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Event-related potentials (ERPs) elicited by self-induced sounds are often smaller than ERPs elicited by identical, but externally generated sounds. This action-related auditory ERP attenuation is more pronounced when self-induced sounds are intermixed with similar sounds generated by an external source. The current study explored whether attentional factors contributed to this phenomenon. Participants performed tone-eliciting actions, while the action-tone contingency and the set of additional action effects (tactile only, tactile and visual) were manipulated in a blocked manner. Previous action-tone contingence-effects were replicated, but the addition of other sensory action consequences did not influence the magnitude of auditory ERP attenuation. This suggests that the amount of attention allocated to concurrent non-auditory action effects does not substantially affect the magnitude of action-related auditory ERP attenuation and is on a par with the assumption that action-related auditory ERP attenuation might be related to the process of distinguishing self-induced stimuli from externally generated ones.The Breast Cancer Gene (BRCA) confers an 8.6-fold higher risk of developing prostate cancer in men ≤ 65 years of age and portends a worse prognosis as compared to noncarriers even in patients with low volume, localized disease. The BRCA2 gene, in particular, imparts a more biologically aggressive form of prostate cancer and a higher prostate cancer specific mortality. From a treatment standpoint, this translates to worse overall clinical outcomes for such patients. The most appropriate screening and management strategy for germline BRCA mutation carriers with prostate cancer is not known. Herein, we present an incidentally discovered prostate cancer in a 61-year-old BRCA1 and BRCA2 germline mutation carrier who was screened and managed using an individualized treatment approach.

To assess the effect of sacral neuromodulation (SNM) in ambulatory spina bifida patients with neurogenic bladder and bowel dysfunction.

We retrospectively reviewed the records of 29 ambulatory spina bifida patients with neurogenic bladder and bowel dysfunction who underwent SNM testing from July 2012 to January 2020. Clinical data and video-urodynamic parameters were collected and compared using the t-test and the chi-square test. The potential risk factors were considered by logistic regression analysis. P < .05 was considered significant.

In the test phase, 21 patients (72.4%) achieved successful improvement of at least 1 symptom. The success rate for chronic urinary retention (26.09%) was significantly lower (P <.05) than that for urgency-frequency syndrome (58.82%) and urinary incontinence (56.25%). The mean neurogenic bowel dysfunction score decreased from 13.3±6.29 to 6.9±5.09 (P <.0001). The urodynamic evaluation showed a significant improvement in the mean maximum cystometric capacity, compliance, and maximum detrusor pressure (P <.05). Implantation was performed in 16 cases (55.17%). The analysis of the risk factors showed that chronic urinary retention was a statistically significant variable (P <.05). No complications were reported in the test phase. The average follow-up time was 41.19±33.06 months. Two patients changed to intermittent catheterization, and 2 patients changed to augmentation cystoplasty.

SNM is effective for neurogenic bladder and bowel dysfunction in patients with ambulatory spina bifida, especially in those without chronic urinary retention. And SNM can also significantly improve the urodynamic parameters of these patients during the storage period.

SNM is effective for neurogenic bladder and bowel dysfunction in patients with ambulatory spina bifida, especially in those without chronic urinary retention. And SNM can also significantly improve the urodynamic parameters of these patients during the storage period.

To evaluate the outcomes of excision and primary anastomosis (EPA) for radiation-associated bulbomembranous stenoses using a multi-institutional analysis. The treatment of radiation-associated urethral stenosis is typically complex owing to the adverse impact of radiation on adjacent tissue.

An IRB-approved multi-institutional retrospective review was performed on patients who underwent EPA for bulbomembranous urethral stenosis following prostate radiotherapy. Preoperative patient demographics, operative technique, and postoperative outcomes were abstracted from 1/2007-6/2018. Success was defined as voiding per urethra without the need for endoscopic treatment and a minimum follow-up of 12 months.

One hundred and thirty-seven patients from 10 centers met study criteria with a mean age of 69.3 years (50-86), stenosis length of 2.3 cm (1-5) and an 86.9% (119/137) success rate at a mean follow-up 32.3 months (12-118). Univariate Cox regression analysis identified increasing patient age (P = .02), stricturenosis length and age are independently associated with surgical failure. Patients should be counseled that further surgery for incontinence may be necessary.

To evaluate the efficacy of interactive virtual reality (iVR) in providing a three-dimensional (3D) experience with the donor's anatomy for surgeons and patients, we present a retrospective, case-controlled study assessing the impact of iVR renal models prior to LDN on both surgical outcomes and patients' understanding of the procedure.

Twenty patients undergoing LDN were prospectively recruited; their contrast-enhanced CT scans were transformed into iVR models. An iVR platform allowed the surgeons to rotate and deconstruct the renal anatomy; patients could also view their anatomy as the procedure was explained to them. Questionnaires assessed surgeons' understanding of renal anatomy after CT alone and after CT+iVR. Surgeons also commented on whether iVR impacted their preoperative plan. Patients assessed their anatomical understanding and anxiety level before and after iVR. Surgical outcomes for the iVR cohort were compared to a retrospectively matched, non-iVR cohort of LDN patients.

Surgeons altered their preoperative plan in 18 of 20 LDNs after viewing iVR models. Patients reported better understanding of their anatomy (5/5) and noted decreased preoperative anxiety (5/5) after viewing iVR. When compared to the non-iVR group, the iVR group had a 25% reduction in median operative time (P < .001). In terms of surgical outcomes, patients in the iVR group had a 40% lower median relative change in postoperative creatinine (P < .001).

Preoperative viewing of iVR models altered the operative approach, decreased the operative time, and improved donor patient outcomes. iVR models also reduced patients' preoperative anxiety.

Preoperative viewing of iVR models altered the operative approach, decreased the operative time, and improved donor patient outcomes. iVR models also reduced patients' preoperative anxiety.Model reduction is an important topic in studies of biological systems. By reducing the complexity of large models through multi-level models while keeping the essence (biological meaning) of the model, model reduction can help answer many important questions about these systems. In this paper, we present a new reduction method based on hierarchical representation and a lumping approach. We used G1/S checkpoint pathway represented in Ordinary Differential Equations (ODE) in Iwamoto et al. (2011) as a case study to present this reduction method. The approach consists of two parts; the first part represents the biological network as a hierarchy (multiple levels) based on protein binding relations, which allowed us to model the biological network at different levels of abstraction. The second part applies different levels (level 1, 2 and 3) of lumping the species together depending on the level of the hierarchy, resulting in a reduced and transformed model for each level. The model at each level is a representatr the three levels) and generate solutions than the original ODE model. Simplification of complex mathematical models is possible and the proposed reduction method has the potential to make an impact across many fields of biomedical research.The neuropeptide S (NPS) system plays an important role in fear and fear memory processing but has also been associated with allergic and inflammatory diseases. Genes for NPS and its receptor NPSR1 are found in all tetrapods. Compared to non-human primates, several non-synonymous single-nucleotide polymorphisms (SNPs) occur in both human genes that collectively result in functional attenuation, suggesting adaptive mechanisms in a human context. To investigate historic and geographic origins of these hypomorphic mutations and explore genetic signs of selection, we analyzed ancient genomes and worldwide genotype frequencies of four prototypic SNPs in the NPS system. Neandertal and Denisovan genomes contain exclusively ancestral alleles for NPSR1 while all derived alleles occur in ancient genomes of anatomically modern humans, indicating that they arose in modern Homo sapiens. Worldwide genotype frequencies for three hypomorphic NPSR1 SNPs show significant regional homogeneity but follow a gradient towards increasing derived allele frequencies that supports an out-of-Africa scenario. Increased density of high-frequency polymorphisms around the three NPSR1 loci suggests weak or possibly balancing selection. A hypomorphic mutation in the NPS precursor, however, was detected at high frequency in Eurasian Neandertal genomes and shows genetic signatures indicating that it was introgressed into the human gene pool, particularly in Southern Europe, by interbreeding with Neandertals. We discuss potential evolutionary scenarios including behavior and immune-based natural selection.Microglia serve key functions in the central nervous system (CNS), participating in the establishment and regulation of synapses and the neuronal network, and regulating activity-dependent plastic changes. As the neuroimmune system, they respond to endogenous and exogenous signals to protect the CNS. In aging, one of the main changes is the establishment of inflamm-aging, a mild chronic inflammation that reduces microglial response to stressors. Neuroinflammation depends mainly on the increased activation of microglia. Microglia over-activation may result in a reduced capacity for performing normal functions related to migration, clearance, and the adoption of an anti-inflammatory state, contributing to an increased susceptibility for neurodegeneration. Oxidative stress contributes both to aging and to the progression of neurodegenerative diseases. Increased production of reactive oxygen species (ROS) and neuroinflammation associated with age- and disease-dependent mechanisms affect synaptic activity and neurotransmission, leading to cognitive dysfunction. Astrocytes prevent microglial cell cytotoxicity by mechanisms mediated by transforming growth factor β1 (TGFβ1). However, TGFβ1-Smad3 pathway is impaired in aging, and the age-related impairment of TGFβ signaling can reduce protective activation while facilitating cytotoxic activation of microglia. A critical analysis on the effect of aging microglia on neuronal function is relevant for the understanding of age-related changes on neuronal function. Here, we present evidence in the context of the "microglial dysregulation hypothesis", which leads to the reduction of the protective functions and increased cytotoxicity of microglia, to discuss the mechanisms involved in neurodegenerative changes and Alzheimer's disease.

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