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.

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.

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.

[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.

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.

The primary immune response to Vaccinia virus vaccination includes cells with a distinct cytotoxic effector CD4 T-cell phenotype.

BACKGROUND: Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. METHODS: We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans. VV-specific T-cells were identified by up-regulation of activation markers directly ex vivo and through cytokine and co-stimulatory molecule expression. At day-13-post primary inoculation with VV, CD38highCD45RO+ CD4 T-cells were purified by cell sorting, RNA isolated and analysed by microarray. Differential expression of up-regulated genes in activated CD4 T-cells was confirmed at the mRNA and protein levels. We compared analyses of VV-specific CD4 T-cells to studies on 12 subjects with primary HIV infection (PHI). VV-specific T-cells lines were established from PBMCs collected post vaccination and checked for cytotoxicity potential. RESULTS: A median 11.9% CD4 T-cells were CD38highCD45RO+ at day-13 post-VV inoculation, compared to 3.0% prior and 10.4% during PHI. Activated CD4 T-cells had an up-regulation of genes related to cytolytic function, including granzymes K and A, perforin, granulysin, TIA-1, and Rab27a. No difference was seen between CD4 T-cell expression of perforin or TIA-1 to VV and PHI, however granzyme k was more dominant in the VV response. At 25:1 effector to target ratio, two VV-specific T-cell lines exhibited 62% and 30% cytotoxicity respectively and CD107a degranulation. CONCLUSIONS: We show for the first time that CD4 CTL are prominent in the early response to VV. Understanding the role of CD4 CTL in the generation of an effective anti-viral memory may help develop more effective vaccines for diseases such as HIV.

Unidirectionally progressive resection of lower left lung carcinoma under video-associated thoracoscopy.

General anesthesia is adopted through double-lumen endotracheal intubation, one-lung ventilation on the contralateral, and intravenous injection. The patient took a 90 degree decubitus on his contralateral side. The operative incisions: the observation port was made in the mid-axillary line of the 7(th) intercostal section, a second horizontal incision of 4 cm as the main operation port at the 4(th) intercostal space between the anterior axillary line and the midclavicular line, and a 3(rd) incision of 1.5 cm as the secondary operation hole at the 9(th) intercostal space between the axillary line and the bottom scapular line. The surgeons were on the ventral side of the patient, and operated with endoscope apparatus in front of the monitor screen.

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.

[Quality of life in patients with esophageal carcinoma undergoing thoracoscopic and laparoscopic esophagectomy and circular stapled cervical esophagogastric anastomosis via retrosternal route].

OBJECTIVE: To evaluate the quality of life (QOL) in patients with esophageal carcinoma after thoracoscopic and laparoscopic esophagectomy and circular stapled cervical esophagogastric anastomosis via retrosternal route or three-incision open surgery. METHODS: A total of 63 patients with middle-upper esophageal carcinoma who underwent radical surgical resection from January 2009 to October 2010 were enrolled in this study. Thirty-three patients underwent combined laparoscopic and thoracoscopic surgery and 30 three-incision open surgery. The EORTC questionnaire QLQ-C30 and QLQ-OES18 were used to evaluate the QOL. RESULTS: There were no significant differences in the clinical data between the two groups except for anastomosis method(P>0.05). In the endoscopy group, there was one patient developed anastomotic leakage(3.0%, 1/33), 1 postoperative wound infection in the neck (3.0%, 1/33), and 1 anastomotic stricture(3.0%, 1/33). In the open group, 8 patients had anastomotic leakage (26.7%, 8/30), 2 had anastomotic stricture (6.7%, 2/30), 1 had wound infection in the neck (3.3%, 1/30), and 6 had pulmonary infection (20.0%, 6/30). All the complications were managed by conservative treatment. The two groups differed in dysphagia, food intake, pain, obstruction, dyspnea, anorexia, fatigue, financial condition, physical function, role function, emotional function, cognitive function, social function and global health level and were more favorable in the endoscopy group(P<0.05), while there were no significant differences in the other dimensions. CONCLUSIONS: The postoperative complication rate is low after thoracoscopic and laparoscopic esophagectomy. Stapled anastomosis is associated with lower rate of anastomotic leak. QOL is better in patients following thoracoscopic and laparoscopic esophagectomy as compared to those following three-incision open surgery.

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.

Complexity in human immunodeficiency virus type 1 (HIV-1) co-receptor usage: roles of CCR3 and CCR5 in HIV-1 infection of monocyte-derived macrophages and brain microglia.

CCR3 has been implicated as a co-receptor for human immunodeficiency virus type 1 (HIV-1), particularly in brain microglia cells. We sought to clarify the comparative roles of CCR3 and CCR5 in the central nervous system (CNS) HIV-1 infection and the potential utility of CCR3 as a target for manipulation via gene transfer. To target CCR3, we developed a single-chain antibody (SFv) and an interfering RNA (RNAi), R3-526. Coding sequences for both were cloned into Tag-deleted SV40-dervied vectors, as these vectors transduce brain microglia and monocyte-derived macrophages (MDM) highly efficiently. These anti-CCR3 transgenes were compared to SFv-CCR5, an SFv against CCR5, and RNAi-R5, an RNAi that targets CCR5, for the ability to protect primary human brain microglia and MDM from infection with peripheral and neurotropic strains of HIV-1. Downregulation of CCR3 and CCR5 by these transgenes was independent from one another. Confocal microscopy showed that CCR3 and CCR5 co-localized at the plasma membrane with each other and with CD4. Targeting either CCR5 or CCR3 largely protected both microglia and MDM from infection by many strains of HIV-1. That is, some HIV-1 strains, isolated from either the CNS or periphery, required both CCR3 and CCR5 for optimal productive infection of microglia and MDM. Some HIV-1 strains were relatively purely CCR5-tropic. None was purely CCR3-tropic. Thus, some CNS-tropic strains of HIV-1 utilize CCR5 as a co-receptor but do not need CCR3, while for other isolates both CCR3 and CCR5 may be required.

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.