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Background Laparoscopic surgery requires specially designed instruments. Bowel tissue damage is considered one of the most serious forms of lesion, specifically perforation of the bowel. Methods An experimental setting was used to manipulate healthy pig bowel tissue via two vacuum instruments. During the experiments, two simple manipulations were performed for both prototypes by two experienced surgeons. Each manipulation was repeated 20 times for each prototype at a vacuum level of 60 kPa and 20 times for each prototype at a vacuum level of 20 kPa. All the manipulations were macroscopically assessed by two experienced surgeons in terms of damage to the bowel. Results In 160 observations, 63 ecchymoses were observed. All 63 ecchymoses were classified as not relevant and negligible. No serosa or seromuscular damages and no perforations were observed. Conclusion Vacuum instruments such as the tested prototypes have the potential to be used as grasper instruments in minimally invasive surgery.

Objective To assess the feasibility of the clinical use of 3 Tesla and 7 Tesla Magnetic Resonance Imaging for early (cT1) glottic carcinoma, including structural assessment of technical image quality and visibility of the tumor; and if feasible, to correlate MRI findings to routine diagnostics. Methods Prospective feasibility study. Twenty patients with primary clinical T1 glottic carcinoma underwent both routine clinical staging and CT. In addition, a 3 T and 7 T MRI protocol, developed for small laryngeal lesions, was performed in a 4‐point immobilization mask, using dedicated surface coils. Afterwards, routine endoscopic direct suspension laryngoscopy under general anaesthesia was performed. Results Only 2 of 7 (29%) of 7 T MRI scans were rated as moderate to good technical image quality. After exclusion of three patients with only mild to moderate dysplasia at the time of MRI, 13 of 17 (76%) of 3 T MRIs were of adequate technical image quality. Tumor visualization was adequate in 8 of 13 (62%) of patients with invasive squamous cell carcinomas. With exclusion of the four MRIs with motion artefacts, the tumor and its boundaries could be adequately seen in 8 of 9 (89%) patients with squamous cell carcinoma versus only one in four (25%) of patients with carcinoma in situ lesions. Conclusions 7 Tesla MRI was considered not feasible. 3 Tesla MRI, with adequate patient selection, namely clinical exclusion of patients with a history of claustrophobia and inclusion of only histologically proven invasive squamous cell carcinoma, can be feasible. Especially with further improvement of MR image quality. Level of Evidence 2B, prospective diagnostic study

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.

Introduction Repetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, thetaburst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients. Materials and Methods We performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy. A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50Hz triplet bursts every 200ms, delivered at 10-minute intertrain-intervals, targeted over the epileptic focus using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints respectively over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive and psychological questionnaires and a seizure diary kept by the patients and/or caregivers. Results Seven subjects (4M:3F; median age 48, IQR 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort. Conclusion We report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633)

Electron transfer in respiratory chains generates the electrochemical potential that serves as energy source for the cell. Prokaryotes can use a wide range of electron donors and acceptors and may have alternative complexes performing the same catalytic reactions as the mitochondrial complexes. This is the case for the alternative complex III (ACIII), a quinol:cytochrome c /HiPIP oxidoreductase. In order to understand the catalytic mechanism of this respiratory enzyme, we determined the structure of ACIII from Rhodothermus marinus at 3.9 Å resolution by single-particle cryo-electron microscopy. ACIII presents a so-far unique structure, for which we establish the arrangement of the cofactors (four iron–sulfur clusters and six c -type hemes) and propose the location of the quinol-binding site and the presence of two putative proton pathways in the membrane. Altogether, this structure provides insights into a mechanism for energy transduction and introduces ACIII as a redox-driven proton pump. Some prokaryotes use alternative respiratory chain complexes, such as the alternative complex III (ACIII), to generate energy. Here authors provide the cryoEM structure of ACIII from Rhodothermus marinus which shows the arrangement of cofactors and provides insights into the mechanism for energy transduction.

Preclinical animal models are indispensable for uncovering disease mechanisms and developing novel therapeutic interventions in synucleinopathies. Key readouts including neuronal cell death, neuroinflammation and alpha-synuclein protein aggregation, are routinely assessed by histological methods. However, traditional characterization of histological samples is labor-intensive and time-consuming. There is a growing need for reproducible and high-throughput tools to capture region- and cell type-specific changes, ultimately improving the predictive value of preclinical studies. To address this, our study introduces a pipeline using convolutional neural networks (CNNs) for high-throughput, unbiased analysis of immunohistological data in mouse brains. We have trained five CNN-based models to autonomously identify brain regions and detect markers of neurodegeneration, neuroinflammation, and alpha-synuclein aggregation. These models provide accurate, region-specific insights at cellular resolution without manual annotation, significantly speeding up analysis time from weeks to minutes. Our approach enhances the precision and efficiency of histological assessments, providing robust, brain-wide results in various animal models of synucleinopathies.

Study Design: Retrospective trends analysis. Objectives: Cervical fusion is a common adjunctive surgical modality used in the treatment of cervical spondylotic myelopathy (CSM). The purpose of this study was to quantify national trends in patient demographics, hospital characteristics, and outcomes in the surgical management of CSM. Methods: This was a retrospective study that used the National Inpatient Sample. The sample included all patients over 18 years of age with a diagnosis of CSM who underwent cervical fusion from 2003 to 2013. The outcome measures were in-hospital mortality, length of stay, and hospital charges. Chi-square tests were performed to compare categorical variables. Independent t tests were performed to compare continuous variables. Results: We identified 62 970 patients with CSM who underwent cervical fusion from 2003 to 2013. The number of fusions performed per year in the treatment of CSM increased from 3879 to 8181. The average age of all fusion patients increased from 58.2 to 60.6 years (P < .001). Length of stay did not change significantly from a mean of 3.7 days. In-hospital mortality decreased from 0.6% to 0.3% (P < .01). Hospital charges increased from $49 445 to $92 040 (P < .001). Conclusions: This study showed a dramatic increase in cervical fusions to treat CSM from 2003 to 2013 concomitant with increasing age of the patient population. Despite increases in average age and number of comorbidities, length of stay remained constant and a decrease in mortality was seen across the study period. However, hospital charges increased dramatically.

ATP synthase membrane rotors consist of a ring of c-subunits whose stoichiometry is constant for a given species but variable across different ones. We investigated the importance of c/c-subunit contacts by site-directed mutagenesis of a conserved stretch of glycines (GxGxGxGxG) in a bacterial c ₁₁ ring. Structural and biochemical studies show a direct, specific influence on the c-subunit stoichiometry, revealing c <₁₁, c ₁₂, c ₁₃, c ₁₄, and c >₁₄ rings. Molecular dynamics simulations rationalize this effect in terms of the energetics and geometry of the c-subunit interfaces. Quantitative data from a spectroscopic interaction study demonstrate that the complex assembly is independent of the c-ring size. Real-time ATP synthesis experiments in proteoliposomes show the mutant enzyme, harboring the larger c ₁₂ instead of c ₁₁, is functional at lower ion motive force. The high degree of compliance in the architecture of the ATP synthase rotor offers a rationale for the natural diversity of c-ring stoichiometries, which likely reflect adaptations to specific bioenergetic demands. These results provide the basis for bioengineering ATP synthases with customized ion-to-ATP ratios, by sequence modifications.

Whiplash injuries typically occur from a motor vehicle collision and lead to chronic whiplash-associated disorders (CWAD) in 20% to 50% of cases. Changes in neurotransmission, metabolism, and networks seem to play a role in the pathogenic mechanism of CWAD. To further elucidate the functional brain alterations, a neurophysiological study was performed to investigate the somatosensory processing of CWAD patients by comparing the event-related potentials (ERPs) resulting from electrical nociceptive stimulation between patients suffering from CWAD and healthy controls (HC). Case-control study. University Hospital in Ghent. In this case-control study (CWAD patients/HC: 50/50), ankle and wrist electrical pain thresholds (EPT), and amplitude and latency of the event-related potentials (ERPs) resulting from 20 electrical stimuli were investigated. Correlations between the ERP characteristics, EPT, self-reported pain, disability, pain catastrophizing, and self-reported symptoms of central sensitization were investigated. Only the latency of the P3 component after left wrist stimulation (t = -2.283; P = 0.023) differed between both groups. In CWAD patients, the ankle EPT correlated with the amplitude of the corresponding P1 (rho s = 0.293; P = 0.044) and P3 (rho s = 0.306; P = 0.033), as well as with the amplitude of the P3 to left wrist stimulation (rho s = 0.343; P = 0.017). Self-reported symptoms of CS correlated with right wrist P3 amplitude (rho s = 0.308; P = 0.030) and latency (rho s = -0.341; P = 0.015), and the worst pain reported during the past week was correlated with left wrist P1 latency (rho s = 0.319; P = 0.029). Although the inclusion criteria stated that CWAD patients had to report a moderate-to-severe pain-related disability, 8 of the included CWAD patients (that scored above this threshold in the inclusion questionnaire), scored below the required cutoff at baseline. The CWAD patients did not show signs of hypersensitivity, but their ERP characteristics were related to the intensity of the applied stimulus, self-reported symptoms of CS, and the worst pain reported during the past week.

The molybdenum storage protein (MoSto) deposits large amounts of molybdenum as polyoxomolybdate clusters in a heterohexameric (αβ)₃ cage-like protein complex under ATP consumption. Here, we suggest a unique mechanism for the ATP-powered molybdate pumping process based on X-ray crystallography, cryoelectron microscopy, hydrogen-deuterium exchange mass spectrometry, and mutational studies of MoSto from Azotobacter vinelandii. First, we show that molybdate, ATP, and Mg2+ consecutively bind into the open ATP-binding groove of the β-subunit, which thereafter becomes tightly locked by fixing the previously disordered N-terminal arm of the α-subunit over the β-ATP. Next, we propose a nucleophilic attack of molybdate onto the γ-phosphate of β-ATP, analogous to the similar reaction of the structurally related UMP kinase. The formed instable phosphoric-molybdic anhydride becomes immediately hydrolyzed and, according to the current data, the released and accelerated molybdate is pressed through the cage wall, presumably by turning aside the Metβ149 side chain. A structural comparison between MoSto and UMP kinase provides valuable insight into how an enzyme is converted into a molecular machine during evolution. The postulated direct conversion of chemical energy into kinetic energy via an activating molybdate kinase and an exothermic pyrophosphatase reaction to overcome a proteinous barrier represents a novelty in ATP-fueled biochemistry, because normally, ATP hydrolysis initiates large-scale conformational changes to drive a distant process.