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Percutaneous tibial neuromodulation is a medical guideline recommended therapy for treating symptoms of overactive bladder. Stimulation is delivered to the tibial nerve via a thin needle placed percutaneously for 30 min once a week for 12-weeks, and monthly thereafter. Studies have shown that this therapy can effectively relieve symptoms of overactive bladder; however, the frequent office visits present a barrier to patients and can impact therapy effectiveness. To mitigate the burden of frequent clinic visits, small implantable devices are being developed to deliver tibial neuromodulation. These devices are implanted during a single minimally invasive procedure and deliver stimulation intermittently, similar to percutaneous tibial neuromodulation. Here, we describe the implant procedure and design of a pivotal study evaluating the safety and effectiveness for an implantable tibial neuromodulation device. The Evaluation of Implantable Tibial Neuromodulation (TITAN 2) pivotal study is a prospective, multicenter, investigational device exemption study being conducted at up to 30 sites in the United States and enrolling subjects with symptoms of overactive bladder., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Una Lee: Consultant, Medtronic, Axonics, Laborie; Primary Investigator, Patient-Centered Outcomes Research Institute, Site Investigator, Cook Myosite Keith Xavier: Consultant for Medtronic Kevin Benson: Consultant for Medtronic Kimberly Burgess: Site investigator for Medtronic Sponsored study Janet Harris-Hicks: Site investigator for Medtronic Sponsored study Robert Simon: Consultant Medtronic and Axoncis Jeffrey Proctor: Site investigator for Medtronic Sponsored study J. Chris Coetzee: Consultant for Medtronic Chris Irwin, Kira Stolen, Katie Bittner, Sarah Offutt, Beth Michaud, Anne Miller and Phillip Falkner are all Employees of Medtronic, (© 2023 The Authors.)

Learning requires neural adaptations thought to be mediated by activity-dependent synaptic plasticity. A relatively non-standard form of synaptic plasticity driven by dendritic calcium spikes, or plateau potentials, has been reported to underlie place field formation in rodent hippocampal CA1 neurons. Here, we found that this behavioral timescale synaptic plasticity (BTSP) can also reshape existing place fields via bidirectional synaptic weight changes that depend on the temporal proximity of plateau potentials to pre-existing place fields. When evoked near an existing place field, plateau potentials induced less synaptic potentiation and more depression, suggesting BTSP might depend inversely on postsynaptic activation. However, manipulations of place cell membrane potential and computational modeling indicated that this anti-correlation actually results from a dependence on current synaptic weight such that weak inputs potentiate and strong inputs depress. A network model implementing this bidirectional synaptic learning rule suggested that BTSP enables population activity, rather than pairwise neuronal correlations, to drive neural adaptations to experience., Competing Interests: AM, YL, KB, CG, IS, JM, SR No competing interests declared, (© 2021, Milstein et al.)

Prenylation of aromatic compounds is a key tailoring reaction in biosynthesis of bioactive indole-diterpenes. Here, we identify NodD1 as the enzyme responsible for the bisprenylation of nodulisporic acid F. This prenyltransferase showed a preference for its natural indole-diterpene substrate whereas other related enzymes were not able to catalyse this conversion.

Accurate diagnosis of traumatic brain injury (TBI) is critical to ensure that patients receive appropriate follow-up care, avoid risk of subsequent injury, and are aware of possible long-term consequences. However, diagnosis of TBI, particularly in the emergency department (ED), can be difficult because the symptoms of TBI are vague and nonspecific, and patients with suspected TBI may present with additional injuries that require immediate medical attention. We performed a retrospective chart review to evaluate accuracy of TBI diagnosis in the ED. Records of 1641 patients presenting to the ED with suspected TBI and a head computed tomography (CT) were reviewed. We found only 47% of patients meeting the American Congress of Rehabilitation Medicine criteria for TBI received a documented ED diagnosis of TBI in medical records. After controlling for demographic and clinical factors, patients presenting at a level I trauma center, with cause of injury other than fall, without CT findings of TBI, and without loss of consciousness were more likely to lack documented diagnosis despite meeting diagnostic criteria for TBI. A greater proportion of patients without documented ED diagnosis of TBI were discharged home compared to those with a documented diagnosis of TBI (58% vs. 40%; p < 0.001). Together, these data suggest that many patients who have sustained a TBI are discharged home from the ED without a documented diagnosis of TBI, and that improved awareness and implementation of diagnostic criteria for TBI is important in the ED and for in- and outpatient providers.

Hypoxylon pulicicidum strain MF5954 (ATCC 74245) (formerly classified as Nodulisporium sp.) is a filamentous fungal species known for its production of the secondary metabolite nodulisporic acid A. We present here the 41.5-Mb draft genome sequence for this organism., (Copyright © 2018 Nicholson et al.)

One in 10 infants in the United States is delivered preterm (ie, before the 37th week of pregnancy), contributing to the significant burden on the national healthcare system. Nevertheless, a lack of agreement continues among obstetric professional societies on guidelines for standardization of the approach to the diagnosis and management of patients with symptoms of preterm labor (PTL). This disparity in consensus has likely resulted in poor identification of women at an increased risk for preterm birth (PTB). This paper presents an overview of several clinical guidelines and recommendations from a variety of studies regarding the use of fetal fibronectin (fFN) testing and transvaginal ultrasound (TVU) cervical length measurement, 2 tools that are used to assess the risk of spontaneous PTB (sPTB) in women with symptoms of PTL. We identify areas of commonality and discord within these publications. Although inconsistencies exist among the published guidelines, algorithms, and studies on how to diagnose and treat women with symptoms of PTL, each of them supports the use of fFN in conjunction with TVU for assessing the risk of sPTB. In addition, we review a case study from a regional hospital system with results demonstrating the benefits to patients and process outcomes when PTL assessment protocols are standardized, incorporating both fFN and TVU test results. In the absence of consensus on this topic, healthcare providers, administrators, and payers must navigate conflicting recommendations and identify areas of agreement for this evaluation within their own local settings.

In CA1 pyramidal neurons, correlated inputs trigger dendritic plateau potentials that drive neuronal plasticity and firing rate modulation. Given the strong electrotonic coupling between soma and axon, the >25 mV depolarization associated with the plateau could propagate through the axon to influence action potential initiation, propagation, and neurotransmitter release. We examined this issue in brain slices, awake mice, and a computational model. Despite profoundly inactivating somatic and proximal axon Na(+) channels, plateaus evoked action potentials that recovered to full amplitude in the distal axon (>150 μm) and triggered neurotransmitter release similar to regular spiking. This effect was due to strong attenuation of plateau depolarizations by axonal K(+) channels, allowing full axon repolarization and Na(+) channel deinactivation. High-pass filtering of dendritic plateaus by axonal K(+) channels should thus enable accurate transmission of gain-modulated firing rates, allowing neuronal firing to be efficiently read out by downstream regions as a simple rate code., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Dendritic ion channels play a critical role in shaping synaptic input and are fundamentally important for synaptic integration and plasticity. In the hippocampal region CA1, somato-dendritic gradients of AMPA receptors and the hyperpolarization-activated cation conductance (I(h)) counteract the effects of dendritic filtering on the amplitude, time-course, and temporal integration of distal Schaffer collateral (SC) synaptic inputs within stratum radiatum (SR). While ion channel gradients in CA1 distal apical trunk dendrites within SR have been well characterized, little is known about the patterns of ion channel expression in the distal apical tuft dendrites within stratum lacunosum moleculare (SLM) that receive distinct input from the entorhinal cortex via perforant path (PP) axons. Here, we measured local ion channels densities within these distal apical tuft dendrites to determine if the somato-dendritic gradients of I(h) and AMPA receptors extend into distal tuft dendrites. We also determined the densities of voltage-gated sodium channels and NMDA receptors. We found that the densities of AMPA receptors, I(h,) and voltage-gated sodium channels are similar in tuft dendrites in SLM when compared with distal apical dendrites in SR, while the ratio of NMDA receptors to AMPA receptors increases in tuft dendrites relative to distal apical dendrites within SR. These data indicate that the somato-dendritic gradients of I(h) and AMPA receptors in apical dendrites do not extend into the distal tuft, and the relative densities of voltage-gated sodium channels and NMDA receptors are poised to support nonlinear integration of correlated SC and PP input.

In T-type Ca(2+) channels, macroscopic I(Ba) is usually smaller than I(Ca), but at high Ca(2+) and Ba(2+), single-channel conductance (gamma) is equal. We investigated gamma as a function of divalent concentration and compared it to macroscopic currents using Ca(V)3.1 channels studied under similar experimental conditions (TEA(o) and K(i)). Single-channel current-voltage relationships were nonlinear in a way similar to macroscopic open-channel I/Vs, so divalent gamma was underestimated at depolarized voltages. To estimate divalent gamma, concentration dependence, i(Div), was measured at voltages <-50 mV. Data were well described by Langmuir isotherms with gamma(max)(Ca(2+)) of 9.5 +/- 0.4 pS and gamma(max)(Ba(2+)) of 10.3 +/- 0.5 pS. Apparent K(M) was lower for Ca(2+) (2.3 +/- 0.7 mM) than for Ba(2+) (7.9 +/- 1.3 mM). A subconductance state with an amplitude 70% that of the main state was observed, the relative occupancy of which increased with increasing Ca(2+). As predicted by gamma, macroscopic G(maxCa) was larger than G(maxBa) at 5 mM (G(max)Ca(2+)/Ba:(2+)1.43 +/- 0.14) and similar at 60 mM (G(max)Ca(2+)/Ba:(2+)1.10 +/- 0.02). However, over the range of activation, I(Ca) was larger than I(Ba) under both conditions. This was a consequence of the fact that V(rev) was more negative for I(Ba) than for I(Ca), so that the driving force determining I(Ba) was smaller than that determining I(Ca) over the range of potentials in standard current-voltage relationships.