Neurotensin orchestrates valence assignment in the amygdala.

The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different projections from the basolateral amygdala (BLA) are potentiated following reward or punishment learning1-7. However, we do not yet understand how valence-specific information is routed to the BLA neurons with the appropriate downstream projections, nor do we understand how to reconcile the sub-second timescales of synaptic plasticity8-11 with the longer timescales separating the predictive cues from their outcomes. Here we demonstrate that neurotensin (NT)-expressing neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting NT concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, whereas PVT-BLA projection-specific knockout of the NT gene (Nts) augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Nts gene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference for active behavioural strategies to reward and punishment predictive cues. In sum, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviourally relevant timescales.

IL-17a promotes sociability in mouse models of neurodevelopmental disorders.

A subset of children with autism spectrum disorder appear to show an improvement in their behavioural symptoms during the course of a fever, a sign of systemic inflammation1,2. Here we elucidate the molecular and neural mechanisms that underlie the beneficial effects of inflammation on social behaviour deficits in mice. We compared an environmental model of neurodevelopmental disorders in which mice were exposed to maternal immune activation (MIA) during embryogenesis3,4 with mouse models that are genetically deficient for contactin-associated protein-like 2 (Cntnap2)5, fragile X mental retardation-1 (Fmr1)6 or Sh3 and multiple ankyrin repeat domains 3 (Shank3)7. We establish that the social behaviour deficits in offspring exposed to MIA can be temporarily rescued by the inflammatory response elicited by the administration of lipopolysaccharide (LPS). This behavioural rescue was accompanied by a reduction in neuronal activity in the primary somatosensory cortex dysgranular zone (S1DZ), the hyperactivity of which was previously implicated in the manifestation of behavioural phenotypes associated with offspring exposed to MIA8. By contrast, we did not observe an LPS-induced rescue of social deficits in the monogenic models. We demonstrate that the differences in responsiveness to the LPS treatment between the MIA and the monogenic models emerge from differences in the levels of cytokine production. LPS treatment in monogenic mutant mice did not induce amounts of interleukin-17a (IL-17a) comparable to those induced in MIA offspring; bypassing this difference by directly delivering IL-17a into S1DZ was sufficient to promote sociability in monogenic mutant mice as well as in MIA offspring. Conversely, abrogating the expression of IL-17 receptor subunit a (IL-17Ra) in the neurons of the S1DZ eliminated the ability of LPS to reverse the sociability phenotypes in MIA offspring. Our data support a neuroimmune mechanism that underlies neurodevelopmental disorders in which the production of IL-17a during inflammation can ameliorate the expression of social behaviour deficits by directly affecting neuronal activity in the central nervous system.

Attractive forces slow contact formation between deformable bodies underwater.

Thermodynamics tells us to expect underwater contact between two hydrophobic surfaces to result in stronger adhesion compared to two hydrophilic surfaces. However, the presence of water changes not only energetics but also the dynamic process of reaching a final state, which couples solid deformation and liquid evacuation. These dynamics can create challenges for achieving strong underwater adhesion/friction, which affects diverse fields including soft robotics, biolocomotion, and tire traction. Closer investigation, requiring sufficiently precise resolution of film evacuation while simultaneously controlling surface wettability, has been lacking. We perform high-resolution in situ frustrated total internal reflection imaging to track underwater contact evolution between soft-elastic hemispheres of varying stiffness and smooth-hard surfaces of varying wettability. Surprisingly, we find the exponential rate of water evacuation from hydrophobic-hydrophobic (adhesive) contact is three orders of magnitude lower than that from hydrophobic-hydrophilic (nonadhesive) contact. The trend of decreasing rate with decreasing wettability of glass sharply changes about a point where thermodynamic adhesion crosses zero, suggesting a transition in mode of evacuation, which is illuminated by three-dimensional spatiotemporal height maps. Adhesive contact is characterized by the early localization of sealed puddles, whereas nonadhesive contact remains smooth, with film-wise evacuation from one central puddle. Measurements with a human thumb and alternatively hydrophobic/hydrophilic glass surface demonstrate practical consequences of the same dynamics: adhesive interactions cause instability in valleys and lead to a state of more trapped water and less intimate solid-solid contact. These findings offer interpretation of patterned texture seen in underwater biolocomotive adaptations as well as insight toward technological implementation.

Micromechanical Origin of Plasticity and Hysteresis in Nestlike Packings.

Disordered packings of unbonded, semiflexible fibers represent a class of materials spanning contexts and scales. From twig-based bird nests to unwoven textiles, bulk mechanics of disparate systems emerge from the bending of constituent slender elements about impermanent contacts. In experimental and computational packings of wooden sticks, we identify prominent features of their response to cyclic oedometric compression: nonlinear stiffness, transient plasticity, and eventually repeatable velocity-independent hysteresis. We trace these features to their micromechanic origins, identified in characteristic appearance, disappearance, and displacement of internal contacts.

Patient and family involvement in Choosing Wisely initiatives: a mixed methods study.

BACKGROUND: Patients are important stakeholders in reducing low-value care, yet mechanisms for optimizing their involvement in low-value care remain unclear. To explore the role of patients in the development and implementation of Choosing Wisely recommendations to reduce low-value care and to assess the likelihood that existing patient resources will change patient health behaviour. METHODS: Three phased mixed-methods study: 1) content analysis of all publicly available Choosing Wisely clinician lists and patient resources from the United States of America and Canada. Quantitative data was summarized with frequencies and free text comments were analyzed with qualitative thematic content analysis; 2) semi-structured telephone interviews with a purposive sample of representatives of professional societies who created Choosing Wisely clinician lists and members of the public (including patients and family members). Interviews were transcribed verbatim, and two researchers conducted qualitative template analysis; 3) evaluation of Choosing Wisely patient resources. Two public partners were identified through the Calgary Critical Care Research Network and independently answered two free text questions "would this change your health behaviour" and "would you discuss this material with a healthcare provider". Free text data was analyzed by two researchers using thematic content analysis. RESULTS: From the content analysis of 136 Choosing Wisely clinician lists, six reported patient involvement in their development. From 148 patient resource documents that were mapped onto a conceptual framework (Inform, Activate, Collaborate) 64% described patient engagement at the level of Inform (educating patients). From 19 interviews stakeholder perceptions of patient involvement in reducing low-value care were captured by four themes: 1) impact of perceived power dynamics on the discussion of low-value care in the clinical interaction, 2) how to communicate about low-value care, 3) perceived barriers to patient involvement in reducing low-value care, and 4) suggested strategies to engage patients and families in Choosing Wisely initiatives. In the final phase of work in response to the question "would this change your health behaviour" two patient partners agreed 'yes' on 27% of patient resources. CONCLUSIONS: Opportunities exist to increase patient and family participation in initiatives to reduce low-value care.

Preprocedural Electrophysiological Monitoring in Craniofacial Surgery for a Patient with Chiari Malformation.

Head and neck positioning is a key element of craniofacial reconstructive surgery and can become challenging when intervention necessitates broad exposure of the calvarium. We present a case of craniosynostosis secondary to Apert's syndrome requiring anterior and posterior cranial vault access during surgical correction. A modified sphinx position was used that required significant neck extension. The patient had concurrent Chiari I malformation with brain stem compression so intraoperative neuromonitoring (IONM) was used to ensure that there were no negative effects on the neural elements with positioning. This highlights benefits of IONM in a setting not typically associated with its use.

Transient ipsilateral mydriasis following carotid artery stenting.

BACKGROUND AND IMPORTANCE: One of the most feared and devastating complications of carotid revascularization procedures is hyperperfusion hemorrhage. The acute onset of an ipsilateral mydriatic pupil following carotid endarterectomy (CEA) or carotid artery stenting (CAS) should prompt immediate neurosurgical evaluation to rule out hyperperfusion injury. CLINICAL PRESENTATION: We describe a case of benign, transient ipsilateral mydriasis following CAS. After undergoing right common and internal carotid artery (ICA) angioplasty and stenting with distal embolic protection, the patient developed anisocoria with a right-sided 5 mm minimally reactive pupil. Imaging demonstrated no acute pathology, and the mydriasis resolved spontaneously within 48 hours. We hypothesise that the pathophysiologic mechanism is secondary to transient ischemia of parasympathetic structures within the petrous/cavernous ICA from arterial ostium occlusion that occurred during device placement. Alternatively, sympathetic stimulation during angioplasty is also plausible. CONCLUSIONS: Although an ipsilateral mydriatic pupil following carotid revascularization necessitates evaluation, it may represent a self-limiting process especially in the absence of other focal neurologic deficits.

Curvature-induced stiffness and the spatial variation of wavelength in wrinkled sheets.

Wrinkle patterns in compressed thin sheets are ubiquitous in nature and technology, from the furrows on our foreheads to crinkly plant leaves, from ripples on plastic-wrapped objects to the protein film on milk. The current understanding of an elementary descriptor of wrinkles--their wavelength--is restricted to deformations that are parallel, spatially uniform, and nearly planar. However, most naturally occurring wrinkles do not satisfy these stipulations. Here we present a scheme that quantitatively explains the wrinkle wavelength beyond such idealized situations. We propose a local law that incorporates both mechanical and geometrical effects on the spatial variation of wrinkle wavelength. Our experiments on thin polymer films provide strong evidence for its validity. Understanding how wavelength depends on the properties of the sheet and the underlying liquid or elastic subphase is crucial for applications where wrinkles are used to sculpt surface topography, to measure properties of the sheet, or to infer forces applied to a film.

Termite mounds harness diurnal temperature oscillations for ventilation.

Many species of millimetric fungus-harvesting termites collectively build uninhabited, massive mound structures enclosing a network of broad tunnels that protrude from the ground meters above their subterranean nests. It is widely accepted that the purpose of these mounds is to give the colony a controlled microclimate in which to raise fungus and brood by managing heat, humidity, and respiratory gas exchange. Although different hypotheses such as steady and fluctuating external wind and internal metabolic heating have been proposed for ventilating the mound, the absence of direct in situ measurement of internal air flows has precluded a definitive mechanism for this critical physiological function. By measuring diurnal variations in flow through the surface conduits of the mounds of the species Odontotermes obesus, we show that a simple combination of geometry, heterogeneous thermal mass, and porosity allows the mounds to use diurnal ambient temperature oscillations for ventilation. In particular, the thin outer flutelike conduits heat up rapidly during the day relative to the deeper chimneys, pushing air up the flutes and down the chimney in a closed convection cell, with the converse situation at night. These cyclic flows in the mound flush out CO2 from the nest and ventilate the colony, in an unusual example of deriving useful work from thermal oscillations.

Hippocampal neural activity reflects the economy of choices during goal-directed navigation.

Distinguishing spatial contexts is likely essential for the well-known role of the hippocampus in episodic memory. We studied whether types of hippocampal neural organization thought to underlie context discrimination are impacted by learned economic considerations of choice behavior. Hippocampal place cells and theta activity were recorded as rats performed a maze-based probability discounting task that involved choosing between a small certain reward or a large probabilistic reward. Different spatial distributions of place fields were observed in response to changes in probability, the outcome of the rats' choice, and whether or not rats were free to make that choice. The degree to which the reward location was represented by place cells scaled with the expected probability of rewards. Theta power increased around the goal location also in proportion to the expected probability of signaled rewards. Furthermore, theta power dynamically varied as specific econometric information was obtained "on the fly" during task performance. Such an economic perspective of memory processing by hippocampal place cells expands our view of the nature of context memories retrieved by hippocampus during adaptive navigation.

Solar-powered ventilation of African termite mounds.

How termite mounds function to facilitate climate control is still only partially understood. Recent experimental evidence in the mounds of a single species, the south Asian termite Odontotermes obesus, suggests that the daily oscillations of radiant heating associated with diurnal insolation patterns drive convective flow within them. How general this mechanism is remains unknown. To probe this, we consider the mounds of the African termite Macrotermes michaelseni, which thrives in a very different environment. By directly measuring air velocities and temperatures within the mound, we see that the overall mechanisms and patterns involved are similar to that in the south Asian species. However, there are also some notable differences between the physiology of these mounds associated with the temporal variations in radiant heating patterns and CO2 dynamics. Because of the difference between direct radiant heating driven by the position of the sun in African conditions, and the more shaded south Asian environments, we see changes in the convective flows in the two types of mounds. Furthermore, we also see that the south Asian mounds show a significant overturning of stratified gases, once a day, while the African mounds have a relatively uniform concentration of CO2 Overall, our observations show that despite these differences, termite architectures can harness periodic solar heating to drive ventilation inside them in very different environments, functioning as an external lung, with clear implications for human engineering.

Elastic sheet on a liquid drop reveals wrinkling and crumpling as distinct symmetry-breaking instabilities.

Smooth wrinkles and sharply crumpled regions are familiar motifs in biological or synthetic sheets, such as rapidly growing plant leaves and crushed foils. Previous studies have addressed both morphological types, but the generic route whereby a featureless sheet develops a complex shape remains elusive. Here we show that this route proceeds through an unusual sequence of distinct symmetry-breaking instabilities. The object of our study is an ultrathin circular sheet stretched over a liquid drop. As the curvature is gradually increased, the surface tension stretching the sheet over the drop causes compression along circles of latitude. The compression is relieved first by a transition into a wrinkle pattern, and then into a crumpled state via a continuous transition. Our data provide conclusive evidence that wrinkle patterns in highly bendable sheets are not described by classical buckling methods, but rather by a theory which assumes that wrinkles completely relax the compressive stress. With this understanding we recognize the observed sequence of transitions as distinct symmetry breakings of the shape and the stress field. The axial symmetry of the shape is broken upon wrinkling but the underlying stress field preserves this symmetry. Thus, the wrinkle-to-crumple transition marks symmetry-breaking of the stress in highly bendable sheets. By contrast, other instabilities of sheets, such as blistering and cracking, break the homogeneity of shape and stress simultaneously. The onset of crumpling occurs when the wrinkle pattern grows to half the sheet's radius, suggesting a geometric, material-independent origin for this transition.

A systematic review of enhanced resurgence paradigms.

Following successful treatment in which problem behavior is reduced, it may reemerge as a function of changes in contextual stimuli or the worsening of reinforcement conditions for an alternative response. Although understudied, preliminary research suggests that simultaneous changes in contextual stimuli and reinforcement conditions may represent particularly exigent treatment challenges that create the condition for additive or superadditive relapse. The purpose of the present review was to systematically examine the relapse literature involving simultaneous changes in contextual stimuli and reinforcement conditions in relapse tests and experimental preparations arranged to evaluate their effect on response recovery. We identified 16 empirical articles spanning 27 experiments. Although all experiments included at least one condition that experienced a change in contextual stimuli and worsening of alternative reinforcement conditions, only two experiments included the comparison conditions needed to precisely evaluate additive and superadditive relapse. Our findings establish the preclinical generality of relapse effects associated with simultaneous changes to reinforcement conditions and contextual stimuli across a range of subjects, schedule arrangements, response topographies, reinforcers, and types of contextual changes. We make several recommendations for future research based on our findings from this nascent and clinically relevant subdomain of the relapse literature.

Geometry for low-inertia aerosol capture: Lessons from fog-basking beetles.

Water in the form of windborne fog droplets supports life in many coastal arid regions, where natural selection has driven nontrivial physical adaptation toward its separation and collection. For two species of Namib desert beetle whose body geometry makes for a poor filter, subtle modifications in shape and texture have been previously associated with improved performance by facilitating water drainage from its collecting surface. However, little is known about the relevance of these modifications to the flow physics that underlies droplets' impaction in the first place. We find, through coupled experiments and simulations, that such alterations can produce large relative gains in water collection by encouraging droplets to "slip" toward targets at the millimetric scale, and by disrupting boundary and lubrication layer effects at the microscopic scale. Our results offer a lesson in biological fog collection and design principles for controlling particle separation beyond the specific case of fog-basking beetles.

A transcription factor atlas of stem cell fate in planarians.

Whole-body regeneration requires the ability to produce the full repertoire of adult cell types. The planarian Schmidtea mediterranea contains over 125 cell types, which can be regenerated from a stem cell population called neoblasts. Neoblast fate choice can be regulated by the expression of fate-specific transcription factors (FSTFs). How fate choices are made and distributed across neoblasts versus their post-mitotic progeny remains unclear. We used single-cell RNA sequencing to systematically map fate choices made in S/G2/M neoblasts and, separately, in their post-mitotic progeny that serve as progenitors for all adult cell types. We defined transcription factor expression signatures associated with all detected fates, identifying numerous new progenitor classes and FSTFs that regulate them. Our work generates an atlas of stem cell fates with associated transcription factor signatures for most cell types in a complete adult organism.

Management of a Growth Hormone-Secreting Pituitary Macroadenoma Associated With Idiopathic Intracranial Hypertension and an Empty Sella.

Idiopathic intracranial hypertension (IIH) is a -condition associated with elevated intracranial pressure (ICP) and frequently presents with headaches, papilledema, and visual loss. Rarely, IIH has been reported in association with acromegaly. Although removal of the tumor may reverse this process, elevated ICP, especially in the setting of an otherwise empty sella, may result in a cerebrospinal fluid (CSF) leak that is exceedingly difficult to manage. We present the first case of a patient with a functional pituitary adenoma causing acromegaly associated with IIH and an otherwise empty sella and discuss our management paradigm for this rare condition.

Transradial Access Failures During Neuroangiography for Patients With Moyamoya.

BACKGROUND: Despite studies continuing to demonstrate the utility of transradial access (TRA) in neuroangiography, minimal data exist regarding predictors of TRA failure. Furthermore, although many patients with moyamoya disease/syndrome will require life-long angiographic evaluation, even less has been reported on the usage of TRA in this population. OBJECTIVE: To perform a matched analysis at our high-volume moyamoya center to determine predictors of TRA failure in these patients. METHODS: A total of 636 patients undergoing TRA for neuroangiography were identified from 2018 to 2020. Demographic and angiographic characteristics including radial artery spasm (RAS), radial anomalies, and access site conversion were compared between patients with moyamoya and the rest of the cohort. A 4:1 matched analysis, based on age and sex, was also performed to eliminate confounding variables. RESULTS: Patients with moyamoya were younger (40 vs 57 years, P < .0001), had smaller radial diameters (1.9 vs 2.6 mm, P < .0001), more commonly had a high brachial bifurcation (25.9% vs 8.5%, P = .008), more frequently experienced clinically significant RAS (40% vs 8.4%, P < .0001), and more often required access site conversion (26.7% vs 7.8%, P = .002). Increasing age was associated with less TRA failures in patients with moyamoya (odds ratio = 0.918) but more failures in the rest of the cohort (odds ratio = 1.034). In the matched analysis, patients with moyamoya continued to experience more radial anomalies, RAS, and access site conversions. CONCLUSION: Patients with moyamoya, when controlling for age and sex, have higher rates of TRA failure during neuroangiography. Increasing age in Moyamoya is inversely correlated with TRA failures suggesting that younger patients with moyamoya are at higher risk of extracranial arteriopathy.

Evaluating Predictors of Successful Postoperative Day 1 Discharge Following Posterior Fossa Tumor Resection.

BACKGROUND: Current trends in surgical neuro-oncology show that early discharges are safe and feasible with shorter lengths of stay (LOS) and fewer thromboembolic complications, fewer hospital-acquired infections, reduced costs, and greater patient satisfaction. Traditionally, infratentorial tumor resections have been associated with longer LOS and limited data exist evaluating predictors of early discharge in these patients. The objective was to assess patients undergoing posterior fossa craniotomies for tumor resection and identify variables associated with postoperative day 1 (POD1) discharge. METHODS: A retrospective review of posterior fossa craniotomies for tumor resection at our institution was performed from 2011 to 2020. Laser ablations, nontumoral pathologies, and biopsies were excluded. Demographic, clinical, surgical, and postoperative data were collected. RESULTS: One hundred and seventy-three patients were identified and 25 (14.5%) were discharged on POD1. Median length of stay (LOS) was 6 days. The POD1 discharges had significantly better preoperative Karnofsky performance scores (P < 0.001) and modified Rankin scores (P = 0.002) and more frequently presented electively (P = 0.006) and without preoperative neurologic deficits (P = 0.021). No statistically significant difference in 30-day readmissions and rates of PE, UTI, and DVT was found. Univariate logistic regression identified better preoperative functional status, elective admission, and lack of preoperative hydrocephalus as predictors of POD1 discharge, however only the latter remained significant in the multivariable model (P = 0.001). CONCLUSIONS: Discharging patients on POD1 is feasible following posterior fossa tumor resection in a select group of patients. Although we found that the only independent predictor for a longer LOS was preoperative hydrocephalus, larger, prospective studies are needed to confirm these findings.

Iatrogenic radial arteriovenous fistula closure via intraluminal compression in a patient with fibromuscular dysplasia.

Fibromuscular dysplasia (FMD) is an arteriopathy of medium-sized vessels causing pathological arterial wall fragility. However, only minimal data exist on evaluating the risk of transradial access (TRA) in these patients. We describe the case of a woman in her 70s who underwent left middle meningeal artery embolisation for an acute-on-chronic subdural haematoma via right TRA. Radial angiography demonstrated significant FMD throughout the entire right upper extremity. To prevent radial spasm, a 23 cm sheath was placed without difficulty. However, follow-up angiography demonstrated the presence of a new radial arteriovenous fistula (AVF) just distal to the brachial bifurcation. Since no forearm haematoma or limb ischaemia developed, the procedure was continued transradially. After embolisation, the guide catheter was removed and follow-up angiography demonstrated resolution of the fistula. This case illustrates that, in the absence of concerning clinical signs, compression from the guide catheter alone may facilitate thrombosis of an acutely identified iatrogenic radial AVF.

Countercontrol: A Relational Frame Theory (RFT) Account and Revival of a 70-Year-Old Skinnerian Term.

Countercontrol is a Skinnerian operant concept that posits that an individual's attempts to exert control over another person's behavior may evoke a countercontrolling response from the person being controlled that functions to avoid or escape the potentially aversive conditions generated by the controller. Despite Skinner's historical concerns regarding the detrimental effects of countercontrol in terms of hindering optimal societal growth and cultural evolution, the concept has not been widely applied within behavior analysis. Drawing from recent developments in rule-governed behavior and relational frame theory, this article seeks to explicate countercontrol from a contemporary behavior analytic perspective and presents several modern-day societal applications. In particular, a relational frame theory account of rule-governed behavior is used as a framework to elucidate the behavioral processes by which rule-following occurs (or fails to occur) in the context of countercontrol. Implications of a renewed focus on countercontrol for understanding pressing societal issues are also discussed.