Expression of Resistin, Chemerin, and Chemerin's Receptor in the Unstable Carotid Atherosclerotic Plaque.

Background and Purpose: Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability. Methods: Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR. Results: Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques (P<0.05), while no difference in ChemR23 mRNA expression was observed. In contrast, greater resistin staining intensity and percentage of cells stained positive were detected in unstable versus stable plaques (P<0.01). Similarly, chemerin and ChemR23 staining intensity and percentage of cells stained were positively associated with plaque instability (P<0.05). No strong sex-specific relationship was observed between adipokines and plaque instability. Conclusions: This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.

Automated Study Challenges the Existence of a Foundational Statistical-Learning Ability in Newborn Chicks.

What mechanisms underlie learning in newborn brains? Recently, researchers reported that newborn chicks use unsupervised statistical learning to encode the transitional probabilities (TPs) of shapes in a sequence, suggesting that TP-based statistical learning can be present in newborn brains. Using a preregistered design, we attempted to reproduce this finding with an automated method that eliminated experimenter bias and allowed more than 250 times more data to be collected per chick. With precise measurements of each chick's behavior, we were able to perform individual-level analyses and substantially reduce measurement error for the group-level analyses. We found no evidence that newborn chicks encode the TPs between sequentially presented shapes. None of the chicks showed evidence for this ability. Conversely, we obtained strong evidence that newborn chicks encode the shapes of individual objects, showing that this automated method can produce robust results. These findings challenge the claim that TP-based statistical learning is present in newborn brains.

Using automated controlled rearing to explore the origins of object permanence.

What are the origins of object permanence? Despite widespread interest in this question, methodological barriers have prevented detailed analysis of how experience shapes the development of object permanence in newborn organisms. Here, we introduce an automated controlled-rearing method for studying the emergence of object permanence in strictly controlled virtual environments. We used newborn chicks as an animal model and recorded their behavior continuously (24/7) from the onset of vision. Across four experiments, we found that object permanence can develop rapidly, within the first few days of life. This ability developed even when chicks were reared in impoverished visual environments containing no object occlusion events. Object permanence failed to develop, however, when chicks were reared in environments containing temporally non-smooth objects (objects moving on discontinuous spatiotemporal paths). These results suggest that experience with temporally smooth objects facilitates the development of object permanence, confirming a key prediction of temporal learning models in computational neuroscience.

Carotid Endarterectomy Outcomes in the Elderly: A Canadian Institutional Experience.

BACKGROUND: Carotid endarterectomy (CEA) is a well-established surgical intervention for stroke prevention in patients with carotid stenosis of all ages. However, the decision to proceed to operate in the elderly involves a more complicated risk-benefit assessment due in part to increased comorbidities and reduced life expectancy. Some studies suggest that CEA is more risky in the elderly with worse outcomes, whereas others have found no difference. Our objective was to evaluate and compare outcomes of CEA between elderly and younger patients at our institution. METHODS: All hospital charts were reviewed for consecutive patients undergoing CEA from the Jewish General Hospital and the Royal Victoria Hospital from October 2009 to December 2015. Primary outcomes were ipsilateral stroke, death, and restenosis at 30 days and 1 year. Secondary outcomes were cranial nerve injury, myocardial infarction (MI), hematoma, wound infection, cerebral hyperperfusion, and transient ischemic attacks within 30 days. Primary and secondary outcomes were compared between patients aged ≥80 years and <80 years. RESULTS: A total of 361 patients were included in this study with a mean age of 70.2 ± 9.5 years (n = 247 [68.4%] male and n = 272 [75.8%] symptomatic). Elderly patients were more often symptomatic (93.8% vs. 71.6%, P < 0.0001) and had an increased length of stay (2.8 ± 5.3 vs. 1.6 ± 1.8, P = 0.001). There was no statistically significant difference in primary outcomes between patients aged <80 years and ≥80 years, including 30-day stroke (1.7% vs. 0%), death (no deaths in either group), restenosis (8.8% vs. 12.3%), 1-year stroke (1.7% vs. 0%), death (0.7% vs. 0%), or restenosis (14.9% vs. 13.8%). However, elderly patients had significantly increased MI risk postoperatively (4.6% vs. 0.7%, P = 0.01). Other complications, including cranial nerve injury (3.7% in <80 years vs. 4.6% in the elderly group), were similar between the groups. CONCLUSIONS: We found that CEA in the elderly does not have an increased risk of stroke or death up to one year postoperatively. However, the postoperative length of stay is increased and complicated by significantly more MIs, which should weigh into the decision of whether to perform CEA on an elderly patient.

Measuring the speed of newborn object recognition in controlled visual worlds.

How long does it take for a newborn to recognize an object? Adults can recognize objects rapidly, but measuring object recognition speed in newborns has not previously been possible. Here we introduce an automated controlled-rearing method for measuring the speed of newborn object recognition in controlled visual worlds. We raised newborn chicks (Gallus gallus) in strictly controlled environments that contained no objects other than a single virtual object, and then measured the speed at which the chicks could recognize that object from familiar and novel viewpoints. The chicks were able to recognize the object rapidly, at presentation rates of 125 ms per image. Further, recognition speed was equally fast whether the object was presented from familiar viewpoints or novel viewpoints (30° and 60° azimuth rotations). Thus, newborn chicks can recognize objects across novel viewpoints within a fraction of a second. These results demonstrate that newborns are capable of both rapid and invariant object recognition at the onset of vision.

Comparison of QSOFA score and SIRS criteria as screening mechanisms for emergency department sepsis.

OBJECTIVES: The Quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA) score has been shown to accurately predict mortality in septic patients and is part of recently proposed diagnostic criteria for sepsis. We sought to ascertain the sensitive of the score in diagnosing sepsis, as well as the diagnostic timeliness of the score when compared to traditional systemic inflammatory response syndrome (SIRS) criteria in a population of emergency department (ED) patients treated in the ED, admitted, and subsequently discharged with a diagnosis of sepsis. METHODS: Electronic health records of 200 patients who were treated for suspected sepsis in our ED and ultimately discharged from our hospital with a diagnosis of sepsis were randomly selected for review from a population of adult ED patients (N=1880). Data extracted included the presence of SIRS criteria and the qSOFA score as well as time required to meet said criteria. RESULTS: In this cohort, 94.5% met SIRS criteria while in the ED whereas only 58.3% met qSOFA. The mean time from arrival to SIRS documentation was 47.1min (95% CI: 36.5-57.8) compared to 84.0min (95% CI: 62.2-105.8) for qSOFA. The median ED "door" to positive SIRS criteria was 12min and 29min for qSOFA. CONCLUSIONS: Although qSOFA may be valuable in predicting sepsis-related mortality, it performed poorly as a screening tool for identifying sepsis in the ED. As the time to meet qSOFA criteria was significantly longer than for SIRS, relying on qSOFA alone may delay initiation of evidence-based interventions known to improve sepsis-related outcomes.

The development of newborn object recognition in fast and slow visual worlds.

Object recognition is central to perception and cognition. Yet relatively little is known about the environmental factors that cause invariant object recognition to emerge in the newborn brain. Is this ability a hardwired property of vision? Or does the development of invariant object recognition require experience with a particular kind of visual environment? Here, we used a high-throughput controlled-rearing method to examine whether newborn chicks (Gallus gallus) require visual experience with slowly changing objects to develop invariant object recognition abilities. When newborn chicks were raised with a slowly rotating virtual object, the chicks built invariant object representations that generalized across novel viewpoints and rotation speeds. In contrast, when newborn chicks were raised with a virtual object that rotated more quickly, the chicks built viewpoint-specific object representations that failed to generalize to novel viewpoints and rotation speeds. Moreover, there was a direct relationship between the speed of the object and the amount of invariance in the chick's object representation. Thus, visual experience with slowly changing objects plays a critical role in the development of invariant object recognition. These results indicate that invariant object recognition is not a hardwired property of vision, but is learned rapidly when newborns encounter a slowly changing visual world.

Enhanced learning of natural visual sequences in newborn chicks.

To what extent are newborn brains designed to operate over natural visual input? To address this question, we used a high-throughput controlled-rearing method to examine whether newborn chicks (Gallus gallus) show enhanced learning of natural visual sequences at the onset of vision. We took the same set of images and grouped them into either natural sequences (i.e., sequences showing different viewpoints of the same real-world object) or unnatural sequences (i.e., sequences showing different images of different real-world objects). When raised in virtual worlds containing natural sequences, newborn chicks developed the ability to recognize familiar images of objects. Conversely, when raised in virtual worlds containing unnatural sequences, newborn chicks' object recognition abilities were severely impaired. In fact, the majority of the chicks raised with the unnatural sequences failed to recognize familiar images of objects despite acquiring over 100 h of visual experience with those images. Thus, newborn chicks show enhanced learning of natural visual sequences at the onset of vision. These results indicate that newborn brains are designed to operate over natural visual input.

Digital Twin Studies for Reverse Engineering the Origins of Visual Intelligence.

What are the core learning algorithms in brains? Nativists propose that intelligence emerges from innate domain-specific knowledge systems, whereas empiricists propose that intelligence emerges from domain-general systems that learn domain-specific knowledge from experience. We address this debate by reviewing digital twin studies designed to reverse engineer the learning algorithms in newborn brains. In digital twin studies, newborn animals and artificial agents are raised in the same environments and tested with the same tasks, permitting direct comparison of their learning abilities. Supporting empiricism, digital twin studies show that domain-general algorithms learn animal-like object perception when trained on the first-person visual experiences of newborn animals. Supporting nativism, digital twin studies show that domain-general algorithms produce innate domain-specific knowledge when trained on prenatal experiences (retinal waves). We argue that learning across humans, animals, and machines can be explained by a universal principle, which we call space-time fitting. Space-time fitting explains both empiricist and nativist phenomena, providing a unified framework for understanding the origins of intelligence.

The Development of Object Recognition Requires Experience with the Surface Features of Objects.

What role does visual experience play in the development of object recognition? Prior controlled-rearing studies suggest that newborn animals require slow and smooth visual experiences to develop object recognition. Here, we examined whether the development of object recognition also requires experience with the surface features of objects. We raised newborn chicks in automated controlled-rearing chambers that contained a single virtual object, then tested their ability to recognize that object from familiar and novel viewpoints. When chicks were reared with an object that had surface features, the chicks developed view-invariant object recognition. In contrast, when chicks were reared with a line drawing of an object, the chicks failed to develop object recognition. The chicks reared with line drawings performed at chance level, despite acquiring over 100 h of visual experience with the object. These results indicate that the development of object recognition requires experience with the surface features of objects.

A Rare Case When Acromegaly Meets Cushing Syndrome.

Acromegaly is very uncommon, as is non-iatrogenic Cushing syndrome; we discuss a patient who was found to have both a pituitary adenoma causing acromegaly and a cortisol-producing adrenal adenoma causing Cushing syndrome within 1 year. She was a healthy, 44-year-old woman who presented with visual changes and was found to have bitemporal hemianopsia and a 3.3-cm pituitary mass along with central hypogonadism, central hypothyroidism, and suppressed adrenocorticotropin and discrepant cortisol. After transsphenoidal resection she had declining, but persistently elevated, insulin-like growth factor 1 (IGF-1), raising concern for persistent acromegaly. She also was experiencing several cushingoid symptoms and was found to have elevated salivary and urinary cortisol. An abdominal computed tomography scan showed a 3.1-cm adrenal adenoma, and she subsequently underwent adrenalectomy. Following adrenalectomy, her cortisol levels normalized, and her IGF-1, growth hormone, and oral glucose tolerance test showed substantial improvement consistent with previous reports linking hypercortisolism and elevated IGF-1 levels. Combinations of pituitary and adrenal disease are seen in a handful of genetic syndromes; however, her clinical presentation and genetics do not fit with known syndromes. This case describes two rare endocrine tumors in one patient and associated limitations of routine laboratory testing.

Ruthenium(II) dichloride complexes of chiral, tetradentate aminosulfoxide ligands: stereoisomerism and redox-induced linkage isomerism.

Ruthenium(II) dichloride complexes of two chiral tetradentate aminosulfoxide ligands, varying only in the N-N linker, were synthesized. With each ligand, two major isomers formed, and these were structurally assigned and characterized through a combination of NMR and UV-vis spectroscopies, X-ray crystallography, and density functional theory calculations. The cis-ß geometric isomer was formed by each ligand, whereas the trans and cis-α geometric isomers were significant components for one ligand only. Cyclic voltammetry studies show that only the cis-ß isomers undergo linkage isomerism upon oxidation to ruthenium(III), whereas the trans and cis-α isomers show simple reversible redox couples.

Failure to learn from repeated mistakes: persistent decision-making impairment as measured by the iowa gambling task in patients with ventromedial prefrontal cortex lesions.

Although frontal patients show impaired decision-making on the Iowa Gambling Task (IGT), there has been no follow-up study to date to determine whether there is recovery of function over time. We examined neurological participants' performance on repeated administrations of the IGT over the course of 6 years. We found that, while non-neurological participants showed considerable improvement due to practice effects on the IGT, patients with ventromedial prefrontal cortex (VMPFC) damage persisted in showing impaired performance on each retest. These results validate the clinical observations that VMPFC dysfunction does not appear to be subject to autonomous recovery over time in real-life. (JINS, 2012, 18, 1-4).

Navigating the Debate on Managing Large (≥4 cm) Thyroid Nodules.

Purpose: Discordant practice guidelines for managing large thyroid nodules may result in unnecessary surgeries and costs. Recent data suggest similar false-negative rates in fine needle aspiration (FNA) biopsies between small (<4 cm) and large (≥4 cm) nodules, indicating that monitoring rather than surgery may be appropriate for large biopsy-negative nodules. We investigated the management of thyroid nodules ≥4 cm to determine the proportion of surgeries not necessary for diagnostic purposes and examined for potential predictors. Methods: This was a retrospective cohort study of patients who received a FNA of nodule(s) ≥4 cm between 11/1/2014 and 10/31/2019 at the University of Vermont Medical Center. A surgery was considered unnecessary if the FNA result was benign in the absence of any of the following: compressive symptoms, family history of thyroid cancer in a first degree relative, history of neck irradiation, toxic nodule or toxic multinodular goiter, or substernal extension. Data were analyzed with Wilcoxon rank sum tests, chi square, or Fisher's exact tests. Results: 177 patients had a ≥4 cm nodule during the timeframe and half (54.2%) had surgery. Patients who underwent surgery were significantly younger (51.5 years vs. 62 years; P < 0.001), more likely to report obstructive symptoms (34.4% vs. 12.1%; P < 0.001) and had a larger nodule size (5.0 cm vs. 4.7 cm; P=0.26). Forty-one patients with benign (Bethesda II) FNA results had surgery, all with negative surgical pathology. Thirteen percentage (23/177) of surgeries were potentially not necessary for diagnostic purposes. Conclusion: Approximately half of our patients with ≥4 cm nodules had surgery, with 13% having surgery not necessary for diagnostic purposes revealing opportunities for improving care and costs.

Care of the intubated emergency department patient.

BACKGROUND: Emergency physicians perform tracheal intubation and initiate mechanical ventilation for critically ill patients on a daily basis. With the current national challenges of intensive care unit bed availability, intubated patients now often remain in the emergency department (ED) for exceedingly long periods of time. As a result, care of the intubated patient falls to the emergency physician (EP). Given the potential for significant morbidity and mortality, it is crucial for the EP to possess the most current, up-to-date information pertaining to the care of intubated patients. DISCUSSION: This article discusses critical aspects in the ED management of intubated and mechanically ventilated patients. Specifically, emphasis is placed on providing adequate sedation and analgesia, limiting the use of neuromuscular blocking agents, correctly setting and adjusting the mechanical ventilator, utilizing appropriate monitoring modalities, and providing key supportive measures. Despite these measures, inevitably, some patients deteriorate while receiving mechanical ventilation. The article concludes with a discussion outlining a step-wise approach to evaluating the intubated patient who develops respiratory distress or circulatory compromise. With this information, the EP can more effectively care for ventilated patients while minimizing morbidity, and ultimately, improving outcome. CONCLUSION: Essential components of the care of intubated ED patients includes administering adequate sedative and analgesic medications, using lung-protective ventilator settings with attention to minimizing ventilator-induced lung injury, elevating the head of the bed in the absence of contraindications, early placement of an orogastric tube, and providing prophylaxis for stress-related mucosal injury and deep venous thrombosis when indicated.

One-shot object parsing in newborn chicks.

Controlled-rearing studies provide the unique opportunity to examine which psychological mechanisms are present at birth and which mechanisms emerge from experience. Here we show that one core component of visual perception-the ability to parse objects from backgrounds-is present when newborn animals see their first object. We reared newborn chicks in strictly controlled environments containing a single object on a single background, then tested the chicks' object parsing and recognition abilities. We found that chicks can parse objects from natural backgrounds at the onset of vision, allowing chicks to recognize objects equally well across familiar and novel backgrounds. We also found that the development of object parsing requires motion cues, akin to the development of object parsing in human infants and newly sighted blind patients. These results demonstrate that newborn brains are capable of "one-shot object parsing" and show that motion cues scaffold object perception from the earliest stages of learning. We conclude that prenatal developmental programs build brain architectures with an object-based inductive bias, allowing animals to solve object perception tasks immediately without extensive experience with objects. We discuss the implications of this finding for developmental psychology, computational neuroscience, and artificial intelligence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Risk of COVID-19 Related Hospitalsation, Intensive Care Unit Admission and Mortality in People With Underlying Asthma or COPD: A Systematic Review and Meta-Analysis.

Background: Several underlying diseases have been associated with unfavorable COVID-19 related outcomes including asthma and Chronic Obstructive Pulmonary Disease (COPD), however few studies have reported risks that are adjusted for confounding variables. This study aimed to examine the adjusted risk of COVID-19 related hospitalsation, intensive care unit (ICU) admission, and mortality in patients with vs. without asthma or COPD. Methods: A systematic review of major databases was undertaken for studies published between 1/12/2019 and 19/4/2021. Studies reporting the adjusted (for one or more confounder) risks of either hospitalsation, ICU admission, or mortality in asthmatics or COPD patients (control group = no asthma or no COPD) were identified. Risk of bias was determined via the QUIPS tool. A random effect meta-analysis was undertaken. Findings: 37 studies were eligible for analysis, with a total of 1,678,992 participants. The pooled ORs of COVID-19 hospitalsation in subjects with asthma and COPD was 0.91 (95% CI 0.76-1.09) and 1.37 (95% CI 1.29-1.46), respectively. For ICU admission, OR in subjects with asthma and COPD was 0.89 (95% CI 0.74-1.07) and 1.22 (95% CI 1.04-1.42), respectively. For mortality, ORs were 0.88 (95% CI 0.77-1.01) and 1.25 (95% CI 1.08-1.34) for asthma and COPD, respectively. Further, the pooled risk of mortality as measured via Cox regression was 0.93 (95% CI 0.87-1.00) for asthma and 1.30 (95% CI 1.17-1.44) for COPD. All of these findings were of a moderate level of certainty. Interpretation: COPD was significantly associated with COVID-19 related hospital admission, ICU admission, and mortality. Asthma was not associated with negative COVID-19 related health outcomes. Individuals with COPD should take precautions to limit the risk of COVID-19 exposure to negate these potential outcomes. Limitations include differing population types and adjustment for differing cofounding variables. Practitioners should note these findings when dealing with patients with these comorbidities. Review Protocol Registration: https://www.crd.york.ac.uk/prospero/.

Distorting Face Representations in Newborn Brains.

What role does experience play in the development of face recognition? A growing body of evidence indicates that newborn brains need slowly changing visual experiences to develop accurate visual recognition abilities. All of the work supporting this "slowness constraint" on visual development comes from studies testing basic-level object recognition. Here, we present the results of controlled-rearing experiments that provide evidence for a slowness constraint on the development of face recognition, a prototypical subordinate-level object recognition task. We found that (1) newborn chicks can rapidly develop view-invariant face recognition and (2) the development of this ability relies on experience with slowly moving faces. When chicks were reared with quickly moving faces, they built distorted face representations that largely lacked invariance to viewpoint changes, effectively "breaking" their face recognition abilities. These results provide causal evidence that slowly changing visual experiences play a critical role in the development of face recognition, akin to basic-level object recognition. Thus, face recognition is not a hardwired property of vision but is learned rapidly as the visual system adapts to the temporal structure of the animal's visual environment.

One-shot learning of view-invariant object representations in newborn chicks.

Can newborn brains perform one-shot learning? To address this question, we reared newborn chicks in strictly controlled environments containing a single view of a single object, then tested their object recognition performance across 24 uniformly-spaced viewpoints. We found that chicks can build view-invariant object representations from a single view of an object: a case of one-shot learning in newborn brains. Chicks can also build the same view-invariant object representation from different views of an object, showing that newborn brains converge on common object representations from different sets of sensory inputs. Finally, by rearing chicks with larger numbers of object views, we found that chicks develop enhanced recognition for familiar views. These results illuminate the earliest stages of object recognition, revealing (1) powerful one-shot learning that builds invariant object representations from the first views of an object and (2) view-based learning that enriches object representations, producing enhanced recognition for familiar views.