Capacitive monitoring system for real-time respiratory motion monitoring during radiation therapy.

This work introduces a novel capacitive-sensing technology capable of detecting respiratory motion with high temporal frequency (200 Hz). The system does not require contact with the patient and has the capacity to sense motion through clothing or plastic immobilization devices. ABSTRACT: PURPOSE: This work presents and evaluates a novel capacitive monitoring system (CMS) technology for continuous detection of respiratory motion during radiation therapy. This modular system provides real-time motion monitoring without any contact with the patient, ionizing radiation, or surrogates such as reflective markers on the skin. MATERIALS AND METHODS: The novel prototype features an array of capacitive detectors that are sensitive to the position of the body and capable of high temporal frequency readout. Performance of this system was investigated in comparison to the RPM infrared (IR) monitoring system (Varian Medical Systems). The prototype included three (5 cm × 10 cm) capacitive copper sensors in one plane, located at a distance of 8-10 cm from the volunteer. Capacitive measurements were acquired for central and lateral-to-central locations during chest free-breathing and abdominal breathing. The RPM IR data were acquired with the reflector block at corresponding positions simultaneously. The system was also tested during deep inspiration and expiration breath-hold maneuvers. RESULTS: Capacitive monitoring system data demonstrate close agreement with the RPM status quo at all locations examined. Cross-correlation analysis on RPM and CMS data showed an average absolute lag of 0.07 s (range: 0.03-0.23 s) for DIBH and DEBH data and 0.15 s (range: 0-0.43 s) for free-breathing. Amplitude difference between the normalized CMS and RPM signal during chest and abdominal breathing was within 0.15 for 94.3% of the data points after synchronization. CMS performance was not affected when the subject was clothed. CONCLUSION: This novel technology permits sensing of both free-breathing and breath-hold respiratory motion. It provides data comparable to the RPM system but without the need for an IR tracking camera in the treatment room or use of reflective markers on the patient.

Improvement of consistency in delineating breast lumpectomy cavity using surgical clips.

BACKGROUND: Delineation of lumpectomy cavity for whole breast radiation therapy after breast conserving surgery can be challenging because of poor visualization of the cavity. The use of surgical clips on lumpectomy cavity walls has been suggested as an effective and low-cost method to improve the accuracy and consistency of lumpectomy cavity delineation. MATERIALS AND METHODS: Twenty-three eligible female breast cancer patients who were treated with lumpectomy and adjuvant radiation therapy were recruited for this study. During breast conserving surgery, four surgical clips were placed on the superior, inferior, lateral, and medial walls of the lumpectomy cavity. Patients were imaged prior and during radiation treatment. Software was developed to anonymize the image sets and digitally remove the clips from the computed tomography images. Three radiation oncologists contoured the lumpectomy cavity volume, with and without presence of clips. Contoured image sets were analyzed with regard to cavity volume, dimensions, and concordance index. Statistical analysis was performed using a paired t-test. RESULTS: The presence of clips significantly increased the average lumpectomy cavity volumes from 23.50 cc to 26.42 cc (P < 0.0001). The presence of clips also significantly increased the mean craniocaudal, anteroposterior, and mediolateral dimensions by 6.8, 2.3, and 2.9 mm, respectively (all P < 0.01). In addition, the presence of surgical clips improved the consistency in delineation in CC dimension by significantly decreasing the standard deviation (P < 0.006). CONCLUSIONS: The presence of surgical clips improves the accuracy of lumpectomy cavity delineation. However, consistency is only improved in CC dimension.

A multi-institutional comparison of retrospective deformable dose accumulation for online adaptive magnetic resonance-guided radiotherapy.

Background and Purpose: Application of different deformable dose accumulation (DDA) solutions makes institutional comparisons after online-adaptive magnetic resonance-guided radiotherapy (OA-MRgRT) challenging. The aim of this multi-institutional study was to analyze accuracy and agreement of DDA-implementations in OA-MRgRT. Material and Methods: One gold standard (GS) case deformed with a biomechanical-model and five clinical cases consisting of prostate (2x), cervix, liver, and lymph node cancer, treated with OA-MRgRT, were analyzed. Six centers conducted DDA using institutional implementations. Deformable image registration (DIR) and DDA results were compared using the contour metrics Dice Similarity Coefficient (DSC), surface-DSC, Hausdorff-distance (HD95%), and accumulated dose-volume histograms (DVHs) analyzed via intraclass correlation coefficient (ICC) and clinical dosimetric criteria (CDC). Results: For the GS, median DDA errors ranged from 0.0 to 2.8 Gy across contours and implementations. DIR of clinical cases resulted in DSC > 0.8 for up to 81.3% of contours and a variability of surface-DSC values depending on the implementation. Maximum HD95%=73.3 mm was found for duodenum in the liver case. Although DVH ICC > 0.90 was found after DDA for all but two contours, relevant absolute CDC differences were observed in clinical cases: Prostate I/II showed maximum differences in bladder V28Gy (10.2/7.6%), while for cervix, liver, and lymph node the highest differences were found for rectum D2cm3 (2.8 Gy), duodenum Dmax (7.1 Gy), and rectum D0.5cm3 (4.6 Gy). Conclusion: Overall, high agreement was found between the different DIR and DDA implementations. Case- and algorithm-dependent differences were observed, leading to potentially clinically relevant results. Larger studies are needed to define future DDA-guidelines.

Evolutionary trajectories of beta-lactamase NDM and DLST cluster in Pseudomonas aeruginosa: finding the putative ancestor.

Pseudomonas aeruginosa has different antibiotic resistance pathways, such as broad-spectrum lactamases and metallo-ß-lactamases (MBL), penicillin-binding protein (PBP) alteration, and active efflux pumps. Polymerase chain reaction (PCR) and sequencing methods were applied for double-locus sequence typing (DLST) and New Delhi metallo-ß-lactamase (NDM) typing. We deduced the evolutionary pathways for DLST and NDM genes of P. aeruginosa using phylogenetic network. Among the analyzed isolates, 62.50% of the P. aeruginosa isolates were phenotypically carbapenem resistance (CARBR) isolates. Characterization of isolates revealed that the prevalence of blaNDM, blaVIM, blaIMP, undetermined carbapenemase, and MexAB-OprM were 27.5%, 2%, 2.5%, 12.5%, and 15%, respectively. The three largest clusters found were DLST t20-105, DLST t32-39, and DLST t32-52. The network phylogenic tree revealed that DLST t26-46 was a hypothetical ancestor for other DLSTs, and NDM-1 was as a hypothetical ancestor for NDMs. The combination of the NDM and DLST phylogenic trees revealed that DLST t32-39 and DLST tN2-N3 with NDM-4 potentially derived from DLST t26-46 along with NDM-1. Similarly, DLST t5-91 with NDM-5 diversified from DLST tN2-N3 with NDM-4. This is the first study in which DLST and NDM evolutionary routes were performed to investigate the origin of P. aeruginosa isolates. Our study showed that the utilization of medical equipment common to two centers, staff members common to two centers, limitations in treatment options, and prescription of unnecessary high levels of meropenem are the main agents that generate new types of resistant bacteria and spread resistance among hospitals.

Targeting and ultrabroad insight into molecular basis of Resistance-nodulation-cell division efflux pumps.

Resistance-nodulation-cell devision (RND) efflux pump variants have attracted a great deal of attention for efflux of many antibiotic classes, which leads to multidrug-resistant bacteria. The present study aimed to discover the interaction between the RND efflux pumps and antibiotics, find the conserved and hot spot residues, and use this information to target the most frequent RND efflux pumps. Protein sequence and 3D conformational alignments, pharmacophore modeling, molecular docking, and molecular dynamics simulation were used in the first level for discovering the function of the residues in interaction with antibiotics. In the second level, pharmacophore-based screening, structural-based screening, multistep docking, GRID MIF, pharmacokinetic modeling, fragment molecular orbital, and MD simulation were utilized alongside the former level information to find the most proper inhibitors. Five conserved residues, containing Ala209, Tyr404, Leu415, Asp416, and Ala417, as well as their counterparts in other OMPs were evaluated as the crucial conserved residues. MD simulation confirmed that a number of these residues had a key role in the performance of the efflux antibiotics; therefore, some of them were hot spot residues. Fourteen ligands were selected, four of which interacted with all the crucial conserved residues. NPC100251 was the fittest OMP inhibitor after pharmacokinetic computations. The second-level MD simulation and FMO supported the efficacy of the NPC100251. It was exhibited that perhaps OMPs worked as the intelligent and programable protein. NPC100251 was the strongest OMPs inhibitor, and may be a potential therapeutic candidate for MDR infections.

Gradient induced spiral drift in heterogeneous excitable media.

Nonlinear excitable systems far from equilibrium can exhibit pattern formation such as spirals, target patterns, etc. One such system is the heterogeneous catalytic reaction of CO with oxygen on platinum single crystals. It has been established that the resonant periodic forcing of spirals in such excitable systems can cause a spiral drift. Here, we investigate the effects of a linear thermal gradient on the spiral dynamics during CO oxidation on platinum (110) for the first time, both in simulations and with experiments. Our results suggest that a spatial thermal gradient established across the surface can act as an internal forcing drive and cause the spiral patterns to drift. This drift has components both parallel and perpendicular to the external gradient.

Discovery of potential inhibitors against New Delhi metallo-ß-lactamase-1 from natural compounds: in silico-based methods.

New Delhi metallo-ß-lactamase variants and different types of metallo-ß-lactamases have attracted enormous consideration for hydrolyzing almost all ß-lactam antibiotics, which leads to multi drug resistance bacteria. Metallo-ß-lactamases genes have disseminated in hospitals and all parts of the world and became a public health concern. There is no inhibitor for New Delhi metallo-ß-lactamase-1 and other metallo-ß-lactamases classes, so metallo-ß-lactamases inhibitor drugs became an urgent need. In this study, multi-steps virtual screening was done over the NPASS database with 35,032 natural compounds. At first Captopril was extracted from 4EXS PDB code and use as a template for the first structural screening and 500 compounds obtained as hit compounds by molecular docking. Then the best ligand, i.e. NPC120633 was used as templet and 800 similar compounds were obtained. As a final point, ten compounds i.e. NPC171932, NPC100251, NPC18185, NPC98583, NPC112380, NPC471403, NPC471404, NPC472454, NPC473010 and NPC300657 had proper docking scores, and a 50 ns molecular dynamics simulation was performed for calculation binding free energy of each compound with New Delhi metallo-ß-lactamase. Protein sequence alignment, 3D conformational alignment, pharmacophore modeling on all New Delhi metallo-ß-lactamase variants and all types of metallo-ß-lactamases were done. Quantum chemical perspective based on the fragment molecular orbital (FMO) method was performed to discover conserved and crucial residues in the catalytic activity of metallo-ß-lactamases. These residues had similar 3D coordinates of spatial location in the 3D conformational alignment. So it is posibble that all types of metallo-ß-lactamases can inhibit by these ten compounds. Therefore, these compounds were proper to mostly inhibit all metallo-ß-lactamases in experimental studies.

Synthesis of some novel coumarin isoxazol sulfonamide hybrid compounds, 3D-QSAR studies, and antibacterial evaluation.

With the progressive and ever-increasing antibacterial resistance pathway, the need for novel antibiotic design becomes critical. Sulfonamides are one of the more effective antibiotics against bacteria. In this work, several novel sulfonamide hybrids including coumarin and isoxazole group were synthesized in five steps starting from coumarin-3-carboxylic acid and 3-amino-5-methyl isoxazole and assayed for antibacterial activity. The samples were obtained in good to high yield and characterized by FT-IR, 13C-NMR, 1H-NMR, CHN and melting point techniques. 3D-QSAR is a fast, easy, cost-effective, and high throughput screening method to predict the effect of the compound's efficacy, which notably decreases the needed price for experimental drug assay. The 3D-QSAR model displayed acceptable predictive and descriptive capability to find r2 and q2 the pMIC of the designed compound. Key descriptors, which robustly depend on antibacterial activity, perhaps were explained by this method. According to this model, among the synthesized sulfonamide hybrids, 9b and 9f had the highest effect on the gram-negative and gram-positive bacteria based on the pMIC. The 3D-QSAR results were confirmed in the experimental assays, demonstrating that our model is useful for developing new antibacterial agents. The work proposes a computationally-driven strategy for designing and discovering new sulfonamide scaffold for bacterial inhibition.

Performance optimization of capacitive motion sensing (CMS) system for intra-fraction motion detection during stereotactic radiosurgery.

The purpose of this investigation is to improve intra-fractional motion detection during cranial stereotactic radiosurgery with a novel capacitive motion sensing (CMS) system. Previous work showed that a capacitive detection system, based on a MPR121 capacitance-to-digital converter, provided a number of advantages over existing patient imaging systems used in the clinic, by uniquely offering ionizing-radiation-free and continuous monitoring without modification to the immobilization mask or treatment room. However, in order to provide submillimeter detection accuracy, the MPR121-based CMS system required relatively large sensors in close proximity to the patient. Therefore, the aim of this investigation was to improve sensitivity of the system, allowing reduction in sensor size and preserving its stable operation in the linear accelerator environment. For this, we developed, characterized and compared motion detection capabilities of four CMS systems based on different capacitance-to-digital converters: MPR121, CPT212B, FDC1004 and FDC2214. Among all candidates, the FDC2214-based system was found to uniquely combine accurate 3D motion detection in real time, with stable performance under ionizing radiation. It exhibited an order of magnitude improvement in sensitivity in comparison with the proof-of-study system, allowing a spatial precision as low as 0.3 mm, and its overall performance was found to satisfy the AAPM practice guidelines of positioning tolerance within 1 mm. Furthermore, the high sensitivity of the system allows both reduction of the sensor area and location more distant from the patient surface, which are key improvements with regard to development of a clinical device.

Intrapatient study comparing 3D printed bolus versus standard vinyl gel sheet bolus for postmastectomy chest wall radiation therapy.

PURPOSE: This patient study evaluated the use of 3-dimensional (3D) printed bolus for chest wall radiation therapy compared with standard sheet bolus with regard to accuracy of fit, surface dose measured in vivo, and efficiency of patient setup. By alternating bolus type over the course of therapy, each patient served as her own control. METHODS AND MATERIALS: For 16 patients undergoing chest wall radiation therapy, a custom 5.0 mm thick bolus was designed based on the treatment planning computed tomography scan and 3D printed using polylactic acid. Cone beam computed tomography scanning was used to image and quantify the accuracy of fit of the 2 bolus types with regard to air gaps between the bolus and skin. As a quality assurance measure for the 3D printed bolus, optically stimulated luminescent dosimetry provided in vivo comparison of surface dose at 7 points on the chest wall. Durations of patient setup and image guidance were recorded and compared. RESULTS: In 13 of 16 patients, the bolus was printed without user intervention, and the median print time was 12.6 hours. The accuracy of fit of the bolus to the chest wall was improved significantly relative to standard sheet bolus, with the frequency of air gaps 5 mm or greater reduced from 30% to 13% (P < .001) and maximum air gap dimension diminished from 0.5 ± 0.3 to 0.3 ± 0.3 mm on average. Surface dose was within 3% for both standard sheet and 3D printed bolus. On average, the use of 3D printed bolus reduced the setup time from 104 to 76 seconds. CONCLUSIONS: This study demonstrates 3D printed bolus in postmastectomy radiation therapy improves fit of the bolus and reduces patient setup time marginally compared with standard vinyl gel sheet bolus. The time savings on patient setup must be weighed against the considerable time needed for the 3D printing process.

Antimicrobial activity of endophytic bacterial populations isolated from medical plants of Iran.

BACKGROUND AND OBJECTIVES: Endophytic actinobacteria colonize inside the plant tissues without causing damages to the host plant. Since these microorganisms colonize in the different parts of plants and can stop plant disease, they have been applied as biological agents for controlling human diseases. The aim of this study was molecular identification and measuring the antimicrobial activity of endophytic Actinomycetes isolated from medicinal plants of Iran. MATERIALS AND METHODS: The total of 23 medicinal plant samples were collected, sterilized, and crushed. Small pieces of the crushed samples were then cultured directly on three selective media. Grown colonies were identified by 16S rRNA gene sequencing method. Each isolate was cultured in TSB medium and then antimicrobial compound was extracted using ethyl acetate and tested against the target bacteria. RESULTS: Sixteen out of 23 bacterial isolates (69%) exhibited antimicrobial activity against the selected pathogenic bacteria, such as Bacillus cereus, Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Citrobacter freundii, Proteus mirabilis, Shigella flexneri and Escherichia coli. CONCLUSION: Our Study showed a high phylogenetic diversity and the potent antibiotic activity of endophytic bacteria in medicinal plants of Iran.

Phenotypic and genotypic characterization of macrolide resistance among Staphylococcus aureus isolates in Isfahan, Iran.

BACKGROUND AND OBJECTIVES: Macrolide, lincosamide and streptogramin B (MLS B) are noteworthy antibiotics for the treatment of Staphylococcus aureus infections. The purpose of this study, was to determine the phenotypic and genotypic characterization of macrolide resistance, among S. aureus, isolated from clinical samples and nasal swabs. MATERIALS AND METHODS: Totally, 162 non-duplicate S. aureus isolates were collected from clinical samples and nasal swabs, from patients and healthcare workers (HCWs), between March 2016 and September 2016, at four teaching hospitals in Isfahan. The antibiotic resistance profile was determined using disk diffusion test and the presence of resistance genes was detected, using PCR. RESULTS: Of 162 S. aureus isolates, 43.8% (71/162) and 34% (55/162) isolates were erythromycin-resistant and methicillin-resistant S. aureus (MRSA), respectively. The prevalence of constitutive MLS B (cMLS B), inducible MLS B (iMLS B), macrolide-streptogramin B-resistant (MS B) and lincosamide-streptogramin-A resistance (LS A) phenotype was 32%, 6%, 6% and 2%, respectively. The most common erythromycin resistance genes, in S. aureus isolates were ermC (35.2%), followed by ermA (20.4%) and msrA (17.3%). Meanwhile, msrA was detected in 43.6% of MRSA isolates. The frequency of coexistence of ermA+ermC+msrA, in S. aureus isolates was 7% and it was only detected in MRSA isolates. CONCLUSION: In the current study, cMLS B phenotype was the most common erythromycin resistance pattern and ermC was the most prevalent gene in erythromycin-resistant isolates. The results revealed that the various mechanisms of erythromycin resistance are expanding in Isfahan.

Bacterial Leakage of Mineral Trioxide Aggregate, Calcium-Enriched Mixture and Biodentine as Furcation Perforation Repair Materials in Primary Molars.

INTRODUCTION: Adequate seal of iatrogenically perforated area within the root canal system can improve the long term treatment prognosis. This in vitro study evaluated the sealing ability of mineral trioxide aggregate (MTA), calcium-enriched mixture (CEM) cement and Biodentine in repair of furcation perforation in primary molars. METHODS AND MATERIALS: A total of 61 freshly extracted primary mandibular second molars were randomly divided into three groups (n=17) and 10 teeth were put in negative (without perforation, n=5) and positive (perforated without repair, n=5) control groups. Turbidity was used as the criteria of bacterial leakage, when detected in the model of dual-chamber leakage. Data were analyzed using the Chi-Square and Kaplan-Meier survival analysis in SPSS software. The level of significance was set at 0.05. RESULTS: All positive samples showed turbidity, whereas none of the negative samples allowed bacterial leakage. There was no significant difference between the number of turbidity samples in repaired teeth with all test materials (P=0.13). No significant difference was also detected in the mean survival time (P>0.05). CONCLUSION: CEM cement and Biodentine showed promising results as perforation repair materials and can be recommended as suitable alternatives of MTA for repair of furcation perforation of primary molars.

Identification of clinical isolates of Acinetobacter baumannii from Iran and study of their heterogeneity.

BACKGROUND: Acinetobacter baumannii has become one of the most serious causative agents of nosocomial infections due to its significant ability to survive on hospital surfaces. It is mainly an emerging opportunistic pathogen infecting patients in intensive care units. This study was aimed to identify the clinical isolates of A. baumannii and to investigate their heterogeneity using polymerase chain reaction (PCR)-based typing methods. METHODS: A total of 197 nonduplicate isolates recovered from a wide range of clinical samples were subjected to conventional cultural and biochemical tests. For those isolates that were preliminary identified as A. baumannii, rpoB-based PCR with subsequent restriction fragment length polymorphism (RFLP) using two restriction enzymes (TagI and HaeIII) was performed to investigate the genetic diversity of the strains and their presumptive relationships with different clinical presentation of the disease caused by this pathogen. RESULTS: In total, 50 isolates (25.4%) were identified as A. baumannii using conventional phenotypic methods with subsequent confirmation by rpoB sequencing. RFLP analysis demonstrated five different restriction enzyme patterns, designated as A-E clusters. Most A. baumannii isolates were categorized under Cluster A (32%). We found no significant relationship between clinical presentation and the clustering of the isolates. CONCLUSION: This study showed that the rpoB region possesses high discriminatory power to identify the isolates to the species level. This marker showed high interspecies variability that might be useful for strain typing. The results also suggest the possibility of the existence of a predominant clone of A. baumannii among infected patients in Iran.

Molecular Methods for Identification of Acinetobacter Species by Partial Sequencing of the rpoB and 16S rRNA Genes.

BACKGROUND: Acinetobacter spp. is a diverse group of Gram-negative bacteria which are ubiquitous in soil and water, and an important cause of nosocomial infections. The purpose of this study was to identify a collection of Acinetobacter spp. clinical isolates accurately and to investigate their antibiotic susceptibility patterns. MATERIALS AND METHODS: A total of 197 non-duplicate clinical isolates of Acinetobacter spp. isolates identified using conventional biochemical tests. The molecular technique of PCR-RFLP and sequence analysis of rpoB and 16S rRNA genes was applied for species identification. Antimicrobial susceptibility test was performed with a disk diffusion assay. RESULTS: Based on 16S rRNA and rpoB genes analysis separately, most of clinical isolates can be identified with high bootstrap values. However, the identity of the isolate 555T was uncertain due to high similarity of A. grimontii and A. junii. Identification by concatenation of 16S rRNA and rpoB confirmed the identity of clinical isolates of Acenitobacer to species level confidently. Accordingly, the isolate 555T assigned as A. grimontii due to 100% similarity to A. grimontii. Moreover, this isolate showed 98.64% to A. junii. Besides, the identity of the isolates 218T and 364T was confirmed as Genomic species 3 and A. calcoaceticus respectively. So, the majority of Acinetobacter spp. isolates, were identified as: A. baumannii (131 isolates, 66%), A. calcoaceticus (9 isolates, 4.5%), and A. genomosp 16 (8 isolates, 4%). The rest of identified species showed the lower frequencies. In susceptibility test, 105 isolates (53%), presented high antibiotic resistance of 90% to ceftriaxone, piperacillin, piperacillin tazobactam, amikacin, and 81% to ciprofloxacin. CONCLUSION: Sequence analysis of the 16S rRNA and rpoB spacer simultaneously was able to do identification of Acinetobacter spp. to species level. A.baumannii was identified as the most prevalent species with high antibiotic resistance. Other species showed lower frequencies ranged from 4 to 9 strains.

Effect of fixed orthodontic therapy on urinary nickel levels: a long-term retrospective cohort study.

Nickel constitutes about 8-60 % of orthodontic alloys. It is known as an allergenic/cytotoxic trace metal. Therefore, it should be investigated in patients undergoing orthodontic treatment which might last for 2 or 3 years. However, no controlled studies have assessed the influence of orthodontic treatments of longer than 5 months on its systemic levels. Thus, the aim of this retrospective cohort study was to evaluate systemic nickel in patients undergoing orthodontic therapy for a minimum period of 1 year. In this study, urinary nickel concentrations in 20 female and 10 male patients being treated with stainless steel appliances were measured using atomic absorption spectrophotometry. The same procedure was done on a control group of the patients' same-gender near-age siblings (n = 30). The effect of treatment and gender on urinary nickel levels were assessed using a repeated-measures two-way analysis of variance (ANOVA) and a Tukey test (α = 0.05). The mean treatment duration was 17.1 ± 6.4 months (range, 12-21). The mean nickel concentrations in male and female patients were 9.67 ± 3.25 and 9.9 ± 3.83 µg/L, respectively. These statistics for male and female control subjects were 6.65 ± 2.57 and 8.43 ± 2.94 µg/L, respectively. The ANOVA showed a statistically significant difference between the urinary nickel levels of the treatment and the control groups (P = 0.009) but not between the genders (P = 0.194). The interaction between gender and treatment was also nonsignificant (P = 0.337). The Tukey test indicated that the increase in nickel was higher in male patients, in comparison to their brothers (P < 0.05). It could be concluded that orthodontic therapy for longer durations with stainless-steel archwires might elevate slightly, but significantly, urinary nickel levels.