Dosimetric comparison of HyperArc and InCise MLC-based CyberKnife plans in treating single and multiple brain metastases.

BACKGROUND AND PURPOSE: This study aimed to compare the dosimetric attributes of two multi-leaf collimator based techniques, HyperArc and Incise CyberKnife, in the treatment of brain metastases. MATERIAL AND METHODS: 17 cases of brain metastases were selected including 6 patients of single lesion and 11 patients of multiple lesions. Treatment plans of HyperArc and CyberKnife were designed in Eclipse 15.5 and Precision 1.0, respectively, and transferred to Velocity 3.2 for comparison. RESULTS: HyperArc plans provided superior Conformity Index (0.91 ± 0.06 vs. 0.77 ± 0.07, p < 0.01) with reduced dose distribution in organs at risk (Dmax, p < 0.05) and lower normal tissue exposure (V4Gy-V20Gy, p < 0.05) in contrast to CyberKnife plans, although the Gradient Indexes were similar. CyberKnife plans showed higher Homogeneity Index (1.54 ± 0.17 vs. 1.39 ± 0.09, p < 0.05) and increased D2% and D50% in the target (p < 0.05). Additionally, HyperArc plans had significantly fewer Monitor Units (MUs) and beam-on time (p < 0.01). CONCLUSION: HyperArc plans demonstrated superior performance compared with MLC-based CyberKnife plans in terms of conformity and the sparing of critical organs and normal tissues, although no significant difference in GI outcomes was noted. Conversely, CyberKnife plans achieved a higher target dose and HI. The study suggests that HyperArc is more efficient and particularly suitable for treating larger lesions in brain metastases.

250 years of flood frequency and discharge in an ungauged Corsican mountain catchment: A dendrogeomorphic reconstruction.

The primary goal of paleoflood hydrology is to estimate the frequency and magnitude of past floods. Botanical evidence, and particularly scars on trees, has been used repeatedly as paleostage indicators to reconstruct peak discharges and flood height. Yet, these reconstructions depend on the presence of visible scars on tree stems which tend to be masked as trees grow older. Here, we estimated flood magnitude using an alternative approach based on growth disturbances in tree-ring series, tree positions and the minimal discharge necessary to submerge the root collar of a tree as estimated by hydraulic modeling. We tested the reliability of this newly developed approach by using the traditional scar-based reconstruction as a benchmark. To this end, we sampled 60 trees showing evidence of flood damage on their stems along a 787-m long segment of the Asco river (Corsica, France). Based on 440 growth disturbances dated in tree-ring series, we reconstructed 28 floods between 1759 and 2020 and 18 during the 20th century. Using the two-dimensional Iber hydraulic model and detailed topographic data of the study site obtained from UAV imagery, we estimated that peak discharges of the 28 reconstructed events ranged between 10 and 210 m3s-1, with 200 m3s-1 being considered as the threshold for extreme floods. Not only do the scar-based and root collar submersion approaches yield similar results, findings are also clearly in line with the sparse information available from historical archives and short gauge station records on past floods. The unprecedented length and depth of the record presented here opens new avenues for climate change and flood impact research.

Capsule Endoscopy-Based Diagnosis of Lung Squamous Cell Carcinoma Associated with Abdominal Pain and Metastasis to Small Intestine: A Case Report.

Gastrointestinal metastases of lung cancer are relatively uncommon, yet occur at a higher frequency than would be expected among patients that exhibit a longer survival interval. Metastases that arise in the small intestines are often associated with no or few symptoms such that their early diagnosis can be challenging. In this report, we describe an extremely rare case of a lung squamous cell carcinoma that had metastasized to the small intestine and was associated with symptoms of abdominal pain. The patient underwent capsule endoscopy which detected an irregular mass in the distal ileum that was hemorrhagic, after which laparoscopic ileal resection and anastomosis in parallel with partial bladder resection were performed. Subsequent pathological biopsy confirmed that the intestinal mass was consistent with metastatic squamous cell carcinoma. With surgery and subsequent maintenance therapy with targeted drugs, the survival of the patient was more than 6 months. As a noninvasive testing strategy, capsule endoscopy can be easily performed to support etiological diagnostic efforts in cases where other diagnostic options are lacking. Early diagnosis and therapeutic intervention can contribute to better prognostic outcomes for GMLC patients.

Unveiling the dynamics of antibiotic resistome, bacterial communities, and metals from the feces of patients in a typical hospital wastewater treatment system.

Bacterial pathogens and antibiotic resistance genes (ARGs) are extensively disseminated into the environment via hospital wastewater (HWW), as it contains large quantities of feces from resident patients. However, studies on the antibiotic resistome and pathogenic bacteria from the gut of resident patients within the hospital wastewater treatment plant (hWWTP) are limited. Here, we examined and compared the occurrence and abundance of ARGs, mobile genetic elements (MGEs), metals, and bacterial communities from the feces of patients in a typical hWWTP system and determined the pathogenic hosts responsible for transferring ARGs. There were 176 ARGs and 43 MGEs detected in the feces of hospitalized patients, 129 genes were persistent, and 88 genes were enriched after HWW treatment, particularly for the blaVEB, blaNDM, and class 1 integron (intI1), with an average of 659-fold, 202-fold, and seven-fold enrichment, respectively. MGEs, especially Is613, in the feces of hospitalized patients were exceptionally abundant and even surpassed the abundance of total ARGs, which explained the persistence of ARGs in hWWTPs due to possible gene mobilization events. Bacteroidetes and Firmicutes were the most abundant phyla in these feces, accounting for 81 % of the total gut microbiota, while Epsilonbacteraeota and Proteobacteria dominated the hWWTPs. Additionally, 54 possible bacterial pathogens were found in the hospital environment, including four "ESKAPE" pathogens and 14 cancer-related pathogens. Many of them were strongly associated with different types of ARGs. Notably, Bacteroides was the major potential ARG-harboring pathogenic genus, as determined by the network analysis, and was highly abundant after the treatment. The altered microbial community was the major contributing factor shaping antibiotic resistome. This study might provide a comprehensive insight into the distribution profiles of ARGs and pathogens from the gut of inpatients throughout the HWW treatment system, which could be used as a reference for optimizing HWW treatment and monitoring public risk.

Superficial peroneal neuromodulation of nonobstructive urinary retention induced by prolonged pudendal afferent activity in cats.

The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can improve nonobstructive urinary retention (NOUR) induced by prolonged pudendal nerve stimulation (PNS). In this exploratory acute study using eight cats under anesthesia, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. A double lumen catheter was inserted via the bladder dome for bladder infusion and pressure measurement and to allow voiding without a physical urethral outlet obstruction. The voided and postvoid residual (PVR) volumes were also recorded. NOUR induced by repetitive (4-13 times) application of 30-min PNS significantly (P < 0.05) reduced voiding efficiency by 49.5 ± 16.8% of control (78.3 ± 7.9%), with a large PVR volume at 208.2 ± 82.6% of control bladder capacity. SPNS (1 Hz, 0.2 ms) at 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during cystometrograms to improve the PNS-induced NOUR. SPNSc and SPNSi applied by nerve cuff electrodes significantly (P < 0.05) increased voiding efficiency to 74.5 ± 18.9% and 67.0 ± 15.3%, respectively, and reduced PVR volume to 54.5 ± 39.0% and 88.3 ± 56.0%, respectively. SPNSc and SPNSi applied noninvasively by skin surface electrodes also improved NOUR similar to the stimulation applied by a cuff electrode. This study indicates that abnormal pudendal afferent activity could be a pathophysiological cause for the NOUR occurring in Fowler's syndrome and a noninvasive superficial peroneal neuromodulation therapy might be developed to treat NOUR in patients with Fowler's syndrome.

Superficial peroneal neuromodulation of persistent bladder underactivity induced by prolonged pudendal afferent nerve stimulation in cats.

The purpose of this study is to determine whether superficial peroneal nerve stimulation (SPNS) can reverse persistent bladder underactivity induced by prolonged pudendal nerve stimulation (PNS). In 16 α-chloralose-anesthetized cats, PNS and SPNS were applied by nerve cuff electrodes. Skin surface electrodes were also used for SPNS. Bladder underactivity consisting of a significant increase in bladder capacity to 157.8 ± 10.9% of control and a significant reduction in bladder contraction amplitude to 56.0 ± 5.0% of control was induced by repetitive (4-16 times) application of 30-min PNS. SPNS (1 Hz, 0.2 ms) at 1.5-2 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) or intermittently (SPNSi) during a cystometrogram (CMG) to determine whether the stimulation can reverse the PNS-induced bladder underactivity. SPNSc or SPNSi applied by nerve cuff electrodes during the prolonged PNS inhibition significantly reduced bladder capacity to 124.4 ± 10.7% and 132.4 ± 14.2% of control, respectively, and increased contraction amplitude to 85.3 ± 6.2% and 75.8 ± 4.7%, respectively. Transcutaneous SPNSc and SPNSi also significantly reduced bladder capacity and increased contraction amplitude. Additional PNS applied during the bladder underactivity further increased bladder capacity, whereas SPNSc applied simultaneously with the PNS reversed the increase in bladder capacity. This study indicates that a noninvasive superficial peroneal neuromodulation therapy might be developed to treat bladder underactivity caused by abnormal pudendal nerve somatic afferent activation that is hypothesized to occur in patients with Fowler's syndrome.

Model Analysis of Post-Stimulation Effect on Axonal Conduction and Block.

OBJECTIVE: To reveal the possible contribution of changes in membrane ion concentration gradients and ion pump activity to axonal conduction/block induced by long-duration electrical stimulation. METHODS: A new model for conduction and block of unmyelinated axons based on the classical Hodgkin-Huxley (HH) equations is developed to include changes in Na+ and K+ concentrations and ion pumps. The effect of long-duration stimulation on axonal conduction/block is analyzed by computer simulation using this new model. RESULTS: The new model successfully simulates initiation, propagation, and block of action potentials induced by short-duration (multiple milliseconds) stimulations that do not significantly change the ion concentrations in the classical HH model. In addition, the activity-dependent effects such as action potential attenuation and broadening observed in animal studies are also successfully simulated by the new model. Finally, the model successfully simulates axonal block occurring after terminating a long-duration (multiple seconds) direct current (DC) stimulation as observed in recent animal studies and reveals 3 different mechanisms for the post-DC block of axonal conduction. CONCLUSION: Ion concentrations and pumps play an important role in post-stimulation effects and activity-dependent effects on axonal conduction/block. The duration of stimulation is a determinant factor because it influences the total charges applied to the axon, which in turn determines the ion concentrations inside and outside the axon. SIGNIFICANCE: Despite recent clinical success of many neurostimulation therapies, the effects of long-duration stimulation on axonal conduction/block are poorly understood. This new model could significantly impact our understanding of the mechanisms underlying different neurostimulation therapies.

Bladder underactivity induced by prolonged pudendal afferent activity in cats.

The purpose of this study was to determine the effects of pudendal nerve stimulation (PNS) on reflex bladder activity and develop an animal model of underactive bladder (UAB). In six anesthetized cats, a bladder catheter was inserted via the urethra to infuse saline and measure pressure. A cuff electrode was implanted on the pudendal nerve. After determination of the threshold intensity (T) for PNS to induce an anal twitch, PNS (5 Hz, 0.2 ms, 2 T or 4 T) was applied during cystometrograms (CMGs). PNS (4-6 T) of 30-min duration was then applied repeatedly until bladder underactivity was produced. Following stimulation, control CMGs were performed over 1.5-2 h to determine the duration of bladder underactivity. When applied during CMGs, PNS (2 T and 4 T) significantly (P < 0.05) increased bladder capacity while PNS at 4 T also significantly (P < 0.05) reduced bladder contraction amplitude, duration, and area under contraction curve. Repeated application of 30-min PNS for a cumulative period of 3-8 h produced bladder underactivity exhibiting a significantly (P < 0.05) increased bladder capacity (173 ± 14% of control) and a significantly (P < 0.05) reduced contraction amplitude (50 ± 7% of control). The bladder underactivity lasted more than 1.5-2 h after termination of the prolonged PNS. These results provide basic science evidence supporting the proposal that abnormal afferent activity from external urethral/anal sphincter could produce central inhibition that underlies nonobstructive urinary retention (NOUR) in Fowler's syndrome. This cat model of UAB may be useful to investigate the mechanism by which sacral neuromodulation reverses NOUR in Fowler's syndrome.

Superficial peroneal neuromodulation of nonobstructive urinary retention in cats.

AIMS: To determine if superficial peroneal nerve stimulation (SPNS) can improve nonobstructive urinary retention (NOUR). METHODS: In α-chloralose anesthetized cats, NOUR was induced by repetitive application (4-16 times) of 30-minute tibial nerve stimulation (TNS: 5 Hz frequency, 0.2 ms pulse width) at 4 to 6 times threshold intensity (T) for inducing toe twitches. SPNS (1 Hz, 0.2 ms) at 2 to 4 times threshold intensity (T) for inducing posterior thigh muscle contractions was applied either continuously (SPNSc) during a cystometrogram (CMG) or during voiding (SPNSv) by a surgically implanted cuff electrode or by skin surface electrodes to determine if the stimulation reduced NOUR induced by prolonged TNS. RESULTS: During control CMGs, efficient (86.4% ± 5.5%) voiding occurred with a postvoid residual (PVR) volume equal to 14.9% ± 6.2% of control bladder capacity. NOUR elicited by prolonged TNS significantly (P < .05) increased bladder capacity to 168.6% ± 15.5% of control, reduced voiding efficiency to 30.4% ± 4.8%, and increased PVR to 109% ± 9.2% of control. Using the implanted cuff electrode, SPNSc and SPNSv significantly (P < .05) increased voiding efficiency to 66.7% ± 7.4% and 65.0% ± 5.9%, respectively, and reduced PVR to 52.2% ± 11.4% and 64.3% ± 11.6%, respectively. SPNSc but not SPNSv significantly (P < .05) reduced bladder capacity to 133.4% ± 15% of control. Transcutaneous SPNSv but not SPNSc also significantly (P < .05) reversed the TNS-induced NOUR responses. CONCLUSIONS: This study shows that SPNS is effective in reversing NOUR induced by prolonged TNS. Transcutaneous SPNS provides the opportunity to develop a noninvasive neuromodulation therapy for NOUR to treat more patients than current sacral neuromodulation therapy.

Development of an Implantable Wireless and Batteryless Bladder Pressure Monitor System for Lower Urinary Tract Dysfunction.

BACKGROUND: Closed-loop neuromodulation based on bladder pressure is an effective therapy for lower urinary tract dysfunction. The catheter-based cystometry normally used for bladder pressure measurement is not conducive to patient health because it will bring great mental stress to the patient and increase the risk of infection. METHOD: This paper designs and implements an implantable wireless and batteryless bladder pressure monitor system that monitors bladder storage in real time by implanting a miniature packaged sensor which transmits the feedback signal to the external receiver through BLE (Bluetooth Low Energy). The implanted part is powered by a dedicated magnetic resonance based wireless power transmission system, which means no battery is needed. RESULTS: The maximum distance to which power can be transmitted is 7cm. The in vitro experiment proves that the system performance can meet the requirement of bladder pressure monitoring. The animal experiment uses rabbits as a model to verify the effectiveness of the system. After implantation, this system can work for a long time without replacing the battery. CONCLUSION: This system can monitor the pressure of the bladder and provide a basis for Closed-loop neuromodulation in patients with lower urinary tract dysfunction.

Localization of Epileptogenic Zone Based on Cortico-Cortical Evoked Potential (CCEP): A Feature Extraction and Graph Theory Approach.

OBJECTIVE: Epilepsy is a chronic brain disease, which is prone to relapse and affects individuals of all ages worldwide, particularly the very young and elderly. Up to one-third of these patients are medically intractable and require resection surgery. However, the outcomes of epilepsy surgery rely upon the clear identification of epileptogenic zone (EZ). The combination of cortico-cortical evoked potential (CCEP) and electrocorticography (ECoG) provides an opportunity to observe the connectivity of human brain network and more comprehensive information that may help the clinicians localize the epileptogenic focus more precisely. However, there is no standard analysis method in the clinical application of CCEPs, especially for the quantitative analysis of abnormal connectivity of epileptic networks. The aim of this paper was to present an approach on the batch processing of CCEPs and provide information relating to the localization of EZ for clinical study. METHODS: Eight medically intractable epilepsy patients were included in this study. Each patient was implanted with subdural grid electrodes and electrical stimulations were applied directly to their cortex to induce CCEPs. After signal preprocessing, we constructed three effective brain networks at different spatial scales for each patient, regarding the amplitudes of CCEPs as the connection weights. Graph theory was then applied to analyze the brain network topology of epileptic patients, and the topological metrics of EZ and non-EZ (NEZ) were compared. RESULTS: The effective connectivity network reconstructed from CCEPs was asymmetric, both the number and the amplitudes of effective CCEPs decreased with increasing distance between stimulating and recording sites. Besides, the distribution of CCEP responses was associated with the locations of EZ which tended to have higher degree centrality (DC) and nodal shortest path length (NLP) than NEZ. CONCLUSION: Our results indicated that the brain networks of epileptics were asymmetric and mainly composed of short-distance connections. The DC and NLP were highly consistent to the distribution of the EZ, and these topological parameters have great potential to be readily applied to the clinical localization of the EZ.