The effects of anthropogenic noise on frogs housed on exhibit at a public aquarium.

Anuran behavior and reproduction are dominated by vocalizations, rendering them vulnerable to the effects of signal masking. For anurans on display in zoos and aquaria, a major source of ambient noise is visitors, which pose a unique source of potential anthropogenic signal masking. Call characteristics (total call duration, and minimum and maximum call frequencies) of three populations of dendrobatids (Dendrobates leucomelas, Epipedobates tricolor, and Ranitomeya imitator) on public display were investigated at time periods of increasing visitor-related noise (closed, off-peak, and peak aquarium visiting hours) to determine if there were changes in call characteristics that correlated with changes in visitor noise levels. The data revealed that call length increased with more visitor noise for D. leucomelas and E. tricolor, with their longest calls during peak hours, and all three species had their shortest calls during closed hours. Both minimum and maximum call frequencies increased with more visitor noise for E. tricolor and R. imitator, with their highest frequencies during peak hours, and lowest frequencies during closed hours. This study found evidence that anurans on public display adjust their vocalizations in the presence of visitor noise. These findings support expanded monitoring of ambient noise for animals on public display to determine if noise poses significant effects that might influence well-being or reproduction.

Large Language Models in Neurology Research and Future Practice.

Recent advancements in generative artificial intelligence, particularly using large language models (LLMs), are gaining increased public attention. We provide a perspective on the potential of LLMs to analyze enormous amounts of data from medical records and gain insights on specific topics in neurology. In addition, we explore use cases for LLMs, such as early diagnosis, supporting patient and caregivers, and acting as an assistant for clinicians. We point to the potential ethical and technical challenges raised by LLMs, such as concerns about privacy and data security, potential biases in the data for model training, and the need for careful validation of results. Researchers must consider these challenges and take steps to address them to ensure that their work is conducted in a safe and responsible manner. Despite these challenges, LLMs offer promising opportunities for improving care and treatment of various neurologic disorders.

Deep learning for risk-based stratification of cognitively impaired individuals.

Quantifying the risk of progression to Alzheimer's disease (AD) could help identify persons who could benefit from early interventions. We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 544, discovery cohort) and the National Alzheimer's Coordinating Center (NACC, n = 508, validation cohort), subdividing individuals with mild cognitive impairment (MCI) into risk groups based on cerebrospinal fluid amyloid-ß levels and identifying differential gray matter patterns. We then created models that fused neural networks with survival analysis, trained using non-parcellated T1-weighted brain MRIs from ADNI data, to predict the trajectories of MCI to AD conversion within the NACC cohort (integrated Brier score: 0.192 [discovery], and 0.108 [validation]). Using modern interpretability techniques, we verified that regions important for model prediction are classically associated with AD. We confirmed AD diagnosis labels using postmortem data. We conclude that our framework provides a strategy for risk-based stratification of individuals with MCI and for identifying regions key for disease prognosis.

Multimodal Microvascular Mapping for Head and Neck, Skull Base Research and Education: An Anatomical Donor Study.

Objective This study was aimed to develop a method combining computed tomography (CT) and fluorescence imaging, allowing identification of microvasculature in anatomical donors and facilitating translational research and education. Methods We investigated homogeneity and radiopacity of 30 different mixtures including radiopaque substances povidone-iodine (Betadine), barium sulfate (BaSO 4 ), and bismuth subsalicylate (Pepto-Bismol) varying in suspension and dilution with agar, latex, or gelatin. Three candidate mixtures were selected for testing the extent of perfusion in renal vasculature to establish methodology. From these candidate mixtures, two were selected for mixture with fluorescein and infusion into cadavers based on their ability to perfuse renal vasculature. The extent to which these two candidate mixtures combined with fluorescein were able to perfuse vasculature in a cadaver head was used to determine which mixture was superior. Results BaSO 4 and bismuth subsalicylate-based mixtures demonstrated superior opacity in vials. In terms of solidifying agents, gelatin-based mixtures demonstrated increased friability and lower melting points compared with the other agents, so only latex and agar-based mixtures were used moving forward past the vial stage. Combinations of BaSO 4 and latex and BaSO 4 and 3% agar were found to perfuse kidneys superiorly to the mixture containing bismuth subsalicylate. Finally, in cadaver heads, the mixture containing BaSO 4 , agar, and fluorescein was found to perfuse the smallest vasculature. Conclusion A final combination of BaSO 4 , 3% agar, and fluorescein proves to be a powerful and novel combination enabling CT imaging, fluorescence imaging, and dissection of vasculature. This paves the way for future translational research and education.

Deep learning for subtyping the Alzheimer's disease spectrum.

In a recent article from Cell Reports Medicine, Kwak et al. generate novel insights about subtyping cognitively impaired individuals based on structural imaging. Quantifying heterogeneity in Alzheimer's disease via subtyping could help us harness new disease-modifying therapies and improve patient care by providing a more targeted approach.

Opposing roles for striatonigral and striatopallidal neurons in dorsolateral striatum in consolidating new instrumental actions.

Comparatively little is known about how new instrumental actions are encoded in the brain. Using whole-brain c-Fos mapping, we show that neural activity is increased in the anterior dorsolateral striatum (aDLS) of mice that successfully learn a new lever-press response to earn food rewards. Post-learning chemogenetic inhibition of aDLS disrupts consolidation of the new instrumental response. Similarly, post-learning infusion of the protein synthesis inhibitor anisomycin into the aDLS disrupts consolidation of the new response. Activity of D1 receptor-expressing medium spiny neurons (D1-MSNs) increases and D2-MSNs activity decreases in the aDLS during consolidation. Chemogenetic inhibition of D1-MSNs in aDLS disrupts the consolidation process whereas D2-MSN inhibition strengthens consolidation but blocks the expression of previously learned habit-like responses. These findings suggest that D1-MSNs in the aDLS encode new instrumental actions whereas D2-MSNs oppose this new learning and instead promote expression of habitual actions.

Interexaminer Agreement in the Radiologic Identification of Apical Periodontitis/Rarefying Osteitis in the National Dental Practice-Based Research Network PREDICT Endodontic Study.

INTRODUCTION: Periapical images are routinely made in endodontics to support diagnosis and treatment decisions, but conventional imaging may not readily demonstrate inflammatory changes. This study aims to quantify disagreement in the radiologic interpretation of apical periodontitis/rarefying osteitis between 2 expert examiners and to determine if differences exist based on anatomic location. METHODS: We used 1717 pretreatment periapical images made before orthograde endodontic treatment as part of the Predicting Outcomes of Root Canal Treatment (PREDICT) study conducted within the National Dental Practice-Based Research Network. Periapical changes were assessed independently by 2 board-certified specialists, an oral and maxillofacial radiologist and an endodontist, blinded to other clinical information. If the examiners disagreed about whether a diagnosis of apical periodontitis/rarefying osteitis was justified, an adjudication was made by a third examiner. RESULTS: The overall prevalence of this radiologic diagnosis in the periapical images was 55%, and interexaminer agreement measured with the Cohen kappa statistic was calculated to be 0.56 (95% confidence interval, 0.52-0.60). Diagnostic disagreements between the 2 examiners occurred for 377 teeth (22%), with disagreements more frequent for jaw location (P = .038) and tooth type (P = .021). Differences between root number (P = .058) and jaw location and tooth groups (P = .069) were found not to be statistically significant. CONCLUSIONS: The variability of diagnostic disagreements across anatomic location and tooth type may reflect the inability of periapical images to reveal bone changes masked by the complexity and density of overlying anatomic structures, a limitation that could potentially be overcome with the use of 3-dimensional imaging.

Testicular torsion: epidemiological risk factors for orchiectomy in pediatric and adult patients.

Testicular torsion is a known cause of morbidity in pediatric patients, but the burden in the adult population is poorly understood. We sought to determine the incidence of testicular torsion and risk factors for orchiectomy in a population encompassing all ages. A cohort analysis of 1625 males undergoing surgery for torsion was performed using the 2011 and 2012 Healthcare Cost and Utilization Project Nationwide Emergency Departments Sample. Patient and hospital factors were examined for association with orchiectomy vs. testicular salvage. The estimated yearly incidence of testicular torsion was 5.9 per 100,000 males ages 1-17 years and 1.3 per 100,000 males ≥18 years. Among those undergoing surgical intervention, orchiectomy was performed in 33.6%. The risk of orchiectomy was highest in patients 1-11 years of age and patients over 50 years of age (46.0% and 69.7% of patients, respectively). Orchiectomy was also associated with public insurance (Medicaid/Medicare) or self-pay as primary payer. While testicular torsion is less common in the adult population, the rate of orchiectomy is high. Those with disadvantaged payer status are also at increased risk for testicular loss.

Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator.

Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and artifactual correlations of neural activity. We address this problem by engineering cell-body-targeted variants of the fluorescent calcium indicators GCaMP6f and GCaMP7f. We screened fusions of GCaMP to natural, as well as artificial, peptides and identified fusions that localized GCaMP to within 50 µm of the cell body of neurons in mice and larval zebrafish. One-photon imaging of soma-targeted GCaMP in dense neural circuits reported fewer artifactual spikes from neuropil, an increased signal-to-noise ratio, and decreased artifactual correlation across neurons. Thus, soma-targeting of fluorescent calcium indicators facilitates usage of simple, powerful, one-photon methods for imaging neural calcium dynamics.

The Canadian Medical Student Ultrasound Curriculum: A Statement From the Canadian Ultrasound Consensus for Undergraduate Medical Education Group.

OBJECTIVES: This study sought to establish by expert review a consensus-based, focused ultrasound curriculum, consisting of a foundational set of focused ultrasound skills that all Canadian medical students would be expected to attain at the end of the medical school program. METHODS: An expert panel of 21 point-of-care ultrasound and educational leaders representing 15 of 17 (88%) Canadian medical schools was formed and participated in a modified Delphi consensus method. Experts anonymously rated 195 curricular elements on their appropriateness to include in a medical school curriculum using a 5-point Likert scale. The group defined consensus as 70% or more experts agreeing to include or exclude an element. We determined a priori that no more than 3 rounds of voting would be performed. RESULTS: Of the 195 curricular elements considered in the first round of voting, the group reached consensus to include 78 and exclude 24. In the second round, consensus was reached to include 4 and exclude 63 elements. In our final round, with 1 additional item added to the survey, the group reached consensus to include an additional 3 and exclude 8 elements. A total of 85 curricular elements reached consensus to be included, with 95 to be excluded. Sixteen elements did not reach consensus to be included or excluded. CONCLUSIONS: By expert opinion-based consensus, the Canadian Ultrasound Consensus for Undergraduate Medical Education Group recommends that 85 curricular elements be considered for inclusion for teaching in the Canadian medical school focused ultrasound curricula.

Population imaging of neural activity in awake behaving mice.

A longstanding goal in neuroscience has been to image membrane voltage across a population of individual neurons in an awake, behaving mammal. Here we describe a genetically encoded fluorescent voltage indicator, SomArchon, which exhibits millisecond response times and is compatible with optogenetic control, and which increases the sensitivity, signal-to-noise ratio, and number of neurons observable several-fold over previously published fully genetically encoded reagents1-8. Under conventional one-photon microscopy, SomArchon enables the routine population analysis of around 13 neurons at once, in multiple brain regions (cortex, hippocampus, and striatum) of head-fixed, awake, behaving mice. Using SomArchon, we detected both positive and negative responses of striatal neurons during movement, as previously reported by electrophysiology but not easily detected using modern calcium imaging techniques9-11, highlighting the power of voltage imaging to reveal bidirectional modulation. We also examined how spikes relate to the subthreshold theta oscillations of individual hippocampal neurons, with SomArchon showing that the spikes of individual neurons are more phase-locked to their own subthreshold theta oscillations than to local field potential theta oscillations. Thus, SomArchon reports both spikes and subthreshold voltage dynamics in awake, behaving mice.

A Teensy microcontroller-based interface for optical imaging camera control during behavioral experiments.

BACKGROUND: Systems neuroscience experiments often require the integration of precisely timed data acquisition and behavioral monitoring. While specialized commercial systems have been designed to meet various needs of data acquisition and device control, they often fail to offer flexibility to interface with new instruments and variable behavioral experimental designs. NEW METHOD: We developed a Teensy 3.2 microcontroller-based interface that is easily programmable, and offers high-speed, precisely timed behavioral data acquisition and digital and analog outputs for controlling sCMOS cameras and other devices. RESULTS: We demonstrate the flexibility and the temporal precision of the Teensy interface in two experimental settings. In one example, we used the Teensy interface to record an animal's directional movement on a spherical treadmill, while delivering repeated digital pulses that can be used to control image acquisition from a sCMOS camera. In another example, we used the Teensy interface to deliver an auditory stimulus and a gentle eye puff at precise times in a trace conditioning eye blink behavioral paradigm, while delivering repeated digital pulses to trigger camera image acquisition. COMPARISON WITH EXISTING METHODS: This interface allows high-speed and temporally precise digital data acquisition and device control during diverse behavioral experiments. CONCLUSION: The Teensy interface, consisting of a Teensy 3.2 and custom software functions, provides a temporally precise, low-cost, and flexible platform to integrate sCMOS camera control into behavioral experiments.

Unique contributions of parvalbumin and cholinergic interneurons in organizing striatal networks during movement.

Striatal parvalbumin (PV) and cholinergic interneurons (CHIs) are poised to play major roles in behavior by coordinating the networks of medium spiny cells that relay motor output. However, the small numbers and scattered distribution of these cells have hindered direct assessment of their contribution to activity in networks of medium spiny neurons (MSNs) during behavior. Here, we build on recent improvements in single-cell calcium imaging combined with optogenetics to test the capacity of PVs and CHIs to affect MSN activity and behavior in mice engaged in voluntary locomotion. We find that PVs and CHIs have unique effects on MSN activity and dissociable roles in supporting movement. PV cells facilitate movement by refining the activation of MSN networks responsible for movement execution. CHIs, in contrast, synchronize activity within MSN networks to signal the end of a movement bout. These results provide new insights into the striatal network activity that supports movement.

Striatal cholinergic receptor activation causes a rapid, selective and state-dependent rise in cortico-striatal ß activity.

Cortico-basal ganglia-thalamic (CBT) ß oscillations (15-30 Hz) are elevated in Parkinson's disease and correlated with movement disability. To date, no experimental paradigm outside of loss of dopamine has been able to specifically elevate ß oscillations in the CBT loop. Here, we show that activation of striatal cholinergic receptors selectively increased ß oscillations in mouse striatum and motor cortex. In individuals showing simultaneous ß increases in both striatum and M1, ß partial directed coherence (PDC) increased from striatum to M1 (but not in the reverse direction). In individuals that did not show simultaneous ß increases, ß PDC increased from M1 to striatum (but not in the reverse direction), and M1 was characterized by persistent ß-high frequency oscillation phase-amplitude coupling. Finally, the direction of ß PDC distinguished between ß sub-bands. This suggests that (1) striatal cholinergic tone exerts state-dependent and frequency-selective control over CBT ß power and coordination; (2) ongoing rhythmic dynamics can determine whether elevated ß oscillations are expressed in striatum and M1; and (3) altered striatal cholinergic tone differentially modulates distinct ß sub-bands.

Comparison of techniques for visualisation of the airway anatomy for ultrasound-assisted intubation: A prospective study of emergency department patients.

PURPOSE: Ultrasound has been shown to be a highly accurate adjunct for confirming endotracheal tube (ETT) placement, however there is no universally accepted scanning technique. The objective of this study was to determine which ultrasound technique provides the highest rate of adequate airway visualisation in a sample of stable emergency department (ED) patients. METHODS: We conducted a prospective observational study using a convenience sample of ED patients. Airway imaging was performed using the following five techniques: 1) transcricothryoid membrane (TCM), 2) suprasternal notch (SSN) without transducer pressure, 3) SSN with pressure, 4) SSN with pressure to the left of the trachea and 5) SSN with pressure to the right of the trachea. A blinded reviewer scored the adequacy of airway visualisation for each technique. RESULTS: A total of 100 patients were enrolled in the study. SSN to the left of the trachea with pressure had the highest rate of adequate airway visualisation (93.0%, 95% CI 86.1-97.1%), followed by 82.0% (95% CI 73.1-89.0%) for SSN with pressure, 74.0% (95% CI 64.3-82.3%) for TCM, 44.0% (95% CI 34.1-54.3%) for SSN without pressure, and 1.0% (95% CI 0.0-5.4%) for SSN to the right of the trachea. In 76.0% (95% CI 66.4-84.0%) of patients, the SSN view was improved by moving the probe off the midline towards the patient's left. CONCLUSIONS: In a sample of ED patients, the airway anatomy relevant for use in endotracheal intubation is best visualised at the SSN to the left of the trachea with transducer pressure applied.

Why a Trash-Strewn Lot Became a Soccer Field.

Five years ago, a coalition of community groups, government agencies and nonprofit organizations was struggling to reduce violent behavior and delinquency among under- privileged youths in a low-income suburban neighborhood about 15 miles north of Tacoma, Washington.

Bilateral Retinal Detachments Caused by Severe Preeclampsia Diagnosed with Point-of-Care Ultrasound.

Bilateral retinal detachments are a rare complication of preeclampsia. We present a case report of a patient with an unknown pregnancy who presented with acute bilateral vision loss and elevated blood pressure. Point-of-care ocular ultrasound revealed bilateral retinal detachments. She was diagnosed with severe preeclampsia and taken for an urgent caesarean section with the delivery of a 26-week-old infant.