Using wearable technology for Posture Regulation to Improve Surgical Ergonomics in the paediatric operating room: the UPRISE trial: a pilot study.

BACKGROUND: The rising prevalence of work-related musculoskeletal disorders has numerous physical, financial, and mental repercussions for surgeons. This study aims to establish whether the use of a wearable posture device can improve the operating time spent in suboptimal, high-risk postures. METHODS: Surgeons were recruited in Phase 1 of this prospective randomised study and baseline postural data was obtained. In Phase 2, participants were randomised to receive either a traditional educational workshop or intraoperative vibrations from the device to correct postural lapses. During minor elective day cases, intraoperative postural data was collected and stratified by forward flexion angle, into five risk categories (negligible to very high). Participants' experience with the sensor was also assessed. RESULTS: A total of 100 surgical procedures (Phase 1: n = 50; Phase 2: n = 50) were performed by eight surgeons of varying seniority. Exposure to the educational intervention increased time spent in suboptimal posture (Phase 1 vs. Phase 2); 47.5% vs. 67.8%, p = 0.05. However, the vibrational intervention significantly reduced this time; 50.0% vs. 20.7%, p = 0.005. Procedure type didn't influence posture although, laparoscopic interventions spent most time in negligible-risk postures; 47.7% vs. 49.3%, compared to open procedures. Surgical consultants spent less time in suboptimal posture compared to fellow/registrars; 30.3% vs. 72.6% (Phase 1) and 33.8% vs. 65.3% (Phase 2). CONCLUSION: Vibrational intervention from the device significantly decreased the time spent in suboptimal, high-risk postures. As procedure type wasn't correlated with postural changes, surgeon-specific factors in regulating posture are paramount. Finally, surgeon experience was positively correlated with improved surgical ergonomics.

A cross-sectional study of pediatric dermatoses in a specialized pigment and skin-of-color center in Australia.

There is a paucity of literature on pediatric skin conditions in skin of color, of which old epidemiological data are likely to become outdated as the ethnic diversity in developed countries such as Australia continues to grow. We analyzed the prevalence of presenting conditions of pediatric patients with skin of color attending an urban dermatology clinic in Melbourne, Australia over an 18-month period. The major presenting issues were vitiligo, atopic dermatitis, and acne vulgaris, the majority of which did not significantly differ by ethnicity; however, there was a statistically significantly higher proportion of Chinese and Indian patients presenting with atopic dermatitis. Given the varying presentations of these conditions in skin of color, our findings highlight the importance of increasing education for dermatologists and health personnel in pigmentary disorders and the need for further focused studies comparing the prevalence of skin disease across ethnicities.

IL-21 contributes to fatal inflammatory disease in the absence of Foxp3+ T regulatory cells.

The cytokine IL-21 has been shown to influence immune responses through both costimulatory effects on effector T cells and opposing inhibitory effects on T regulatory cells (Tregs). To distinguish the effect of IL-21 on the immune system from that of its effect on Tregs, we analyzed the role of IL-21/IL-21R signaling in mice made genetically deficient in IL-2, which exhibit a deficit in IL-2-dependent Foxp3 regulatory T cells and suffer from a fatal multiorgan inflammatory disease. Our findings demonstrate that in the absence of IL-21/IL-21R signaling, Il2(-/-) mice retained a deficiency in Tregs yet exhibited a reduced and delayed inflammatory disease. The improved health of Il2(-/-)Il21r(-/-) mice was reflected in reduced pancreatitis and hemolytic anemia and this was associated with distinct changes in lymphocyte effector populations, including the reduced expansion of both T follicular helper cells and Th17 cells and a compensatory increase in IL-22 in the absence of IL-21R. IL-21/IL-21R interactions were also important for the expansion of effector and memory CD8(+) T cells, which were critical for the development of pancreatitis in Il2(-/-) mice. These findings demonstrate that IL-21 is a major target of immune system regulation.

IL-21-producing Th cells in immunity and autoimmunity.

IL-21 is a member of the common γ-chain signaling family of cytokines. Analyses of the behavior of immune cells in response to IL-21 in vitro and studies of mice deficient in IL-21 or its receptor indicate that IL-21 has a role in lymphocyte activation, proliferation, differentiation, and survival. IL-21-producing CD4(+) Th cells constitute a broad array of helper subtypes including T follicular helper cells and Th17 cells. Both autocrine and paracrine utilization of IL-21 contributes to the overall signal transduction pathways of the Ag receptor to influence the growth and survival of lymphocytes. The redundancy that IL-21 exhibits in lymphoid organs during immune responses is in stark contrast to the evidence that pharmacological neutralization of this cytokine can halt inflammation in nonlymphoid organs where IL-21 becomes the dominant voice.

IL-21 promotes CD8+ CTL activity via the transcription factor T-bet.

CD8(+) T cells are fundamental for immune-mediated clearance of viral infections and contribute to immune pathology in autoimmune diseases such as type 1 diabetes. To execute these functions, CD8(+) T cells must differentiate into CTLs, a process that is precisely regulated by a variety of cytokines, costimulatory molecules, and transcription factors. IL-21 is an IL-2 family cytokine and a growth factor for multiple lymphocyte effector lineages, including cytotoxic CD8(+) T cells. Recent studies demonstrate that loss of IL-21 signaling results in reduced viral clearance in models of lymphocytic choriomeningitis virus infection, and also protection from type 1 diabetes in the NOD model. This is most likely the result of impaired CD8(+) CTL function in the absence of IL-21 signaling. Currently, the mechanisms by which IL-21 promotes CTL differentiation in CD8(+) T cells remain unclear, particularly the identity of the relevant transcription factor(s). We show that IL-21 promotes CTL function in vitro and killing of pancreatic islets in vivo via the use of transgenic mice expressing IL-21 in pancreatic ß cells. We demonstrate that IL-21 induces the expression of the transcription factor T-bet in CD8(+) T cells, predominantly via STAT1, and that T-bet is required for the induction of cytolytic molecules, including perforin and granzyme B in response to IL-21. Finally, we show that IL-21-induced CTL function is T-bet dependent, as T-bet deficiency results in defective IL-21-dependent cytotoxicity in CD8(+) T cells in vitro and in vivo. Thus, IL-21 drives CD8(+) CTL differentiation via the actions of the transcription factor T-bet.

Overexpression of the Ctla-4 isoform lacking exons 2 and 3 causes autoimmunity.

CTLA-4 is a potent inhibitor of T cell activation, primarily upon binding to its costimulatory ligands (B7.1 and B7.2) expressed on APCs. However, variants of CTLA-4 can also function independently of B7 molecules. 1/4CTLA-4 is a highly conserved isoform encoded by exons 1 and 4 of the Ctla4 gene that lacks the ligand-binding and the transmembrane domains, and as yet, its function is not known. To investigate the function of 1/4CTLA-4, we generated transgenic (Tg) mice overexpressing this variant. Cytokine production by 1/4CTLA-4 Tg T cells was elevated compared with wild type T cells. The frequency of CD44(high) memory T cells in 1/4CTLA-4 Tg mice was increased, and as the mice aged, the frequency further increased. 1/4CTLA-4 Tg mice >1 y old had increased expression of T cell activation markers and developed spontaneous autoimmunity, including elevated production of autoantibodies. In contrast with young 1/4CTLA-4 Tg mice, aged 1/4CTLA-4 Tg mice had elevated frequencies of Foxp3(+) regulatory T cells, but the regulatory T cells from these mice were not able to inhibit colitis development. Collectively, these data suggest that the function of the 1/4CTLA-4 isoform is distinct from that of CTLA-4 in that it enhances T cell activation and promotes autoimmunity rather than inhibiting immune responses.

Interprofessional Learning in Multidisciplinary Healthcare Teams Is Associated With Reduced Patient Mortality: A Quantitative Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study is to identify quantitative evidence for the efficacy of interprofessional learning (IPL) to improve patient outcomes. METHODS: We conducted a systematic review and meta-analysis of quantitative patient outcomes after IPL in multidisciplinary healthcare teams reported in the Medline, Scopus, PsycInfo, Embase, and CINAHL databases. RESULTS: In 2022, we screened 15,248 reports to include 20 and extracted rates of mortality and primary outcomes in conventional care groups and intervention groups (involving initiatives to promote IPL in multidisciplinary teams). The meta-analysis of the 13 studies reporting mortality outcomes demonstrated that the 7166 patients in the intervention group had a significant 28% (95% confidence interval [CI], 40%-14%; P < 0.0003) reduced risk of dying compared with the 6809 patients in the conventional care group. The meta-analysis of the 14 studies reporting other treatment-related adverse outcomes demonstrated that the 4789 patients in the intervention group had a significant 23% (95% CI, 33%-12%; P < 0.0001) reduced risk of experiencing an adverse outcome during care compared with the 4129 patients in the conventional care group. Sensitivity analysis, involving the exclusion of the 20% of individual studies with the widest 95% CIs, confirmed the precision and reliability of our findings. CONCLUSIONS: We believe that our results are the first to demonstrate significant quantitative evidence for the efficacy of IPL to translate into changes in clinical practice and improved patient outcomes. Our results reinforce earlier qualitative work of the value of IPL, but further prospective quantitative and mixed-methods research is needed to better define such benefits.

Incidence and risk factors of complications during central venous access devices removal in children.

PURPOSE: To quantify the rates and identify risk factors for the complications of central venous access devices (CVADs) removal in children. METHOD: Retrospective (2018-2023) review of children undergoing CVADs removal at a single institution. Data are reported as frequency, percentages and median. Logistic regression analysis was used to identify risk factors associated with difficult removal. Receiver Operating Characteristic Curve (ROC) analysis was conducted to identify the age cut-off and positive likelihood ratio (+LH) for the indwelling time associated with complicated removal. p-Value <0.05 were considered statistically significant. RESULTS: We identified 208 CVAD removals with a median age of 7.2 (0.2-18.4) years including 116 (55.8%) males. The median CVAD placement duration was 1.26 years (0.4-5.7) years. Indications for insertion included acute lymphoblastic leukaemia (ALL; 78/208, 37.5%), lymphomas (31/208, 14.9%), other malignancies (58/208, 27.9%). Removal indications included completion of treatment (144/208, 69.2%), infection (22/208, 10.6%), malfunction (7/208, 3.4%) and other reasons (35/208, 16.8%). There were 20 (9.6%) complications characterised by difficulty removing the CVAD. Complicated removals were more likely to occur in children with ALL as the primary diagnosis (p = 0.001); independently of the indication for insertion, longer indwelling time was associated with higher risk of complicated removal (p < 0.001). Indwelling time >2.09 years was associated with a 2.87 increased risk of difficult removal. CONCLUSION: In our experience, almost 10% of CVAD removals in children result in complications. These findings are associated with an indwelling time >2 years; strategies to prevent complicated removals should be considered in children requiring long-term central venous access.

International differences and inaccuracies in the public advertising about calcaneal apophysitis: an audit of websites originating in Australia, UK and USA.

BACKGROUND: Calcaneal apophysitis is a common condition in childhood. Parents often seek online information for children's' health care concerns prior to seeking care. Therefore, we aimed to evaluate the credibility, readability, and accuracy of calcaneal apophysitis advertising on popular websites in three countries. METHODS: We used content analysis of publicly accessible data. This involved identifying the top 50 websites in each country from their hit rates. We used elements of validated tools to audit and determine frequencies relevant to credibility (e.g. publisher), readability (e.g. literacy score) and accuracy (e.g. alignment with evidence). Data were analysed quantitatively and reported against each element. RESULTS: Websites were predominantly hosted by private health services (n = 118, 79%). The mean (SD) SMOG (readability) score was 9.3 (4.5). The majority of websites (n = 140, 93%) provided at least one treatment recommendation, and less than 10% (n = 11) of websites advertised treatments fully aligned with evidence. Use of treatment modalities without evidence and with high risk to children were also found including surgery, extracorporeal shock wave therapy and laser. CONCLUSIONS: Calcaneal apophysitis online advertising is mostly curated by clinicians. Clinicians should consider revising online advertising to increase understandability and accuracy to reduce health care wastage, risk, and low value care.

Clinical documentation requirements for the accurate coding of hospital-acquired urinary tract infections in Australia.

Aims We evaluated the accuracy of medical coders in distinguishing the aetiology of urinary tract infection according to clinical documentation. Methods The clinical documentation of patients coded as having had a hospital-acquired urinary tract infection from January to June 2020 at two Melbourne hospitals were assessed for community or hospital acquisition. Results We found that 48.89% of cases were inaccurately categorised as hospital-acquired, due to insufficient detail in clinical documentation. Risk factors for hospital-acquired urinary tract infection were present in at least 30% of correctly categorised cases. Conclusions Clinical documentation is not filled out with sufficient detail or in a timely enough manner for clinical coders to distinguish between hospital or community origin.

Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells.

IL-27 has recently been identified as a differentiation factor for the generation of IL-10-producing regulatory type 1 (Tr1) T cells. However, how IL-27 induces the expansion of Tr1 cells has not been elucidated. In this study we demonstrate that IL-27 drives the expansion and differentiation of IL-10-producing murine Tr1 cells by inducing three key elements: the transcription factor c-Maf, the cytokine IL-21, and the costimulatory receptor ICOS. IL-27-driven c-Maf expression transactivates IL-21 production, which acts as an autocrine growth factor for the expansion and/or maintenance of IL-27-induced Tr1 cells. ICOS further promotes IL-27-driven Tr1 cells. Each of those elements is essential, because loss of c-Maf, IL-21-signaling, or ICOS decreases the frequency of IL-27-induced differentiation of IL-10-producing Tr1 cells.

Genetic evidence that the differential expression of the ligand-independent isoform of CTLA-4 is the molecular basis of the Idd5.1 type 1 diabetes region in nonobese diabetic mice.

Idd5.1 regulates T1D susceptibility in nonobese diabetic (NOD) mice and has two notable candidate genes, Ctla4 and Icos. Reduced expression of one of the four CTLA-4 isoforms, ligand-independent CTLA-4 (liCTLA-4), which inhibits in vitro T cell activation and cytokine production similarly to full-length CTLA-4 (flCTLA-4), has been hypothesized to increase type 1 diabetes (T1D) susceptibility. However, further support of this hypothesis is required since the Idd5.1 haplotypes of the diabetes-susceptible NOD and the resistant B10 strains differ throughout Ctla4 and Icos. Using haplotype analysis and the generation of novel Idd5.1-congenic strains that differ at the disease-associated Ctla4 exon 2 single-nucleotide polymorphism, we demonstrate that increased expression of liCTLA-4 correlates with reduced T1D susceptibility. To directly assess the ability of liCTLA-4 to modulate T1D, we generated liCTLA-4-transgenic NOD mice and compared their diabetes susceptibility to nontransgenic littermates. NOD liCTLA-4-transgenic mice were protected from T1D to the same extent as NOD.B10 Idd5.1-congenic mice, demonstrating that increased liCTLA-4 expression alone can account for disease protection. To further investigate the in vivo function of liCTLA-4, specifically whether liCTLA-4 can functionally replace flCTLA-4 in vivo, we expressed the liCTLA-4 transgene in CTLA-4(-/-) B6 mice. CTLA-4(-/-) mice expressing liCTLA-4 accumulated fewer activated effector/memory CD4(+) T cells than CTLA-4(-/-) mice and the transgenic mice were partially rescued from the multiorgan inflammation and early lethality caused by the disruption of Ctla4. These results suggest that liCTLA-4 can partially replace some functions of flCTLA-4 in vivo and that this isoform evolved to reinforce the function of flCTLA-4.

Ideal Anatomical Landmark Points for Thoracic Esophagus Segmentation in the Chinese Population.

Introduction: The standards of esophagus segmentation remain different between the Japan Esophageal Society (JES) guideline and the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) guideline. This study aimed to present variations in the location of intrathoracic esophageal adjacent anatomical landmarks (EAALs) and determine an appropriate method for segmenting the thoracic esophagus based on the relatively fixed EAALs. Patients and Methods: The distances from the upper incisors to the upper border of the esophageal hiatus, lower border of the inferior pulmonary vein (LPV), tracheal bifurcation, lower border of the azygous vein (LAV), and thoracic inlet were measured in the patients undergoing thoracic surgery. The median distances between the EAALs and the specified starting points, as well as reference value ranges and ratios, were obtained. The variation coefficients of distances and ratios from certain starting points to different EAALs were calculated and compared to determine the relatively fixed landmarks. Results: This study included 305 patients. The average distance from the upper incisors to the upper border of the cardia, the midpoint between the tracheal bifurcation and esophageal hiatus (MTBEH), LPV, LAV, tracheal bifurcation, and thoracic inlet were 41.6, 35.3, 34.8, 29.4, 29.5, and 20.3 cm, respectively. The distances from the upper incisors or thoracic inlet to any intrathoracic EAALs in men were higher than in women. In addition, the height, weight, and body mass index (BMI) were correlated with the distances. The ratio of the distance between the upper incisors and tracheal bifurcation to the distance between the upper incisors and upper border of the cardia and the ratio of the distance between the thoracic inlet and tracheal bifurcation to the distance between the thoracic inlet and upper border of the cardia possessed relatively smaller coefficients of variation. Conclusion: The distances from the EAALs to the upper incisors vary with height, weight, BMI, and gender. Compared with distance, the ratios are more suitable for esophagus segmentation. Tracheal bifurcation and MTBEH are ideal EAALs for thoracic esophagus segmentation, and this is consistent with the JES guideline recommendation.

Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression.

The de novo generation of Foxp3+ regulatory T (Treg) cells in the peripheral immune compartment and the differentiation of Th17 cells both require TGF-beta, and IL-6 and IL-21 are switch factors that drive the development of Th17 cells at the expense of Treg cell generation. The major vitamin A metabolite all-trans retinoic acid (RA) not only enforces the generation of Treg cells but also inhibits the differentiation of Th17 cells. Herein we show that RA enhances TGF-beta signaling by increasing the expression and phosphorylation of Smad3, and this results in increased Foxp3 expression even in the presence of IL-6 or IL-21. RA also inhibits the expression of IL-6Ralpha, IRF-4, and IL-23R and thus inhibits Th17 development. In vitro, RA significantly promotes Treg cell conversion, but in vivo during the development of experimental autoimmune encephalomyelitis it does not increase the frequency of Treg cells in the face of an ongoing inflammation. However, RA suppresses the disease very efficiently by inhibiting proinflammatory T cell responses, especially pathogenic Th17 responses. These data not only identify the signaling mechanisms by which RA can affect both Treg cell and Th17 differentiation, but they also highlight that in vivo during an autoimmune reaction, RA suppresses autoimmunity mainly by inhibiting the generation of effector Th17 cells.

Australian medical student expectations of work-life balance as a doctor.

This article was migrated. The article was marked as recommended. Objectives: To explore the perceptions of medical students on achieving good work-life balance after graduation, and their opinions on parenting having an impact on their future careers. Methods: Cross-sectional cohort study of an online survey was distributed to students from all medical schools in Australia through the General Practice Students Network. Main outcome measures: Medical student perceptions on the effects of their future careers on the ability to maintain work-life balance and whether future parenting would impact their careers. Both quantitative and qualitative responses were collected. Results:The majority of survey respondents believed their careers would have a moderate or significant impact on the ability to achieve work-life balance. Thematic analysis revealed medical students perceived medical careers as lacking flexibility, being time-consuming, and potentially detrimental to health. Surveyed students indicated both parenting goals and specialty choice needed to be considered when planning their career. Conclusions: Australian medical students expressed significant concerns about their ability to juggle parenting and achieve work-life balance within the realities of a medical career.

[Expressions of TAK1 and TAB1 in esophageal cancer and their correlation with prognosis].

OBJECTIVE: To detect the expressions of transforming growth factor-ß (TGF-ß)-activated kinase (TAK1) and TGF-ß- activated protein kinase 1 (TAB1) in esophageal cancer tissues and explore their correlations with the clinicopathological features and prognosis of the patients. METHODS: The expressions of TAK1 and TAB1 in 84 esophageal cancer tissues and paired adjacent tissues was detected using immunohistochemical staining. The correlations of different patterns of TAK1 and TAB1 expressions (TAK1 alone, TAB1 alone, and both) with the clinicopathological features of the patients were analyzed. The correlation between TAK1 and TAB1 was assessed based on GEPIA datasets. Kaplan-Meier survival analysis was used to analyze the recurrence-free survival of the patients in relation with TAK1 and TAB1 expressions. RESULTS: TAK1 and TAB1 were highly expressed in 65.5% (55/84) and 52.4% (44/84) of the esophageal cancer tissues, respectively. The expression of TAK1, TAB1 and their co-expression were all correlated with tumor invasion depth, lymph node metastasis, and TNM staging (P < 0.05). A strong correlation was found between TAK1 and TAB1 expressions. A high expression of TAK1 and TAK1/TAB1 co-expression both predicted a poor recurrence-freed survival of the patients (P < 0.05). CONCLUSIONS: TAK1 and TAB1 are associated with the progression and prognosis of esophageal cancer and can serve as new prognostic biomarkers for esophageal cancer and as potential molecular targets for therapies.

Clues to asthma pathogenesis from microarray expression studies.

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), tissue remodeling, and airflow obstruction. The pathogenesis of asthma is only partly understood, and there is an urgent need for improved therapeutic strategies for this disease. Microarray technology has considerable promise as a tool for discovery of novel asthma therapeutic targets, although the field is still in its infancy. A number of studies have described expression profiles derived from human asthmatic lung tissue, mouse airway tissue, or from key cell types associated with asthma, but to date relatively few studies have exploited these findings to discover new pathways involved in the pathogenesis of asthma. Among the genes to have been identified by array studies and validated by further studies are monokine induced by interferon (IFN)-gamma, fatty acid binding proteins (FABP), and complement factor 5 (C5). Here we provide examples of microarray approaches to the discovery of new molecules associated with asthma. We anticipate that these types of analyses will provide considerable insight into asthma pathogenesis and will provide a wealth of new molecules for downstream analyses such as gene deficient mouse studies, or monoclonal antibody production.

IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2.

T follicular regulatory (Tfr) cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Here we show that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. The number of IL-2-dependent FoxP3+ regulatory T cells is increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions influence the phenotype of T follicular cells, reducing the expression of CXCR4 and inhibiting the expansion of Tfr cells after T-cell-dependent immunization. The negative effect of IL-21 on Tfr cells in mice is cell intrinsic and associated with decreased expression of the high affinity IL-2 receptor (CD25). Bcl-6, expressed in abundance in Tfr cells, inhibits CD25 expression and IL-21-mediated inhibition of CD25 is Bcl-6 dependent. These findings identify a mechanism by which IL-21 reinforces humoral immunity by restricting Tfr cell proliferation.