Striatal mechanisms of turning behaviour following unilateral dopamine depletion in mice.

Unilateral dopamine (DA) depletion produces ipsiversive turning behaviour, and the injection of DA receptor agonists can produce contraversive turning, but the underlying mechanisms remain unclear. We conducted in vivo recording and pharmacological and optogenetic manipulations to study the role of DA and striatal output in turning behaviour. We used a video-based tracking programme while recording single unit activity in both putative medium spiny projection neurons (MSNs) and fast-spiking interneurons (FSIs) in the dorsal striatum bilaterally. Our results suggest that unilateral DA depletion reduced striatal output from the depleted side, resulting in asymmetric striatal output. Depletion systematically altered activity in both MSNs and FSIs, especially in neurons that increased firing during turning movements. Like D1 agonist SKF 38393, optogenetic stimulation in the depleted striatum increased striatal output and reversed biassed turning. These results suggest that relative striatal outputs from the two cerebral hemispheres determine the direction of turning: Mice turn away from the side of higher striatal output and towards the side of the lower striatal output.

Serial-section atlas of the Tritonia pedal ganglion.

The pedal ganglion of the nudibranch gastropod Tritonia diomedea has been the focus of neurophysiological studies for more than 50 yr. These investigations have examined the neural basis of behaviors as diverse as swimming, crawling, reflex withdrawals, orientation to water flow, orientation to the earth's magnetic field, and learning. Despite this sustained research focus, most studies have confined themselves to the layer of neurons that are visible on the ganglion surface, leaving many neurons, which reside in deeper layers, largely unknown and thus unstudied. To facilitate work on such neurons, the present study used serial-section light microscopy to generate a detailed pictorial atlas of the pedal ganglion. One pedal ganglion was sectioned horizontally at 2-µm intervals and another vertically at 5-µm intervals. The resulting images were examined separately or combined into stacks to generate movie tours through the ganglion. These were also used to generate 3D reconstructions of individual neurons and rotating movies of digitally desheathed whole ganglia to reveal all surface neurons. A complete neuron count of the horizontally sectioned ganglion yielded 1,885 neurons. Real and virtual sections from the image stacks were used to reveal the morphology of individual neurons, as well as the major axon bundles traveling within the ganglion to and between its several nerves and connectives. Extensive supplemental data are provided, as well as a link to the Dryad Data Repository site, where the complete sets of high-resolution serial-section images can be downloaded. NEW & NOTEWORTHY Because of the large size and relatively low numbers of their neurons, gastropod mollusks are widely used for investigations of the neural basis of behavior. Most studies, however, focus on the neurons visible on the ganglion surface, leaving the majority, located out of sight below the surface, unexamined. The present light microscopy study generates the first detailed visual atlas of all neurons of the highly studied Tritonia pedal ganglion.

Use of Indocyanine Green to Detect Intraoperative Staple-Line Leaks in Robotic Bariatric Surgery: An Observational Cohort Study.

Background Bariatric surgeries aid weight loss in patients with morbid obesity, yet staple-line leaks pose safety concerns. Multiple methods are used to help identify these links. Intraluminal indocyanine green (ICG) has been shown to be useful in other applications, and its use in robotic bariatric surgeries is underexplored. Objective The primary objective of this research project was to demonstrate the usage of intraluminal ICG in detecting staple-line leaks during robotic sleeve gastrectomy and robotic gastric bypass. Settings The research was conducted at Bronxcare Health System between June 2022 and June 2023. Methods We studied 150 consecutive participants undergoing robotic sleeve gastrectomy or robotic gastric bypass. Intraluminal ICG was used in each case in order to identify leaks. Data on comorbidities, detected intraoperative leaks, and detected postoperative leaks were collected. Results Out of the 150 patients who underwent robotic bariatric surgeries (139 for sleeve gastrectomy and 11 for gastric bypass), four cases (two for each procedure) were identified with intraoperative leaks using ICG, resulting in an overall 2.66% incidence rate. In those four patients with intraoperative leaks, reinforcing sutures and a drain were placed. Following the surgeries, none of the patients had radiologic or clinical leaks identified. Conclusions Intraluminal ICG presents a novel approach for detecting staple-line leaks in robotic bariatric surgery. Future studies can be done to look at a larger series of patients and compare leak detection rates between ICG and other methods.

Characteristics of Patients Undergoing Bariatric Surgery in an Inner-City Minority Population: A Pre and Postoperative Comparison Between Patients With and Without Obstructive Sleep Apnea.

Background Obese patients are at an increased risk of obstructive sleep apnea (OSA). Bariatric surgery or weight loss surgery is an important therapeutic measure in obese patients for the management of weight and comorbidities. Data are scarce in inner-city Hispanic and Black patients who undergo bariatric surgery, which eventually leads to health disparity in this minority population. Differences between patients with and without OSA have not been assessed in this population. This study aims to answer these questions. Methodology The study was conducted in a high-volume hospital in the Bronx, New York. Before bariatric surgery, patients underwent a preoperative evaluation that included a variety of blood tests, a sleep study, esophagogastroduodenoscopy, and echocardiography. They also underwent basic anthropometric measurements, such as weight, height, and body mass index (BMI), before surgery and 6 months and 12 months postoperatively. Additional calculations were made using these anthropometric measures, namely, total weight loss, excess weight loss, and delta BMI. Results Most patients were Hispanic (85.2%), with a mean age of 41.9 ± 10.8 years. We found that of the 108 patients included in the study, 69.4% (70/108) had OSA. Preoperative BMI in the study was 43.9 ± 13 kg/m2. Postoperatively, the mean decrease in BMI was 12.3 ± 14.5 kg/m2. Total weight loss and excess weight loss were 30.2 ± 14.3 and 52.6 ± 16.6, respectively. Conclusions In this study, no significant difference was noted in patients with or without OSA in either the laboratory or anthropometric parameters.

A Displaced Intrauterine Device Eroding Into the Sigmoid Colon.

A 36-year-old female presented to the gynecology office eight weeks after the placement of a ParaGard intrauterine device (IUD). Upon gynecologic examination, the strings of the IUD were not found. Magnetic resonance imaging was performed which reported the IUD embedded in the sigmoid colon. Initial diagnostic laparoscopy was done without bowel preparation and revealed an IUD embedded within the sigmoid colon and mesocolon. Colonoscopy did not reveal any breach of the colonic lumen. A second diagnostic laparoscopy was planned with the robotic-assisted technique after bowel preparation. Intraoperative findings during the second operation identified the IUD embedded in the antimesenteric side of the sigmoid colon with surrounding scar tissue to the uterus. The IUD was sharply freed using robotic scissors and the resulting serosal defect was sutured in layers with buttress made of appendices epiploica. The patient recovered well and had an excellent outcome. Our article highlights the minimally invasive method of dealing with a displaced IUD. The use of the robotic technique was helpful in our case to achieve an excellent outcome.

Mechanisms of action selection and timing in substantia nigra neurons.

The timing of actions is critical for adaptive behavior. In this study we measured neural activity in the substantia nigra as mice learned to change their action duration to earn food rewards. We observed dramatic changes in single unit activity during learning: both dopaminergic and GABAergic neurons changed their activity in relation to behavior to reflect the learned instrumental contingency and the action duration. We found the emergence of "action-on" neurons that increased firing for the duration of the lever press and mirror-image "action-off" neurons that paused at the same time. This pattern is especially common among GABAergic neurons. The activity of many neurons also reflected confidence about the just completed action and the prospect of reward. Being correlated with the relative duration of the completed action, their activity could predict the likelihood of reward collection. Compared with the GABAergic neurons, the activity of dopaminergic neurons was more commonly modulated by the discriminative stimulus signaling the start of each trial, suggesting that their phasic activity reflected sensory salience rather than any reward prediction error found in previous work. In short, these results suggest that (1) nigral activity is highly plastic and modified by the learning of the instrumental contingency; (2) GABAergic output from the substantia nigra can simultaneously inhibit and disinhibit downstream structures, while the dopaminergic output also provide bidirectional modulation of the corticostriatal circuits; (3) dopaminergic and GABAergic neurons show similar task-related activity, although DA neurons are more responsive to the trial start signal.

Learning Risk-aware Costmaps for Traversability in Challenging Environments.

One of the main challenges in autonomous robotic exploration and navigation in unknown and unstructured environments is determining where the robot can or cannot safely move. A significant source of difficulty in this determination arises from stochasticity and uncertainty, coming from localization error, sensor sparsity and noise, difficult-to-model robot-ground interactions, and disturbances to the motion of the vehicle. Classical approaches to this problem rely on geometric analysis of the surrounding terrain, which can be prone to modeling errors and can be computationally expensive. Moreover, modeling the distribution of uncertain traversability costs is a difficult task, compounded by the various error sources mentioned above. In this work, we take a principled learning approach to this problem. We introduce a neural network architecture for robustly learning the distribution of traversability costs. Because we are motivated by preserving the life of the robot, we tackle this learning problem from the perspective of learning tail-risks, i.e. the conditional value-at-risk (CVaR). We show that this approach reliably learns the expected tail risk given a desired probability risk threshold between 0 and 1, producing a traversability costmap which is more robust to outliers, more accurately captures tail risks, and is more computationally efficient, when compared against baselines. We validate our method on data collected by a legged robot navigating challenging, unstructured environments including an abandoned subway, limestone caves, and lava tube caves.

Predictors of supportive message expression and reception in an interactive cancer communication system.

Social support in computer-mediated settings is an important variable in health communication research, yet little is known about the factors that influence the amount of social support one gives and receives in online support groups. To shed some light on this issue, the authors examined demographics, disease-related factors, psychosocial factors, and strategies for coping with breast cancer as potential determinants of which patients provide support to others and which ones consume it. Data collected from 177 participants in the Comprehensive Health Enhancement Support System "Living With Breast Cancer" program revealed that individuals who are younger, have higher levels of positive reframing, and lower levels of self-blame are more likely to provide emotional support in online settings. In contrast, individuals who are more educated, have less perceived availability of social support, and have lower levels of religious coping are more likely to receive emotional support from others. The authors discuss the theoretical and practical implications for providing effective psychosocial support for women with breast cancer.

Early-pregnancy prediction of risk for pre-eclampsia using maternal blood leptin/ceramide ratio: discovery and confirmation.

OBJECTIVE: This study aimed to develop a blood test for the prediction of pre-eclampsia (PE) early in gestation. We hypothesised that the longitudinal measurements of circulating adipokines and sphingolipids in maternal serum over the course of pregnancy could identify novel prognostic biomarkers that are predictive of impending event of PE early in gestation. STUDY DESIGN: Retrospective discovery and longitudinal confirmation. SETTING: Maternity units from two US hospitals. PARTICIPANTS: Six previously published studies of placental tissue (78 PE and 95 non-PE) were compiled for genomic discovery, maternal sera from 15 women (7 non-PE and 8 PE) enrolled at ProMedDx were used for sphingolipidomic discovery, and maternal sera from 40 women (20 non-PE and 20 PE) enrolled at Stanford University were used for longitudinal observation. OUTCOME MEASURES: Biomarker candidates from discovery were longitudinally confirmed and compared in parallel to the ratio of placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) using the same cohort. The datasets were generated by enzyme-linked immunosorbent and liquid chromatography-tandem mass spectrometric assays. RESULTS: Our discovery integrating genomic and sphingolipidomic analysis identified leptin (Lep) and ceramide (Cer) (d18:1/25:0) as novel biomarkers for early gestational assessment of PE. Our longitudinal observation revealed a marked elevation of Lep/Cer (d18:1/25:0) ratio in maternal serum at a median of 23 weeks' gestation among women with impending PE as compared with women with uncomplicated pregnancy. The Lep/Cer (d18:1/25:0) ratio significantly outperformed the established sFlt-1/PlGF ratio in predicting impending event of PE with superior sensitivity (85% vs 20%) and area under curve (0.92 vs 0.52) from 5 to 25 weeks of gestation. CONCLUSIONS: Our study demonstrated the longitudinal measurement of maternal Lep/Cer (d18:1/25:0) ratio allows the non-invasive assessment of PE to identify pregnancy at high risk in early gestation, outperforming the established sFlt-1/PlGF ratio test.

A multidisciplinary approach to carotid body tumors surgical management.

Carotid body tumors (CBTs) are rare and usually require complex surgical resection. We present a case of a large 7-cm CBT successfully treated in a community cancer center using a multidisciplinary team approach. A 32-year-old male referred for surgical evaluation of an asymptomatic right neck mass. CT angiography showed a 7-cm tumor encasing the carotid vessels, including the bifurcation (Shamblin III). Preoperative angiography and embolization were performed by interventional radiology. The patient underwent surgical removal of the CBTs and required surgical reconstruction with a common carotid to internal carotid bypass using a polytetrafluoroethylene interposition graft. The hypoglossal nerve, vagus nerve and glossopharyngeal nerve were identified, meticulously dissected and preserved. The patient did well after surgery and recovered with no complications. This report examines the diagnosis, preoperative workup and surgical management of CBTs using a multidisciplinary team approach.

Small bowel intussusception in marijuana users.

Intussusception occurs when one portion of bowel 'telescopes' into another due to a lead point created by a range of benign or pathologic process. Intussusception mostly occurs in children. Although adult intussusception (AI) is rare, accounting for <5% of intestinal obstructions, it is more concerning in adults as malignancy accounts for nearly 65% of lead points in AI. Patients present with severe abdominal pain concerning for an acute abdomen along with a degree of bowel obstruction. We have experienced a total of 11 patients within recent years presenting with symptoms of an acute abdomen due to AI. None of these patients were found to have a pathologic process creating a lead point. However, we found that all of them were marijuana users. In this report, we compare their management, hospital course and review of the literature discussing proposed mechanisms that suggest an association between cannabis and intussusception.

Media advocacy and underage drinking policies: a study of Louisiana news media from 1994 through 2003.

The communications literature firmly establishes the significant role of media advocacy in setting public agenda and influencing the direction of public opinion on social issues. Recent public health campaigns embrace media advocacy as an integral part of efforts to change public health policies, yet further studies are needed on the best strategies to promote legislative action. This article examines press coverage in the Baton Rouge Advocate and the New Orleans Times-Picayune newspapers and Louisiana State legislation pertaining to underage drinking from January 1994 to June 2003 and focuses on evidence of media priming and framing of underage drinking and four related legislative policies. High press coverage of alcohol bills during the legislative process was associated with defeated legislation, whereas little or no press coverage was associated with bills successfully passed into law. The authors conclude that more work is needed to understand how media advocacy strategies may hinder enactment of bills.

Heart-specific Rpd3 downregulation enhances cardiac function and longevity.

Downregulation of Rpd3, a homologue of mammalian Histone Deacetylase 1 (HDAC1), extends lifespan in Drosophila melanogaster. Once revealed that long-lived fruit flies exhibit limited cardiac decline, we investigated whether Rpd3 downregulation would improve stress resistance and/or lifespan when targeted in the heart. Contested against three different stressors (oxidation, starvation and heat), heart-specific Rpd3 downregulation significantly enhanced stress resistance in flies. However, these higher levels of resistance were not observed when Rpd3 downregulation was targeted in other tissues or when other long-lived flies were tested in the heart-specific manner. Interestingly, the expressions of anti-aging genes such as sod2, foxo and Thor, were systemically increased as a consequence of heart-specific Rpd3 downregulation. Showing higher resistance to oxidative stress, the heart-specific Rpd3 downregulation concurrently exhibited improved cardiac functions, demonstrating an increased heart rate, decreased heart failure and accelerated heart recovery. Conversely, Rpd3 upregulation in cardiac tissue reduced systemic resistance against heat stress with decreased heart function, also specifying phosphorylated Rpd3 levels as a significant modulator. Continual downregulation of Rpd3 throughout aging increased lifespan, implicating that Rpd3 deacetylase in the heart plays a significant role in cardiac function and longevity to systemically modulate the fly's response to the environment.

Individualized use of methadone and opioid rotation in the comprehensive management of cancer pain associated with poor prognostic indicators.

This case report describes a patient affected by a neuropathic pain syndrome, which was secondary to a renal cell carcinoma metastatic to the spine, and complicated by incidental components and somatization. Due to a rapid development of tolerance and toxicity from hydromorphone, a rotation to methadone was made, with a decrease of the morphine equivalent daily dose (MEDD) from 1050 to 36. After 4 mos of good pain relief, a switch over back to hydromorphone was necessary due to worsening pain, associated with myoclonus and sedation secondary to methadone; the MEDD this time escalated from 480 to 4950. The use of hydromorphone was complicated by the onset of intractable nausea and sedation. After 2 wks, the patient was rotated again to methadone, with a decrease of the MEDD to 24. He achieved good pain control and was free of opioid toxicity. Our findings illustrate a role of methadone in the management of cancer pain associated with poor prognostic indicators, the development of tolerance towards its effects, and the regaining of sensitivity to methadone, by temporary rotation to another opioid. Possible mechanism for opioid tolerance and its reversal are discussed.

Secondary Sclerosing Cholangitis due to Gallbladder Adenocarcinoma.

Sclerosing cholangitis is a chronic cholestatic liver disease defined by both inflammatory and fibrotic changes of the biliary tract leading to diffuse stricture formation. This entity exists in both a primary and secondary form. Here we present a rare case of secondary sclerosing cholangitis due to direct metastasis from a gallbladder adenocarcinoma. A 55-year-old morbidly obese male presented electively with a 2-week history of low back pain and scleral icterus for 2 days. He also described severe epigastric pain that worsened postprandially and a 13 kg weight loss over the previous month. The patient denied any personal or familial history of malignancy or prior liver disease. Laboratory evaluation revealed mild elevation of transaminases with moderately elevated alkaline phosphatase and total bilirubin. Imaging included ultrasound and contrast-enhanced computed tomography of the abdomen and pelvis showing multiple large gallstones and a large tissue density mass within the fundus of the gallbladder. Subsequent endoscopic ultrasound was performed revealing celiac and portal lymphadenopathy with fine needle aspirations demonstrating adenocarcinoma. Over the next 15 days, bilirubin progressively increased. Magnetic resonance cholangiopancreatography was unremarkable. Liver biopsy, performed to exclude other etiologies of liver failure, demonstrated biliary cholestasis. Endoscopic retrograde cholangiopancreatography was then performed and an occlusion cholangiogram revealed diffuse multifocal stricturing of the intrahepatic bile ducts and moderate stenosis of the common bile duct without proximal ductal dilatation. Thus secondary sclerosing cholangitis due to gallbladder adenocarcinoma was diagnosed.

Bidirectional modulation of substantia nigra activity by motivational state.

A major output nucleus of the basal ganglia is the substantia nigra pars reticulata, which sends GABAergic projections to brainstem and thalamic nuclei. The GABAergic (GABA) neurons are reciprocally connected with nearby dopaminergic neurons, which project mainly to the basal ganglia, a set of subcortical nuclei critical for goal-directed behaviors. Here we examined the impact of motivational states on the activity of GABA neurons in the substantia nigra pars reticulata and the neighboring dopaminergic (DA) neurons in the pars compacta. Both types of neurons show short-latency bursts to a cue predicting a food reward. As mice became sated by repeated consumption of food pellets, one class of neurons reduced cue-elicited firing, whereas another class of neurons progressively increased firing. Extinction or pre-feeding just before the test session dramatically reduced the phasic responses and their motivational modulation. These results suggest that signals related to the current motivational state bidirectionally modulate behavior and the magnitude of phasic response of both DA and GABA neurons in the substantia nigra.

Dynamic changes in single unit activity and γ oscillations in a thalamocortical circuit during rapid instrumental learning.

The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) together form a thalamocortical circuit that has been implicated in the learning and production of goal-directed actions. In this study we measured neural activity in both regions simultaneously, as rats learned to press a lever to earn food rewards. In both MD and mPFC, instrumental learning was accompanied by dramatic changes in the firing patterns of the neurons, in particular the rapid emergence of single-unit neural activity reflecting the completion of the action and reward delivery. In addition, we observed distinct patterns of changes in the oscillatory LFP response in MD and mPFC. With learning, there was a significant increase in theta band oscillations (6-10 Hz) in the MD, but not in the mPFC. By contrast, gamma band oscillations (40-55 Hz) increased in the mPFC, but not in the MD. Coherence between these two regions also changed with learning: gamma coherence in relation to reward delivery increased, whereas theta coherence did not. Together these results suggest that, as rats learned the instrumental contingency between action and outcome, the emergence of task related neural activity is accompanied by enhanced functional interaction between MD and mPFC in response to the reward feedback.

Motivational state and reward content determine choice behavior under risk in mice.

Risk is a ubiquitous feature of the environment for most organisms, who must often choose between a small and certain reward and a larger but less certain reward. To study choice behavior under risk in a genetically well characterized species, we trained mice (C57BL/6) on a discrete trial, concurrent-choice task in which they must choose between two levers. Pressing one lever (safe choice) is always followed by a small reward. Pressing the other lever (risky choice) is followed by a larger reward, but only on some of the trials. The overall payoff is the same on both levers. When mice were not food deprived, they were indifferent to risk, choosing both levers with equal probability regardless of the level of risk. In contrast, following food or water deprivation, mice earning 10% sucrose solution were risk-averse, though the addition of alcohol to the sucrose solution dose-dependently reduced risk aversion, even before the mice became intoxicated. Our results falsify the budget rule in optimal foraging theory often used to explain behavior under risk. Instead, they suggest that the overall demand or desired amount for a particular reward determines risk preference. Changes in motivational state or reward identity affect risk preference by changing demand. Any manipulation that increases the demand for a reward also increases risk aversion, by selectively increasing the frequency of safe choices without affecting frequency of risky choices.

A wireless multi-channel recording system for freely behaving mice and rats.

To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.