MEDITERRANEAN DIET AND ITS IMPACT ON THE ILLNESS CHARACTERISTIC OF YOUTH WITH IRRITABLE BOWEL CONDITION.

Irritable Bowel Disorder (IBD) is a prevalent digestive illness that frequently affects young people and drastically decreases the Quality of Life (QoL). Adults with IBD indications may find relief from their symptoms through nutritional changes like the Mediterranean-style diet. Concerning the seriousness of symptoms, QoL, and additional pertinent results in young people with IBD, this investigation seeks to determine the impact of the Mediterranean-style diet. 200 individuals with IBD who met the Rome-IV criterion and were between the ages of 13 and 19 were enrolled in the present research. A Mediterranean-style diet was provided to the Study Group (SG), which consisted of 100 individuals, while the Control Group (CG), which consisted of 100 patients, followed the usual diet. Various laboratory and clinical characteristics were also assessed at the beginning and end of the study, in addition to IBD values. The Mediterranean-style diet has been demonstrated to be effective and tolerated well in kids and teenagers with IBD. The IBD -SSS (from 148±42.3 to 224±71) IBD -QoL (from 76.7±8.1 to 61.3±9.8), and cumulative IBD rating (from 29.3±11.7 to 32.6±12.1) all showed notable increases in individuals who followed well to this diet. The CG, in comparison, did not show any significant enhancements in these factors. This indicates that a Mediterranean-style diet might provide therapeutic advantages for IBD individuals, especially those who keep adherent to it, concerning symptom severity and QoL. The Mediterranean-style diet proved to be both secure and associated with notable improvements in IBD rates in young and adolescents with IBD.

Dynamic Contrast-enhanced Magnetic Resonance Imaging Evaluation of Whole Tumour Perfusion Heterogeneity Predicts Distant Disease-free Survival in Locally Advanced Rectal Cancer.

AIMS: To evaluate diffusion-weighted imaging and dynamic contrast-enhanced magnetic resonance imaging for the prediction of disease-free survival (DFS) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: Patients with stage II or III rectal adenocarcinoma undergoing neoadjuvant chemoradiotherapy (CRT) and surgery were eligible. Patients underwent multi-parametric magnetic resonance imaging (diffusion-weighted imaging and dynamic contrast-enhanced) before CRT, during CRT (week 3) and after CRT (1 week prior to surgery). Whole tumour apparent diffusion coefficient (ADC) and Ktrans histogram quantiles (10th, 25th, 50th, 75th, 90th) were extracted for analysis. The associations between ADC and Ktrans at three timepoints with time to relapse were analysed as a continuous variable using a Cox proportional hazard model. RESULTS: Thirty-three patients were included in this analysis. The median follow-up was 4.4 years. No patient had locoregional relapse. Nine patients developed distant metastases. The hazard ratios for after CRT Ktrans 10th (P = 0.035), 25th (P = 0.048), 50th (P = 0.046) and 75th (P = 0.045) quantiles were statistically significant for DFS. The best Ktrans cut-off point after CRT for predicting relapse was 28 × 10-3 mL/g/min (10th quantile), with a higher Ktrans value predicting distant relapse. The 4-year DFS probability was 0.93 for patients with after CRT Ktrans value ≤28 × 10-3 mL/g/min versus 0.45 for patients with after CRT Ktrans value >28 × 10-3 mL/g/min. ADC was not able to predict DFS. CONCLUSIONS: Patients with higher Ktrans values after CRT (before surgery) in a histogram analysis of whole tumour heterogeneity had a significantly lower 4-year distant DFS and could be considered for more intense systemic therapy.

[Preliminary experience of transoral robotic surgery for oropharyngeal carcinoma].

Objective: To investigate the oncological and functional efficacy and safety of transoral robotic surgery (TORS) in the treatment of oropharyngeal carcinoma. Methods: Twenty-six patients with oropharyngeal cancer were enrolled who underwent TORS at Beijing United Hospital from June 1, 2017 to December 31, 2020. Among them, 22 patients were males and 4 were females, aged 39 to 76 years old. T1-2 patients accounted for 88.5% (23/26). Clinicopathological data including the time of removal of gastric and endotracheal tube were collected. The SPSS software package was used for survival analysis, and the overall survival rate and disease-free survival rate were calculated. Results: All the 26 patients with oropharyngeal cancer received TORS without conversion to open surgery, and 20 of them underwent simultaneous cervical lymph node dissection. TORS operation time ranged from 65 to 360 minutes with an average of 215 minutes. Intraoperative blood loss ranged from 5 to 600 ml with an average of 70 ml. Four patients (15.4%) underwent tracheotomy, of whom 3 patients had the removals of tracheal tubes within 1 month after surgery and 1 case remained to wear a tube by the end of follow-up. Twelve patients (46.2%) underwent gastric tube implantation, among them, 11 patients had removals of gastric tubes within 1 month after surgery and 1 patient died of oropharyngeal hemorrhage 13 days after operation. One patient (3.8%) had a positive surgical margin and others had pathologically negative surgical margins. Sixteen patients (61.5%) received postoperative radiotherapy, of whom 11 patients (42.3%) received platinum-based concurrent chemotherapy. The median follow-up time was 21.5 months (0.4 to 45 months). The overall survival and the disease-free survival rates were 83.0% and 75.8%, respectively. Conclusion: The application of TORS in treatment of oropharyngeal cancer can achieve good oncological and functional outcomes in selected patients.

Results of in situ fixation of Andersson lesion by posterior approach in 35 cases.

STUDY OBJECTIVE: Due to the rarity of the Andersson lesion (AL), the literature is ambiguous regarding the type of surgical fixation, need for debridement and deformity correction. The purpose of this retrospective study is to evaluate the efficacy, feasibility and functional outcome of posterior fixation in AL. MATERIALS AND METHODS: This study included 35 patients having thoracolumbar AL operated for in situ fixation and fusion with minimum of 24-month follow-up. VAS (Visual Analogue Score) back pain, ODI (Oswestry Disability Index), Frankel's grade were compared and analyzed. Union status was noted with complications. RESULTS: The mean age of 35 patients was 56.34(± 11.3) years with average follow-up of 51.49 months. Two patients had AL at two levels. 27/37 AL were at discal level. Average estimated blood loss (EBL) was 276.43 ml and duration of surgery was 130.43 min. On an average, operated segments needed 7.77 screws. There were ten minor complications without long-term sequel. Neurological improvement was noted in 30 patients. Average preoperative VAS score improved from 8.69 to 3.14, ODI score improved from 68.76 to 18.77 at final follow-up which were significant (p < 0.05). There was significant improvement in Frankel's grading (Z = - 4.354, P = 0.00). CONCLUSIONS: Surgical management of AL by posterior approach and posterior stabilization can give satisfactory results without the need of extensive anterior reconstruction, bone grafting or deformity correction procedures without added morbidity and complications.

Thoracic Spine Stenosis: Does Ultrasonic Osteotome Improve Outcome in Comparison to Conventional Technique?

INTRODUCTION: To investigate the efficacy of Ultrasonic Bone Scalpel (UBS) in thoracic spinal stenosis (TSS) in comparison to traditional technique. MATERIAL AND METHODS: A total of 55 patients who had undergone conventional surgery (Group A) are compared with 45 patients of UBS (Group B) in TSS. The primary outcome measure of Modified Japanese Orthopaedic Association score (m JOA) with neurological complications and dural injury were assessed. Secondary outcome measures of total blood loss (TBL), time duration of surgery (ORT) and length of hospital stay (LHS) were analysed. RESULTS: The pre-operative mJOA score 5.00(4.00-6.00) in the group A and 5.00(4.00-6.00) in the group B improved to 7.00(7.00-8.00) in the group A and 9.00(9.00-10.00) in the group B, respectively (P<0.001) at final average follow-up of 117.55 months for group A and 75.69 months in group B. More significant grade of myelopathy improvement and mJOA recovery rate (RR) were noted in group B. The TBL, ORT and LHS were more favourable in group B as compared to group A (p<0.0001). The group A had 9 (16.36%) neurological deficits compared to 2 (4.44%) in group B (p<0.001). Dural tears occurred in both groups (A=11, B=9). It was more frequent and not repairable in group A but without significant statistical difference. CONCLUSION: UBS can reduce neurological deficits and improve outcomes in TSS. Secondarily, reduced blood loss, lesser surgical time and reduced LHS are significant added advantages of this new technology.

Quantitative MRI: Defining repeatability, reproducibility and accuracy for prostate cancer imaging biomarker development.

INTRODUCTION: Quantitative MRI (qMRI) parameters have been increasingly used to develop predictive models to accurately monitor treatment response in prostate cancer after radiotherapy. To reliably detect changes in signal due to treatment response, predictive models require qMRI parameters with high repeatability and reproducibility. The purpose of this study was to measure qMRI parameter uncertainties in both commercial and in-house developed phantoms to guide the development of robust predictive models for monitoring treatment response. MATERIALS AND METHODS: ADC, T1, and R2* values were acquired across three 3 T scanners with a prostate-specific qMRI protocol using the NIST/ISMRM system phantom, RSNA/NIST diffusion phantom, and an in-house phantom. A B1 field map was acquired to correct for flip angle inhomogeneity in T1 maps. All sequences were repeated in each scan to assess within-session repeatability. Weekly scans were acquired on one scanner for three months with the in-house phantom. Between-session repeatability was measured with test-retest scans 6-months apart on all scanners with all phantoms. Accuracy, defined as percentage deviation from reference value for ADC and T1, was evaluated using the system and diffusion phantoms. Repeatability and reproducibility coefficients of variation (%CV) were calculated for all qMRI parameters on all phantoms. RESULTS: Overall, repeatability CV of ADC was <2.40%, reproducibility CV was <3.98%, and accuracy ranged between -8.0% to 2.7% across all scanners. Applying B1 correction on T1 measurements significantly improved the repeatability and reproducibility (p<0.05) but increased error in accuracy (p<0.001). Repeatability and reproducibility of R2* was <4.5% and <7.3% respectively in the system phantom across all scanners. CONCLUSION: Repeatability, reproducibility, and accuracy in qMRI parameters from a prostate-specific protocol was estimated using both commercial and in-house phantoms. Results from this work will be used to identify robust qMRI parameters for use in the development of predictive models to longitudinally monitor treatment response for prostate cancer in current and future clinical trials.

Pelvic organ motion and dosimetric implications during horizontal patient rotation for prostate radiation therapy.

PURPOSE: Gantry-free radiation therapy systems utilizing patient rotation would be simpler and more cost effective than the conventional gantry-based systems. Such a system could enable the expansion of radiation therapy to meet global demand and reduce capital costs. Recent advances in adaptive radiation therapy could potentially be applied to correct for gravitational deformation during horizontal patient rotation. This study aims to quantify the pelvic organ motion and the dosimetric implications of horizontal rotation for prostate intensity-modulated radiation therapy (IMRT) treatments. METHODS: Eight human participants who previously received prostate radiation therapy were imaged in a clinical magnetic resonance imaging (MRI) scanner using a bespoke patient rotation system (PRS). The patients were imaged every 45 degrees during a full roll rotation (0-360 degrees). Whole pelvic bone, prostate, rectum, and bladder motion were compared to the supine position using dice similarity coefficient (DSC) and mean absolute surface distance (MASD). Prostate centroid motion was compared in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) direction prior to and following pelvic bone-guided rigid registration. Seven-field prostate IMRT treatment plans were generated for each patient rotation angles under three adaption scenarios: No plan adaption, rigid planning target volume (PTV)-guided alignment to the prostate, and plan re-optimization. Prostate, rectum, and bladder doses were compared for each adaption scenario. RESULTS: Pelvic bone motion within the PRS of up to 53 mm relative to the supine position was observed for some participants. Internal organ motion was greatest at the 180-degree PRS couch angle (prone), with prostate centroid motion range < 2 mm LR, 0 mm to 14 mm SI, and -11 mm to 4 mm AP. Rotation with no adaption of the treatment plan resulted in an underdose to the PTV -- in some instances up to 75% (D95%: 78 ± 0.3 Gy at supine to 20 ± 15.0 Gy at the 225-degree PRS couch angle). Bladder dose was reduced during the rotation by up to 98% (V60 Gy: 15.0 ± 9.4% supine to 0.3 ± 0.5% at the 225-degree PRS couch angle). In some instances, the rectum dose increased during rotation (V60Gy: 20.0 ± 4.5% supine to 25.0 ± 15.0% at the 135-degree PRS couch angle). Rigid PTV-guided alignment resulted in PTV coverage which, though statistically lower (P < 0.05 for all D95% values), was within 1 Gy of the supine plans. Plan re-optimization resulted in a statistically equivalent PTV coverage compared to the supine plans (P > 0.05 for all D95% metrics and all within ±0.4 Gy). For both rigid PTV-guided alignment and plan re-optimization, rectum dose volume metrics were reduced compared to the supine position between the 90- and 225-degree PRS couch angles (P < 0.05). Bladder dose volume metrics were not impacted by rotation. CONCLUSION: Pelvic bone and internal organ motion are present during patient rotation. Rigid PTV-guided alignment to the prostate will be a requirement if prostate IMRT is to be safely delivered using patient rotation. Plan re-optimization for each PRS couch angle to account for anatomical deformations further improves the PTV coverage.

Anatomical deformation due to horizontal rotation: towards gantry-free radiation therapy.

Gantry-free radiation therapy systems may be simpler and more cost effective, particularly for MRI-guided photon or hadron therapy. This study aims to understand and quantify anatomical deformations caused by horizontal rotation with scan sequences sufficiently short to facilitate integration into an MRI-guided workflow. Rigid and non-rigid pelvic deformations due to horizontal rotation were quantified for a cohort of 8 healthy volunteers using a bespoke patient rotation system and a clinical MRI scanner. For each volunteer a reference scan was acquired at 0° followed by sequential faster scans in 45° increments through to 360°. All fast scans were registered to the 0° image via a three-step process: first, images were aligned using MR visible couch markers. Second, the scans were pre-processed then rigidly registered to the 0° image. Third, the rigidly registered scans were non-rigidly registered to the 0° image to assess soft tissue deformation. The residual differences after rigid and non-rigid registration were determined from the transformation matrix and the deformation vector field, respectively. The rigid registration yielded mean rotations of ⩽2.5° in all cases. The average 3D translational magnitudes range was 5.8 ± 2.9 mm-30.0 ± 11.0 mm. Translations were most significant in the left-right (LR) direction. Smaller translations were observed in the anterior-posterior (AP) and superior-inferior (SI) directions. The maximum deformation magnitudes range was: 10.0 ± 0.9 mm-28.0 ± 2.8 mm and average deformation magnitudes range: 2.3 ± 0.6 mm-7.5 ± 1.0 mm. Average non-rigid deformation magnitude was correlated with BMI (correlation coefficient 0.84, p  = 0.01). Rigid pelvic deformations were most significant in the LR direction but could be accounted for with on-line adjustments. Non-rigid deformations can be significant and will need to be accounted for in order to facilitate the delivery of gantry-free therapy with an automated patient rotation system.

Allosteric Site Inhibitor Disrupting Auto-Processing of Malarial Cysteine Proteases.

Falcipains are major haemoglobinases of Plasmodium falciparum required for parasite growth and development. They consist of pro- and mature domains that interact via 'hot-spot' interactions and maintain the structural integrity of enzyme in zymogen state. Upon sensing the acidic environment, these interactions dissociate and active enzyme is released. For inhibiting falcipains, several active site inhibitors exist, however, compounds that target via allosteric mechanism remains uncharacterized. Therefore, we designed and synthesized six azapeptide compounds, among which, NA-01 & NA-03 arrested parasite growth by specifically blocking the auto-processing of falcipains. Inhibitors showed high affinity for enzymes in presence of the prodomain without affecting the secondary structure. Binding of NA-03 at the interface induced rigidity in the prodomain preventing structural reorganization. We further reported a histidine-dependent activation of falcipain. Collectively, for the first time we provide a framework for blocking the allosteric site of crucial haemoglobinases of the human malaria parasite. Targeting the allosteric site could provide high selectivity and less vulnerable to drug resistance.

Imaging performance of a dedicated radiation transparent RF coil on a 1.0 Tesla inline MRI-linac.

This work describes the first imaging studies on a 1.0 Tesla inline MRI-Linac using a dedicated transmit/receive RF body coil that has been designed to be completely radio transparent and provide optimum imaging performance over a large patient opening. A series of experiments was performed on the MRI-Linac to investigate the performance and imaging characteristics of a new dedicated volumetric RF coil: (1) numerical electromagnetic simulations were used to measure transmit efficiency in two patient positions; (2) image quality metrics of signal-to-noise ratio (SNR), ghosting and uniformity were assessed in a large diameter phantom with no radiation beam; (3) radiation induced effects were investigated in both the raw data (k-space) and image sequences acquired with simultaneous irradiation; (4) radiation dose was measured with and without image acquisition; (5) RF heating was studied using an MR-compatible fluoroptic thermometer and; (6) the in vivo image quality and versatility of the coil was demonstrated in normal healthy subjects for both supine and standing positions. Daily phantom measurements demonstrated excellent imaging performance with stable SNR over a period of 3 months (42.6 ± 0.9). Simultaneous irradiation produced no statistical change in image quality (p > 0.74) and no interference in raw data for a 20 × 20 cm radiation field. The coil was found to be efficient over large volumes and negligible RF heating was observed. Volunteer scans acquired in both supine and standing positions provided artefact free images with good anatomical visualisation. The first completely radio transparent RF coil for use on a 1.0 Tesla MRI-Linac has been described. There is no impact on either the imaging or dosimetry performance with a simultaneous radiation beam. The open design enables imaging and radiotherapy guidance in a variety of positons.

Electrical burn injury: a comparison of outcomes of high voltage versus low voltage injury in an Indian scenario.

Electrical burn injury (EBI) is a mutilating form of injury. The objective of this study was to evaluate the various aspects of EBI and analyse the differences between high voltage injury (HVI) and low voltage injury (LVI). A retrospective study was conducted by reviewing the medical records of all burn admissions from June 2016 to May 2017. A total of 1572 patients were admitted, of which 385 (24.49%) had suffered an electrical injury. 104 (27.01%) patients sustained LVI and 281 (72.98%) HVI. One hundred patients from both groups were randomly selected using the chit method, in order to analyse their differences. In our study, the mean age was 35.23±19.96 in the HVI group and 24.15±14.39 years in the LVI group. Most of the injuries were work related. Events during the early phase of admission included a rise in serum creatine phosphokinases, myoglobinuria, renal failure, abnormal cardiac events and other concomitant injuries in the HVI group (p<0.001). Unfavourable outcomes in the form of amputations, prolonged hospital stay and high mortality rate were observed in the HVI group (8.5%) (p<0.027). However, LVI cannot be overlooked as number of reconstructive surgeries and mean number of operations showed no significant difference between both groups. HVI has a disastrous impact on burn survivors but LVI cannot be underestimated. We advocate a low threshold for managing associated injuries, education on safety principles, for men at work especially, and infrastructure improvement by the state to bring changes to the present scenario.

Les brûlures électrothermiques (BET) sont des blessures particulièrement mutilantes. Le but de cette étude rétrospective, conduite à partir des dossiers des patients hospitalisés entre juin 2016 et mai 2017 est d'analyser les BET et de comparer celles par bas voltage (BBV) à celles par haut voltage (BHV). Parmi les 1 572 patients, 385 (24,69%) avaient une BET dont 104 (27,01%) BBV et 281 (72,98%) BHV. Nous avons tiré au sort 100 dossiers de chaque groupe. L'âge du groupe BHV est de 32,23 +/- 19,96 ans, celui de BBV de 24,15 +/- 14,39 ans. La plupart des accidents ont lieu au travail. Le groupe BHV est plus à risque de complications initiales (rhabdomyolyse avec élévation des CPK, myoglobinurie, insuffisance rénale, complications cardiaques) et a plus fréquemment des lésions associées (p<0,001). La mortalité (8,5%) est plus élevée dans le groupe BHV, ainsi que le nombre d'amputations ainsi que la durée de séjour. Toutefois, il ne faut pas minimiser la gravité des BBV car le nombre d'intervention, initiales et de reconstruction, est superposable à celui observé dans les BHV. La prise en charge doit être spécialisée même en cas de BBV et la prévention (mesures de sécurité en particulier au travail, amélioration des infrastructures) doit être améliorée.

Synthesis, Spectral Characterization, Thermal and Optical Studies of Novel Complexes: 4-(Dimethylamino)benzylidene-4-acetamideaniline and 4-(Dimethylamino)benzylidene-4-nitroaniline.

The phase diagram representing solid-liquid equilibrium of entire range of composition and thermodynamic studies of two binary organic systems of 4-dimethylaminobenzaldehyde (DMAB) with two NLO active compounds, p-aminoacetanilide (PAA) and p-nitroaniline (PNA), have been studied by solid state synthetic route. Both systems are independently forming a new entity called intermolecular complex (IMC) and two eutectics on either side of intermolecular complexes. The various thermodynamic parameters such as heat of mixing, entropy of fusion, roughness parameter, interfacial energy and excess thermodynamic functions of IMCs and eutectics were calculated using the heat of fusion values. The TGA and DTA studies were performed to understand the physico-chemical, thermal behavior and unique identity of newly synthesized organic complexes, 4-(dimethylamino)benzylidene-4-acetamideaniline (DMABPAA) and 4-(dimethylamino)benzylidene-4-nitroaniline (DMABPNA), and their respective enthalpy of fusion values were found to be 30.01 and 37.26 kJ mol- 1. The higher melting point of both the novel complexes than their parent's compounds reveal the strong molecular interaction between parent components to yield the complex. The FTIR spectral analysis predicts the disappearance of aldehyde peaks of DMAB and NH2 peaks of PAA and PNA while the appearance of entirely new peaks than that of parent's compounds are the supportive for the formation of new molecular entities. These findings are further supported by FTNMR spectrum studies by observation of disappearance of proton peak of aldehyde of DMAB and amine peaks of PAA and PNA rather formation of new imine proton peak or peaks were observed. The appearance of new peaks in Powder XRD of complexes than those of parent components is further indicative for the formation of complexes. The absorption spectrum of DMABPAA and DMABPNA showed intra-molecular charge-transfer (ICT) excited state absorption at 258 and 241 nm, respectively. Both the IMCs, DMABPAA and DMABPNA, show strong fluorescence with quantum yield 0.66 and 0.93, respectively, in methanol solution.

Association of heterogenicity of Helicobacter pylori cag pathogenicity island with peptic ulcer diseases and gastric cancer.

OBJECTIVE: To investigate the frequency and integrity of certain cag pathogenicity island genes (cagPAI) in Helicobacter pylori strains and their association with peptic ulcer disease (PUD) and gastric cancer. MATERIAL AND METHODS: We enrolled 240 adult patients [120 with functional dyspepsia (FD), 50 with PUD and 70 with gastric cancer] undergoing upper gastrointestinal endoscopy. H. pylori infection was diagnosed when either culture or any two of the three tests (rapid urease test, histopathology and specific ureA PCR) were positive. DNA extracted from H. pylori isolates and positive gastric tissues were tested by PCR for the presence of different genes of cagPAI using specific primers. RESULTS: A total of 122 (51%) patients were H. pylori positive. Frequencies of cagPAI genes cagA, cagE, cagT and cagM in H. pylori strains from different groups of patients were as follows: functional dyspepsia 73, 83, 76 and 60%, PUD 70, 94, 91, 70% and gastric cancer 75, 95, 90 and 70%, respectively. Risk associated for the presence of PUD and gastric cancer with cagPAI genes cagE, cagT and cagM was 5.0-, 4.6- and 4.1- and 3.0-, 2.8- and 2.5-folds, respectively. Prevalence of intact cagPAI was significantly higher in PUD and gastric cancer compared to functional dyspepsia (PUD vs. functional dyspepsia, 71% vs. 38%, P = 0.01; gastric cancer vs. functional dyspepsia, 75% vs. 38%, P < 0.01). Intact cagPAI was associated with increased risk for the presence of PUD (odds ratio 5.2, 95% CI 2.4-11.3) and for the presence of gastric cancer (odds ratio 4.5, 95% CI 2.3-7.1). CONCLUSIONS: cagPAI integrity and its different genes are linked to different forms of gastric disease and so may have a role in pathogenesis, diagnosis and management.

Towards real-time MRI-guided 3D localization of deforming targets for non-invasive cardiac radiosurgery.

Radiosurgery to the pulmonary vein antrum in the left atrium (LA) has recently been proposed for non-invasive treatment of atrial fibrillation (AF). Precise real-time target localization during treatment is necessary due to complex respiratory and cardiac motion and high radiation doses. To determine the 3D position of the LA for motion compensation during radiosurgery, a tracking method based on orthogonal real-time MRI planes was developed for AF treatments with an MRI-guided radiotherapy system. Four healthy volunteers underwent cardiac MRI of the LA. Contractile motion was quantified on 3D LA models derived from 4D scans with 10 phases acquired in end-exhalation. Three localization strategies were developed and tested retrospectively on 2D real-time scans (sagittal, temporal resolution 100 ms, free breathing). The best-performing method was then used to measure 3D target positions in 2D-2D orthogonal planes (sagittal-coronal, temporal resolution 200-252 ms, free breathing) in 20 configurations of a digital phantom and in the volunteer data. The 3D target localization accuracy was quantified in the phantom and qualitatively assessed in the real data. Mean cardiac contraction was ⩽ 3.9 mm between maximum dilation and contraction but anisotropic. A template matching approach with two distinct template phases and ECG-based selection yielded the highest 2D accuracy of 1.2 mm. 3D target localization showed a mean error of 3.2 mm in the customized digital phantoms. Our algorithms were successfully applied to the 2D-2D volunteer data in which we measured a mean 3D LA motion extent of 16.5 mm (SI), 5.8 mm (AP) and 3.1 mm (LR). Real-time target localization on orthogonal MRI planes was successfully implemented for highly deformable targets treated in cardiac radiosurgery. The developed method measures target shifts caused by respiration and cardiac contraction. If the detected motion can be compensated accordingly, an MRI-guided radiotherapy system could potentially enable completely non-invasive treatment of AF.

Technical Note: Experimental results from a prototype high-field inline MRI-linac.

PURPOSE: The pursuit of real-time image guided radiotherapy using optimal tissue contrast has seen the development of several hybrid magnetic resonance imaging (MRI)-treatment systems, high field and low field, and inline and perpendicular configurations. As part of a new MRI-linac program, an MRI scanner was integrated with a linear accelerator to enable investigations of a coupled inline MRI-linac system. This work describes results from a prototype experimental system to demonstrate the feasibility of a high field inline MR-linac. METHODS: The magnet is a 1.5 T MRI system (Sonata, Siemens Healthcare) was located in a purpose built radiofrequency (RF) cage enabling shielding from and close proximity to a linear accelerator with inline (and future perpendicular) orientation. A portable linear accelerator (Linatron, Varian) was installed together with a multileaf collimator (Millennium, Varian) to provide dynamic field collimation and the whole assembly built onto a stainless-steel rail system. A series of MRI-linac experiments was performed to investigate (1) image quality with beam on measured using a macropodine (kangaroo) ex vivo phantom; (2) the noise as a function of beam state measured using a 6-channel surface coil array; and (3) electron contamination effects measured using Gafchromic film and an electronic portal imaging device (EPID). RESULTS: (1) Image quality was unaffected by the radiation beam with the macropodine phantom image with the beam on being almost identical to the image with the beam off. (2) Noise measured with a surface RF coil produced a 25% elevation of background intensity when the radiation beam was on. (3) Film and EPID measurements demonstrated electron focusing occurring along the centerline of the magnet axis. CONCLUSIONS: A proof-of-concept high-field MRI-linac has been built and experimentally characterized. This system has allowed us to establish the efficacy of a high field inline MRI-linac and study a number of the technical challenges and solutions.

Novel PGS/PCL electrospun fiber mats with patterned topographical features for cardiac patch applications.

Nano- and micro-scale topographical features play a critical role in the induction and maintenance of various cellular properties and functions, including morphology, adhesion, gene regulation, and cell-to-cell communication. In addition, recent studies have indicated that the structure and function of heart tissue are also sensitive to mechanical cues at the nano- and micro-scale. Although fabrication methods exist for generating topographical features on polymeric scaffolds for cell culture, current techniques, especially those with nano-scale resolution, are typically complex, prohibitively expensive and not accessible to most biology laboratories. Here, we present a simple and tunable fabrication method for the production of patterned electrospun fibers that simulate the complex anisotropic and multi-scale architecture of cardiac tissue, to promote cardiac cell alignment. This method is based on the combination of electrospinning and soft lithography techniques, in which electrospun fibers, based on a blend of poly(glycerol sebacate) and poly(caprolactone), were collected on a patterned Teflon-coated silicon wafer with imprinted topographical features. Different surface topographies were investigated, such as squares and grooves, with constant or different interspatial distances. In vitro cell culture studies successfully demonstrated the alignment of both C2C12 myoblasts and neonatal rat cardiomyocytes on fabricated electrospun patterned surfaces. C2C12 cells were cultured over a period of 72h to study the effect of topographical cues on cell morphology. Cells attached within the first 8h after seeding and after 24h most of the cells started to align responding to the topographical cues. Similarly, cardiomyocytes responded to the topographical features by aligning themselves and by expressing Connexin 43 along cellular junctions. Summarizing, we have developed a new method with the potential to significantly promote cardiac tissue engineering by fabricating electrospun fibers with defined topographical features to guide and instruct donor and/or host cells.

Expression analysis of bZIP transcription factor encoding genes in response to water deficit stress in rice.

In plants, basic region/leucine zipper motif (bZIP) transcription factors regulate several developmental processes and activate genes in response to biotic and abiotic stresses. Role of stress responsive bZIP transcription factors was studied in paddy in relation to different stages of development and water deficit stress (WDS) in a drought tolerant cultivar N22 and susceptible IR 64. Further, relative water content (RWC), membrane stability index (MSI) and abscisic acid (ABA) content were measured as indices of WDS at different stages of development and levels of stress. Expression of stress responsive bZIP transcription factors was directly correlated to developmental stage and WDS and indirectly to RWC, MSI and ABA content.

Arginyltransferase suppresses cell tumorigenic potential and inversely correlates with metastases in human cancers.

Arginylation is an emerging post-translational modification mediated by arginyltransferase (ATE1) that is essential for mammalian embryogenesis and regulation of the cytoskeleton. Here, we discovered that Ate1-knockout (KO) embryonic fibroblasts exhibit tumorigenic properties, including abnormally rapid contact-independent growth, reduced ability to form cell-cell contacts and chromosomal aberrations. Ate1-KO fibroblasts can form large colonies in Matrigel and exhibit invasive behavior, unlike wild-type fibroblasts. Furthermore, Ate1-KO cells form tumors in subcutaneous xenograft assays in immunocompromised mice. Abnormal growth in these cells can be partially rescued by reintroduction of stably expressed specific Ate1 isoforms, which also reduce the ability of these cells to form tumors. Tumor array studies and bioinformatics analysis show that Ate1 is downregulated in several types of human cancer samples at the protein level, and that its transcription level inversely correlates with metastatic progression and patient survival. We conclude that Ate1-KO results in carcinogenic transformation of cultured fibroblasts, suggesting that in addition to its previously known activities Ate1 gene is essential for tumor suppression and also likely participates in suppression of metastatic growth.