[Application and advances of nanozyme-loaded tissue engineering scaffolds in wound repair].

At present, effective reconstruction of the integrity and functionality of damaged skin tissue remains an important medical problem in the field of wound repair. In recent years, the rapid development of nanozymes and tissue engineering scaffolds in the field of regenerative medicine has made it possible to develop new skin wound repair materials. Based on the process of skin wound repair and regeneration, this review briefly describes the nanozymes and its catalytic mechanism. At the same time, the common tissue engineering scaffolds loaded with nanozymes and their manufacturing strategies are introduced, the application of tissue engineering scaffolds loaded with nanozymes during the stages of anti-bacteria and anti-inflammation in the process of wound repair is summarized, and their future development direction is discussed.

[Transcriptomic analysis of the ΔPaLoc mutant of Clostridioides difficile and verification of its toxicity].

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.

Photon beam energy dependent single-arc volumetric modulated arc optimization.

PURPOSE: The purpose of this work was to present a new single-arc mixed photon (6&18MV) VMAT (SAMP) optimization framework that concurrently optimizes for two photon energies with corresponding partial arc lengths. METHODS AND MATERIALS: Owing to simultaneous optimization of energy dependent intensity maps and corresponding arc locations, the proposed model poses nonlinearity. Unique relaxation constraints based on McCormick approximations were introduced for linearization. Energy dependent intensity maps were then decomposed to generate apertures. Feasibility of the proposed framework was tested on a sample of ten prostate cancer cases with lateral separation ranging from 34 cm (case no.1) to 52 cm (case no.6). The SAMP plans were compared against single energy (6MV) VMAT (SE) plans through dose volume histograms (DVHs) and radiobiological parameters including normal tissue complication probability (NTCP) and equivalent uniform dose (EUD). RESULTS: The contribution of higher energy photon beam optimized by the algorithm demonstrated an increase for cases with a lateral separation >40 cm. SAMP-VMAT notably improved bladder and rectum sparing in large size cases. Compared to single energy, SAMP-VMAT plans reduced bladder and rectum NTCP in cases with large lateral separation. With the exception of one case, SAMP-VMAT either improved or maintained femoral heads compared to SE-VMAT. SAMP-VMAT reduced the nontarget tissue integral dose in all ten cases. CONCLUSIONS: A single-arc VMAT optimization framework comprising mixed photon energy partial arcs was presented. Overall results underline the feasibility and potential of the proposed approach for improving OAR sparing in large size patients without compromising the target homogeneity and coverage.

[Involvement of Src kinase in the down-regulation of ultra-rapid delayed rectifier K(+)current induced by tumor necrosis factor-α in cardiomyocytes].

Objective: To investigate whether inflammatory factor tumor necrosis factor-α (TNF-α) is involved in the electrical remodeling of cardiomyocytes by regulating ultra-rapid delayed rectifier K(+) current (I(kur)) and the role of Src kinase. Methods: H9c2 cells, embryonic cardiomyocytes of rat, were cultured in Dulbecco's modified Eagle's medium (DMEM) and atrium-derived HL-1 cells were cultured in Claycomb medium. Both H9c2 and HL-1 cells were cultured at 37 ℃ with 5% CO(2). Cells cultured in normal conditions without additional treatment served as control group. Experimental groups were treated with different concentration of TNF-α (25 or 50 or 100 ng/ml) for 24 hours. To study whether Src specific inhibitor PP1 could abrogate the effect of TNF-α, cells were pre-treated with 10 µmol/L PP1 for 1 hour, followed by TNF-α (100 ng/ml) for 24 hours. Western blot and the whole cell patch clamp technique were used to detect the protein expression of Kv1.5 and Src and I(kur) in each group. Results: (1) In H9c2 cells, high concentration of TNF-α treatment (100 ng/ml) significantly reduced the Kv1.5 protein expression compared with control group and TNF-α 25 ng/ml group (both P<0.05). Compared with control group, the expression of p-Src protein was higher in 25 ng/ml, 50 ng/ml, 100 ng/ml TNF-α group (all P<0.05), but there was no statistical difference in the expression of Src protein among groups (P>0.05). In addition, the current density of I(kur) was decreased in 50 ng/ml, 100 ng/ml TNF-α group (both P<0.05). Furthermore, the expression of Kv1.5 protein and the current density of I(kur) were increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (both P<0.05). There was no statistical difference in the expression of Kv1.5 protein and the current density of I(kur) between the control group and PP1+TNF-α group (both P>0.05). (2) In atrium-derived HL-1 cells, the expression of Kv1.5 protein was reduced in 100 ng/ml TNF-α group compared with control group and TNF-α 25 ng/ml group (both P<0.01). In addition, the expression of p-Src protein was increased in TNF-α 100 ng/ml group compared with control group (P<0.05), but there was no statistical difference in the protein expression of Src among groups (P>0.05). The expression of Kv1.5 protein was increased in PP1+TNF-α group compared with TNF-α 100 ng/ml group (P<0.05). Conclusion: TNF-α is involved in the pathogenesis of atrial fibrillation, probably via decreasing I(kur) current density in atrium-derived myocytes through the activation of Src kinase.

[Proximal femoral nails antirotation and dynamic hip screws for fixation of unstable intertrochanteric fractures of femur: A meta-analysis].

OBJECTIVE: To evaluate the efficacy and safety of proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) for unstable intertrochanteric fractures using meta-analysis. METHODS: The PubMed, Embase, Cocharane Central Register of Controlled Trials, Google Scholar, China Science and Technology Papers and Citation Database (CSTPCD) and China Journal Full-text Database (CNKI) were searched for published randomized controlled trials before January 1, 2019. Two researchers independently screened the literature in the light of the inclusion and exclusion criteria, evaluated the quality of the studies and extracted the data which were consisted of clinical efficacy indexes, such as incision length, operation time,intraoperative blood loss, weight-bearing time,fracture-healing time, Harris hip score and safety indicators like complications. Meta-analysis was performed with the Revman 5.3 software provided by Cochrane Community in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standard. RESULTS: Nine randomized controlled trials met the requirement with a total of 779 patients, of whom 383 were fixed with PFNA and 396 with DHS. Meta-analysis demonstrated that PFNA was associated with smaller surgical incision length [MD=-7.43, 95%CI (-9.31, -5.55), P<0.05], shorter operation time [MD=-22.76, 95%CI (-29.57, -11.95), P<0.05], less intraoperative blood loss [MD=-216.34, 95%CI (-275.18, - 157.49), P<0.05], earlier weight bearing after surgery [MD=-12.34, 95%CI (-17.71, -6.97), P<0.05], shorter fracture healing time [MD=-5.00, 95%CI (-7.73, -2.26), P<0.05], higher postoperative Harris hip score [MD=12.22, 95%CI (3.88, 20.55), P<0.05], higher rate of excellent Harris hip score [OR=3.56, 95%CI (1.44, 8.81), P<0.05] and lower incidence rate of postoperative complications [OR=0.48, 95%CI (0.33, 0.70), P<0.05], such as hip varus, wound infection, urinary tract infection, pulmonary infection, pressure sore, deep vein thrombosis, pulmonary embolism, heart failure and cerebral infraction when compared with DHS. No statistical difference was shown between the groups when it came to subgroup analysis by age. However, there was no significant difference (P>0.05) in the duration of hospitalization and the complications resulting in the occurrences of internal fixation loosening, such as femoral shaft fracture (during or post operation), internal fixation fracture, cut-out, displacement or retraction. CONCLUSION: Current published evidence supports the superiority of PFNA to DHS for unstable intertrochanteric fractures in terms of clinical efficacy. The conclusion was limited because of the relatively low quality of evidence with low strength of confidence. Large scale and high-quality randomized controlled trials are required to validate the safety of PFNA and DHS for unstable intertrochanteric fractures.

[Multi-level analysis on factors affecting the adherence to early antithrombotic therapy among people with acute ischemic stroke].

Objective: To explore the patient and hospital related determinants of adherence to early antithrombotic therapy among patients with acute ischemic stroke (AIS). Methods: AIS patients aged 50 years old or above who were eligible for early antithrombotic therapy, were included from the China National Stroke Registry Ⅱ (CNSR Ⅱ) project. Characteristics related to patients and hospitals were collected. Univariate analysis method was conducted to explore the correlation between hospital or patient-related determinants and early antithrombotic therapy. A 2-level logistic regression model was set up to identify patient and hospital-related variables that were associated with the adherence to early antithrombotic therapy, with patient as level 1 and hospital as level 2. Results: A total of 16 910 patients were included in the study, with 14 332 (84.75%) of them having received early antithrombotic therapy. Results from the univariate analysis showed that the patient determinants to early antithrombotic therapy would include age, type of health insurance, average income and history of dyslipidemia. Hospital determinants would include factors as: level and region of the hospital, academic status, with/without stroke unit, quality control on single disease and the percentage of neurological beds in total beds (P<0.05). Data on multilevel model showed that the patient-related determinants on early antithrombotic therapy would include age, gender, average income, history of hypertension, National Institutes of Health Stroke Scale (NIHSS) score at admission while hospital related determinants would include percentage of neurological beds in total beds, and region of the hospital (P<0.05). Conclusions: The quality of a hospital was associated with the adherence to early antithrombotic therapy. AIS patients at advanced age or with high NIHSS score at admission should be paid more attention.

Robotically-Assisted Sonic Therapy for Renal Ablation in a Live Porcine Model: Initial Preclinical Results.

PURPOSE: To demonstrate the feasibility of Robotically Assisted Sonic Therapy (RAST)-a noninvasive and nonthermal focused ultrasound therapy based on histotripsy-for renal ablation in a live porcine model. MATERIALS AND METHODS: RAST ablations (n = 11) were performed in 7 female swine: 3 evaluated at 1 week (acute) and 4 evaluated at 4 weeks (chronic). Treatment groups were acute bilateral (3 swine, 6 ablations with immediate computed tomography [CT] and sacrifice); chronic single kidney (3 swine, 3 ablations; CT at day 0, week 1, and week 4 after treatment, followed by sacrifice); and chronic bilateral (1 swine, 2 ablations). Treatments were performed using a prototype system (VortxRx; HistoSonics, Inc) and targeted a 2.5-cm-diameter sphere in the lower pole of each kidney, intentionally including the central collecting system. RESULTS: Mean treatment time was 26.4 minutes. Ablations had a mean diameter of 2.4 ± 0.3 cm, volume of 8.5 ± 2.4 cm3, and sphericity index of 1.00. Median ablation volume decreased by 96.1% over 4 weeks. Histology demonstrated complete lysis with residual blood products inside the ablation zone. Temporary collecting system obstruction by thrombus was observed in 4/11 kidneys (2 acute and 2 chronic) and resolved by 1 week. There were no urinary leaks, main vessel thromboses, or adjacent organ injuries on imaging or necropsy. CONCLUSIONS: In this normal porcine model, renal RAST demonstrated complete histologic destruction of the target renal tissue while sparing the urothelium.

Robotically Assisted Sonic Therapy (RAST) for Noninvasive Hepatic Ablation in a Porcine Model: Mitigation of Body Wall Damage with a Modified Pulse Sequence.

PURPOSE: Robotically assisted sonic therapy (RAST) is a nonthermal, noninvasive ablation method based on histotripsy. Prior animal studies have demonstrated the ability to create hepatic ablation zones at the focal point of an ultrasound therapy transducer; however, these treatments resulted in thermal damage to the body wall within the path of ultrasound energy delivery. The purpose of this study was to evaluate the efficacy and safety of a pulse sequence intended to mitigate prefocal body wall injury. MATERIALS AND METHODS: Healthy swine (n = 6) underwent hepatic RAST (VortxRx software version 1.0.1.3, HistoSonics, Ann Arbor MI) in the right hepatic lobe. A 3.0 cm spherical ablation zone was prescribed for each. Following treatment, animals underwent MRI which was utilized for ablation zone measurement, evaluation of prefocal injury, and assessment of complications. Each animal was euthanized, underwent necropsy, and the tissue was processed for histopathologic analysis of the ablation zone and any other sites concerning for injury. RESULTS: No prefocal injury was identified by MRI or necropsy in the body wall or tissues overlying the liver. Ablation zones demonstrated uniform cell destruction, were nearly spherical (sphericity index = 0.988), and corresponded closely to the prescribed size (3.0 × 3.1 × 3.4 cm, p = 0.70, 0.36, and 0.01, respectively). Ablation zones were associated with portal vein (n = 3, one occlusive) and hepatic vein thrombosis (n = 4, one occlusive); however, bile ducts remained patent within ablation zones (n = 2). CONCLUSIONS: Hepatic RAST performed with a modified ultrasound pulse sequence in a porcine model can mitigate prefocal body wall injuries while maintaining treatment efficacy. Further study of hepatic RAST appears warranted, particularly in tumor models.

Evaluation of mixed energy partial arcs for volumetric modulated arc therapy for prostate cancer.

PURPOSE: The purpose of this work was to investigate the dosimetric impact of mixed energy (6-MV, 15-MV) partial arcs (MEPAs) technique on prostate cancer VMAT plans. METHODS: This work involved prostate only patients, planned with 79.2 Gy in 44 fractions to the planning target volume (PTV). Femoral heads, bladder, and rectum were considered organs at risk. This study was performed in two parts. For each of the 25 patients in Part 1, two single-energy single-arc plans, a 6 MV-SA plan and a 15 MV-SA plan, and a third MEPA plan involving composite of 6-MV anterior-posterior partial arcs and a 15-MV lateral partial arc weighted 1:2 were created. The dosimetric difference between MEPA(6/15 MV 1:2 weighted) and 6 MV-SA plans, and MEPA(6/15 MV 1:2 weighted) and 15 MV-SA plans were measured. In the Part 2 of this study, a second MEPAs plan (6 MV anterior-posterior arcs and 15 MV lateral arcs weighted 1:1), (MEPA 6/15 MV 1:1 weighted), was generated for 15 patients and compared only with two single-energy partial arcs plans, a 6 and a 15 MV-PA, to investigate the influence of the energy only. Dosimetric parameters of each structure, total monitor-units (MUs), homogeneity index (HI), and conformity number (CN) were analyzed. RESULTS: In Part 1, no statistically significant differences were observed for mean dose to PTV and CN for MEPAs (6/15 MV 1:2 weighted) vs 6 and 15 MV-SA. MEPAs (6/15 MV 1:2 weighted) increased HI compared to 6 and 15 MV-SA (P < 0.0005; P < 0.0005). MEPAs (6/15 MV 1:2 weighted) produced significantly lower mean doses to rectum, bladder, and MUs/fraction, but higher mean doses to femoral heads, compared to 6 MV-SA (P < 0.0005) and 15 MV-SA (P < 0.0005). The results of Part 2 of this study showed that, in comparison to 6 and 15 MV-PA, MEPAs (6/15 MV 1:1 weighted) plans significantly improved CNs (P < 0.0005; P < 0.0005) and produced significantly lower mean doses to the rectum and bladder (P < 0.0005; P < 0.0005). While mean doses to the PTV and femoral heads of MEPAs (6/15 MV 1:1 weighted) plans were statistically comparable to 6 MV-PA (P > 0.05), MEPAs (6/15 MV 1:1 weighted) increased mean doses to left (P = 0.04) and right (P = 0.04) femoral heads compared to 15 MV-PA. MEPAs (6/15 MV 1:1 weighted) resulted in significantly lower total MUs compared to 6 MV-PA (P < 0.0005) and 15 MV-PA (P = 0.04). CONCLUSION: The study for prostate radiotherapy demonstrated that a choice of MEPAs for VMAT has the potential to minimize doses to OARs and improve dose conformity to PTV, at the expense of a moderate increase in mean dose to the femoral heads.

Characterization of a 2.5 MV inline portal imaging beam.

A new megavoltage (MV) energy was recently introduced on Varian TrueBeam linear accelerators for imaging applications. This work describes the experimental characterization of a 2.5 MV inline portal imaging beam for commissioning, routine clinical use, and quality assurance purposes. The beam quality of the 2.5 MV beam was determined by measuring a percent depth dose, PDD, in water phantom for 10 × 10 cm2 field at source-to-surface distance 100 cm with a CC13 ion chamber, plane parallel Markus chamber, and GafChromic EBT3 film. Absolute dosimetric output calibration of the beam was performed using a traceable calibrated ionization chamber, following the AAPM Task Group 51 procedure. EBT3 film measurements were also performed to measure entrance dose. The output stability of the imaging beam was monitored for five months. Coincidence of 2.5 MV imaging beam with 6 MV therapy beam was verified with hidden-target cubic phantom. Image quality was studied using the Leeds and QC3 phantom. The depth of maximum dose, dmax, and percent dose at 10 cm depth were, respectively, 5.7 mm and 51.7% for CC13, 6.1 mm and 51.9% for Markus chamber, and 5.1 mm and 51.9% for EBT3 film. The 2.5 MV beam quality is slightly inferior to that of a 60Co teletherapy beam; however, an estimated kQ of 1.00 was used for output calibration purposes. The beam output was found to be stable to within 1% over a five-month period. The relative entrance dose as measured with EBT3 films was 63%, compared to 23% for a clinical 6 MV beam for a 10 × 10 cm2 field. Overall coincidence of the 2.5 MV imaging beam with the 6 MV clinical therapy beam was within 0.2 mm. Image quality results for two com-monly used imaging phantoms were superior for the 2.5 MV beam when compared to the conventional 6 MV beam. The results from measurements on two TrueBeam accelerators show that 2.5 MV imaging beam is slightly softer than a therapeutic 60Co beam, it provides superior image quality than a 6 MV therapy beam, and has excellent output stability. These 2.5 MV beam characterization results can serve as reference for clinics planning to commission and use this novel energy-image modality.

Development of a residency program in radiation oncology physics: an inverse planning approach.

Over the last two decades, there has been a concerted effort in North America to organize medical physicists' clinical training programs along more structured and formal lines. This effort has been prompted by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP) which has now accredited about 90 residency programs. Initially the accreditation focused on standardized and higher quality clinical physics training; the development of rounded professionals who can function at a high level in a multidisciplinary environment was recognized as a priority of a radiation oncology physics residency only lately. In this report, we identify and discuss the implementation of, and the essential components of, a radiation oncology physics residency designed to produce knowledgeable and effective clinical physicists for today's safety-conscious and collaborative work environment. Our approach is that of inverse planning, by now familiar to all radiation oncology physicists, in which objectives and constraints are identified prior to the design of the program. Our inverse planning objectives not only include those associated with traditional residencies (i.e., clinical physics knowledge and critical clinical skills), but also encompass those other attributes essential for success in a modern radiation therapy clinic. These attributes include formal training in management skills and leadership, teaching and communication skills, and knowledge of error management techniques and patient safety. The constraints in our optimization exercise are associated with the limited duration of a residency and the training resources available. Without compromising the knowledge and skills needed for clinical tasks, we have successfully applied the model to the University of Calgary's two-year residency program. The program requires 3840 hours of overall commitment from the trainee, of which 7%-10% is spent in obtaining formal training in nontechnical "soft skills".

Is tissue harmonic ultrasound imaging (THI) of the prostatic urethra and rectum superior to brightness (B) mode imaging? An observer study.

Quality ultrasound images are an essential part of prostate brachytherapy procedure. The authors have previously reported that tissue harmonic ultrasound images (THI) are superior to brightness (B) mode for the prostate. The objective of the current study was to compare both imaging modes for visualization of the prostatic urethra and rectum. B and THI mode transrectal ultrasound images were acquired for ten patients. The prostatic urethra and rectal wall were contoured by a radiation oncologist (RO) and five observers on randomly presented images. The contours on one patient were repeated four additional times by four observers. All the images were qualitatively scored using a five-level Likert scale. The values of the Pearson product-moment correlation coefficients showed that the observers were in close agreement with the RO. Two sample paired student t-test showed that the rectum volumes with THI were significantly smaller than B-mode, but no significant difference for urethra. Two-factor analysis of variances showed significant observer variability in defining the rectum and urethra in both imaging modes. Observer consistency of the rectum volumes, estimated by standard deviations as percentages of means was significantly improved for THI. The Likert scale based qualitative assessment supported quantitative observations. The significant improvement in image quality of the prostate (reported previously) and rectum with THI may offer better-quality treatment plans for prostate brachytherapy and potential improvement in local control.

Energy response of EBT3 radiochromic films: implications for dosimetry in kilovoltage range.

The objective of this study is to evaluate the suitability of recently introduced radiochromic film EBT3 for clinical dosimetry in the kilovoltage (kV) range. For this purpose, a kV X-ray irradiator, X RAD 320ix in the range 70 to 300 kVp, a clinical 60Co source, a 6 MV and an 18 MV X-ray clinical beam from a Varian linear accelerator were calibrated following AAPM dosimetry protocols. EBT3 films from two different EBT3 batches were placed side-by-side on the surface of a water phantom; doses from 0.5 to 4 Gy were delivered. Similarly, irradiations were performed for 60Co and 6 and 18 MV beams in a water equivalent phantom. Films were reproducibly placed at the center of a flatbed scanner and 48-bit RGB scans were obtained both pre- and postirradiations. Net optical density (netOD) and response for a given radiation quality relative to 60Co was determined for each EBT3 film. The netOD of the red color showed reproducible response (within 1%) for both batches when irradiated using the 60Co source. For a given dose of 1 Gy of kVp X-ray, the response relative to 60Co using the three color channels (red, green, and blue) decreases with decrease in kVp, reaching a maximum underresponse of ~ 20% for the 70 kVp. A significant underresponse of ~ 5% was observed at 300kVp. Responses of MV X-ray beams with respect to 60Co at the 1 Gy dose level showed no statistically significant difference. A relatively small difference in the response was observed between the two EBT3 batches used in this study in the kV X-ray range.

Effect of Acuros XB algorithm on monitor units for stereotactic body radiotherapy planning of lung cancer.

Stereotactic body radiotherapy (SBRT) is a curative regimen that uses hypofractionated radiation-absorbed dose to achieve a high degree of local control in early stage non-small cell lung cancer (NSCLC). In the presence of heterogeneities, the dose calculation for the lungs becomes challenging. We have evaluated the dosimetric effect of the recently introduced advanced dose-calculation algorithm, Acuros XB (AXB), for SBRT of NSCLC. A total of 97 patients with early-stage lung cancer who underwent SBRT at our cancer center during last 4 years were included. Initial clinical plans were created in Aria Eclipse version 8.9 or prior, using 6 to 10 fields with 6-MV beams, and dose was calculated using the anisotropic analytic algorithm (AAA) as implemented in Eclipse treatment planning system. The clinical plans were recalculated in Aria Eclipse 11.0.21 using both AAA and AXB algorithms. Both sets of plans were normalized to the same prescription point at the center of mass of the target. A secondary monitor unit (MU) calculation was performed using commercial program RadCalc for all of the fields. For the planning target volumes ranging from 19 to 375cm(3), a comparison of MUs was performed for both set of algorithms on field and plan basis. In total, variation of MUs for 677 treatment fields was investigated in terms of equivalent depth and the equivalent square of the field. Overall, MUs required by AXB to deliver the prescribed dose are on an average 2% higher than AAA. Using a 2-tailed paired t-test, the MUs from the 2 algorithms were found to be significantly different (p < 0.001). The secondary independent MU calculator RadCalc underestimates the required MUs (on an average by 4% to 5%) in the lung relative to either of the 2 dose algorithms.

Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells.

Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.

Involvement of Src tyrosine kinase and protein kinase C in the expression of macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac muscle cells

Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an important role in the pathogenesis of atrial fibrillation; however, the upstream regulation of MIF in atrial myocytes remains unclear. In the present study, we investigated whether and how MIF is regulated in response to the renin-angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real-time PCR, and Western blot. The result indicated that MIF was expressed in the cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II, stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels increased in a dose-dependent manner and were completely abolished in the presence of catalase. H2O2-induced MIF production was completely inhibited by tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells. These results suggest that MIF is upregulated by HL-1 cells in response to redox stress, probably by the activation of Src and PKC.

Chest radiological findings of influenza A H1N1 pneumonia.

OBJECTIVE: The objective of this study was to review chest radiographs (CXR) and chest computer tomography (CT) findings in patients with influenza A H1N1 virus pneumonia. MATERIALS AND METHODS: Of ninety-eight patients with influenza A H1N1 infections seen in the General Hospitals of Villa Scassi, Genoa, and Sestri Levante from September 2009 to December 2009, twenty-eight developed pneumonia. The initial CXR were evaluated for radiological patterns: (ground-glass, consolidation, nodules, reticulation), distribution, and extent of the disease. Chest CT scans were reviewed for the same findings. A new radiographic score (CXR score) was used to evaluate the severity of the illness. RESULTS: The predominant radiological findings on chest CT in the patients at presentation were unilateral or bilateral multifocal ground glass opacities (84.5% of the patients). Consolidation areas had a peribronchovascular and subpleural predominance and were found mainly in the middle and upper zones of the lung. Reticular opacities were found in about 20% of the cases. The most outstanding CXR and chest CT features of the disease were basal and axial alveolar consolidation and ground-glass opacities. The severity of disease as determinate by need for mechanical ventilation was greater in patients with a greater number of lobes involved and a higher CXR score. CONCLUSION: Bilateral ground-glass opacities and areas of consolidation were the predominant radiological findings of influenza A (H1N1) virus pneumonia. Multifocal bilateral opacities and CXR score are strictly correlated with the severity of the illness.

Inter-sheet-effect-inspired graphene sensors: design, fabrication and characterization.

With their sub-nanometer inter-sheet spacing, few-layer graphenes (FLGs) are alignment-free building blocks for nanosensors based on the inter-sheet effects. In this paper, we have tackled the challenges towards batch fabrication of inter-sheet graphene sensors through controlled layer engineering, edge tailoring and selective electrode fabrication on different atomic layers. An oxygen plasma etching (OPE) technique is developed to remove graphene layer by layer, enabling the batch fabrication of FLGs in a controllable fashion because of the faster speed and readiness of patterning of this process as compared to the conventional mechanical exfoliation. Vapor sensing experiments have shown that 'inter-sheet' sensors possess a higher sensitivity than conventional 'intra-sheet' ones. Vapor sensitivity is improved more than two times in normalized resistance changes by taking the 'inter-sheet' design upon exposure to 0.5% ethanol-nitrogen mixture and 500 Pa water vapor environments, respectively. These remarkable improvements can mainly be attributed to the inter-sheet effects such as electron tunneling, chemical doping, physical insertion and enhanced edge effects. Such effects may result from molecule adsorption/desorption, force/displacement, pressure, surface tension or thermal energy, and can potentially remarkably enrich the applicable transduction mechanisms.