Transcutaneous Electrical Stimulation of the Abdomen, Ear, and Tibial Nerve Modulates Bladder Contraction in a Rat Detrusor Overactivity Model:A Pilot Study

Purpose: The global prevalence of overactive bladder (OAB) is estimated at 11.8%. Despite existing treatment options such as sacral neuromodulation, a substantial number of patients remain untreated. One potential alternative is noninvasive transcutaneous electrical stimulation. This form of stimulation does not necessitate the implantation of an electrode, thereby eliminating the need for highly skilled surgeons, expensive implantable devices, or regular hospital visits. We hypothesized that alternative neural pathways can impact bladder contraction. Methods: In this pilot study, we conducted transcutaneous electrical stimulation of the abdominal wall (T6-L1), the ear (vagus nerve), and the ankle (tibial nerve) of 3 anesthetized female Sprague-Dawley rats. Stimulation was administered within a range of 20 Hz to 20 kHz, and its impact on intravesical pressure was measured. We focused on 3 primary outcomes related to intravesical pressure: (1) the pressure change from the onset of a contraction to its peak, (2) the average duration of contraction, and (3) the number of contractions within a specified timeframe. These measurements were taken while the bladder was filled with either saline or acetic acid (serving as a model for OAB). Results: Transcutaneous stimulation of the abdominal wall, ear, and ankle at a frequency of 20 Hz decreased the number of bladder contractions during infusion with acetic acid. As revealed by a comparison of various stimulation frequencies of the tibial nerve during bladder infusion with acetic acid, the duration of contraction was significantly shorter during stimulation at 1 kHz and 3 kHz relative to stimulation at 20 Hz (P=0.025 and P=0.044, respectively). Conclusions: The application of transcutaneous electrical stimulation to the abdominal wall, ear, and tibial nerve could provide less invasive and more cost-effective treatment options for OAB relative to percutaneous tibial nerve stimulation and sacral neuromodulation. A follow-up study involving a larger sample size is recommended.</p

Retrieval of bindings between task-irrelevant stimuli and responses can facilitate behaviour under conditions of high response certainty

Repetition priming can be driven by the encoding and retrieval of stimulus-response (S-R) bindings. When a previously encoded S-R binding is retrieved, and is congruent with the response currently required, it can bias response-selection processes towards selecting the retrieved response, resulting in facilitation. Previous studies have used classification tasks at retrieval. Here, two (or more) response options are competing, and it is likely that any evidence (e.g., an S-R binding) in favour of one option will be utilized to effect a decision. Thus, S-R effects are likely to be seen when using such a task. It is unclear whether such effects can be seen under conditions of higher response certainty, when participants are explicitly cued to make a response. Across two experiments, evidence for a modulating influence of S-R bindings is seen despite using a response cueing method at retrieval to minimize response uncertainty and despite stimuli being task irrelevant. Finally, the results suggest that responses within these S-R bindings are coded at the level of left versus right hand, and not a more fine-grained within-hand thumb versus index finger. The results underline the resilience of S-R effects, suggesting that they are present even under conditions where no explicit object-oriented decision is required

The HEPHAISTOS study: compliance and adherence with a novel orthotic device for calf muscle unloading

The present manuscript seeks to discuss methodological aspects regarding the application of the novel unloading orthosis 'HEPHAISTOS' that has been specifically developed to study physiological effects of muscular unloading without altering the impact of gravitational loading. The 'HEPHAISTOS' has been applied in an ambulatory clinical interventional study. During gait, the 'HEPHAISTOS' significantly reduces activation and force production of calf muscles while it completely retains body mass-related force on the tibia. Eleven healthy male subjects participated in the study and followed their normal everyday lives while wearing the orthosis. Several measurement sessions have been performed to investigate the time course of structural and functional adaptations during intervention and recovery. Follow-up measurements were performed for one year after the intervention. In consideration of the experiences of a unique ambulant unloading study, organizational and methodological recommendations are discussed in this manuscript. Activity monitoring data obtained with portable accelerometers reveal unchanged gait activities and good subject compliance throughout the intervention. Moreover, electromyography (EMG) and motion data investigating gait properties on reambulation day are illustrated. These data show that during the initial steps following removal of 'HEPHAISTOS', gait was significantly asynchronous indicating an acutely altered motor control in the unloaded lower leg muscles

Parametric Method Performance for Dynamic 3'-Deoxy-3'-18F-Fluorothymidine PET/CT in Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Carcinoma Patients Before and During Therapy

The objective of this study was to validate several parametric methods for quantification of 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET in advanced-stage non-small cell lung carcinoma (NSCLC) patients with an activating epidermal growth factor receptor mutation who were treated with gefitinib or erlotinib. Furthermore, we evaluated the impact of noise on accuracy and precision of the parametric analyses of dynamic 18F-FLT PET/CT to assess the robustness of these methods. Methods: Ten NSCLC patients underwent dynamic 18F-FLT PET/CT at baseline and 7 and 28 d after the start of treatment. Parametric images were generated using plasma input Logan graphic analysis and 2 basis functions-based methods: a 2-tissue-compartment basis function model (BFM) and spectral analysis (SA). Whole-tumor-averaged parametric pharmacokinetic parameters were compared with those obtained by nonlinear regression of the tumor time-activity curve using a reversible 2-tissue-compartment model with blood volume fraction. In addition, 2 statistically equivalent datasets were generated by countwise splitting the original list-mode data, each containing 50% of the total counts. Both new datasets were reconstructed, and parametric pharmacokinetic parameters were compared between the 2 replicates and the original data. Results: After the settings of each parametric method were optimized, distribution volumes (VT) obtained with Logan graphic analysis, BFM, and SA all correlated well with those derived using nonlinear regression at baseline and during therapy (R2 ≥ 0.94; intraclass correlation coefficient > 0.97). SA-based VT images were most robust to increased noise on a voxel-level (repeatability coefficient, 16% vs. >26%). Yet BFM generated the most accurate K1 values (R2 = 0.94; intraclass correlation coefficient, 0.96). Parametric K1 data showed a larger variability in general; however, no differences were found in robustness between methods (repeatability coefficient, 80%-84%). Conclusion: Both BFM and SA can generate quantitatively accurate parametric 18F-FLT VT images in NSCLC patients before and during therapy. SA was more robust to noise, yet BFM provided more accurate parametric K1 data. We therefore recommend BFM as the preferred parametric method for analysis of dynamic 18F-FLT PET/CT studies; however, SA can also be used

Summary of the 2024 Update of the European Association of Urology Guidelines on Neurourology

Background and objective: Most patients with neurourological disorders require lifelong medical care. The European Association of Urology (EAU) regularly updates guidelines for diagnosis and treatment of these patients. The objective of this review is to provide a summary of the 2024 updated EAU guidelines on neurourology. Methods: A structured literature review covering the timeframe 2021–2023 was conducted for the guideline update. A level of evidence and a strength rating were assigned for each recommendation on the basis of the literature data. Key findings and limitations: Neurological conditions significantly affect urinary, sexual, and bowel function, and lifelong management is required for neurourological patients to maintain their quality of life and prevent urinary tract deterioration. Early diagnosis and effective treatment are key, and comprehensive clinical assessments, including urodynamics, are crucial. Management should be customised to individual needs and should involve a multidisciplinary approach and address sexuality and fertility. Lifelong monitoring and follow-up highlight the importance of continuous care for neurourological patients. Conclusions and clinical implications: The 2024 EAU guidelines on neurourology provide an up-to-date overview of available evidence on diagnosis, treatment, and follow-up for neurourological patients. Patient summary: Neurological disorders very frequently affect the lower urinary tract and sexual and bowel function and patients need lifelong management. We summarise the updated European Association of Urology guidelines on neurourology to provide patients and caregivers with the latest insights for optimal health care support.</p