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Given the health benefits of carotenoids, it is crucial to evaluate their levels in patients undergoing malabsorptive procedures like one anastomosis gastric bypass (OAGB). This study aimed to assess serum carotenoid levels before and 6 months following OAGB. Prospectively collected data from patients who underwent primary OAGB were analyzed. Data included anthropometrics, dietary intake assessments, and biochemical tests. Serum samples were analyzed for lipid profile and serum carotenoids, including lutein, zeaxanthin, α-carotene, β-carotene, phytofluene, ζ-carotene, and lycopene. Data from 27 patients (median age 47.0 years and 55.6% female) were available before and 6 months post-OAGB. The median pre-surgical BMI was 39.5 kg/m 2 , and the median excess weight loss at 6 months post-surgery was 63.9%. Significant decreases in all carotenoid levels were observed over time ( p < 0.001 for all). A median relative decline of 65.1% in absolute total carotenoid levels and 12.7% in total cholesterol levels were found. No associations were observed between changes in clinical outcomes and carotenoid levels during the study period. This study reveals significant decreases in carotenoid levels within the first 6 months following OAGB. Nutritional intervention studies are needed to explore how incorporating carotenoid-rich foods affects post-surgery carotenoid levels and clinical outcomes.

As the global population ages, understanding of the effect of aging on visual perception is of growing importance. This study investigates age-related changes in adulthood along size perception through the lens of three visual illusions: the Ponzo, Ebbinghaus, and Height-width illusions. Utilizing the Bayesian conceptualization of the aging brain, which posits increased reliance on prior knowledge with age, we explored potential differences in the susceptibility to visual illusions across different age groups in adults (ages 20-85 years). To this end, we used the BTPI (Ben-Gurion University Test for Perceptual Illusions), an online validated battery of visual illusions developed in our lab. The findings revealed distinct patterns of age-related changes for each of the illusions, challenging the idea of a generalized increase in reliance on prior knowledge with age. Specifically, we observed a systematic reduction in susceptibility to the Ebbinghaus illusion with age, while susceptibility to the Height-width illusion increased with age. As for the Ponzo illusion, there were no significant changes with age. These results underscore the complexity of age-related changes in visual perception and converge with previous findings to support the idea that different visual illusions of size are mediated by distinct perceptual mechanisms., (© 2024. The Author(s).)

While a vast amount of research has focused on understanding the capacity limits of visual working memory (VWM), little is known about how VWM resources are employed in unforced behavior and how they correlate with individual capacity constraints. We present a novel, openly available, and easy-to-administer paradigm enabling participants to freely utilize their VWM capacity. Participants had to reconstruct an array of colored squares. In each trial, they were allowed to alternate between the memory array and the reconstruction screen as many times as they wished, each time choosing how many items to reconstruct. This approach allowed us to estimate the number of utilized items, as well as the accuracy of the reconstruction. In addition, VWM capacity was measured using a change detection task. In two experiments, we show that participants tend to under-utilize their VWM resources, performing well below their capacity limits. Surprisingly, while the extent to which participants utilized their VWM was highly reliable, it was uncorrelated with VWM capacity, suggesting that VWM utilization is limited due to strategic considerations rather than capacity limits., (© 2024. The Author(s).)

Current studies suggest that individuals estimate the value of their choices based on observed feedback. Here, we ask whether individuals also update the value of their unchosen actions, even when the associated feedback remains unknown. One hundred seventy-eight individuals completed a multi-armed bandit task, making choices to gain rewards. We found robust evidence suggesting latent value updating of unchosen actions based on the chosen action's outcome. Computational modeling results suggested that this effect is mainly explained by a value updating mechanism whereby individuals integrate the outcome history for choosing an option with that of rejecting the alternative. Properties of the deliberation (i.e., duration/difficulty) did not moderate the latent value updating of unchosen actions, suggesting that memory traces generated during deliberation might take a smaller role in this specific phenomenon than previously thought. We discuss the mechanisms facilitating credit assignment to unchosen actions and their implications for human decision-making.

Visual illusions provide a powerful tool for probing the mechanisms that underlie perception. While most previous studies of visual illusions focused on average group-level performance, less attention has been devoted to individual differences in susceptibility to illusions. Unlike in other perceptual domains, in which there are established, validated tools to measure individual differences, such tools are not yet available in the domain of visual illusions. Here, we describe the development and validation of the BTPI (Ben-Gurion University Test for Perceptual Illusions), a new online battery designed to measure susceptibility to the influence of three prominent size illusions: the Ebbinghaus, the Ponzo, and the height-width illusions. The BTPI also measures perceptual resolution, reflected by the just noticeable difference (JND), to detect size differences in the context of each illusion. In Experiment 1 (N = 143), we examined performance in typical self-paced tasks, whereas in Experiment 2 (N = 69), we employed a fixed presentation duration paradigm. High test-retest reliability scores were found for all illusions, with little evidence for intercorrelations between different illusions. In addition, lower perceptual resolution (larger JND) was associated with a larger susceptibility to the illusory effect. The computerized task battery and analysis codes are freely available online.

Goal-directed behavior relies on maintaining relevant goals in working memory (WM) and updating them when required. Computational modeling, behavioral, and neuroimaging work has previously identified the processes and brain regions involved in selecting, updating, and maintaining declarative information, such as letters and pictures. However, the neural substrates that underlie the analogous processes that operate on procedural information, namely, task goals, are currently unknown. Forty-three participants were therefore scanned with fMRI while performing a procedural version of the reference-back paradigm that allowed for the decomposition of WM updating processes into gate-opening, gate-closing, task switching, and task cue conflict components. Significant behavioral costs were observed for each of these components, with interactions indicating facilitation between gate-opening and task switching, and a modulation of cue conflict by gate state. In neural terms, opening the gate to procedural WM was associated with activity in medial pFC, posterior parietal cortex (PPC), the basal ganglia (BG), thalamus, and midbrain, but only when the task set needed to be updated. Closing the gate to procedural WM was associated with frontoparietal and BG activity specifically in conditions where conflicting task cues had to be ignored. Task switching was associated with activity in the medial pFC/ACC, PPC, and BG, whereas cue conflict was associated with PPC and BG activity during gate closing but was abolished when the gate was already closed. These results are discussed in relation to declarative WM and to gating models of WM., (© 2023 Massachusetts Institute of Technology.)

Goal-directed behavior requires maintaining the relevant goal in working memory (WM) and using it to guide behavior. The contents of WM should be regulated, so only relevant goals, but not irrelevant ones, are maintained. Computational models suggest that a gate, which is closed by default, separates WM from perceptual input. Transient opening of the gate enables WM updating. Indeed, previous studies show that updating WM with relevant information is controlled, effortful, and slow. In contrast to the above, here we show that WM updating with goal information is faster and more accurate than not updating. A multiple-cue task-switching paradigm is introduced. Participants were presented with a sequence of task cues, followed by a single probe. They needed to respond to each cue using its corresponding key. The cues were presented in red or blue. When the probe appeared, participants had to judge it using the task cued by the most recent red (but not blue) cue. Accordingly, they had to update their WM when the cue appeared in red, but not when it was blue (the color mapping was counterbalanced in Experiment 2). In two experiments, we show that performance in update trials was faster and more accurate than in no-update trials, suggesting that updating, rather than not-updating, is the default mode of operation., (© 2022. The Psychonomic Society, Inc.)

This study aimed to describe nutritional and lifestyle parameters following one-anastomosis gastric bypass (OAGB). A multicenter study among OAGB patients across Israel ( n = 277) and Portugal ( n = 111) was performed. Patients were approached according to the time elapsed since surgery. An online survey with information regarding demographics, anthropometrics, and nutritional and lifestyle aspects was administered in both countries simultaneously. Respondents from Israel (pre-surgery age of 41.6 ± 11.0 years, 75.8% females) and Portugal (pre-surgery age of 45.6 ± 12.3 years, 79.3% females) reported changes in their appetite (≤94.0% and ≤94.6%), changes in their taste (≤51.0 and ≤51.4%), and intolerance to specific foods (i.e., red meat, pasta, bread, and rice). Bariatric surgery-related eating recommendations were generally followed well, but a trend toward lower adherence was evident in groups with longer time elapsed since surgery in both countries. Most respondents from Israel and Portugal reported participation in follow-up meetings with a surgeon (≤94.0% and 100%) and a dietitian (≤92.6% and ≤100%), while far fewer reported participation in any follow-up meeting with a psychologist/social worker (≤37.9% and ≤56.1%). Patients following OAGB might experience changes in appetite, taste, and intolerance to specific foods. Adherence to bariatric surgery-related eating recommendations is not always satisfying, especially in the longer term post-surgery.

Background: Reports of long-term (> 5-15-year) outcomes assessing the safety and efficacy of primary revisional laparoscopic sleeve gastrectomy (LSG) are few., Methods: Retrospective long-term comparisons of primary (pLSG) and revisional (rLSG) procedures were matched for gender, age ± 5 years, and body mass index (BMI) ± 5 kg/m 2 . Weight loss, associated medical condition status, and patient satisfaction were evaluated., Results: Between May 1, 2006, and December 31, 2016, 194 matched patients with severe obesity (mean BMI 44.1 ± 6.7 kg/m 2 ; age 44.2 ± 10.0 years, 67.0% female) underwent pLSG (n = 97) or rLSG (n = 97) and were followed for a mean 12.1 ± 1.5 vs 7.6 ± 2.1 years. Respective mean weight regain from nadir was 15.0 ± 14.4 kg vs 11.9 ± 12.2 kg. Respective percent mean total weight loss and excess weight loss were 20.9 ± 12.7% and 51.8 ± 33.1%, and 18.3 ± 12.8% and 43.4 ± 31.6% at last follow-up, with no significant difference between groups. Resolution of type 2 diabetes (HbA1 C  < 6.5%, off medications) was 23.1% vs 11.1%; hypertension 36.0% vs 16.0%; and hyperlipidemia 37.1% vs 35.3%. Patients in the pLSG group were significantly more satisfied with LSG (59.8% vs 43.3%, p < 0.05) and more likely to choose the procedure again., Conclusions: There were no significant differences in long-term weight loss or associated medical condition outcomes in matched pLSG and rLSG patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Through 2018, three calcitonin gene-related peptide pathway-targeted monoclonal antibodies (CGRP mAbs) had received US Food and Drug Administration (FDA) approval for migraine prevention: erenumab, fremanezumab, and galcanezumab., Methods: This retrospective analysis evaluated adverse events (AEs) spontaneously reported to the FDA Adverse Event Reporting System (FAERS) safety surveillance database during the first 6 months post-approval of erenumab (May 2018 to November 2018), fremanezumab (September 2018 to March 2019), and galcanezumab (September 2018 to March 2019). Reporting rates (RR) per 1000 exposed patients were calculated from number of reported events (when product classified as "primary suspect") in each AE category and estimated number of treated patients based on de-identified prescription data (IQVIA database) and were ranked on the basis of frequency for each product., Results: RR per 1000 exposed patients for "migraine" (erenumab, 4.89; fremanezumab, 1.01; galcanezumab, 2.99), "headache" (3.32, 1.27, 3.07), and "drug ineffective" (3.68, 1.14, 1.69) were commonly reported for all three products, as were migraine-associated symptoms ("nausea": 2.94, 0.91, 1.09) and "injection-site" reactions ("pain": 2.94, 0.8, 4.9; "swelling": 0.56, 0.53, 1.25; "pruritus": 0.26, 0.63, 1.14; "erythema": 0.58, 0.71, 1.58). "Constipation" ranked second for erenumab (4.90) but did not make the top ten events for fremanezumab (0.46) or galcanezumab (0.76); cardiovascular events did not rank in the top ten AEs for any product. The frequency of serious outcomes was low, with ≤ 2% of AEs categorized as serious across the CGRP mAbs., Conclusion: These results aid in supporting the safety profile of CGRP mAbs in the real-world setting and may provide clinicians and patients with additional insight when considering migraine preventive treatments., (© 2022. The Author(s).)

It is commonly held that attending to items facilitates their encoding into working memory (WM). This implies that the content of WM is updated with new input as a consequence of directing attention to it. On the other hand, abundant research shows that WM updating is rather slow and effortful, suggesting that shielding WM representation against incoming input, rather than its updating, is the default. To resolve this discrepancy, we suggest that while updating item-to-context associations is costly, updating a single item is fast and is automatically carried out as part of directing attention to items, for example as part of response selection. Participants performed a choice-RT task, in which stimuli appeared within frames, and needed to update their WM with the most recent red item that appeared in each frame. The need for updating was manipulated, so that some trials required updating and others did not. Experiment 1 (N = 25) showed that updating was slower than not updating with a set-size of two items, that required item-context binding, but faster when the set-size only involved one item. Experiment 2 (N = 28) replicated this finding. Experiment 3 (N = 20) showed that the slower no-update RTs are due to the removal of erroneously updated information. In contrast to previous findings, these results suggest that updating can be effortless and obligatory., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Background: Long-term laparoscopic sleeve gastrectomy (LSG) outcomes in patients with obesity are scarce. We aimed to examine the outcomes and subjective experience of patients who underwent primary LSG with long-term follow-up., Methods: The study is a retrospective observational analysis of patients who underwent primary LSG in a single center with 5-15 years of follow-up. Patients' hospital chart data supplemented by a detailed follow-up online questionnaire and telephone interview were evaluated., Results: The study sample included 578 patients (67.0% female) with 8.8 ± 2.5 years of mean follow-up, with a response rate to the survey of 82.8%. Mean baseline age and body mass index (BMI) were 41.9 ± 10.6 years and 42.5 ± 5.5 kg/m 2 , respectively. BMI at nadir was 27.5 ± 4.9 kg/m 2 , corresponding to a mean excess weight loss (EWL) of 86.9 ± 22.8%. Proportion of patients with weight regain, defined as nadir ≥ 50.0% EWL, but at follow-up < 50.0% EWL, was 34.6% (n = 200) and the mean weight regain from nadir was 13.3 ± 11.1 kg. BMI and EWL at follow-up were 32.6 ± 6.4 kg/m 2 and 58.9 ± 30.1%, respectively. The main reasons for weight regain given by patients included "not following guidelines," "lack of exercise," "subjective impression of being able to ingest larger quantities of food in a meal," and "not meeting with the dietitian." Resolution of obesity-related conditions at follow-up was reported for hypertension (51.7%), dyslipidemia (58.1%) and type 2 diabetes (72.2%). The majority of patients (62.3%) reported satisfaction with LSG., Conclusions: In the long term, primary LSG was associated with satisfactory weight and health outcomes. However, weight regain was notable., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: To describe gastrointestinal-related side-effects reported following the One Anastomosis Gastric Bypass (OAGB)., Methods: A multicenter study among OAGB patients across Israel ( n  = 277) and Portugal ( n  = 111) who were recruited to the study based on time elapsed since surgery was performed. An online survey with information on demographics, anthropometrics, medical conditions, and gastrointestinal outcomes was administered in both countries simultaneously., Results: Respondents from Israel (pre-surgery age of 41.6 ± 11.0 years, 75.8% females) and Portugal (pre-surgery age of 45.6 ± 12.3 years, 79.3% females) presented mean excess weight loss of 51.0 ± 19.9 and 62.4 ± 26.5%, 89.0 ± 22.0 and 86.2 ± 21.4%, and 89.9 ± 23.6 and 98.2 ± 20.9% ( P  < 0.001 for both countries), at 1-6 months, 6-12 months, and 1-5 years post-surgery, respectively. Median Gastrointestinal Symptom Rating Scale score was similar between time elapsed since surgery groups among respondents from Israel and Portugal (≤1.97 and ≤2.12). A notable proportion of respondents from Israel and Portugal at all time points reported 1-3 bowel movements per day (≤62.8 and ≤87.6%), Bristol stool scale categories which represent diarrhea-like stools (≤51.9 and ≤56.3%), having discomfort due to flatulence (≤79.4 and ≤90.2%), and mild to severe dyspepsia symptoms (≤50.5 and ≤73.0%)., Conclusions: A notable proportion of OAGB patients might experience certain gastrointestinal symptoms postoperatively, including flatulence, dyspepsia, and diarrhea-like stools.

Calcitonin gene-related peptide (CGRP) pathway-targeted treatments have been shown to be efficacious in the prevention of episodic and chronic migraine. Currently approved therapies include monoclonal antibodies (mAbs) that target CGRP (eptinezumab, fremanezumab, and galcanezumab) and the CGRP receptor (erenumab), and small molecule CGRP receptor antagonists (atogepant and rimegepant). While CGRP pathway-targeted treatments are generally well-tolerated, in a review article by Holzer and Holzer-Petsche published in the January 2022 issue of Frontiers in Physiology the authors discussed the role of the CGRP pathway in gastrointestinal physiology, with a specific focus on constipation associated with the use of CGRP pathway-targeted treatments. The authors state that real-world surveys have shown constipation to be a "major adverse event" reported in "more than 50% of patients treated with erenumab, fremanezumab or galcanezumab." As described in the current commentary, the limited data from the cited references in the review article by Holzer and Holzer-Petsche do not support that statement., Competing Interests: KM and JS were employed by the company of Teva Pharmaceuticals. MO, VRC, LK, and XN were employed by the company of Teva Branded Pharmaceutical Products R&D, Inc. YK was employed by the company of Teva Pharmaceutical Industries Ltd. KC was formerly employed by the company of Teva Branded Pharmaceutical Products R&D, Inc. Medical writing and editorial support were provided by Tamara Stevenson, PhD, of Lumanity Communications, Inc., and were funded by Teva Pharmaceutical Industries., (Copyright © 2022 Mackenzie, Ortega, Kessler, Campos, Krasenbaum, Carr, Ning and Stratton.)

Background: Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, has demonstrated efficacy for preventive treatment of episodic and chronic migraine. Since calcitonin gene-related peptide is expressed within the cardio- and cerebrovascular system and may have cardioprotective effects, it is critical to understand the cardio- and cerebrovascular safety of fremanezumab., Methods: This was a pooled analysis of three randomized, double-blind, placebo-controlled, phase 3, 12-week trials in which patients with episodic migraine or chronic migraine received quarterly fremanezumab, monthly fremanezumab, or placebo. Incidences of overall and serious adverse events were analyzed. Cardio- and cerebrovascular adverse events (CVAEs) were analyzed in subgroups stratified by cardio- and cerebrovascular medical history, cardiovascular risk factors (CVRFs), and use of cardio- and cerebrovascular medications or triptans., Results: Two thousand, eight hundred and forty-two patients were included in the study. Overall (58-65%) and serious adverse events (<1-2%) occurred in similar proportions across fremanezumab and placebo groups. CVAEs were infrequent, regardless of cardio- and cerebrovascular medical history (2-6%). CVAEs occurred in low, similar proportions of patients with CVRFs and those using cardio- and cerebrovascular medications or triptans. No cardio- and cerebrovascular signals were identified., Conclusion: Fremanezumab demonstrated a favorable overall and cardio- and cerebrovascular safety profile in more than 2800 patients with episodic migraine or chronic migraine, regardless of cardio- and cerebrovascular medical history, CVRFs, or medication use. Trial Registrations: NCT02629861 (HALO EM, https://clinicaltrials.gov/ct2/show/NCT02629861), NCT02621931 (HALO CM, https://clinicaltrials.gov/ct2/show/NCT02621931), NCT03308968 (FOCUS, https://clinicaltrials.gov/ct2/ show/NCT03308968).

One anastomosis gastric bypass (OAGB) is an emerging bariatric procedure, yet data on its effect on the gastrointestinal tract are lacking. This study sought to evaluate the incidence of small-intestinal bacterial overgrowth (SIBO) following OAGB; explore its effect on nutritional, gastrointestinal, and weight outcomes; and assess post-OABG occurrence of pancreatic exocrine insufficiency (PEI) and altered gut microbiota composition. A prospective pilot cohort study of patients who underwent primary-OAGB surgery is here reported. The pre-surgical and 6-months-post-surgery measurements included anthropometrics, glucose breath-tests, biochemical tests, gastrointestinal symptoms, quality-of-life, dietary intake, and fecal sample collection. Thirty-two patients (50% females, 44.5 ± 12.3 years) participated in this study, and 29 attended the 6-month follow-up visit. The mean excess weight loss at 6 months post-OAGB was 67.8 ± 21.2%. The glucose breath-test was negative in all pre-surgery and positive in 37.0% at 6 months ( p = 0.004). Positive glucose breath-test was associated with lower reported dietary intake and folate levels and higher vitamin A deficiency rates ( p ≤ 0.036). Fecal elastase-1 test (FE1) was negative for all pre-surgery and positive in 26.1% at 6 months ( p = 0.500). Both alpha and beta diversity decreased at 6 months post-surgery compared to pre-surgery ( p ≤ 0.026). Relatively high incidences of SIBO and PEI were observed at 6 months post-OAGB, which may explain some gastrointestinal symptoms and nutritional deficiencies.

Introduction: Weight bias, stigma, and discrimination are common among healthcare professionals. We aimed to evaluate whether an online education module affects weight bias and knowledge about obesity in a private medical center setting., Methods: An open-label randomized controlled trial was conducted among all employees of a chain of private medical centers in Israel (n = 3,290). Employees who confirmed their consent to participate in the study were randomized into intervention or control (i.e., "no intervention") arms. The study intervention was an online 15-min educational module that included obesity, weight bias, stigma, and discrimination information. Questionnaires on Anti-Fat Attitudes (AFA), fat-phobia scale (F-scale), and beliefs about the causes of obesity were answered at baseline (i.e., right before the intervention), 7 days, and 30 days post-intervention., Results: A total of 506, 230, and 145 employees responded to the baseline, 7-day, and 30-day post-intervention questionnaires, respectively. Mean participant age was 43.3 ± 11.6 years, 84.6% were women, and 67.4% held an academic degree. Mean F-scale scores and percentage of participants with above-average fat-phobic attitudes (≥3.6) significantly decreased only within the intervention group over time (p ≤ 0.042). However, no significant differences between groups over time were observed for AFA scores or factors beliefs to cause obesity., Conclusions: A single exposure to an online education module on weight bias and knowledge about obesity may confer only a modest short-term improvement in medical center employees' fat-phobic attitudes toward people with obesity. Future studies should examine if reexposure to such intervention could impact weight bias, stigma, and discrimination among medical center staff in the long-term., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Identifying patients at increased risk for severe COVID-19 is of high priority during the pandemic as it could affect clinical management and shape public health guidelines. In this study we assessed whether a second PCR test conducted 2-7 days after a SARS-CoV-2 positive test could identify patients at risk for severe illness. Analysis of a nationwide electronic health records data of 1683 SARS-CoV-2 positive individuals indicated that a second negative PCR test result was associated with lower risk for severe illness compared to a positive result. This association was seen across different age groups and clinical settings. More importantly, it was not limited to recovering patients but also observed in patients who still had evidence of COVID-19 as determined by a subsequent positive PCR test. Our study suggests that an early second PCR test may be used as a supportive risk-assessment tool to improve disease management and patient care., (© 2021. The Author(s).)

Fremanezumab (AJOVY; Teva Pharmaceutical Industries Ltd, Netanya, Israel), approved for the preventive treatment of migraine, is available as a subcutaneous injection either once a month or once every 3 months using an autoinjector or a prefilled syringe. The present study evaluated the pharmacokinetic (PK) bioequivalence of a single subcutaneous injection of fremanezumab 225 mg administered using an autoinjector compared to a prefilled syringe in healthy volunteers. Blood samples for PK and antidrug antibodies were collected before and after dosing. Safety and tolerability assessments included physical examinations, adverse event reporting, laboratory evaluations, and immunogenicity. Following single-dose administration, the mean concentration-time profiles for the 2 treatment groups (autoinjector, n = 106; and prefilled syringe, n = 110) were similar. The point estimates for the back-transformed ratio (autoinjector/prefilled syringe) of geometric least squares means of maximum plasma concentration, area under the plasma concentration-time curve from time 0 to the time of the last measurable drug concentration, and area under the plasma concentration-time curve from time 0 extrapolated to infinity were 1.03, 1.04, and 1.05, respectively, with the 90% confidence intervals entirely contained within bioequivalence margins of 0.8 to 1.25. For both groups, median time to maximum observed concentration was 5 days and mean terminal elimination half-life was approximately 29 days. Treatment-related adverse events were reported by 39 (36%) subjects in the autoinjector group and 26 (24%) in the prefilled syringe group, and the majority were nonserious injection site reactions. The incidence of treatment-emergent antidrug antibody response was low and evenly distributed between the autoinjector (n = 3; 3%) and prefilled syringe (n = 4; 4%) groups. These results indicate that the fremanezumab autoinjector presentation provides an easy-to-use bioequivalent PK profile with a similar safety and tolerability profile to that of the prefilled syringe., (© 2021 Teva Pharmaceutical Industries Ltd. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Background: Potential fremanezumab doses for pediatric patients were evaluated using pharmacokinetic modeling and simulation. An open-label phase 1 pharmacokinetic and safety study was conducted in pediatric patients with migraine. This study's results together with refinement of the adult population pharmacokinetic model were used to determine fremanezumab dose recommendations for phase 3 pediatric studies., Methods: Initial application of the adult model suggested that a 75 mg dose in pediatric patients would match exposures determined safe and efficacious in adults; thus, in the phase 1 study, 15 patients, aged 6-11 years and weighing 17-45 kg received a single subcutaneous 75 mg fremanezumab dose. The sparse pharmacokinetic data collected were used to refine the adult model and simulate concentration-time profiles for monthly subcutaneous doses (60 to 225 mg) in a virtual pediatric population., Results: In the phase 1 pediatric study, the safety profile was similar to that of adults. A two-compartment model with first-order absorption and elimination and body weight effects on clearance and central volume was found to adequately describe the pediatric pharmacokinetic data., Conclusions: Using exposure matching to the effective adult fremanezumab dose (225 mg subcutaneous monthly), modeling and simulations predict recommended dose of 120 mg in pediatric patients weighing < 45 kg. Registration: The phase 1 study of this report is registered at EudraCT with the identifier 2018-000734-35.

Background: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) selectively targets the calcitonin gene-related peptide and has proven efficacy for the preventive treatment of migraine. In this study, we evaluated the long-term efficacy, safety, and tolerability of monthly and quarterly fremanezumab., Methods: Episodic migraine and chronic migraine patients completing the 12-week double-blind period of the FOCUS trial entered the 12-week open-label extension and received 3 monthly doses of fremanezumab (225 mg). Changes from baseline in monthly migraine days, monthly headache days of at least moderate severity, days of acute headache medication use, days with photophobia/phonophobia, days with nausea or vomiting, disability scores, and proportion of patients achieving a ≥50% or  ≥75% reduction in monthly migraine days were evaluated., Results: Of the 807 patients who completed the 12-week double-blind treatment period and entered the open-label extension, 772 patients completed the study. In the placebo, quarterly fremanezumab, and monthly fremanezumab dosing regimens, respectively, patients had fewer average monthly migraine days (mean [standard deviation] change from baseline: - 4.7 [5.4]; - 5.1 [4.7]; - 5.5 [5.0]), monthly headache days of at least moderate severity (- 4.5 [5.0]; - 4.8 [4.5]; - 5.2 [4.9]), days per month of acute headache medication use (- 4.3 [5.2]; - 4.9 [4.6]; - 4.8 [4.9]), days with photophobia/phonophobia (- 3.1 [5.3]; - 3.4 [5.3]; - 4.0 [5.2]), and days with nausea or vomiting (- 2.3 [4.6]; - 3.1 [4.5]; - 3.0 [4.4]). During the 12-week open-label extension, 38%, 45%, and 46% of patients, respectively, achieved a ≥50% reduction and 16%, 15%, and 20%, respectively, achieved a ≥75% reduction in monthly migraine days. Disability scores were substantially improved in all 3 treatment groups. There were low rates of adverse events leading to discontinuation (<1%)., Conclusion: Fremanezumab demonstrated sustained efficacy up to 6 months and was well tolerated in patients with episodic migraine or chronic migraine and documented inadequate response to multiple migraine preventive medication classes., Trial Registration: ClinicalTrials.gov NCT03308968 (FOCUS)., (© 2021. The Author(s).)

An influential view of working memory (WM) holds that its contents are controlled by a selective gating mechanism that allows for relevant perceptual information to enter WM when opened, but shields WM contents from interference when closed. In support of this idea, prior studies using the reference-back paradigm have established behavioral costs for opening and closing the gate between perception and WM. WM also frequently requires input from long-term memory (LTM), but it is currently unknown whether a similar gate controls the selection of LTM representations into WM, and how WM gating of perceptual vs. LTM sources of information relate to each other. To address these key theoretical questions, we devised a novel version of the reference-back paradigm, where participants switched between gating perceptual and LTM information into WM. We observed clear evidence for gate opening and closing costs in both cases. Moreover, the pattern of costs associated with gating and input source-switching indicated that perceptual and LTM information is gated into WM via a single gate, and rely on a shared source-selection mechanism. These findings extend current models of WM gating to encompass LTM information, and outline a new functional WM architecture., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Establishing the way people decide to use or avoid information when making a decision is of great theoretical and applied interest. In particular, the "big data revolution" enables decision-makers to harness the wisdom of crowds (WoC) toward reaching better decisions. The WoC is a well-documented phenomenon that highlights the potential superiority of collective wisdom over that of an individual. However, individuals may fail to utilize the power of collective wisdom as a means for optimizing decision outcomes. Using a random dot motion task, the present study examined situations in which decision-makers must choose between relying on their personal information or relying on the WoC in their decision. Although the latter was always the reward-maximizing choice, a substantial part of the participants chose to rely on their own observation and also advised others to do so. This choice tendency was associated with higher confidence, but not with better task performance, and hence reflects overconfidence. Acknowledging and understanding this decision bias may help mitigating it in applied settings., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Bariatric surgery (BS) has proven to be highly efficacious in the treatment of obesity and its comorbidities. However, careful patient selection is critical for its success. Thus, patients should undergo medical, behavioral, and nutritional assessment by a multidisciplinary team. From the nutritional point of view, BS candidates should undergo nutritional assessment, preparation, and education by a registered dietitian in the preoperative period. Currently, detailed specified and comprehensive information on these topics is lacking. The present narrative review aimed to summarize the available literature concerning both the preoperative nutritional assessment components and the preoperative nutritional preparation and education components of patients planning to undergo BS. Current literature indicates that proper management before BS should include a comprehensive nutritional assessment, in which it is advisable to perform a clinical interview to assess patients' medical background, weight management history, eating patterns and pathologies, oral health, physical activity habits, nutritional status, supplementation usage, BS knowledge, surgery expectations and anthropometric measurements. Nutritional preparation and educational strategies should include an individualized preoperative weight-loss nutrition program, improvement of glycemic control, micronutrients deficiencies correction, eating and lifestyle habits adaptation, physical activity initiation, and strengthening knowledge on obesity and BS. At this stage, more well-designed intervention and long-term cohort studies are needed in order to formulate uniform evidence-based nutritional guidelines for patients who plan to undergo BS, including populations at higher nutritional risk. Moreover, postoperative outcomes of presurgical nutritional intervention programs should be studied., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

One anastomosis gastric bypass/Mini Gastric Bypass (OAGB/MGB) is an emerging bariatric surgery (BS) technique. We evaluated and compared attitudes of bariatric surgeons and dietitians towards the considerations for choosing BS-type ("Decision-making"), the contributing factors to the rise of OAGB/MGB in Israel ("OAGB/MGB-rise") and notions regarding the occurrence of gastrointestinal (GI) symptoms and nutritional deficiencies following OAGB/MGB. Anonymous online surveys were distributed. The participants were asked to rate by a 10-point Likert scale (0 = not at all; 100 = very much/often) their attitudes towards "Decision-making", "OAGB/MGB-rise" and occurrence of GI symptoms and nutritional deficiencies following OAGB/MGB. For "Decision-making" and "OAGB/MGB-rise", items were considered prioritized where ≥ 50% of the group considered them as 'very-important' (rating ≥ 80). Data on age, sex, years-in-practice and main workplace were also collected. A total of 106 professionals participated in the survey (42 surgeons; 64 dietitians). The respective mean age, years-in-practice and sex were 52.3 ± 8.7 vs. 42.3 ± 9.0 years, 21.0 ± 10.8 vs. 15.5 ± 9.2 years and 85.7% vs. 3.1% males. The inter-observer agreement for prioritized items related to "Decision-making" was fair (Kappa = 0.250; P = 0.257) and both groups prioritized patient's BMI, comorbidities and compliance. The inter-observer agreement for prioritized items related to "OAGB/MGB-rise" was moderate (Kappa = 0.550; P = 0.099) and both groups prioritized ease of performance, shorter operation duration and failure of former restrictive BS. Surgeons reported lower occurrence of nutritional deficiencies and GI symptoms as adverse effects of OAGB/MGB (P ≤ 0.033). The study highlights the views of bariatric surgeons and dietitians concerning factors that underpin the rise of OABG/MGB in Israel and possible rates of GI symptoms and nutritional deficiencies associated with this modality.

Background: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have been shown to be effective in migraine prevention. Eptinezumab, erenumab, fremanezumab, and galcanezumb have shown efficacy in clinical trials along with favorable safety and tolerability profiles. Although erenumab is a human mAb and the others have been humanized to varying degrees, they all have the capacity to provoke immune reactions. The present review article aims to discuss the current relationship between mAbs targeting the CGRP pathway (CGRP mAbs) and immunogenicity and their potential clinical implications., Findings: The incidence of patients developing anti-drug antibodies (ADAs), their titer, and clinical significance are highly variable and depend on a variety of different drug and patient factors. Neutralizing ADAs (NAbs) bind to and inhibit or reduce the pharmacologic activity of the biologic drug molecule, whereas non-neutralizing antibodies (Non-NAbs) bind to the biologic drug molecule without affecting pharmacologic activity in an in vitro test, although pharmacokinetics and drug clearance may be affected. A direct comparison of immunogenicity data across clinical trials with different biologics is not possible due to a lack of standardized assays. Several phase 2, phase 3, and long-term studies evaluating CGRP mAbs for migraine prevention have reported immunogenicity data (5 studies each for eptinezumab, erenumab, fremanezumab, and galcanezumab). Across these studies, prevalence of ADAs varied, ranging from < 1% to ~ 18%. Neutralizing ADAs were slightly less common, with a prevalence ranging from 0 to 12%. Adverse events related to ADA formation were rare., Conclusions: As more CGRP mAb studies are conducted and more long-term follow-up data become available, evidence is increasing that immunogenicity rates of biologic therapies for migraine are low, and adverse events related to ADAs are rare. Taken together, these results add to the growing body of evidence for the safety and tolerability of this class of migraine medications.

Working memory (WM) needs to protect current content from interference and simultaneously be amenable to rapid updating with newly relevant information. An influential model suggests these opposing requirements are met via a BG-thalamus gating mechanism that allows for selective updating of PFC WM representations. A large neuroimaging literature supports the general involvement of PFC, BG, and thalamus, as well as posterior parietal cortex, in WM. However, the specific functional contributions of these regions to key subprocesses of WM updating, namely, gate opening, content substitution, and gate closing, are still unknown, as common WM tasks conflate these processes. We therefore combined fMRI with the reference-back task, specifically designed to tease apart these subprocesses. Participants compared externally presented face stimuli to a reference face held in WM, while alternating between updating and maintaining this reference, resulting in opening versus closing the gate to WM. Gate opening and substitution processes were associated with strong BG, thalamic, and frontoparietal activation, but intriguingly, the same activity profile was observed for sensory cortex supporting task stimulus processing (i.e., the fusiform face area). In contrast, gate closing was not reliably associated with any of these regions. These findings provide new support for the involvement of the BG in gate opening, as suggested by the gating model, but qualify the model's assumptions by demonstrating that gate closing does not seem to depend on the BG and that gate opening also involves task-relevant sensory cortex.

Parental mentalization refers to parents' capacity to treat their children as having minds of their own and consider the mental states underlying their behaviors. This study examined the roles of mothers' executive functions (EFs), a group of processes supporting self-regulation, in 2 aspects of parental mentalization-spontaneity as measured by mind-mindedness (MM), and complexity as measured by parental reflective functioning (PRF)-while examining child- and family related contextual-moderators. Ninety-nine mothers of 66-month-old preschool children (40 full-term, 59 preterm) completed EFs tasks, were interviewed regarding their child and coparenting, and rated their perception of their child as being difficult (i.e., difficult behavior and negative emotionality). EFs were unrelated to MM. However, EFs were related to PRF when children were rated as more difficult, and when mothers reported high coparenting dissatisfaction; moreover, EFs and PRF were associated among mothers of full-term children, but not in the preterm group. Findings indicate that EFs contribute to the complexity and coherence of maternal mentalization, especially in contexts in which regulation is required for being able to consider the child's mind (difficult child, coparenting dissatisfaction), but not in stressful contexts that are likely to elicit automaticity (prematurity). EFs, however, do not seem to contribute to spontaneous attribution of mental states to the child, when complexity is not considered. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background & Aims: One Anastomosis Gastric Bypass (OAGB) has been accepted as an effective treatment for morbid obesity. However, data are scarce regarding nutritional implications of this procedure. Thus, our aim was to describe the health and nutritional status 12-20 months following OAGB surgery., Methods: A prospective cohort study on patients who underwent OAGB surgery from January 2016 to May 2017 in a large, multi-disciplinary, bariatric clinic. Pre-surgery data including demographic details, anthropometrics, co-morbidities, blood tests and lifestyle habits were obtained from the patients' medical records. Follow-up evaluations were performed 12-20 months post-surgery and data collected included anthropometrics, blood tests, eating and lifestyle parameters, adherence to follow-up regime and gastrointestinal (GI) related side effects. In addition, patients were asked to rate their overall state of health (OSH) from 0 to 100 using a visual analogue scale (VAS)., Results: Eighty-six OAGB patients (72.1% women) were tested 14.7 ± 2.0 months post-operatively. Their mean age and BMI preoperatively were 46.1 ± 11.4 years and 42.0 ± 4.9 kg/m 2 , respectively. The mean % excess weight loss at 12-20 months postoperatively was 88.4 ± 19.3%. Lipid and glucose profiles were significantly improved at 12-20 months postoperatively compared to baseline (P < 0.001 for all). Relatively high proportions of nutritional deficiencies were found pre-operatively and postoperatively for iron (33.9% vs. 23.7%, P = 0.238), folate (30.9% vs. 11.8%, P = 0.004), vitamin D (56.6% vs. 17.0%, P < 0.001) and hemoglobin (16.7% vs. 42.9%, P < 0.001). Postoperatively, most participants reported taking multivitamin, calcium, vitamin D and vitamin B12 supplementation (≥62.8%), having participated in at least 6 meetings with a dietitian (51.8%) and presently doing physical activity (69.4%). The mean postoperative OSH VAS score was 88.2 ± 12.3, but most participants reported on flatulence (67.4%) and some reported on diarrhea (25.6%) as GI side effects of the surgery., Conclusions: Substantial improvements in health and anthropometric parameters are found in the short-term follow-up after OAGB, with a satisfactory reported quality of life and adherence to recommendations. However, a high prevalence of some GI side effects, nutritional deficiencies and specially anemia is a matter of concern., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Purpose: To examine associations of patients' attendance to follow-up meetings with a registered dietitian (RD) and physical exercise practices with weight loss during the 1 year following laparoscopic sleeve gastrectomy (SG)., Methods: Of 241 patients with obesity who underwent SG during 2012, 184 (76.3%) participated in a 1-year follow-up telephone interview and had information on number of RD follow-up meetings. Clinical information was available from computerized patient files. Multiple logistic regression analysis, adjusting for propensity score, was computed to reveal factors associated with greater weight loss., Results: The mean %TWL was 31.4 ± 6.1 and the mean number of reported RD meetings during the year following SG was 4.6. The proportion of physically active patients increased by 15% (from 23 to 42) among those who attended at least 3 RD follow-up meetings (n = 123), and by 5% (from 18 to 23) among those who attended fewer than 3 meetings (n = 61) (p = 0.05). Patients conducting physical exercise reported a lower level of pain/discomfort on the EQ5D quality-of-life questionnaire (p = 0.03). The adjusted regression model revealed no association between the number of RD follow-up meetings and weight-reduction success, but physical exercise during the year following SG conferred a 2.6 times greater odds of belonging to the upper two tertiles of the % excess body weight loss ( 95% CI 1.2-5.3)., Conclusions: Patients with better adherence to RD follow-up meetings were also more physically active. Patients on physical exercise also achieved greater weight reduction following SG, and reported less pain or discomfort. Nutritional counselling and physical exercise are necessary to ensure maximal and sustainable benefits from SG.  LEVEL OF EVIDENCE: Level III, Cohort study.

Dissociative absorption (DA) is a tendency to become completely immersed in a stimulus while neglecting to attend to one's surroundings. Theoretically, DA implies automatic functioning in areas that are outside the focus of attention. This study examined whether high absorbers indeed act more automatically, i.e., with decreased meta-consciousness for, and therefore poor memory of, their own actions, along with reduced sense of agency (SoA). High and low absorbers (N = 63) performed three DA-promoting tasks: choice-reaction time (CRT), Tetris, and free writing. Participants were tested on memory of task details and self-reported their state SoA. As hypothesized, trait DA was correlated with impaired autobiographical memory for self-generated writing. However, DA was not related to episodic memory disruptions in externally-generated content tasks (Tetris, CRT). In most tasks, DA was associated with decreased SoA. Absorbers' specific difficulty in identifying self-generated content suggests that their memory failures stem from reduced accessibility to self-actions and intentions., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The P3b is an extensively studied neurophysiological phenomenon that is predominantly explained in the cognitive neuroscience literature as reflecting context updating, presumably in working memory (WM). Despite the prevalence and influence of the context updating hypothesis, direct empirical support for the role of WM updating in eliciting the P3b is still missing. The present study was designed to address the empirical gap in understanding the functional role of P3b in general, and specifically in relation to WM updating. A mass-univariate approach was used to test the unique contribution of WM updating, categorization, and stimulus probability to the P3b. The results indicated that the P3b is only modulated by the categorization process, a finding that challenges the WM updating hypothesis. Taken together these results, we suggest that the P3b reflects a WM guided target identification mechanism, which operates as part of a goal-directed learning strategy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Optimal working memory (WM) functioning depends on a control mechanism that balances between maintenance and updating by closing or opening the gate to WM, respectively. Here, we examined the neural oscillation correlates of WM updating and of the control processes involved in gating. The reference-back paradigm was employed to manipulate gate opening, gate closing, and updating independently and examine how the control functions involved in these processes are mapped to oscillatory EEG activity. The results established that different oscillatory patterns were associated with the control process related to gate opening than in gate closing. During the time of gate closing, a relative increase in theta power was observed over midfrontal electrodes. This theta response is a known EEG signature of cognitive control that is proposed here to reflect reactive conflict resolution, achieved by closing the gate when facing irrelevant information. On the other hand, proactive gate opening in preparation for relevant information was associated with an increase in relative delta power over parietal-occipital electrodes. Finally, WM updating was associated with relative increase in delta power over midfrontal electrodes, suggesting a functional role of delta oscillations in WM updating.

Maternal mentalization refers to a mother's capacity to understand mental-states of herself and her child and to regard her child as a psychological agent. In mother-infant interactions, this capacity is commonly conceptualized as maternal mind-mindedness, which can be divided into two dimensions: appropriate and nonattuned interpretations of the infants' mental-states. Appropriate mind-mindedness refers to interpretations that seem to be compatible with the infant's behaviors, whereas nonattuned mind-mindedness refers to noncompatible interpretations. The aim of this study was to investigate the cognitive mechanisms that contribute to mind-mindedness. Specifically, we investigated the role of executive functions in appropriate and nonattuned mind-mindedness, and the moderating roles of two infant-related factors, prematurity (as a stressful context) and child temperament (as a context of unpredictability and negative emotionality). To this end, mother-infant free play interactions were coded for mind-mindedness in a sample of 102 mothers and their 6-month-old infants (61 preterm, 41 full-term). When children were 66-months old, mothers completed cognitive tasks that assessed working memory updating, resistance to interference, response inhibition, and shifting. Appropriate mind-mindedness was positively associated with updating, and this link was stronger when infant temperament was rated as more difficult. Furthermore, among mothers of full-term infants, mothers' resistance to interference was negatively associated with nonattuned mind-mindedness. This link was not evident in the stressful context of premature birth. Mothers' response inhibition and shifting were not associated with either of the mind-mindedness dimensions. Implications on understanding variability in maternal mentalization during mother-infant interactions and the roles of executive functions in parenting are discussed., Competing Interests: The authors have declared that no competing interests exist.

Over the last couple of decades, a vast amount of research has been dedicated to understanding the nature and the architecture of visual short-term memory (VSTM), the mechanism by which currently relevant visual information is maintained. According to discrete-capacity models, VSTM is constrained by a limited number of discrete representations held simultaneously. In contrast, shared-resource models regard VSTM as limited in resources, which can be distributed flexibly between varying numbers of representations; and a new interference model posits that capacity is limited by interference among items. In this article, we begin by reviewing benchmark findings regarding the debate over VSTM limitations, focusing on whether VSTM storage is all-or-none and on whether object complexity affects capacity. After that, we put forward a hybrid framework of VSTM architecture, arguing that this system is composed of a two-level hierarchy of memory stores, each containing a different set of representations: (1) perceptual memory, a resourcelike level containing analog automatically formed representations of visual stimuli in varying degrees of activation, and (2) visual working memory, in which a subset of three to four items from perceptual memory are bound to conceptual representations and to their locations, thus conveying discrete (digital/symbolic) information which appears quantized. While perceptual memory has a large capacity and is relatively nonselective, visual working memory is restricted in the number of items that can be maintained simultaneously, and its content is regulated by a gating mechanism.

Removal has been suggested to play a key role in controlling the contents of working memory. The present study examined the aftereffects of removal in a working memory updating task. Participants performed the reference-back paradigm, a version of the n-back task that is composed of two trial types: reference trials that required working memory updating and comparison trials that did not require updating. N-2 repetition effects-the difference in performance between trials that presented the same stimulus as the one presented two trials before (ABA sequences) and trials in which the stimulus differed from the two previous stimuli (ABC sequences)-were examined. In two experiments, n-2 repetition costs were observed within sequences of reference trials, while n-2 repetition benefits were observed within sequences of comparison trials. This pattern suggests that removal takes place during working memory updating. Furthermore, automatic formation and updating of representation outside working memory, which takes place in comparison trials and gives rise to n-2 repetition benefits, does not involve removal. Removal, demonstrated by phenomena such as n-2 repetition costs, is therefore proposed to be a marker for the utilization of working memory within a given task., (© 2018 New York Academy of Sciences.)

What happens to goal-relevant information in working memory after it is no longer needed? Here, we review evidence for a selective removal process that operates on outdated information to limit working memory load and hence facilitates the maintenance of goal-relevant information. Removal alters the representations of irrelevant content so as to reduce access to it, thereby improving access to the remaining relevant content and also facilitating the encoding of new information. Both behavioral and neural evidence support the existence of a removal process that is separate from forgetting due to decay or interference. We discuss the potential mechanisms involved in removal and characterize the time course and duration of the process. In doing so, we propose the existence of two forms of removal: one is temporary, and reversible, which modifies working memory content without impacting content-to-context bindings, and another is permanent, which unbinds the content from its context in working memory (without necessarily impacting long-term forgetting). Finally, we discuss limitations on removal and prescribe conditions for evaluating evidence for or against this process., (© 2018 New York Academy of Sciences.)