Smart enzyme-free amplification dual-mode self-powered platform designed on two-dimensional networked graphdiyne and DNA nanorods for ultra-sensitive detection of breast cancer biomarkers.

Research has shown that microRNAs exhibit regular dysregulation in cancers, making them potential biomarkers for cancer diagnosis. However, achieving specific and sensitive detection of microRNAs has been a challenging task. To address this issue, two-dimensional networked graphdiyne is used to fabricate a self-powered biosensor and establish a new approach for ultra-responsive dual-mode detection of miRNA-141, a breast cancer biomarker. This method detects miRNA-141 using both electrochemical and colorimetric modes by measuring the output electrical signal of an enzyme-based biofuel cell and the RGB blue value of the electrolyte solution. Tetrahedral DNA and DNA nanorods also are immobilized on the electrode as a biocathode and methylene blue is used as the electron acceptor, which is fixed in the DNA phosphate backbone through electrostatic adsorption. The bioanode catalyzes the oxidation of glucose to produce electrons, which reduces methylene blue to its reduced form, resulting in a high open-circuit voltage (EOCV) and a highger RGB Blue value, enabling dual-mode detection. A reliable linear correlation is observed between EOCV values and miRNA-141 concentrations ranging from 0.0001 to 100 pM, with a detection limit of 21.9 aM (S/N = 3). Additionally, the colorimetric mode also demonstrates a reliable linear correlation with a concentration range of 0.0001-10000 pM, and this method can detect a concentration of 22.2 aM (S/N = 3). This innovative research realizes sensitive and accurate determination of miRNA-141 and provides an important new method for cancer diagnosis.

AAPM WGDCAB Report 372: A joint AAPM, ESTRO, ABG, and ABS report on commissioning of model-based dose calculation algorithms in brachytherapy.

The introduction of model-based dose calculation algorithms (MBDCAs) in brachytherapy provides an opportunity for a more accurate dose calculation and opens the possibility for novel, innovative treatment modalities. The joint AAPM, ESTRO, and ABG Task Group 186 (TG-186) report provided guidance to early adopters. However, the commissioning aspect of these algorithms was described only in general terms with no quantitative goals. This report, from the Working Group on Model-Based Dose Calculation Algorithms in Brachytherapy, introduced a field-tested approach to MBDCA commissioning. It is based on a set of well-characterized test cases for which reference Monte Carlo (MC) and vendor-specific MBDCA dose distributions are available in a Digital Imaging and Communications in Medicine-Radiotherapy (DICOM-RT) format to the clinical users. The key elements of the TG-186 commissioning workflow are now described in detail, and quantitative goals are provided. This approach leverages the well-known Brachytherapy Source Registry jointly managed by the AAPM and the Imaging and Radiation Oncology Core (IROC) Houston Quality Assurance Center (with associated links at ESTRO) to provide open access to test cases as well as step-by-step user guides. While the current report is limited to the two most widely commercially available MBDCAs and only for 192 Ir-based afterloading brachytherapy at this time, this report establishes a general framework that can easily be extended to other brachytherapy MBDCAs and brachytherapy sources. The AAPM, ESTRO, ABG, and ABS recommend that clinical medical physicists implement the workflow presented in this report to validate both the basic and the advanced dose calculation features of their commercial MBDCAs. Recommendations are also given to vendors to integrate advanced analysis tools into their brachytherapy treatment planning system to facilitate extensive dose comparisons. The use of the test cases for research and educational purposes is further encouraged.

Validation of the TOPAS Monte Carlo toolkit for LDR brachytherapy simulations.

PURPOSE: This work has the purpose of validating the Monte Carlo toolkit TOol for PArticle Simulation (TOPAS) for low-dose-rate (LDR) brachytherapy uses. METHODS AND MATERIALS: Simulations of 12 LDR sources and 2 COMS eye plaques (10 mm and 20 mm in diameter) and comparisons with published reference data from the Carleton Laboratory for Radiotherapy Physics (CLRP), the TG-43 consensus data and the TG-129 consensus data were performed. Sources from the IROC Houston Source Registry were modeled. The OncoSeed 6711 and the SelectSeed 130.002 were also modeled for historical reasons. For each source, the dose rate constant, the radial dose function and the anisotropy functions at 0.5, 1 and 5 cm were extracted. For the eye plaques (loaded with 125I sources), dose distribution maps, dose profiles along the central axis and transverse axis were calculated. RESULTS: Dose rate constants for 11 of the 12 sources are within 4% of the consensus data and within 2% of the CLRP data. The radial dose functions and anisotropy functions are mostly within 2% of the CLRP data. In average, 92% of all voxels are within 1% of the CLRP data for the eye plaques dose distributions. The dose profiles are within 0.5% (central axis) and 1% (transverse axis) of the reference data. CONCLUSION: The TOPAS MC toolkit was validated for LDR brachytherapy applications. Single-seed and multi-seed results agree with the published reference data. TOPAS has several benefits such as a simplified approach to MC simulations and an accessible brachytherapy package including comprehensive learning resources.

Comparison of novel shielded nasopharynx applicator designs for intracavitary brachytherapy.

PURPOSE: Nasopharyngeal brachytherapy is limited in part by the radiotolerance of nearby organs like the soft palate. This study explores several novel shielding designs for an intracavitary applicator to significantly reduce soft palate dose while adhering to the constraints of standard treatment procedure. METHODS: The Monte Carlo code TOPAS is used to characterize each prototype under typical high-dose-rate treatment conditions. Mucosal surface dose maps are collected to evaluate the shields on their dose reduction to the central and soft palate planning points and uniformity in their shielding profile. Practicality with respect to patient comfort and pretreatment imaging is discussed. History-by-history standard deviations are calculated for each simulation. RESULTS: A design with elliptical tubing containing bundles of tantalum wires provides the most significant attenuation with 39% and 27% dose reduction to the center and soft palate locations, respectively. Another design utilizing miniature lead spheres loaded into a constructed cavity shows 27% and 24% dose reduction to the same locations while providing more uniform shielding and several practical benefits. Both shields are designed to be completely removable for applicator insertion and pretreatment imaging. The mean and maximum standard error of relative dose measurements was 0.36 and 1.14 percentage points, respectively. CONCLUSION: Each shielding design presented in this study provides a novel approach to safely and effectively shield healthy tissue during intracavitary nasopharyngeal brachytherapy. Analysis performed using Monte Carlo suggests that the design using metal spheres most practically shields the soft palate and should be advanced to the next stages of clinical optimization.

Validation of the TOPAS Monte Carlo toolkit for HDR brachytherapy simulations.

PURPOSE: The goal of this work is to validate the user-friendly Geant4-based Monte Carlo toolkit TOol for PArticle Simulation (TOPAS) for brachytherapy applications. METHODS AND MATERIALS: Brachytherapy simulations performed with TOPAS were systematically compared with published TG-186 reference data. The photon emission energy spectrum, the air-kerma strength, and the dose-rate constant of the model-based dose calculation algorithm (MBDCA)-WG generic Ir-192 source were extracted. For dose calculations, a track-length estimator was implemented. The four Joint AAPM/ESTRO/ABG MBDCA-WG test cases were evaluated through histograms of the local and global dose difference volumes. A prostate, a palliative lung, and a breast case were simulated. For each case, the dose ratio map, the histogram of the global dose difference volume, and cumulative dose-volume histograms were calculated. RESULTS: The air-kerma strength was (9.772 ± 0.001) × 10-8 U Bq-1 (within 0.3% of the reference value). The dose-rate constant was 1.1107 ± 0.0005 cGy h-1 U-1 (within 0.01% of the reference value). For all cases, at least 96.9% of voxels had a local dose difference within [-1%, 1%] and at least 99.9% of voxels had a global dose difference within [-0.1%, 0.1%]. The implemented track-length estimator scorer was more efficient than the default analog dose scorer by a factor of 237. For all clinical cases, at least 97.5% of voxels had a global dose difference within [-1%, 1%]. Dose-volume histograms were consistent with the reference data. CONCLUSIONS: TOPAS was validated for high-dose-rate brachytherapy simulations following the TG-186 recommended approach for MBDCAs. Built on top of Geant4, TOPAS provides broad access to a state-of-the-art Monte Carlo code for brachytherapy simulations.

Bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia: a rare case report.

BACKGROUND: Cerebral venous sinus thrombosis (CVST), a rare cause of cerebral infarction, is often unrecognized at initial presentation. We report the case of a patient with bilateral corpus callosum and corona radiata infarction due to cerebral venous sinus thrombosis presenting as headache and acute reversible aphasia. CASE PRESENTATION: A 30-year-old female patient presented with headache, vomiting, and motor aphasia. She was 20 days post-partum and had a lower than normal food intake following a normal vaginal delivery. Brain magnetic resonance images revealed a bilateral corpus callosum and corona radiata infarction. MR venography (MRV) and digital subtraction angiography (DSA) images showed a signal void in the anterior aspect of the superior sagittal sinus and inferior sagittal sinus, ophthalmic vein expansion, and the reversed direction of venous flow. In addition, images showed non-visualization of the left transverse sinus. The left slender sigmoid sinus and small internal jugular vein were also noted. The diagnosis of cerebral venous thrombosis was considered based on the above findings. The patient was managed with anticoagulation therapy, and recovered substantially after treatment. CONCLUSIONS: Bilateral corpus callosum and corona radiata infarction is very rare. However, for patients who clinically show cranial hypertension and neurological deficits during the puerperium period, the possibility of CVST should be considered. Furthermore, DSA plays an important role in the diagnosis of CVST, and should be routinely checked. Early diagnosis is crucial for the patient suffering from CVST.

[Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice].

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

Rehmannioside A attenuates cognitive deficits in rats with vascular dementia (VD) through suppressing oxidative stress, inflammation and apoptosis.

Vascular dementia (VD) is a degenerative cerebrovascular disorder, leading to progressive decline of cognitive abilities and memory. Rehmannioside A (ReA) is isolated from Rehmanniae Radix, which exhibits protective role against various diseases. The present study was performed to calculate the possible neuroprotective effects of ReA on VD. Here, the morris water maze (MWM) test and electrophysiological recordings indicated that ReA reduced cognitive deficits. Additionally, through hematoxylin and eosin (H&E) and Nissl staining, ReA attenuated the histological alterations of hippocampus in rats with VD. ReA group significantly reduced oxidative stress, inflammatory response and apoptosis in the hippocampus of rats with VD, which was linked to the activation of nuclear erythroid related factor-2 (Nrf2), while the inactivation of nuclear factor-κB (NF-κB) and Caspase-3. Further, the anti-oxidative, anti-inflammatory and anti-apoptosis abilities of ReA were confirmed in cells stimulated by hydrogen peroxide. Overall, the results above demonstrated the protective effects of ReA against cognitive deficits and indicated the potential value of ReA in the therapy of VD in future.

Large-conductance calcium-activated potassium channels mediate lipopolysaccharide-induced activation of murine microglia.

Large-conductance calcium-activated potassium (BK) channels are ubiquitously expressed in most cell types where they regulate many cellular, organ, and organismal functions. Although BK currents have been recorded specifically in activated murine and human microglia, it is not yet clear whether and how the function of this channel is related to microglia activation. Here, using patch-clamping, Griess reaction, ELISA, immunocytochemistry, and immunoblotting approaches, we show that specific inhibition of the BK channel with paxilline (10 µm) or siRNA-mediated knockdown of its expression significantly suppresses lipopolysaccharide (LPS)-induced (100 ng/ml) BV-2 and primary mouse microglial cell activation. We found that membrane BK current is activated by LPS at a very early stage through Toll-like receptor 4 (TLR4), leading to nuclear translocation of NF-κB and to production of inflammatory cytokines. Furthermore, we noted that BK channels are also expressed intracellularly, and their nuclear expression significantly increases in late stages of LPS-mediated microglia activation, possibly contributing to production of nitric oxide, tumor necrosis factor-α, and interleukin-6. Of note, a specific TLR4 inhibitor suppressed BK channel expression, whereas an NF-κB inhibitor did not. Taken together, our findings indicate that BK channels participate in both the early and the late stages of LPS-stimulated murine microglia activation involving both membrane-associated and nuclear BK channels.

A GPU-based multi-criteria optimization algorithm for HDR brachytherapy.

Currently in HDR brachytherapy planning, a manual fine-tuning of an objective function is necessary to obtain case-specific valid plans. This study intends to facilitate this process by proposing a patient-specific inverse planning algorithm for HDR prostate brachytherapy: GPU-based multi-criteria optimization (gMCO). Two GPU-based optimization engines including simulated annealing (gSA) and a quasi-Newton optimizer (gL-BFGS) were implemented to compute multiple plans in parallel. After evaluating the equivalence and the computation performance of these two optimization engines, one preferred optimization engine was selected for the gMCO algorithm. Five hundred sixty-two previously treated prostate HDR cases were divided into validation set (100) and test set (462). In the validation set, the number of Pareto optimal plans to achieve the best plan quality was determined for the gMCO algorithm. In the test set, gMCO plans were compared with the physician-approved clinical plans. Our results indicated that the optimization process is equivalent between gL-BFGS and gSA, and that the computational performance of gL-BFGS is up to 67 times faster than gSA. Over 462 cases, the number of clinically valid plans was 428 (92.6%) for clinical plans and 461 (99.8%) for gMCO plans. The number of valid plans with target [Formula: see text] coverage greater than 95% was 288 (62.3%) for clinical plans and 414 (89.6%) for gMCO plans. The mean planning time was 9.4 s for the gMCO algorithm to generate 1000 Pareto optimal plans. In conclusion, gL-BFGS is able to compute thousands of SA equivalent treatment plans within a short time frame. Powered by gL-BFGS, an ultra-fast and robust multi-criteria optimization algorithm was implemented for HDR prostate brachytherapy. Plan pools with various trade-offs can be created with this algorithm. A large-scale comparison against physician approved clinical plans showed that treatment plan quality could be improved and planning time could be significantly reduced with the proposed gMCO algorithm.

Role of Xingnaojing combined with naloxone in treating intracerebral haemorrhage: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Xingnaojing injection (XNJ) sharpen the mind and induce consciousness and are widely used in acute phases of intracerebral hemorrhage (ICH). Naloxone hydrochloride injection (NX) performs equally well and replace the effects of morphine-like substances to promote conscious awareness. The applications of XNJ combined with NX for ICH show some advantages compared with NX applied individually. The aim of this systematic review is to evaluate the effectiveness and safety of XNJ combined with NX for ICH. METHODS: Comprehensive searches were conducted in 8 medical databases (PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, CBM and Wanfang database) from inceptions to October 2017 for randomized controlled trials (RCTs) that compared the applications of XNJ and NX with NX applied individually in ICH. Literature screening, assessing risk of bias and data extraction were conducted by 2 reviewers independently. According to the Cochrane Collaboration's RevMan5.3 software to perform the data analysis. RESULTS: 32 RCTs (3068 cases) were selected and the quality of studies were low. All trials compared XNJ and NX with NX applied individually. The overall meta-analysis results showed that XNJ combined with NX have significant effect on clinical efficacy (OR 3.78, 95% CI: 3.03-4.73; P < .00001), GCS score (MD 3.86, 95% CI: 3.46-4.25; P < .00001), coma duration (MD -5.59, 95% CI: -6.96 to -4.22; P < .00001), NIHSS score (MD -6.24, 95% CI: -8.05 to -4.42; P < .00001), Barthel Index score (MD 14.12, 95% CI: 6.7-21.54; P < .0002), cerebral hematoma volume (MD -6.05, 95% CI: -6.85 to -5.24; P < .00001) than NX applied individually. Adverse events reported in 4 studies and included mild discomfort symptoms. CONCLUSION: The effectiveness and safety of XNJ combined with NX for ICH cannot be determined due to the low quality of literature, publication bias and heterogeneity. More rigorous RCTs are necessary to verify the role of XNJ combined with NX in the treatment of ICH.

Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury.

We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day) (CsA), and IR plus vehicle (Vehicle). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion (MCAO). Cerebral infarct areas were measured by triphenyl tetrazolium chloride staining. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining (HE) and Nissl staining. Ultrastructural features of mitochondria and mitophagy in the penumbra of the ischemic cortex were observed by transmission electron microscopy. Mitophagy was detected by immunofluorescence labeled with LC3B and VDAC1. Autophagy lysosome formation was observed by immunofluorescence labeled with LC3B and Lamp1. The expression of LC3B, Beclin1, and Lamp1 was analyzed by Western blot. The rats subjected to MCAO showed worsened neurological score and cell ischemic damage. These were all significantly reversed by XXMD or CsA. Moreover, XXMD/CsA notably downregulated mitophagy and reduced the increase in LC3, Beclin1, and Lamp1 expression induced by cerebral ischemia and reperfusion. The findings demonstrated that XXMD exerted neuroprotective effect via downregulating LC3, Beclin1, Lamp1, and mitochondrial p62 expression level, thus leading to the inhibition of mitophagy.

Mitophagy is activated in brain damage induced by cerebral ischemia and reperfusion via the PINK1/Parkin/p62 signalling pathway.

This study examined the course of mitophagy following cerebral ischemia with reperfusion and the role of the PTEN-induced kinase 1 (PINK1)/Parkin/p62 signalling pathway. The middle cerebral artery of male Sprague-Dawley rats was occluded for 90 min and was followed by different time-points of reperfusion. Cerebral infarct areas were detected by 2,3,5-triphenyl tetrazolium chloride staining, while brain damage was observed by haematoxylin and eosin staining. Levels of LC3, Beclin1 and LAMP-1 were estimated by western blots. LC3B location was observed in various cells in the neurovascular unit. In addition, PINK1 accumulation in damaged mitochondria and Parkin/p62 mitochondrial translocation were investigated by double immunofluorescence staining. Finally, the levels of PINK1, Parkin and p62 expression in mitochondrial fractions were estimated by western blots. Cerebral ischemia with different time-points of reperfusion resulted in infarct in the territory of the middle cerebral artery accompanied by overall brain damage. In addition, we found up-regulation of LC3B, Beclin1, and LAMP-1, as well as mitophagy activation after reperfusion, with peak expression of these proteins at 24 h after reperfusion. Electron microscopy and immunofluorescence indicated that LC3B was primarily located in neurons, although lower levels of expression were found in astrocytes and even less in vascular endothelial cells. Moreover, significant increases in PINK1 accumulation in the outer membrane of mitochondria and increased Parkin/p62 mitochondrial translocation were shown at 24 h after reperfusion. These findings suggest that the PINK1/Parkin/p62 signalling pathway was involved in the pathophysiological processes following ischemia and reperfusion.

Intratumoral Injection of Low-Energy Photon-Emitting Gold Nanoparticles: A Microdosimetric Monte Carlo-Based Model.

Gold nanoparticles (Au NPs) distributed in the vicinity of low-dose rate (LDR) brachytherapy seeds could multiply their efficacy thanks to the secondary emissions induced by the photoelectric effect. Injections of radioactive LDR gold nanoparticles (LDR Au NPs), instead of conventional millimeter-size radioactive seeds surrounded by Au NPs, could further enhance the dose by distributing the radioactivity more precisely and homogeneously in tumors. However, the potential of LDR Au NPs as an emerging strategy to treat cancer is strongly dependent on the macroscopic diffusion of the NPs in tumors, as well as on their microscopic internalization within the cells. Understanding the relationship between interstitial and intracellular distribution of NPs, and the outcomes of dose deposition in the cancer tissue is essential for considering future applications of radioactive Au NPs in oncology. Here, LDR Au NPs (103Pd:Pd@Au-PEG NPs) were injected in prostate cancer tumors. The particles were visualized at time-points by computed tomography imaging ( in vivo), transmission electron microscopy ( ex vivo), and optical microscopy ( ex vivo). These data were used in a Monte Carlo-based dosimetric model to reveal the dose deposition produced by LDR Au NPs both at tumoral and cellular scales. 103Pd:Pd@Au-PEG NPs injected in tumors produce a strong dose enhancement at the intracellular level. However, energy deposition is mainly confined around vesicles filled with NPs, and not necessarily close to the nuclei. This suggests that indirect damage caused by the production of reactive oxygen species might be the leading therapeutic mechanism of tumor growth control, over direct damage to the DNA.

A generic TG-186 shielded applicator for commissioning model-based dose calculation algorithms for high-dose-rate 192 Ir brachytherapy.

PURPOSE: A joint working group was created by the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) with the charge, among others, to develop a set of well-defined test case plans and perform calculations and comparisons with model-based dose calculation algorithms (MBDCAs). Its main goal is to facilitate a smooth transition from the AAPM Task Group No. 43 (TG-43) dose calculation formalism, widely being used in clinical practice for brachytherapy, to the one proposed by Task Group No. 186 (TG-186) for MBDCAs. To do so, in this work a hypothetical, generic high-dose rate (HDR) 192 Ir shielded applicator has been designed and benchmarked. METHODS: A generic HDR 192 Ir shielded applicator was designed based on three commercially available gynecological applicators as well as a virtual cubic water phantom that can be imported into any DICOM-RT compatible treatment planning system (TPS). The absorbed dose distribution around the applicator with the TG-186 192 Ir source located at one dwell position at its center was computed using two commercial TPSs incorporating MBDCAs (Oncentra® Brachy with Advanced Collapsed-cone Engine, ACE™, and BrachyVision ACUROS™) and state-of-the-art Monte Carlo (MC) codes, including ALGEBRA, BrachyDose, egs_brachy, Geant4, MCNP6, and Penelope2008. TPS-based volumetric dose distributions for the previously reported "source centered in water" and "source displaced" test cases, and the new "source centered in applicator" test case, were analyzed here using the MCNP6 dose distribution as a reference. Volumetric dose comparisons of TPS results against results for the other MC codes were also performed. Distributions of local and global dose difference ratios are reported. RESULTS: The local dose differences among MC codes are comparable to the statistical uncertainties of the reference datasets for the "source centered in water" and "source displaced" test cases and for the clinically relevant part of the unshielded volume in the "source centered in applicator" case. Larger local differences appear in the shielded volume or at large distances. Considering clinically relevant regions, global dose differences are smaller than the local ones. The most disadvantageous case for the MBDCAs is the one including the shielded applicator. In this case, ACUROS agrees with MC within [-4.2%, +4.2%] for the majority of voxels (95%) while presenting dose differences within [-0.12%, +0.12%] of the dose at a clinically relevant reference point. For ACE, 95% of the total volume presents differences with respect to MC in the range [-1.7%, +0.4%] of the dose at the reference point. CONCLUSIONS: The combination of the generic source and generic shielded applicator, together with the previously developed test cases and reference datasets (available in the Brachytherapy Source Registry), lay a solid foundation in supporting uniform commissioning procedures and direct comparisons among treatment planning systems for HDR 192 Ir brachytherapy.

Validation of the Oncentra Brachy Advanced Collapsed cone Engine for a commercial (192)Ir source using heterogeneous geometries.

PURPOSE: To validate the Advanced Collapsed cone Engine (ACE) dose calculation engine of Oncentra Brachy (OcB) treatment planning system using an (192)Ir source. METHODS AND MATERIALS: Two levels of validation were performed, conformant to the model-based dose calculation algorithm commissioning guidelines of American Association of Physicists in Medicine TG-186 report. Level 1 uses all-water phantoms, and the validation is against TG-43 methodology. Level 2 uses real-patient cases, and the validation is against Monte Carlo (MC) simulations. For each case, the ACE and TG-43 calculations were performed in the OcB treatment planning system. ALGEBRA MC system was used to perform MC simulations. RESULTS: In Level 1, the ray effect depends on both accuracy mode and the number of dwell positions. The volume fraction with dose error ≥2% quickly reduces from 23% (13%) for a single dwell to 3% (2%) for eight dwell positions in the standard (high) accuracy mode. In Level 2, the 10% and higher isodose lines were observed overlapping between ACE (both standard and high-resolution modes) and MC. Major clinical indices (V100, V150, V200, D90, D50, and D2cc) were investigated and validated by MC. For example, among the Level 2 cases, the maximum deviation in V100 of ACE from MC is 2.75% but up to ~10% for TG-43. Similarly, the maximum deviation in D90 is 0.14 Gy between ACE and MC but up to 0.24 Gy for TG-43. CONCLUSION: ACE demonstrated good agreement with MC in most clinically relevant regions in the cases tested. Departure from MC is significant for specific situations but limited to low-dose (<10% isodose) regions.

A generic high-dose rate (192)Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism.

PURPOSE: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) (192)Ir source and a virtual water phantom were designed, which can be imported into a TPS. METHODS: A hypothetical, generic HDR (192)Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic (192)Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra(®) Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS™ ]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201)(3) voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR (192)Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by different investigators. MC results were then compared against dose calculated using TG-43 and MBDCA methods. RESULTS: TG-43 and PSS datasets were generated for the generic source, the PSS data for use with the ace algorithm. The dose-rate constant values obtained from seven MC simulations, performed independently using different codes, were in excellent agreement, yielding an average of 1.1109 ± 0.0004 cGy/(h U) (k = 1, Type A uncertainty). MC calculated dose-rate distributions for the two plans were also found to be in excellent agreement, with differences within type A uncertainties. Differences between commercial MBDCA and MC results were test, position, and calculation parameter dependent. On average, however, these differences were within 1% for ACUROS and 2% for ace at clinically relevant distances. CONCLUSIONS: A hypothetical, generic HDR (192)Ir source was designed and implemented in two commercially available TPSs employing different MBDCAs. Reference dose distributions for this source were benchmarked and used for the evaluation of MBDCA calculations employing a virtual, cubic water phantom in the form of a CT DICOM image series. The implementation of a generic source of identical design in all TPSs using MBDCAs is an important step toward supporting univocal commissioning procedures and direct comparisons between TPSs.

Acupuncture reduced apoptosis and up-regulated BDNF and GDNF expression in hippocampus following hypoxia-ischemia in neonatal rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Acupuncture attenuates neuronal damages following ischemia. AIM OF THE STUDY: The purpose of the present study was to investigate the beneficial effects of acupuncture on hypoxia-ischemia induced brain damages in neonatal rats. MATERIALS AND METHODS: Male postnatal 7 days rats were randomly divided into 3 groups: sham control (sham), hypoxia-ischemia (HI), and HI plus acupuncture treatment (HI+Acu). The rats in HI and HI+Acu groups were submitted to model of neonatal HI, established by occluding the left common carotid artery followed by a 3.5h period of hypoxia (8% O2-92% N2). At 24h after HI, animals were stimulated by acupuncture treatment once a day and the treatment continued during 4 weeks, 5days/week. Behavioral functions, learning and memory ability, and body weight were observed at different time-points after HI. DNA fragmentation assay were performed with TUNEL staining to evaluate apoptosis and expression levels of mitochondrial Bcl-2, mitochondrial Bax, Cleaved caspase 3, Cleaved caspase 9 in the damaged hippocampus were detected by western blotting 28 days following HI. GDNF, BDNF levels in hippocampus were also determined. RESULTS: The results showed that acupuncture significantly promoted growth and development, improved neurobehavioral function, learning and memory ability after 20 days' treatment. Furthermore, we obtained one interesting finding that acupuncture attenuated cellular apoptosis and up-regulated GDNF and BDNF levels in hippocampus. CONCLUSIONS: All of these results suggest that acupuncture as a potential treatment may exert neuroprotective effects via inhibiting cellular apoptosis, increased GDNF and BDNF expression levels in rat hippocampus experiencing HI.

Effect of atovastatin treatment on porcine circovirus 2 infection in BALB/c mice.

The HMG-CoA reductase (HMGCR) pathway is an important metabolic route, which is not only present in almost every organism, but also involves virus infection. It has recently been shown that expression levels of IFN-responsive genes were significantly increased in HMGCR-downregulated cells and HMGCR inhibitor-treated cells. The aim of this study was to determine whether inhibition of HMGCR by atovastatin would significantly affect Porcine circovirus type 2 (PCV2) infection and immunological reaction in BALB/c mice. The results showed atovastatin significantly stimulated PCV2 replication in vivo. Immunological reaction in atovastatin-treated mice was also significantly enhanced during PCV2 infection. Atovastatin also enhanced PCV2-induced illness in mice. The results of this study will provide new insight into the role of atovastatin in PCV2 infection.

Markerless Deletion System for Escherichia coli Using Short Homologous Sequences and Positive-Negative Selectable Cassette.

Red homologous recombination has been extensively used in recombineering. Because foreign sequences, such as antibiotic resistance genes, FRT-sites, or loxP-sites, are often unwanted in mutant Escherichia coli, we established a markerless deletion system containing short homologous sequences, a positive-selectable marker (kan), and a negative-selectable marker (sacB) for E. coli. For markerless deletion of a specific region of the E. coli genome, a two-step recombination procedure using two different PCR fragments, which were amplified from pUC57-kan-sacB and pUC57-298, was performed. The generation of a pheA-tyrA deficient mutant demonstrated that this markerless deletion system was a simple and efficient method to generate markerless chromosomal deletions in E. coli.