formula does not always produce symptomatic or histologic resolution, suggesting that exposure to ingested aeroallergens drives their disease. EoE patients demonstrate symptomatic exacerbation from July to September correlating with higher grass and ragweed pollen counts. We present a 7-year-old tracheostomy- and gastrostomy-dependent girl who was found on surveillance endoscopy to have profound eosinophilic infiltration throughout the esophagus with inflammatory changes including basal cell hyperplasia on histology. She responded partially to topical corticosteroid therapy with fluticasone and had complete resolution of esophageal eosinophilic infiltrate with subcutaneous dupilumab., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

In addition to the severe impact of acute respiratory disease during the SARS-CoV-2 pandemic, the issue of "Long COVID" illness has impacted large numbers of patients following the initial infection. Wide ranges of Long Covid incidence have been reported, ranging from 30 to 87%. Long COVID has a variety of clinical manifestations, including gastrointestinal symptoms. Here, we report a case of persistent abdominal pain, 3 months following a SARS-CoV-2 diagnosis, associated with chronic colonic inflammation and the presence of mucosal SARS-CoV-2 virions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Purpose: The purpose of this study was to determine multiple return to sport rates, long-term clinical outcomes and safety for subtalar arthroscopy for sinus tarsi syndrome., Methods: Subtalar arthroscopies performed for sinus tarsi syndrome between 2013 and 2018 were analyzed. Twenty-two patients were assessed (median age: 28 (IQR 20-40), median follow-up 60 months (IQR 42-76). All patients were active in sports prior to the injury. The primary outcome was the return to pre-injury type of sport rate. Secondary outcomes were time and rate of return to any type of sports, return to performance and to improved performance. Clinical outcomes consisted of Numerous Rating Scale of pain, Foot and Ankle Outcome Score, 36-item Short Form Survey and complications and re-operations., Results: Fifty-five percent of the patients returned to their preoperative type of sport at a median time of 23 weeks post-operatively (IQR 9.0-49), 95% of the patients returned to any type and level sport at a median time of 12 weeks post-operatively (IQR 4.0-39), 18% returned to their preoperative performance level at a median time of 25 weeks post-operatively (IQR 8.0-46) and 5% returned to improved performance postoperatively at 28 weeks postoperatively (one patient). Median NRS in rest was 1.0 (IQR 0.0-4.0), 2.0 during walking (IQR 0.0-5.3) during walking, 3.0 during running (IQR 1.0-8.0) and 2.0 during stair-climbing (IQR 0.0-4.5). The summarized FAOS score was 62 (IQR 50-90). The median SF-36 PCSS and the MCSS were 46 (IQR 41-54) and 55 (IQR 49-58), respectively. No complications and one re-do subtalar arthroscopy were reported., Conclusion: Six out of ten patients with sinus tarsi syndrome returned to their pre-injury type of sport after being treated with a subtalar arthroscopy. Subtalar arthroscopy yields effective outcomes at long-term follow-up concerning patient-reported outcome measures in athletic population, with favorable return to sport level, return to sport time, clinical outcomes and safety outcome measures., Level of Evidence: IV., (© 2020. The Author(s).)

Extracellular vesicles (EVs) are emerging in tissue engineering as promising acellular tools, circumventing many of the limitations associated with cell-based therapies. Epigenetic regulation through histone deacetylase (HDAC) inhibition has been shown to increase differentiation capacity. Therefore, this study aimed to investigate the potential of augmenting osteoblast epigenetic functionality using the HDAC inhibitor Trichostatin A (TSA) to enhance the therapeutic efficacy of osteoblast-derived EVs for bone regeneration. TSA was found to substantially alter osteoblast epigenetic function through reduced HDAC activity and increased histone acetylation. Treatment with TSA also significantly enhanced osteoblast alkaline phosphatase activity (1.35-fold), collagen production (2.8-fold) and calcium deposition (1.55-fold) during osteogenic culture ( P ≤ 0.001). EVs derived from TSA-treated osteoblasts (TSA-EVs) exhibited reduced particle size (1-05-fold) ( P  > 0.05), concentration (1.4-fold) ( P  > 0.05) and protein content (1.16-fold) ( P ≤ 0.001) when compared to untreated EVs. TSA-EVs significantly enhanced the proliferation (1.13-fold) and migration (1.3-fold) of human bone marrow stem cells (hBMSCs) when compared to untreated EVs ( P ≤ 0.05). Moreover, TSA-EVs upregulated hBMSCs osteoblast-related gene and protein expression (ALP, Col1a, BSP1 and OCN) when compared to cells cultured with untreated EVs. Importantly, TSA-EVs elicited a time-dose dependent increase in hBMSCs extracellular matrix mineralisation. MicroRNA profiling revealed a set of differentially expressed microRNAs from TSA-EVs, which were osteogenic-related. Target prediction demonstrated these microRNAs were involved in regulating pathways such as 'endocytosis' and 'Wnt signalling pathway'. Moreover, proteomics analysis identified the enrichment of proteins involved in transcriptional regulation within TSA-EVs. Taken together, our findings suggest that altering osteoblasts' epigenome accelerates their mineralisation and promotes the osteoinductive potency of secreted EVs partly due to the delivery of pro-osteogenic microRNAs and transcriptional regulating proteins. As such, for the first time we demonstrate the potential to harness epigenetic regulation as a novel engineering approach to enhance EVs therapeutic efficacy for bone repair., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Circulating nucleic acids, encapsulated within small extracellular vesicles (EVs), provide a remote cellular snapshot of biomarkers derived from diseased tissues, however selective isolation is critical. Current laboratory-based purification techniques rely on the physical properties of small-EVs rather than their inherited cellular fingerprints. We established a highly-selective purification assay, termed EV-CATCHER, initially designed for high-throughput analysis of low-abundance small-RNA cargos by next-generation sequencing. We demonstrated its selectivity by specifically isolating and sequencing small-RNAs from mouse small-EVs spiked into human plasma. Western blotting, nanoparticle tracking, and transmission electron microscopy were used to validate and quantify the capture and release of intact small-EVs. As proof-of-principle for sensitive detection of circulating miRNAs, we compared small-RNA sequencing data from a subset of small-EVs serum-purified with EV-CATCHER to data from whole serum, using samples from a small cohort of recently hospitalized Covid-19 patients. We identified and validated, only in small-EVs, hsa-miR-146a and hsa-miR-126-3p to be significantly downregulated with disease severity. Separately, using convalescent sera from recovered Covid-19 patients with high anti-spike IgG titers, we confirmed the neutralizing properties, against SARS-CoV-2 in vitro, of a subset of small-EVs serum-purified by EV-CATCHER, as initially observed with ultracentrifuged small-EVs. Altogether our data highlight the sensitivity and versatility of EV-CATCHER., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper., (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Background: Artificial intelligence is touted as the future of medicine. Classical algorithms for the detection of common bile duct stones (CBD) have had poor clinical uptake due to low accuracy. This study explores the challenges of developing and implementing a machine-learning model for the prediction of CBD stones in patients presenting with acute biliary disease (ABD)., Methods: All patients presenting acutely to Christchurch Hospital over a two-year period with ABD were retrospectively identified. Clinical data points including lab test results, demographics and ethnicity were recorded. Several statistical techniques were utilised to develop a machine-learning model. Issues with data collection, quality, interpretation and barriers to implementation were identified and highlighted., Results: Issues with patient identification, coding accuracy, and implementation were encountered. In total, 1315 patients met inclusion criteria. Incorrect international classification of disease 10 (ICD-10) coding was noted in 36% (137/382) of patients recorded as having CBD stones. Patients with CBD stones were significantly older and had higher aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin and gamma-glutamyl transferase (GGT) levels (p < 0.001). The no information rate was 81% (1070/1315 patients). The optimum model developed was the gradient boosted model with a PPV of 67%, NPV of 87%, sensitivity of 37% and a specificity of 96% for common bile duct stones., Conclusion: This paper highlights the utility of machine learning in predicting CBD stones. Accuracy is limited by current data and issues do exist around both the ethics and practicality of implementation. Regardless, machine learning represents a promising new paradigm for surgical practice.

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases., (© 2020 The Authors. Medicinal Research Reviews published by Wiley Periodicals LLC.)