A 73-Year-Old Woman With Progressive Shortness of Breath and Right-Sided Hemithorax Opacity.

CASE PRESENTATION: A 73-year-old frail woman presented with 3 months of progressively worsening exertional dyspnea, mild cough with white mucus, voice changes, and few episodes of dysphagia. She denied weight loss, night sweats, chest pain, or hemoptysis. Medical history was significant for hypertension, remote 30 years of tobacco use, and regular alcohol use. She had neither asbestos nor occupational exposure. She had no family history of malignancy.

Intraoperative Cytology for Video-Assisted Thoracic Surgery: A Quality Improvement Analysis.

BACKGROUND: Frozen section is a standard of care procedure during thoracic surgery when an immediate diagnosis is needed. An alternative procedure is intraoperative cytology. Video-assisted thoracic surgery is currently widely used for thoracic surgical procedures. The aim of this study was to assess intraoperative cytology together with frozen section for accuracy, turnaround time, and total response time during video-assisted thoracic surgery. METHODS: We included patients having video-assisted thoracic surgery between August 2018 and February 2019 at our institution. A cytopathologist and a surgical pathologist independently performed intraoperative cytology and frozen sections, respectively. Final histologic diagnosis was the reference standard. Intraoperative cytology, frozen section turnaround, and total response times were analyzed. RESULTS: A total of 52 specimens from 27 patients were included. The intraoperative cytology correlated with final histology in 98% of cases. Frozen section correlated with final histology in 100% of cases. Intraoperative cytology turnaround and total response times were equal (mean, 4.35 minutes; range, 2-15 minutes). Mean frozen section turnaround and response times were 26.2 minutes (range, 9-61 minutes) and 36.7 minutes (range, 16-90 minutes), respectively. We found a statistically significant difference between intraoperative cytology and frozen section turnaround time and total response times (P < .001). CONCLUSIONS: This study highlights that intraoperative cytology could be as accurate as frozen section and considerably faster during video-assisted thoracic surgery (P < .001). Total response time could potentially be used as a quality metric for video-assisted thoracic surgery.

Corrigendum: Gradual extinction prevents the return of fear: implications for the discovery of state.

[This corrects the article DOI: 10.3389/fnbeh.2013.00164.].

Investigation of Machine Learning and Deep Learning Approaches for Detection of Mild Traumatic Brain Injury from Human Sleep Electroencephalogram.

Traumatic Brain Injury (TBI) is a highly prevalent and serious public health concern. Most cases of TBI are mild in nature, yet some individuals may develop following-up persistent disability. The pathophysiologic causes for those with persistent postconcussive symptoms are most likely multifactorial and the underlying mechanism is not well understood, although it is clear that sleep disturbances feature prominently in those with persistent disability. The sleep electroencephalogram (EEG) provides a direct window into neuronal activity during an otherwise highly stereotyped behavioral state, and represents a promising quantitative measure for TBI diagnosis and prognosis. With the ever-evolving domain of machine learning, deep convolutional neural networks, and the development of better architectures, these approaches hold promise to solve some of the long entrenched challenges of personalized medicine for uses in recommendation systems and/or in health monitoring systems. In particular, advanced EEG analysis to identify putative EEG biomarkers of neurological disease could be highly relevant in the prognostication of mild TBI, an otherwise heterogeneous disorder with a wide range of affected phenotypes and disability levels. In this work, we investigate the use of various machine learning techniques and deep neural network architectures on a cohort of human subjects with sleep EEG recordings from overnight, in-lab, diagnostic polysomnography (PSG). An optimal scheme is explored for the classification of TBI versus non-TBI control subjects. The results were promising with an accuracy of ∼95% in random sampling arrangement and ∼70% in independent validation arrangement when appropriate parameters were used using a small number of subjects (10 mTBI subjects and 9 age- and sex-matched controls). We are thus confident that, with additional data and further studies, we would be able to build a generalized model to detect TBI accurately, not only via attended, in-lab PSG recordings, but also in practical scenarios such as EEG data obtained from simple wearables in daily life.

Fabrication of Highly Sensitive Pt-black Electrochemical Sensors for GABA Detection.

GABA (Gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the central nervous system of mammals. It is known to be related with various neurological disorders. GABA plays a crucial role in normal neuronal activity, information processing and plasticity, and neuronal network synchronization. To date, microdialysis has been widely used to monitor the level of GABA but the temporal and spatial resolution is limited. Besides, electrochemical sensors for neurotransmitter measurement, having high temporal and spatial resolution, overcome this problem. Here, using a cost-effective method of electrodeposition of platinum black (Pt-black), a highly sensitive, GABA specific, amperometric electrochemical sensor is fabricated. Nanostructured Pt-black increases the active surface area of the electrode contributing to higher sensitivity. Along with that, a self-referencing site and an exclusion layer are integrated to increase the selectivity and the signal-to-noise ratio (SNR) of the biosensor. This provides a prototype for a highly sensitive GABA sensor that could later be used to study various neurological disorders related to GABA concentrations.Clinical Relevance- This electrochemical sensor allows real-time monitoring of major inhibitory neurotransmitter (GABA) with high sensitivity which can be used for studying various neurological disorders.

Optimising rapid on-site evaluation-assisted endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes: The real-time cytopathology intervention process.

INTRODUCTION: Lymph node sampling by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the state of art procedure for staging the mediastinum and hilar regions in lung cancer patients. Our experience of implementing the real-time cytopathology intervention (RTCI) process for intraoperative EBUS-TBNAs is presented. This study is aimed to describe in detail the RTCI process for EBUS-TBNAs, and assess its utility and diagnostic yield before and after its implementation in parallel to conventional rapid on-site evaluation (c-ROSE). METHODS: A retrospective review of all EBUS-TBNAs between July 2016 and July 2017 at the University of Rochester Medical Center was performed. Final diagnoses, patient clinical data, and number of non-diagnostic samples (NDS) were reviewed. The numbers of NDS obtained from EBUS-TBNAs with no cytology assistance (NCA), with RTCI and with c-ROSE were analysed. RESULTS: Non-diagnostic lymph node samples were found in 20 out of 116 (17%), three out of 114 (2.6%) and 33 out of 286 (11.5%) cases with NCA, RTCI and c-ROSE, respectively. Application of statistical analysis revealed significant difference in the NDS between the groups of cases in the operating room with NCA and RTCI (P = .005). The different settings and variables between the cases performed using RTCI in the operating room and those assisted with c-ROSE in the bronchoscopy suite preclude legitimate comparison. CONCLUSION: Our results indicate that the use of RTCI could yield a significantly low proportion of NDS when assisting EBUS-TBNA of mediastinal and hilar lymph node for lung cancer patients enhancing the diagnostic efficiency of the procedure.

Early life sleep disruption alters glutamate and dendritic spines in prefrontal cortex and impairs cognitive flexibility in prairie voles.

Early life experiences are crucial for proper organization of excitatory synapses within the brain, with outsized effects on late-maturing, experience-dependent regions such as the medial prefrontal cortex (mPFC). Previous work in our lab showed that early life sleep disruption (ELSD) from postnatal days 14-21 in the highly social prairie vole results in long lasting impairments in social behavior. Here, we further hypothesized that ELSD alters glutamatergic synapses in mPFC, thereby affecting cognitive flexibility, an mPFC-dependent behavior. ELSD caused impaired cued fear extinction (indicating cognitive inflexibility), increased dendritic spine density, and decreased glutamate immunogold-labeling in vesicular glutamate transporter 1 (vGLUT1)-labeled presynaptic nerve terminals within mPFC. Our results have profound implications for neurodevelopmental disorders in humans such as autism spectrum disorder that also show poor sleep, impaired social behavior, cognitive inflexibility, as well as altered dendritic spine density and glutamate changes in mPFC, and imply that poor sleep may cause these changes.

Early life sleep disruption is a risk factor for increased ethanol drinking after acute footshock stress in prairie voles.

Early postnatal experiences are important for shaping the development of the stress response and may contribute to the later emergence of alcohol use disorders. We have previously found that early life sleep disruption impairs social development and alters GABA neurons in the brain of adult prairie voles, a socially monogamous rodent that displays natural ethanol preference in the laboratory. However, it is unclear whether these effects on social behavior are due, in part, to overall anhedonia and/or altered behavioral response to stress. To address this question, litters containing prairie vole pups were sleep disrupted by gentle cage agitation for 7 consecutive days from postnatal days (P) 14 to 21 (early life sleep disruption, or ELSD group) or allowed to sleep undisturbed (Control). Adult voles underwent a 2-bottle choice ethanol drinking procedure integrated with a single session of footshocks. Ethanol intake after footshock was measured as well as c-Fos immunoreactivity in the lateral and central amygdala. ELSD animals showed increased ethanol consumption and increased neural activity in these amygdala regions after footshock compared to control animals. There were no differences in baseline ethanol drinking prior to exposure to a stressor. These results suggest that early life sleep disruption in prairie voles does not produce anhedonia but can have long-lasting effects on stress reactivity. In addition to shaping species-typical social behavior, early life sleep may be important in the development of stress induced ethanol consumption and the activation of limbic pathways associated with stress. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism.

Sleep complaints are an early clinical symptom of neurodegenerative disorders. Patients with Parkinson's disease (PD) experience sleep disruption (SD). The objective of this study was to determine if preexisting, chronic SD leads to a greater loss of tyrosine hydroxylase (TH) within the striatum and the substantia nigra following chronic/progressive exposure with the neurotoxin, 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male mice underwent chronic SD for 4 weeks, then injected with vehicle (VEH) or increasing doses of MPTP for 4 weeks. There was a significant decrease in the plasma corticosterone levels in the MPTP group, an increase in the SD group, and a return to the VEH levels in the SD+MPTP group. Protein expression levels for TH in the striatum (terminals) and substantia nigra pars compacta (dopamine [DA] cell counts) revealed up to a 78% and 38% decrease, respectively, in the MPTP and SD+MPTP groups compared to their relevant VEH and SD groups. DA transporter protein expression increased in the striatum in the MPTP versus VEH group and in the SN/midbrain between the SD+MPTP and the VEH group. There was a main effect of MPTP on various gait measures (e.g., braking) relative to the SD or VEH groups. In the SD+MPTP group, there were no differences compared to the VEH group. Thus, SD, prior to administration of MPTP, has effects on serum corticosterone and gait but more importantly does not potentiate greater loss of TH within the nigrostriatal pathway compared to the MPTP group, suggesting that in PD patients with SD, there is no exacerbation of the DA cell loss.

Differing effects of familiarity/kinship in the social transmission of fear associations and food preferences in rats.

Despite its apparent adaptive advantages, past research has found that greater familiarity and/or familial relatedness of a social demonstrator does not enhance social learning in the social transmission of food preference paradigm. This finding runs counter to research examining the effects of demonstrator characteristics in fear-mediated social learning paradigms, in which increased familiarity and/or relatedness of a demonstrator promotes higher rates of learning in observer rats. In our first experiment, we were able to corroborate the finding that increased familiarity/relatedness to the demonstrator does not enhance acquisition of a socially transmitted food preference. Furthermore, on examination of the social behavior between observers and their demonstrators during the acquisition of a socially transmitted food preference, no analogous relationship between social contact and expression of the learned preference was observed. In our second experiment, we provide further evidence that familiarity/relatedness may enhance the social acquisition of a fear response to an otherwise neutral auditory cue and demonstrate that this effect is not solely the result of increased social contact between the observer and their demonstrator during acquisition. Despite similar levels of post-cue contact in both observer types, a positive correlation was observed between post-cue social contact and expression of a socially acquired fear behavior when the observer was familiar/related to their demonstrator but not novel/unrelated. These findings both validate previous research on the role of familiarity/relatedness in these two social learning paradigms and provide further behavioral evidence that unique social mechanisms may serve to mediate the social transmission of fear.

Early-life sleep disruption increases parvalbumin in primary somatosensory cortex and impairs social bonding in prairie voles.

Across mammals, juveniles sleep more than adults, with rapid eye movement (REM) sleep at a lifetime maximum early in life. One function of REM sleep may be to facilitate brain development of complex behaviors. Here, we applied 1 week of early-life sleep disruption (ELSD) in prairie voles (Microtus ochrogaster), a highly social rodent species that forms lifelong pair bonds. Electroencephalographic recordings from juvenile voles during ELSD revealed decreased REM sleep and reduced γ power compared to baseline. ELSD impaired pair bond formation and altered object preference in adulthood. Furthermore, ELSD increased GABAergic parvalbumin immunoreactivity in the primary somatosensory cortex in adulthood, a brain region relevant to both affected behaviors. We propose that, early in life, sleep is crucial for tuning inhibitory neural circuits and the development of species-typical affiliative social behavior.

Acoustic prepulse inhibition in male and female prairie voles: Implications for models of neuropsychiatric illness.

Sensory gating, the ability to suppress sensory information of irrelevant stimuli, is affected in several neuropsychiatric diseases, notably schizophrenia and autism. It is currently unclear how these deficits interact with other hallmark symptoms of these disorders, such as social withdrawal and difficulty with interpersonal relationships. The highly affiliative prairie vole (Microtus ochrogaster) may be an ideal model organism to study the neurobiology underlying social behavior. In this study, we assessed unimodal acoustic sensory gating in male and female prairie voles using the prepulse inhibition (PPI) paradigm, whereby a lower amplitude sound (prepulse) decreases the startle response to a high amplitude sound (pulse) compared to the high amplitude sound alone. Prairie voles showed evidence of PPI at all prepulse levels compared to pulse alone, with both males and females showing similar levels of inhibition. However, unlike what has been reported in other rodent species, prairie voles did not show a within-session decrease in startle response to the pulse alone, nor did they show a decrease in startle response to the pulse over multiple days, highlighting their inability to habituate to startling stimuli (short- and long-term). When contrasted with a cohort of male wildtype C57Bl/6J mice that underwent a comparable PPI protocol, individual voles showed significantly higher trial-by-trial variability as well as longer latency to startle than mice. The benefits and caveats to using prairie voles in future sensory gating experiments are discussed.

Gait and Conditioned Fear Impairments in a Mouse Model of Comorbid TBI and PTSD.

STUDY OBJECTIVES: Traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) commonly cooccur. Approaches to research and treatment of these disorders have been segregated, despite overlapping symptomology. We and others have hypothesized that comorbid TBI + PTSD generates worse symptoms than either condition alone. We present a mouse model of comorbid TBI + PTSD to further explore this condition. METHODS: A mouse model of TBI + PTSD was generated using the single prolonged stress (SPS) protocol in combination with the controlled cortical impact (CCI) protocol. This resulted in four experimental groups: control, TBI, PTSD, and TBI + PTSD. Behavioral phenotyping included gait analysis, contextual fear conditioning, acoustic startle response, and prepulse inhibition. RESULTS: Mice in the TBI + PTSD group showed a significantly impaired gait compared to their counterparts with TBI alone as well as control mice. Mice in the TBI + PTSD group showed significantly impaired contextual fear recall compared to controls. Prepulse inhibition testing revealed intact acoustic startle and auditory sensory gating. CONCLUSIONS: These results indicate that SPS paired with CCI in mice produces unique behavioral impairments in gait and fear recall that are not present in either condition alone. Further studies are underway to examine additional behavioral, physiological, and pathological phenotypes in this combined model of TBI + PTSD.

Fear Conditioning by Proxy: Social Transmission of Fear Between Interacting Conspecifics.

We describe a method of social fear transmission to a discrete auditory cue in freely behaving rats. Extending beyond traditional observer/demonstrator paradigms, rats are allowed to physically interact and integrate cues from all sensory modalities. In the protocol described in this article, "observer" rats experience social fear conditioning through a proxy cage mate that serves as a "demonstrator" during retrieval of a cued fear memory. We find that a specific auditory cue can come to elicit fear expression in an animal with no foot shock experience simply by interacting with a conspecific expressing a conditioned response in the presence of an otherwise benign stimulus. In this "fear conditioning by proxy" paradigm, we have demonstrated that some, but not all, rats display conditioned responding (e.g., freezing) to a cue after interacting with a cage mate during fear memory retrieval. The amount of freezing exhibited by this fear conditioned "by proxy" rat 24 hr after learning critically depends on social influences, including social relationships and social interactions during learning. © 2018 by John Wiley & Sons, Inc.

Differential effects of predictable vs. unpredictable aversive experience early in development on fear memory and learning in adulthood.

We examined the enduring effects of predictable versus unpredictable fear conditioning early in life on memory and relearning in adulthood. At postnatal Day 17 or 25 (P17 or P25), rats either remained naïve, or were fear conditioned using paired (predictable) or unpaired (unpredictable) presentations of white noise and foot shocks. At 2 months of age (adulthood), each group was fear conditioned (or reconditioned) with either paired or unpaired training, and then was tested for fear extinction the next day. Initial findings replicate previous work from our lab and others, demonstrating a difference in adult memory retention based on age of acquisition. Specifically, rats that received paired conditioning at P25, but not P17, show increased freezing to the cue when tested in adulthood. We further show that paired as well as unpaired conditioning at P17 potentiates paired conditioning in adulthood; however, paired, but not unpaired, conditioning at P25 potentiates paired and unpaired conditioning in adulthood. These findings suggest that early predictable versus unpredictable aversive learning at P17 or P25 differentially modulate memory retention and future learning. (PsycINFO Database Record

Post-retrieval extinction in adolescence prevents return of juvenile fear.

Traumatic experiences early in life can contribute to the development of mood and anxiety disorders that manifest during adolescence and young adulthood. In young rats exposed to acute fear or stress, alterations in neural development can lead to enduring behavioral abnormalities. Here, we used a modified extinction intervention (retrieval+extinction) during late adolescence (post-natal day 45 [p45]), in rats, to target auditory Pavlovian fear associations acquired as juveniles (p17 and p25). The effects of adolescent intervention were examined by assessing freezing as adults during both fear reacquisition and social transmission of fear from a cagemate. Rats underwent testing or training at three time points across development: juvenile (p17 or p25), adolescent (p45), and adult (p100). Retrieval+extinction during late adolescence prevented social reinstatement and recovery over time of fears initially acquired as juveniles (p17 and p25, respectively). Adolescence was the only time point tested here where retrieval+extinction prevented fear recall of associations acquired 20+ days earlier.

Dominance status predicts social fear transmission in laboratory rats.

Acquiring information about stimuli that predict danger, through either direct experience or inference from a social context, is crucial for individuals' ability to generate appropriate behaviors in response to threats. Utilizing a modified demonstrator-observer paradigm (fear conditioning by proxy) that allows for free interaction between subjects, we show that social dominance hierarchy, and the interactive social behaviors of caged rats, is predictive of social fear transmission, with subordinate rats displaying increased fear responses after interacting with a fear-conditioned dominant rat during fear retrieval. Fear conditioning by proxy conserves some of the pathways necessary for direct fear learning (e.g., lateral amygdala) but is unique in that it requires regions necessary for emotional regulation (e.g., anterior cingulate cortex), making this paradigm an important tool for evaluating learning and behavior in the laboratory setting.

Fight, Flight, or Freeze? The Answer May Depend on Your Sex.

Pavlovian fear conditioning is one of the most common and well-understood methods for studying fear learning. However, research is predominantly performed in males. Recently, in a classical Pavlovian fear conditioning paradigm, Gruene and colleagues described an active conditioned fear response ('darting') prevalent in female rats that better maintain an extinction memory.

Anastomotic Leakage Following Esophagectomy.

Anastomotic leaks remain a significant clinical challenge following esophagectomy with foregut reconstruction. Despite an increasing understanding of the multiple contributing factors, advancements in perioperative optimization of modifiable risks, and improvements in surgical, endoscopic, and percutaneous management techniques, leaks remain a source of major morbidity associated with esophageal resection. The surgeon should be well versed in the principles underlying the cause of leaks, and strategies to minimize their occurrence. Appropriately diagnosed and managed, most anastomotic leaks following esophagectomy can be brought to a successful resolution.