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Background Early identification of patients at high risk of prolonged mechanical ventilation is important in critical care. Sarcopenia, the loss of muscle mass and function, has been reported to be associated with extended mechanical ventilation and prolonged ICU stay. Although ultrasound is noninvasive and widely used in critical care, there is no standard method of using it to assess sarcopenia. Objectives The study aims to investigate the relationship between outcomes of critically ill patients and the ratio of BMI to the thickness of rectus abdominis measured by a standardised ultrasound examination. Design A retrospective cohort study. Setting Surgical ICU of a tertiary referral hospital, from October 2017 to June 2018. The thickness of rectus abdominis was measured while performing extended focused assessment sonography for trauma. BMI was divided by the thickness of rectus abdominis over the upper abdomen to derive the BMI-RA thickness ratio. Patients Sixteen male and 11 female patients admitted to ICU after major abdominal surgery. Main outcome measures The primary outcome was in-hospital mortality, and the secondary outcomes were durations of mechanical ventilation, ICU stay and hospital stay. The disease severity, serum albumin level and BMI-RA thickness ratio were also analysed. Results Ultrasound measurement was easy to perform without adverse effects. The BMI-RA thickness ratio was significantly higher in nonsurvivors and was associated with ICU stay, hospital stay and duration of mechanical ventilation. Multivariate logistic regression showed that the BMI-RA thickness ratio was a predictor of in-hospital mortality. Conclusion The BMI-RA thickness ratio is related to the outcomes of patients transferred to ICU after major abdominal surgery. Measuring the thickness of rectus abdominis by ultrasound is well tolerated and easy to perform in surgical ICU. Larger prospective studies are required to confirm current findings.

Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16+ buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRasG12V, luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRasG12V, luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV+ tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 305–19. ©2018 AACR.

Immunotherapy has emerged as a promising treatment strategy for the control of HPV-associated malignancies. Various therapeutic HPV vaccines have elicited potent antigen-specific CD8+ T cell mediated antitumor immune responses in preclinical models and are currently being tested in several clinical trials. Recent evidence indicates the importance of local immune activation, and higher number of immune cells in the site of lesion correlates with positive prognosis. Granulocyte macrophage colony-stimulating factor (GMCSF) has been reported to posses the ability to induce migration of antigen presentation cells and CD8+ T cells. Therefore, in the current study, we employ a combination of systemic therapeutic HPV DNA vaccination with local GMCSF application in the TC-1 tumor model. We show that intramuscular vaccination with CRT/E7 DNA followed by GMCSF intravaginal administration effectively controls cervicovaginal TC-1 tumors in mice. Furthermore, we observe an increase in the accumulation of E7-specific CD8+ T cells and dendritic cells in vaginal tumors following the combination treatment. In addition, we show that GMCSF induces activation and maturation in dendritic cells and promotes antigen cross-presentation. Our results support the clinical translation of the combination treatment of systemic therapeutic vaccination followed by local GMCSF administration as an effective strategy for tumor treatment.

Many studies have introduced electrode patterns to improve current crowding and enhance the light output power of LEDs. This study conducted experimental and numerical analysis to investigate the influence of electrode design on the luminous efficiency of LEDs. An extended p-electrode was used to relieve current crowding commonly encountered at the edge of conventional electrodes. Unfortunately, an extension of the p-electrode obscures light emitted from the active layer. Therefore, we fabricated arrays of holes, 3 or 5 μm in diameter, on the electrodes and compared their effectiveness in enhancing light output efficiency. Optical measurements demonstrated that increasing the diameter of the holes led to an increase in light output power. The maximum output power of the proposed LED was 48.1 mW for an array of 5 μm holes, which is higher than that of 43.8 mW for the conventional LED. At a current injection of 500 mA, the output power of the proposed LED (5 μm holes) was 47.7 mW, which is nearly double that of conventional LED (23.7 mW). Numerical analysis was also used to simulate the distribution of current density in the active layer of the LEDs. The relationship between current spreading length and internal quantum efficiency were used to calculate the distribution of luminous intensity. Further modeling was performed to simulate light output power via Monte Carlo ray tracing. The results of numerical simulation are in strong agreement with those obtained from experiments.

Purpose Tumor necrosis factor (TNFα) is a proinflammatory cytokine and has been a target for intervention in human sepsis. However, inhibition of TNF-α with a high dose of a TNF-receptor fusion protein in patients with septic shock worsened patient survival. This study was designed to investigate whether blocking TNF-α enhances mortality in infected burn mice through the induction of IL-1β. Methods WT or Tnfrsf1a −/− mice received Pseudomonas aeruginosa injection in the back at 8 h after burn injury. The animals were sacrificed at 24 h after burn and lung tissues were harvested and examined for determining myeloperoxidase (MPO) activity, pulmonary microvascular dysfunction, NF-κB DNA binding activity, and IL-1β expression. Also, the lung and blood were harvested for bacterial count assay. Result Thermal injury alone induced NF-κB DNA binding activity and neutrophil infiltration in the lung in WT but not in Tnfrsf1a −/− mice. A 50% total body surface area (TBSA) burn induced a significant increase of mortality in WT compared with Tnfrsf1a −/− mice. In contrast, P. aeruginosa injection with a 30% TBSA burn pretreatment enhanced IL-1β expression, bacterial counts in lung and blood, pulmonary microvascular dysfunction, and mortality in Tnfrsf1a −/− mice compared with WT mice. Injection of the IL-1 receptor antagonist, Anakinra, reduced P. aeruginosa infection with burn pretreatment-induced blood bacterial counts, IL-1β levels as well as permeability of lung, and mortality in Tnfrsf1a −/− mice. Conclusions Our findings suggest that thermal injury induces lung NF-κB activation and neutrophil sequestration through TNFα signaling. However, blocking TNF-α enhances P. aeruginosa infection-induced lung damage in burn mice via induction of IL-1β. Using an IL-1 receptor antagonist combined with the neutralization of TNF-α could be a useful strategy for decreasing P. aeruginosa infection-induced mortality in burn patients.

This study simulated in situ bioremediation for diesel-contaminated soil by a column operation. Several bioremediation approaches were conducted to examine the feasibility. Four lab-scale soil columns were operated specific to the following approaches: nutrient enhancement (NE), bioaugmentation (BA), biostimulation (BS), and sterilized soil (SS). Within 330 days of operation, the residual total petroleum hydrocarbon-diesel (TPH(subscript d)) was degraded from 10,290 mg TPH(subscript d)/dry soil to 3026, 1851. 4105, and 6506 mg TPH(subscript d)/kg dry soil by Columns NE, BA, US. and SS, respectively. The diesel-degradation efficiency was 67%, 80%. 45%, and 24%, accordingly. Microbial diversity was monitored with molecular biotechnology DGGE It was found that introduced bacteria CC-CF3 and CC-JG39 become undetectable after 90 days of operation, hut another introduced bacteria, CC-RS1, evidently remained with small signals during the last time stage of operation.

Background Human Papillomavirus is responsible for over 99 % of cervical cancers and is associated with cancers of the head and neck. The currently available prophylactic vaccines against HPV do not generate therapeutic effects against established HPV infections and associated lesions and disease. Thus, the need for a therapeutic vaccine capable of treating HPV-induced malignancies persists. Synthetic long peptides vaccination is a popular antigen delivery method because of its safety, stability, production feasibility, and its need to be processed by professional antigen presenting cells before it can be presented to cytotoxic CD8+ T lymphocytes. Cancers in the buccal mucosa have been shown to elicit cancer-related inflammations that are capable of recruiting inflammatory and immune cells to generate antitumor effects. In the current study, we evaluated the therapeutic potential of synthetic HPV long peptide vaccination in the absence of adjuvant in the TC-1 buccal tumor model. Result We show that intratumoral vaccination with E7 long peptide alone effectively controls buccal TC-1 tumors in mice. Furthermore, we observed an increase in systemic as well as local E7-specific CD8+ T cells in buccal tumor-bearing mice following the vaccination. Finally, we show that induction of immune responses against buccal tumors by intratumoral E7 long peptide vaccination is independent of CD4+ T cells, and that the phenomenon may be related to the unique environment associated with mucosal tissues. Conclusion Our results suggest the possibility for clinical translation of the administration of adjuvant free therapeutic long peptide vaccine as a potentially effective and safe strategy for mucosal HPV-associated tumor treatment. Electronic supplementary material The online version of this article (doi:10.1186/s13578-016-0083-9) contains supplementary material, which is available to authorized users.

Immunotherapy has emerged as a promising approach that can be used in conjunction with conventional chemotherapy and radiotherapy to further improve the survival rate of patients with advanced cancer. We have recently shown in previous studies that chemotherapy and radiation therapy can alter the tumor microenvironment and allow intratumoral vaccination to prime the adaptive immune system leading to the generation of antigen-specific cell-mediated immune responses. Here, we investigated whether intratumoral injection of a foreign immunodominant peptide (GP33) and the adjuvant CpG into tumors following cisplatin chemotherapy could lead to potent antitumor effects and antigen-specific cell-mediated immune responses. We observed that treatment with all three agents produced the most potent antitumor effects compared to pairwise combinations. Moreover, treatment with cisplatin, CpG and GP33 was able to control tumors at a distant site, indicating that our approach is able to induce cross-presentation of the tumor antigen. Treatment with cisplatin, CpG and GP33 also enhanced the generation of GP33-specific and E7-specific CD8+ T cells and decreased the number of MDSCs in tumor loci, a process found to be mediated by the Fas-FasL apoptosis pathway. The treatment regimen presented here represents a universal approach to cancer control.

BackgroundThe influence of the gut flora on lung inflammatory reaction against bacterial challenge remains undefined. This study was designed to investigate whether gut flora enhances lung defense againstE.colipneumonia through TLR4 signaling.MethodsC3H/HeN (WT) mice and C3H/HeJ (TLR4 deficient) mice were treated with antibiotics in drinking water for 4 weeks to deplete gut commensal microflora. At week 3, drinking water was supplemented with lipopolysaccharide (LPS); a ligand for TLR4, to trigger TLRs in intestinal tract. At the end of 4thweek,E.coliwas injected to trachea to induceE.colipneumonia.ResultsWe found that commensal depletion by antibiotic pretreatment beforeE.colipneumonia challenge induced a 30% decrease of MPO activity in the lung, a significant decrease of bacterial killing activity of alveolar macrophage, and bacterial counts in C3H/HeN mice but not in C3H/HeJ (TLR4 deficient) mice. LPS, a TLR4 ligand, supplementation during antibiotic pretreatment reversed these effects and decreasedE.colipneumonia-induced mortality in C3H/HeN mice. Furthermore, commensal depletion induced a suppression of NF-κB DNA binding activity and an increase of KC, MIP-2, IL-1β expression in the lung in C3H/HeN mice but not in C3H/HeJ mice.ConclusionsTaken together with that commensal depletion increasedE.colipneumonia-induced mortality and LPS supplementation decreased it, we conclude that gut flora enhances bacterial clearance againstE.colipneumonia through TLR4.

A 59-year-old woman presented to our hospital after 2 days f progressive abdominal pain, nausea and vomiting. The physial examination showed a distended abdomen, hypoactive bowel ounds, and diffuse abdominal tenderness. The laboratory tests evealed white-cell count of 6450 per cubic millimetre with 78% eutrophils. A contrast enhanced computed tomographic scan of he abdomen revealed lipomatosis of small bowel and causing owel obstruction (Fig. 1). An explorative laparotomy discovered ipomatosis of small intestine andmesentery (Fig. 2A), which were ausing intestinal obstruction. Segmental resection of tumournvolved intestine was performed. The pathological diagnosis was onfirmed with lipomatous polyposis of ileum. Under microscopy ections, the specimen showed small intestinal tissuewithmultiple ubmucosal lipomatous nodules and composed of abnormal collecions of mature adipose tissue (Panel 2B). The patient started oral ntakewithwater at postoperative day 7 and regular diet at postoprative day 9. Postoperative wound infection was presented. After ound change dressing, the patient was discharged in good health month later. Primary small intestinal tumoursareuncommon,whichaccount or about 1% of all gastrointestinal tumours, and primary lipomas f the small intestine are rare [1]. Most patients are presentedwith aroxysmal abdominal pain, haemorrhage of digestive tract, and bdominal masses. Surgical intervention should be considered if ausing intestinal obstruction secondary to intussusception.

In the spectral range 34500–40000 cm −1 , two molecular species were detected by means of laser-induced fluorescence in the 193 nm photolysis of acetylene: one is C 2 (a 3 Π u ), the other is most likely C 2 H( X ). The identification of C 2 H is based u the rotational constants ( B ″ = 1.4397–1.4534 cm −1 ), the deuterium isotope effect on the vibronic bands, and the wavelength-resolved fluorescence.

An autostereoscopic display provides users great enjoyment of stereo visualization without uncomfortable and inconvenient drawbacks of wearing stereo glasses. However, bandwidth constraints of current multi-view 3D display severely restrict the number of views that can be simultaneously displayed without degrading resolution or increasing display cost unacceptably. An alternative to multiple view presentation is that the position of observer can be measured by using viewer-tracking sensor. It is a very important module of the viewer-tracking component for fluently rendering and accurately projecting the stereo video. In order to render stereo content with respect to user's view points and to optically project the content onto the left and right eyes of the user accurately, the real-time viewer tracking technique that allows the user to move around freely when watching the autostereoscopic display is developed in this study. It comprises the face detection by using multiple eigenspaces of various lighting conditions, fast block matching for tracking four motion parameters of the user's face region. The Edge Orientation Histogram (EOH) on Real AdaBoost to improve the performance of original AdaBoost algorithm is also applied in this study. The AdaBoost algorithm using Haar feature in OpenCV library developed by Intel to detect human face and enhance the accuracy performance with rotating image. The frame rate of viewer tracking process can achieve up to 15 Hz. Since performance of the viewer tracking autostereoscopic display is still influenced under variant environmental conditions, the accuracy, robustness and efficiency of the viewer-tracking system are evaluated in this study.

Chemotherapy and/or radiation therapy are widely used as cancer treatments, but the antitumor effects they produce can be enhanced when combined with immunotherapies. Chemotherapy kills tumor cells, but it also releases tumor antigen and allows the cross-presentation of the tumor antigen to trigger antigen-specific cell-mediated immune responses. Promoting CD4+ T helper cell immune responses can be used to enhance the cross-presentation of the tumor antigen following chemotherapy. The pan HLA-DR binding epitope (PADRE peptide) is capable of generating antigen-specific CD4+ T cells that bind various MHC class II molecules with high affinity and has been widely used in conjunction with vaccines to improve their potency by enhancing CD4+ T cell responses. Here, we investigated whether intratumoral injection of PADRE and the adjuvant CpG into HPV16 E7-expressing TC-1 tumors following cisplatin chemotherapy could lead to potent antitumor effects and antigen-specific cell-mediated immune responses. We observed that treatment with all three agents produced the most potent antitumor effects compared to pairwise combinations. Moreover, treatment with cisplatin, CpG and PADRE was able to control tumors at a distant site, indicating that our approach is able to induce cross-presentation of the tumor antigen. Treatment with cisplatin, CpG and PADRE also enhanced the generation of PADRE-specific CD4+ T cells and E7-specific CD8+ T cells and decreased the number of MDSCs in tumor loci. The treatment regimen presented here represents a universal approach to cancer control.

Background Loss of intestinal integrity is a critical contributor to excessive inflammation following severe trauma or major surgery. In the case of enterocyte damage, intestinal fatty acid-binding protein (IFABP) is released into the extracellular space. Excessive production of interleukin (IL)-6 can induce systemic inflammatory response syndrome (SIRS). However, the correlation of IL-6 with gut barrier failure and bacterial translocation in critically ill patients has not been well characterized. Purposes To define the relationship between enteric bacterial loads and IL-6 levels in patients with SIRS. Methods Variables related to prognosis and treatment were measured in 85 patients with SIRS upon admission to the emergency room. IL-6 and IFABP were measured using an enzyme-linked immunosorbent assay. Enteric bacterial loads in blood were measured through quantitative real-time polymerase chain reaction with primers specific for enteric bacteria. Results Multivariate analysis revealed a positive correlation between enteric bacterial loads and IL-6 levels in blood. Elevated IFABP concentration was associated with low blood pressure, high respiration rate, hyperglycemia, and high Sequential Organ Failure Assessment score. Elevated C-reactive protein concentrations were associated with higher soluble CD14 levels in blood. Conclusion Enterocyte damage is associated with hypotension and tachypnia in patients with SIRS. Gut function failure may permit enteric bacteria to enter the blood, thereby elevating IL-6 levels and inducing a systemic inflammatory response, resulting in multiple organ failure.