Author Correction: Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as causative factors.

Correction to: Eur Rev Med Pharmacol Sci 2023; 27 (6 Suppl): 127-136-DOI: 10.26355/eurrev_202312_34697 After publication and following some post-publication concerns, the authors have applied the following corrections to the galley proof. -       The conflict of interest section has been amended as follows: J. Kaftalli and G. Marceddu are employees at MAGI EUREGIO. K. Donato is employee at MAGI EUREGIO and MAGISNAT. M. Bertelli is president of MAGI EUREGIO, MAGISNAT, and MAGI's LAB. G. Bonetti, K. Dhuli, A. Macchia, and P.E. Maltese are employees at MAGI's LAB. M. Bertelli, P.E. Maltese, K. Louise Herbst, Sa. Michelini, Se. Michelini, and P. Chiurazzi are patent inventors (US20220362260A1). M. Bertelli, P.E. Maltese, G. Marceddu are patent inventors (US20230173003A1). M. Bertelli, K. Dhuli and P.E. Maltese are patent inventors (WO2022079498A1). M. Bertelli, P.E. Maltese, Sa. Michelini, Se. Michelini, P. Chiurazzi, K. Louise Herbst, J. Kaftalli, K. Donato, and A. Bernini are patent applicants (Application Number 18/516,241). M. Bertelli, K. Donato, P. Chiurazzi, G. Marceddu, K. Dhuli, G. Bonetti and J. Kaftalli are patent applicants (Application Number: 18/466.879). M. Bertelli, G. Bonetti, G. Marceddu, K. Donato, K. Dhuli, J. Kaftalli, Sa. Michelini, and K. Louise Herbst are patent applicants (Application Number 63/495,155). The remaining authors have no conflict of interest to disclose. -       Figure 5 has been modified as follows to better distinguish outliers: -       The legend of Figure 5 has to be modified as follows: Relative expression of AKR1C1 and AKR1C3 in different groups (CTR = non affected controls, L = lipedema patients without overexpression of AKR1C2, L-over = Lipedema patients with overexpression of AKR1C2), showing that lipedema patients expressed AKR1C1 and AKR1C3 levels similar to the control group. Outliers are reported as black triangles. There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/34697.

The effect of age and sex on peak oxygen uptake during upper and lower body exercise: A systematic review.

BACKGROUND: Large scale population norms for peak oxygen uptake (VO2peak) during cycle ergometry (CE) have been published for men and women across a wide range of ages. Although upper body functional capacity has an important role in activities of daily living far less is known regarding the effect of age and sex on upper body functional capacity (i.e. arm crank ergometry; ACE). The aim of this review was to determine the effect of age and sex on VO2peak obtained during ACE and CE in the same participants. METHOD: The review was pre-registered with PROSEPERO (Ref: CRD42022349566). A database search using Academic Search Complete including CINAHL complete, CINHAL Ultimate, Medline, PubMed, SPORTDiscus was undertaken. RESULTS: The initial search yielded 460 articles which was reduced to 243 articles following removal of duplicates. Twenty-five articles were subsequently excluded based on title resulting in 218 articles considered for retrieval. Following review of the abstracts, 78 further articles were excluded leaving 140 to be assessed for eligibility. Eighty-five articles were subsequently excluded, resulting in 55 articles being included. The decrease in VO2peak with age during CE was consistent with previous studies. Decreases in VO2peak during ACE with age, although paralleling those of CE, appeared to be of greater functional importance. When changes in VO2peak were considered below the age of 50 years little change was observed for absolute VO2peak during ACE and CE. In contrast, relative VO2peak demonstrated decreases in VO2peak for both ACE and CE likely reflecting increases in body mass and body fat percentage with age. After 50 years of age absolute and relative VO2peak demonstrated more similar and subtle responses. Heterogeneity across studies for both absolute and relative VO2peak between ACE and CE was large. Although strict inclusion criteria were applied, the inter-individual variation in sample populations was likely the main source of heterogeneity. There was a considerable lack data sets available for ages above 40 years of age. CONCLUSIONS: These responses suggest that upper body VO2peak decreases in line with that of the lower body but, due to the lower peak values achieved during ACE, decreases in VO2peak may have more profound functional impact compared to that for the lower body. Using absolute and relative measures of VO2peak results in different age-related profiles when considered below 50 years of age. To further our understanding of whole body ageing more data is required for participants in mid and later life. The association between VO2peak and underlying physiological factors with age needs to be studied further, particularly in conjunction with activities of daily living and independent living.

The influence of fear of falling on the control of upright stance across the lifespan.

BACKGROUND: Standing at height, and subsequent changes in emotional state (e.g., fear of falling), lead to robust alterations in balance in adults. However, little is known about how height-induced postural threat affects balance performance in children. Children may lack the cognitive capability necessary to inhibit the processing of threat and fear-related stimuli, and as a result, may show more marked (and perhaps detrimental) changes in postural control compared to adults. This work explored the emotional and balance responses to standing at height in children, and compared responses to young and older adults. METHODS: Children (age: 9.7 ± 0.8 years, n = 38), young adults (age: 21.8 ± 4.0 years, n = 45) and older adults (age: 73.3 ± 5.0 years, n = 15) stood in bipedal stance in two conditions: at ground level and 80 cm above ground. Centre of pressure (COP) amplitude (RMS), frequency (MPF) and complexity (sample entropy) were calculated to infer postural performance and strategy. Emotional responses were quantified by assessing balance confidence, fear of falling and perceived instability. RESULTS: Young and older adults demonstrated a postural adaptation characterised by increased frequency and decreased amplitude of the COP, in conjunction with increased COP complexity (sample entropy). In contrast, children demonstrated opposite patterns of changes: they exhibited an increase in COP amplitude and decrease in both frequency and complexity when standing at height. SIGNIFICANCE: Children and adults adopted different postural control strategies when standing at height. Whilst young and older adults exhibited a potentially protective "stiffening" response to a height-induced threat, children demonstrated a potentially maladaptive and ineffective postural adaptation strategy. These observations expand upon existing postural threat related research in adults, providing important new insight into understanding how children respond to standing in a hazardous situation.

Precision medicine for psychotic disorders: objective assessment, risk prediction, and pharmacogenomics.

Psychosis occurs inside the brain, but may have external manifestations (peripheral molecular biomarkers, behaviors) that can be objectively and quantitatively measured. Blood biomarkers that track core psychotic manifestations such as hallucinations and delusions could provide a window into the biology of psychosis, as well as help with diagnosis and treatment. We endeavored to identify objective blood gene expression biomarkers for hallucinations and delusions, using a stepwise discovery, prioritization, validation, and testing in independent cohorts design. We were successful in identifying biomarkers that were predictive of high hallucinations and of high delusions states, and of future psychiatric hospitalizations related to them, more so when personalized by gender and diagnosis. Top biomarkers for hallucinations that survived discovery, prioritization, validation and testing include PPP3CB, DLG1, ENPP2, ZEB2, and RTN4. Top biomarkers for delusions include AUTS2, MACROD2, NR4A2, PDE4D, PDP1, and RORA. The top biological pathways uncovered by our work are glutamatergic synapse for hallucinations, as well as Rap1 signaling for delusions. Some of the biomarkers are targets of existing drugs, of potential utility in pharmacogenomics approaches (matching patients to medications, monitoring response to treatment). The top biomarkers gene expression signatures through bioinformatic analyses suggested a prioritization of existing medications such as clozapine and risperidone, as well as of lithium, fluoxetine, valproate, and the nutraceuticals omega-3 fatty acids and magnesium. Finally, we provide an example of how a personalized laboratory report for doctors would look. Overall, our work provides advances for the improved diagnosis and treatment for schizophrenia and other psychotic disorders.

Developing a Natural History Model for Duchenne Muscular Dystrophy.

BACKGROUND: The aim of this study was to pool multiple data sets to build a patient-centric, data-informed, natural history model (NHM) for Duchenne muscular dystrophy (DMD) to estimate disease trajectory across patient lifetime under current standard of care in future economic evaluations. The study was conducted as part of Project HERCULES, a multi-stakeholder collaboration to develop tools to support health technology assessments of new treatments for DMD. METHODS: Health states were informed by a review of NHMs for DMD and input from clinicians, patients and caregivers, and defined using common outcomes in clinical trials and real-world practice. The primary source informing the NHM was the Critical Path Institute Duchenne Regulatory Science Consortium (D-RSC) database. This was supplemented with expert input obtained via an elicitation exercise, and a systematic literature review and meta-analysis of mortality data. RESULTS: The NHM includes ambulatory, transfer and non-ambulatory phases, which capture loss of ambulation, ability to weight bear and upper body and respiratory function, respectively. The NHM estimates patients spend approximately 9.5 years in ambulatory states, 1.5 years in the transfer state and the remainder of their lives in non-ambulatory states. Median predicted survival is 34.8 years (95% CI 34.1-35.8). CONCLUSION: The model includes a detailed disease pathway for DMD, including the clinically and economically important transfer state. The NHM may be used to estimate the current trajectory of DMD in economic evaluations of new treatments, facilitating inclusion of a lifetime time horizon, and will help identify areas for further research.

Aldo-keto reductase 1C2 (AKR1C2) as the second gene associated to non-syndromic primary lipedema: investigating activating mutation or overexpression as causative factors.

OBJECTIVE: Lipedema is a debilitating chronic condition predominantly affecting women, characterized by the abnormal accumulation of fat in a symmetrical, bilateral pattern in the extremities, often coinciding with hormonal imbalances. PATIENTS AND METHODS: Despite the conjectured role of sex hormones in its etiology, a definitive link has remained elusive. This study explores the case of a patient possessing a mutation deletion within the C-terminal region of Aldo-keto reductases Member C2 (AKR1C2), Ser320PheTer2, that could lead to heightened enzyme activity. A cohort of 19 additional lipedema patients and 2 additional affected family members14 were enrolled in this study. The two additional affected family members are relatives of the patient with the AKR1C1 L213Q variant, which is included in the 19 cohorts and described in literature. RESULTS: Our investigation revealed that AKR1C2 was overexpressed, as quantified by qPCR, in 5 out of 21 (24%) lipedema patients who did not possess mutations in the AKR1C2 gene. Collectively, these findings implicate AKR1C2 in the pathogenesis of lipedema, substantiating its causative role. CONCLUSIONS: This study demonstrates that the activating mutation in the enzyme or its overexpression is a causative factor in the development of lipedema. Further exploration and replication in diverse populations will bolster our understanding of this significant connection.

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 2 - Biliopancreatic Diversion.

Obesity significantly increases the risk of developing metabolic and cardiovascular diseases. The most effective management tool for both obesity and type 2 diabetes (T2D) is bariatric/metabolic surgery. Delayed postprandial plasma triglyceride clearance contributes to the development of atherosclerosis in patients with T2D. Biliopancreatic diversion (BPD) was shown to be the most effective procedure in long-term T2D remission. However, the effect of BPD on postprandial metabolic profile has not been studied so far. In this pilot study, we therefore examined the changes in postprandial glucose, insulin, and triglyceride in women with severe obesity and T2D before surgery and then two and ten years after BPD. The studied cohort included 7 women (mean age at baseline=49.3±8.2 years) with severe obesity (mean BMI= 45.7±2.9 kg/m?) and T2D. A standardized liquid mixed-meal test was carried out in all subjects and the mean postprandial levels of plasma glucose, insulin, and triglyceride were analyzed by standard laboratory procedures. For statistical evaluation, ANOVA with Bonferroni multiple comparisons was used. Ten years after BPD not only a significant reduction of an average BMI (F=32.9, p<0.001) but also significant declines in mean postprandial plasma levels of glucose (F=155.3, p<0.001), insulin (F=69.8, p<0.001), and triglyceride (F=139.9, p<0.001) were demonstrated. The observed changes in postprandial metabolic profile may contribute to improved cardiometabolic health after bariatric surgery.

Flexible tape-drive target system for secondary high-intensity laser-driven sources.

We present the development of a flexible tape-drive target system to generate and control secondary high-intensity laser-plasma sources. Its adjustable design permits the generation of relativistic MeV particles and x rays at high-intensity (i.e., ≥1 × 1018 W cm-2) laser facilities, at high repetition rates (>1 Hz). The compact and robust structure shows good mechanical stability and a high target placement accuracy (<4 µm RMS). Its compact and flexible design allows for mounting in both the horizontal and vertical planes, which makes it practical for use in cluttered laser-plasma experimental setups. The design permits ∼170° of access on the laser-driver side and 120° of diagnostic access at the rear. A range of adapted apertures have been designed and tested to be easily implemented to the targetry system. The design and performance testing of the tape-drive system in the context of two experiments performed at the COMET laser facility at the Lawrence Livermore National Laboratory and at the Advanced Lasers and Extreme Photonics (ALEPH) facility at Colorado State University are discussed. Experimental data showing that the designed prototype is also able to both generate and focus high-intensity laser-driven protons at high repetition rates are also presented.

Postprandial Triglyceride, Glucose and Insulin Levels 10 Years After Bariatric Surgery in Women With Severe Obesity - A Pilot Study: Part 1 - Laparoscopic Greater Curvature Plication.

The long-term effects of bariatric surgery on postprandial profiles in patients with obesity and type 2 diabetes (T2D) have not yet been investigated. Therefore, this study examined postprandial profiles before laparoscopic greater curvature plication (LGCP), and then at 2 and 10 years after surgery.The studied cohort included 10 women (mean age= 54.4±5 years) with obesity (mean BMI= 42.5±7.8 kg/m?) and T2D who underwent LGCP. All subjects underwent a standardized liquid mixed-meal test. For statistical evaluation, ANOVA with Bonferroni multiple comparison was used. Mean postprandial levels were significantly decreased 2 years after surgery. Responses 10 years after the surgery also remained significantly lower than before surgery. Changes observed during the follow-up were significant: glucose: F=34.5, p<0.001; insulin: F=49.3, p<0.001; triglycerides F=9.2, p<0.001. The long-term favorable effects of bariatric surgery on cardiometabolic health may be partly mediated by reductions in postprandial glucose, insulin, and triglyceride levels.

The Endocannabinoid System and Its Relationship to Human Reproduction.

The endocannabinoid system is among the most important regulators of human reproduction. It already applies at the level of the sperm and the egg, plays an important role in the fertilization of the egg, its implantation, regulates the function of the placenta and participates in childbirth. The aim of this work is to summarize the knowledge accumulated so far and to show that the endocannabinoid system must be perfectly regulated in order to maintain a physiological pregnancy from implantation to delivery. Only an exceptional interplay of enzymes such as NAPE-PDL or FAAH, endogenous cannabinoids and cannabinoid receptors CB1 and CB2 can ensure the proper functioning of the reproductive organs and thus lead to delivery on time. Changes in the endocannabinoid system can lead to a number of pathological conditions, e.g., during blastocyst implantation, retardation of embryo development, impaired placental function or miscarriage. Soon, we can expect not only an understanding of all the regulatory events associated with the endocannabinoid system and other regulatory systems that participate in reproduction, but also several possibilities for pharmacotherapeutic interventions that can modify the formation, degradation and effect of endocannabinoids. It cannot be ruled out that some components of the endocannabinoid system could become a marker for monitoring pregnancy and childbirth.

The Endocannabinoid System - The Prediction of Spontaneous Preterm Birth in High-Risk Women: Protocol of a Study.

Spontaneous preterm birth (sPTB) is a major cause of perinatal morbidity and mortality, even in developed countries. Prediction of sPTB is therefore a valuable tool to reduce the associated risks. The current standard for the prediction of sPTB consists, in addition to anamnestic data, of previous sPTB and previous second trimester miscarriage, measurement of cervical length by transvaginal ultrasound (TVU CL) together with assessment of fetal fibronectin levels in cervicovaginal fluid. Other evaluation parameters, such as the level of endocannabinoids in the pregnant woman's blood, could increase the sensitivity of this management. Endocannabinoids (eCBs) are a part of the endocannabinoid system (ECS); out of them anandamide (arachidonoyl-ethanolamide, AEA), in particular, plays an important role in the regulation of pregnancy and childbirth. We present the protocol for an open, non-randomized study to evaluate concentrations of AEA and other endocannabinoids: 2 linoleoylglycerol (2-AG), 2 linoleoylglycerol (2-LG), 2 oleoylglycerol (2-OG), and 2 arachidonoyldopamine (2-ADOPA or also NADA) in the blood of pregnant women as potential predictors of sPTB. In a total of 230 women with a history of sPTB or miscarriage, eCBs levels between 22 and 28 weeks of gestation will be assessed from maternal blood, in addition to the standard procedure. The aim of the study is to determine the relationship between blood concentrations of the endocannabinoids tested and the risk of sPTB. The results of this study will describe the prognostic significance of maternal blood eCBs levels for sPTB, and could subsequently enable improved screening programs for early identification of sPTB.

AKR1C1 and hormone metabolism in lipedema pathogenesis: a computational biology approach.

OBJECTIVE: Lipedema is an autosomal dominant genetic disease that mainly affects women. It is characterized by excess deposition of subcutaneous adipose tissue, pain, and anxiety. The genetic and environmental etiology of lipedema is still largely unknown. Although considered a rare disease, this pathology has been suggested to be underdiagnosed or misdiagnosed as obesity or lymphedema. Steroid hormones seem to be involved in the pathogenesis of lipedema. Indeed, aldo-keto reductase family 1 member C1 (AKR1C1), a gene coding for a protein involved in steroid hormones metabolism, was the first proposed to be correlated with lipedema. PATIENTS AND METHODS: In this study, we employed a molecular dynamics approach to assess the pathogenicity of AKR1C1 genetic variants found in patients with lipedema. Moreover, we combined information theory and structural bioinformatics to identify AKR1C1 polymorphisms from the gnomAD database that could predispose to the development of lipedema. RESULTS: Three genetic variants in AKR1C1 found in patients with lipedema were disruptive to the protein's function. Furthermore, eight AKR1C1  variants found in the general population could predispose to the development of lipedema. CONCLUSIONS: The results of this study provide evidence that AKR1C1 may be a key gene in lipedema pathogenesis, and that common polymorphisms could predispose to lipedema development.

Effects of free versus restricted arm movements on postural control in normal and modified sensory conditions in young and older adults.

The purpose of this study was to explore the effects of arm movements on postural control when standing under different sensory conditions in healthy young and older adults. Fifteen young (mean ± SD age; 21.3 ± 4.2 years) and 15 older (mean ± SD age; 73.3 ± 5.0 years) adults completed the modified Romberg test, which uses four task manipulations (i.e. eyes open and eyes closed on a firm and foam surface) to compromise the fidelity of sensory feedback mechanisms. Each participant completed the tasks under two arm movement conditions: restricted and free arm movements. Centre of pressure (COP) range and frequency were calculated to characterise postural performance and strategy, respectively. Older adults showed greater COP range with restricted compared to free arm movements during all modified sensory conditions, with these effects most prominent in the medio-lateral (ML) plane (all p < .05, Cohen's d = 0.69-1.61). Compared to the free arm movement condition, there was an increase in ML displacement and frequency when arm movements were restricted during only the most challenging (i.e. vestibular dominant) task in young adults (all p < .05, d = 0.645-0.83). Finally, main age effects for the arm restriction cost (p < .05) indicates a greater reliance on an upper body strategy in older compared to young adults, independent of sensory availability/accuracy. These findings indicate that older adults compensate for the loss of accuracy in sensory input by increasing reliance on upper body movement strategies.

Deconstructing sex: Strategies for undoing binary thinking in neuroendocrinology and behavior.

The scientific community widely recognizes that "sex" is a complex category composed of multiple physiologies. Yet in practice, basic scientific research often treats "sex" as a single, internally consistent, and often binary variable. This practice occludes important physiological factors and processes, and thus limits the scientific value of our findings. In human-oriented biomedical research, the use of simplistic (and often binary) models of sex ignores the existence of intersex, trans, non-binary, and gender non-conforming people and contributes to a medical paradigm that neglects their needs and interests. More broadly, our collective reliance on these models legitimizes a false paradigm of human biology that undergirds harmful medical practices and anti-trans political movements. Herein, we continue the conversations begun at the SBN 2022 Symposium on Hormones and Trans Health, providing guiding questions to help scientists deconstruct and rethink the use of "sex" across the stages of the scientific method. We offer these as a step toward a scientific paradigm that more accurately recognizes and represents sexed physiologies as multiple, interacting, variable, and unbounded by gendered preconceptions. We hope this paper will serve as a useful resource for scientists who seek a new paradigm for researching and understanding sexed physiologies that improves our science, widens the applicability of our findings, and deters the misuse of our research against marginalized groups.

CT Perfusion Does Not Modify the Effect of Reperfusion in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment in the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing endovascular treatment, many patients still do poorly. We investigated whether CTP modifies the effect of near-complete reperfusion on clinical outcomes, ie, whether poor clinical outcomes despite near-complete reperfusion can be partly or fully explained by CTP findings. MATERIALS AND METHODS: Data are from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Admission CTP was processed using RAPID software, generating relative CBF and CBV volume maps at standard thresholds. CTP lesion volumes were compared in patients with-versus-without near-complete reperfusion. Associations between each CTP metric and clinical outcome (90-day mRS) were tested using multivariable logistic regression, adjusted for baseline imaging and clinical variables. Treatment-effect modification was assessed by introducing CTP lesion volume × reperfusion interaction terms in the models. RESULTS: CTP lesion volumes and reperfusion status were available in 410/1105 patients. CTP lesion volumes were overall larger in patients without near-complete reperfusion, albeit not always statistically significant. Increased CBF <34%, CBV <34%, CBV <38%, and CBV <42% lesion volumes were associated with worse clinical outcome (ordinal mRS) at 90 days. CTP core lesion volumes did not modify the treatment effect of near-complete recanalization on clinical outcome. CONCLUSIONS: CTP did not modify the effect of near-complete reperfusion on clinical outcomes. Thus, CTP cannot explain why some patients with near-complete reperfusion have poor clinical outcomes.

Pediatric head and neck manifestations associated with multiple endocrine neoplasia syndromes.

INTRODUCTION: Multiple endocrine neoplasia (MEN) syndromes are a group of hereditary cancer syndromes that can predispose children to endocrine neoplasms developing within the head and neck. OBJECTIVE: To examine the neoplastic manifestations of MEN type 1 (MEN1) and MEN type 2 (MEN2) in the pediatric head and neck. METHODS: Single-institution, retrospective review of pediatric MEN between 2005 and 2022. RESULTS: Fifty-three children were genetically confirmed with MEN (15 MEN1, 34 MEN2A, and 4 MEN2B), while three patients received clinical diagnoses of MEN1. The male to female ratio was essentially equal (1.15:1), and a documented family history of cancer was present in 89% (50/56). After multidisciplinary evaluation, a familial MEN diagnosis was confirmed in 91% (51/56). The mean ages of initial presentation and surgical intervention were 8.9 years (SD 5) and 9.8 years (SD 4.8), respectively. Although patients with MEN2 received surgery earlier than patients with MEN1 (8.7 vs 12.7 years), surgical patients with MEN2 in this cohort were older relative to current American Thyroid Association (ATA) guidelines primarily due to late presentation. Thyroid malignancies were identified in 36% (9/25) of thyroidectomy specimens (21 MEN2A, 4 MEN2B), with medullary thyroid carcinoma (MTC) present in five MEN2A patients and three MEN2B patients (89%), and papillary thyroid carcinoma (PTC) present in one MEN2A patient (11%). Nearly 90% (8/9) of thyroid malignancies were occult, with some occurring earlier than predicted by current guidelines (ATA-MOD and ATA-H). Central neck dissections were performed in 24% (2 MEN1, 2 MEN2A, and 4 MEN2B), with two MEN2B (50%) demonstrating cervical lymph node (LN) metastases. Additional histopathologic findings included C-cell hyperplasia in 57% (12/21) of MEN2A thyroidectomy patients. Of the eight MEN1 parathyroidectomy patients, four demonstrated parathyroid hyperplasia and four presented with parathyroid adenoma. CONCLUSION: Nearly 60% required head and neck procedures. While MEN1 guidelines were appropriate for our cohort, we identified patients with MEN2 that developed MTC earlier than expected based on current ATA guidelines, including children in categories considered lower risk. In conjunction with a multidisciplinary approach, pediatric head and neck surgeons should be aware of the potential need for earlier surgical intervention in the pediatric MEN2 population.

Testing image-velocimetry methods for turbulence diagnostics.

Two image-based velocity-inference techniques, cross-correlation time-delay estimation (CCTDE) and dynamic time warping (DTW), were tested. These techniques are conventionally used in the study of plasma dynamics, but they can be applied to any data where features propagate across the image field-of-view. Differences between the techniques were investigated, which showed that the shortcomings of each technique are complemented well by the strengths of the other. Thus, the techniques should be used in conjunction with each other for optimal velocimetry. For ease of use, an example workflow that applies the results in this paper to experimental measurements is provided for both techniques. The findings were based on a thorough analysis of the uncertainties for both techniques. Specifically, the accuracy and precision associated with inferred velocity fields were systematically tested using synthetic data. Novel findings are presented that strongly improve the performance of both techniques, some of which are as follows: CCTDE was able to operate accurately under most conditions with an inference frequency as short as 1 per 32 frames, as opposed to the typical 1 per ≥256 frames used in the literature; an underlying pattern in CCTDE accuracy depending on the magnitude of the underlying velocity was found; spurious velocities due to the barber pole illusion can now be predicted prior to CCTDE velocimetry through a simple analysis; DTW was more robust against the barber pole illusion than CCTDE; DTW performance with sheared flows was tested; DTW was able to reliably infer accurate flow fields from data with as low as 8 × 8 spatial channels; and however, if the flow direction was unknown prior to DTW analysis, DTW could not reliably infer any velocities.

Automated Segmentation of Intracranial Thrombus on NCCT and CTA in Patients with Acute Ischemic Stroke Using a Coarse-to-Fine Deep Learning Model.

BACKGROUND AND PURPOSE: Identifying the presence and extent of intracranial thrombi is crucial in selecting patients with acute ischemic stroke for treatment. This article aims to develop an automated approach to quantify thrombus on NCCT and CTA in patients with stroke. MATERIALS AND METHODS: A total of 499 patients with large-vessel occlusion from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial were included. All patients had thin-section NCCT and CTA images. Thrombi contoured manually were used as reference standard. A deep learning approach was developed to segment thrombi automatically. Of 499 patients, 263 and 66 patients were randomly selected to train and validate the deep learning model, respectively; the remaining 170 patients were independently used for testing. The deep learning model was quantitatively compared with the reference standard using the Dice coefficient and volumetric error. The proposed deep learning model was externally tested on 83 patients with and without large-vessel occlusion from another independent trial. RESULTS: The developed deep learning approach obtained a Dice coefficient of 70.7% (interquartile range, 58.0%-77.8%) in the internal cohort. The predicted thrombi length and volume were correlated with those of expert-contoured thrombi (r = 0.88 and 0.87, respectively; P < .001). When the derived deep learning model was applied to the external data set, the model obtained similar results in patients with large-vessel occlusion regarding the Dice coefficient (66.8%; interquartile range, 58.5%-74.6%), thrombus length (r = 0.73), and volume (r = 0.80). The model also obtained a sensitivity of 94.12% (32/34) and a specificity of 97.96% (48/49) in classifying large-vessel occlusion versus non-large-vessel occlusion. CONCLUSIONS: The proposed deep learning method can reliably detect and measure thrombi on NCCT and CTA in patients with acute ischemic stroke.

Effects of arm movement strategies on emotional state and balance control during height-induced postural threat in young adults.

BACKGROUND: It is firmly established that postural threat seems to lead to an increased reliance on an ankle control ('stiffening') strategy. However, little is known about how postural threat affects performance in challenging tasks that require the use of upper body postural control strategies for stability. It is logical to assume that in such conditions, being able to utilise an upper body strategy may reduce the reliance on such ankle stiffening strategy. RESEARCH QUESTION: The objective of this study was to determine how arm movement influences balance control during a challenging balance task performed under conditions of postural threat. METHODS: Thirty young adults (mean ± SD age; 22.0 ± 4.0 years) balanced in tandem stance whilst standing at both ground-level (no threat) and 0.8 m above ground (threat). In both conditions, participants performed the task under two different arm positions: restricted arm movements and free arm movements. Postural sway amplitude and frequency were calculated to infer postural stiffening response. Self-reported emotional responses were quantified by assessing balance confidence, fear of falling, perceived stability, and conscious balance processing. RESULTS: Independent of arm movements, postural threat evoked an increase in fear of falling and conscious balance processing, and reductions in balance confidence and perceived stability. These threat-related changes in emotional state were further amplified when arm movements were restricted. Whilst significant increases in sway frequency during threat were observed in both arm conditions, reductions in sway amplitude were only observed during the restricted arm movement condition. SIGNIFICANCE: We propose that these responses likely reflect a fear-related cautious strategy intended to reduce the postural destabilisation associated with individuals being unable to use their arms to counter any destabilisation, as would normally be the case in daily life.