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Objective: 8-30 % of patients who present with aneurysmal subarachnoid hemorrhage (aSAH) have multiple intracranial aneurysms (MIA). Although prompt treatment to secure ruptured aneurysms (RA) is standard of care, there is no clear consensus regarding whether incidental unruptured aneurysms (UA) should be treated during the same procedural time as the RA. This study aims to examine the effect of treatment of UA during the same procedural time as treatment for the RA (concurrent treatment) versus delaying the treatment of an UA after discharging the patient (delayed treatment)., Methods: This is a retrospective review of the medical records of patients with the diagnosis of aSAH and MIA admitted to a single neurocritical care unit between 2013 and 2021, and who underwent treatment of at least 1 aneurysm during the index hospitalization. Data was divided in 2 groups: concurrent treatment (2 or more aneurysms treated), and delayed treatment (1 aneurysm treated). Clinical and radiological data including demographic characteristics, modified Fisher Scale (mFS), treatment modality (clipping or endovascular), ventriculoperitoneal shunt (VPS) rates, surgical/procedural complications, delayed cerebral ischemia (DCI), length of stay (LOS), modified Rankin Score (mRS) and type of insurance of the patients during the hospitalization were collected., Results: We identified 109 patients with aSAH and MIA, who fit criteria. The median age was 58 (48-67) years old. 91 were female (83.5 %). A total of 287 aneurysms were found, 109 were ruptured. 64 patients underwent treatment of a single aneurysm (delayed treatment group), and 45 patients underwent treatment of 2 or more aneurysms (concurrent treatment group). mFS were similar in both groups (p=.56). Clipping (52.3 %) was the treatment modality most frequently used. No significant differences in surgical/procedural complications (p=.54) or VPS (p=.91) rates were seen among the 2 groups. No significant differences in delayed cerebral ischemia rates were seen (p=.85) There were no significant differences between the mRS at discharge (mRS 0-3 v 4-6 (p=.78)), LOS in the ICU (12 vs 13 (p=.58) days) and LOS in the hospital (16 vs 14.5 (p=.95) days) between the delayed and concurrent treatment groups respectively., Conclusions: No difference in functional status at discharge was observed between delayed treatment versus concurrent treatment. Treatment of most or all surgically amenable aneurysms, at the time when the RA is being treated, does not increase the risk of DCI or poor outcomes at discharge., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Objectives: Social determinants of health (SDOH) are important contributors to poor stroke-related outcomes. While some have suggested that this association is driven by the increased incidence of stroke observed with poor SDOH, others have raised concerns regarding disparities in acute stroke care. This study aimed to determine the association between SDOH and the administration of thrombolytic therapy and mechanical thrombectomy among patients with acute ischemic stroke., Methods: A retrospective cohort analysis was conducted using Texas Emergency Department Public Use Data (2016-2019), including adult patients diagnosed with acute ischemic stroke. The risk ratios (RRs) of administering thrombolysis and thrombectomy based on variables representing SDOH and a collective measure (Social Vulnerability Index [SVI]) were computed using mixed-effects Poisson regression models accounting for the nested nature of patients in hospitals and neighborhoods. The Charlson comorbidity score was considered as a covariate., Results: Of the 139,852 patients with ischemic stroke (female, 51.7%; White, 67.2%; Black, 16.6%; Hispanic, 25.1%), 16,831 (12.3%) received thrombolytic therapy and 5,951 (4.3%) received mechanical thrombectomy. Age older than 65 years (RR 0.578 [0.537-0.621]) vs 18-45 years, Black (RR 0.801 [0.761-0.844]) vs White, Hispanic (RR 0.936 [0.895-0.98]) vs non-Hispanic, Medicare/Medicaid/Veterans Affairs (VA) (RR 0.917 [0.882-0.954]) or uninsured (RR 0.883 [0.833-0.935]) vs private insurance, and rural (RR 0.782 [0.723-0.845]) vs urban dwelling were less likely to be associated with thrombolysis. Patients in the highest quintile based on the SVI were less likely to receive thrombolysis than those in the lowest quintile (RR 0.926 [0.867-0.989]). Patients were less likely to receive thrombectomy if they were 65 years and older (RR 0.787 [0.691-0.895]), belonged to the Black race (RR 0.745 [0.679-0.818]) or Hispanic ethnicity (RR 0.919 [0.851-0.992]), had Medicare/Medicaid/VA insurance (RR 0.909 [0.851-0.971]), or were from a rural area (RR 0.909 [0.851-0.971]). Similarly, SVI decreased the likelihood of undergoing mechanical thrombectomy (RR 0.842 [0.747-0.95])., Discussion: Despite many improvements in stroke management, SDOH continue to be a significant driver of treatment access for acute ischemic stroke. While our findings are limited to Texas, our results should raise awareness and promote more studies regarding the effects of these SDOH at the national and international levels.

Atypical connectivity patterns have been observed for individuals with autism spectrum disorders (ASD), particularly across the triple-network model. The current study investigated brain-behavior relationships in the context of social skills and executive function profiles for ASD youth. We calculated connectivity measures from diffusion tensor imaging using Bayesian estimation and probabilistic tractography. We replicated prior structural equation modeling of behavioral measures with total default mode network (DMN) connectivity to include comparisons with central executive network (CEN) connectivity and CEN-DMN connectivity. Increased within-CEN connectivity was related to metacognitive strengths. Our findings indicate behavior regulation difficulties in youth with ASD may be attributable to impaired connectivity between the CEN and DMN and social skill difficulties may be exacerbated by impaired within-DMN connectivity., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: L-theanine is a non-protein-forming amino acid found in tea. Previous research shows high doses (100-400 mg) of L-theanine enhances attention, mainly by reducing mind wandering and distracter processing. We hypothesized that these indirect mechanisms could significantly improve the performance of low-level attentional tasks, whereas the relative contribution could be less in complex attentional tasks that require active, higher-order processing of target stimuli., Methods: To test this hypothesis, we conducted a double-blind, placebo-controlled, counterbalanced, four-way crossover study in 32 healthy young adults, where we compared the effects of three doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water), administered before and 50 min after dosing, on three attentional tasks from the Cambridge Neuropsychological Test Automated Battery [viz. Reaction Time (RTI)-visuomotor speed, Rapid Visual Information Processing (RVP)-sustained attention, and Stop Signal Task (SST)-inhibitory control]. Results were analyzed in dose × time repeated measures ANOVA models, with subsequent pairwise comparisons., Results: Active doses significantly improved reaction times in the RTI (100-200 mg) and RVP (200-400 mg) tasks from baseline ( p  < 0.05), but once controlled for the change-from-baseline caused by placebo, only the RTI simple reaction times showed significant improvements, following 100 mg (Δ = 16.3 ms, p  = 0.009) and 200 mg (Δ = 16.9 ms, p  = 0.009) of L-theanine., Conclusions: Consistent with our hypothesis, these findings suggest that L-theanine significantly improves attention in simple visuomotor tasks, but not in more complex sustained attention tasks, or executive control tasks that require top-down inhibition of pre-active responses.

Background: Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by amyloid-β (Aβ) plaques. Systemic inflammation and obesity may exacerbate AD pathogenesis. We previously reported anti-inflammatory and anti-obesity effects of EPA in mice., Objectives: We aimed to determine whether EPA reduces obesity-associated metabolic dysfunctions and Aβ accumulation in AD amyloidogenic mice., Methods: Two-mo-old APPswe/PS1dE9 transgenic (TG) mice and non-TG littermates were randomly assigned to low fat (LF; 10% kcal fat), high fat (HF; 45% kcal fat), or EPA (36 g/kg)-supplemented HF diets. Body composition, glucose tolerance, and energy expenditure were measured, and serum and brain metabolic markers were tested 38 wk postintervention. Outcomes were statistically analyzed via 3-factor ANOVA, modeling genotype, sex, and diet interactions., Results: HF-fed males gained more weight than females (Δ = 61 mg; P < 0.001). Compared with LF, HF increased body weights of wild-type (WT) males (Δ = 31 mg; P < 0.001). EPA reduced HF-induced weight gain in WT males (Δ = 24 mg; P = 0.054) but not in females. HF mice showed decreased glucose clearance and respiratory energy compared with LF-fed groups (Δ = -1.31 g/dL; P < 0.001), with no significant effects of EPA. However, EPA conferred metabolic improvements by decreasing serum leptin and insulin (Δ = -2.51 g/mL and Δ = -0.694 ng/mL, respectively compared with HF, P ≤ 0.05) and increasing adiponectin (Δ = 21.6 ng/mL; P < 0.001). As we expected, TG mice expressed higher serum and brain Aβ than WT mice (Δ = 0.131 ng/mL; P < 0.001 and Δ = 0.56%; P < 0.01, respectively), and EPA reduced serum Aβ 1-40 in TG males compared with HF (Δ = 0.053 ng/mL; P ≤ 0.05)., Conclusions: To our knowledge, this is the first report that EPA reduces serum Aβ 1-40 in obese AD male mice, warranting further investigations into tissue-specific mechanisms of EPA in AD., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: A systematic and meta-analysis was conducted to examine the evidence of the effects of botulinum toxin A on chronic tension-type headache., Methods: Cochrane, Embase, Ovid, ProQuest, PubMed, Scopus, Web-of-Science databases, and ClinicallTrials.gov registry were systematically searched for studies examining the effects of botulinum toxin A on tension-type headaches. The records were screened by two independent reviewers using pre-determined eligibility criteria. DerSimonian Liard random-effects meta-analyses were performed using the 'meta' package (5.2-0) in R (4.2.0). Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's Tool RoB 2 and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Clinical significance was determined using pre-defined minimal clinically important differences., Results: Eleven controlled trials were included (390 botulinum toxin A, 297 controls). Botulinum toxin A was associated with significant improvements in standardized headache intensity (-0.502 standard deviations [-0.945, -0.058]), headache frequency (-2.830 days/month [-4.082, -1.578]), daily headache duration (-0.965 [-1.860, -0.069]) and the frequency of acute pain medication use (-2.200 days/month [-3.485, -0.915]) vs controls. Botulinum toxin A-associated improvements exceeded minimal clinically important differences for headache intensity, frequency, and acute pain medication use. A 79% (28%, 150%) greater response rate was observed for botulinum toxin A vs controls in improving chronic tension-type headache. Treatment of eight chronic tension-type headache patients was sufficient to elicit a therapeutic response in one patient., Conclusions: Corroborating the current mechanistic evidence, our meta-analysis supports the utility of botulinum toxin A for managing chronic tension-type headaches. However, due to limitations in the quality of evidence, adequately-powered high-quality controlled trials examining the effects of Botulinum toxin A on chronic tension-type headache are warranted., Registration: Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42020178616).

Importance: Although the increased risk of obesity among individuals with autism has been well established, evidence on the association between autism, cardiometabolic disorders, and obesity remains inconclusive., Objective: To examine the association between autism spectrum disorders and cardiometabolic diseases in a systematic review and meta-analysis., Data Sources: PubMed, Scopus, Web of Science, ProQuest, Embase, and Ovid databases were searched from inception through July 31, 2022, without restrictions on date of publication or language., Study Selection: Observational or baseline data of interventional studies reporting the prevalence of cardiometabolic risk factors (ie, diabetes, hypertension, dyslipidemia, atherosclerotic macrovascular disease) among children and/or adults with autism and matched with participants without autism were included., Data Extraction and Synthesis: Screening, data extraction, and quality assessment were performed independently by at least 2 researchers. DerSimonian-Laird random-effects meta-analyses were performed using the meta package in R., Main Outcomes and Measures: Relative risks (RRs) of diabetes, hypertension, dyslipidemia, and atherosclerotic macrovascular disease among individuals with autism were the primary outcomes. Secondary outcomes included the RR of type 1 and type 2 diabetes, heart disease, stroke, and peripheral vascular disease., Results: A total of 34 studies were evaluated and included 276 173 participants with autism and 7 733 306 participants without autism (mean [range] age, 31.2 [3.8-72.8] years; pooled proportion [range] of female individuals, 47% [0-66%]). Autism was associated with greater risks of developing diabetes overall (RR, 1.57; 95% CI, 1.23-2.01; 20 studies), type 1 diabetes (RR, 1.64; 95% CI, 1.06-2.54; 6 studies), and type 2 diabetes (RR, 2.47; 95% CI, 1.30-4.70; 3 studies). Autism was also associated with increased risks of dyslipidemia (RR, 1.69; 95% CI, 1.20-2.40; 7 studies) and heart disease (RR, 1.46; 95% CI, 1.42-1.50; 3 studies). Yet, there was no significantly associated increased risk of hypertension and stroke with autism (RR, 1.22; 95% CI, 0.98-1.52; 12 studies; and RR, 1.19; 95% CI, 0.63-2.24; 4 studies, respectively). Meta-regression analyses revealed that children with autism were at a greater associated risk of developing diabetes and hypertension compared with adults. High between-study heterogeneity was a concern for several meta-analyses., Conclusions and Relevance: Results suggest that the associated increased risk of cardiometabolic diseases should prompt clinicians to vigilantly monitor individuals with autism for potential contributors, signs of cardiometabolic disease, and their complications.

Background: Frequency, microbiology, and outcomes of necrotizing soft tissue infections (NSTIs) could vary across the United States because of differences in locoregional and environmental factors. We synthesized the literature from across the regions of the United States on NSTIs in a systematic review/meta-analysis. Methods: PubMed, ProQuest, Scopus, and Web of Science databases were systematically searched and screened. DerSimonian-Laird random-effects meta-analyses were performed using 'meta' package in R to determine pooled prevalences. Meta-regression analyses examined moderator effects of risk factors. Results: Twenty-seven studies (2,242 total patients) were included. Pooled prevalences of polymicrobial and monomicrobial infections were 52.2% and 39.9%, respectively. The prevalence of monomicrobial NSTIs increased over the last two decades (p = 0.018), whereas polymicrobial infections declined (p = 0.003). Meta-regression analysis showed that most polymicrobial NSTIs were Fournier gangrene (p < 0.001), whereas monomicrobial NSTIs mostly affected extremities (p < 0.001). Staphylococcus aureus was the most common organism isolated (predominantly in the South), followed by Bacteroides spp. (predominately in the East) and Streptococcus pyogenes . Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 11.9% of NSTIs, mainly in the South. The overall mortality rate was 17.8% and declined over last two decades (p < 0.001), with the lowest rate reported in the last decade at 13% without any regional differences. Conclusions: Advancement in the management of NSTIs may have contributed to the observed decline in NSTI-related mortality in the United States. However, the proportion of monomicrobial NSTIs seems to be increasing, possibly because of increased comorbidities affecting extremities. Causative organisms varied by region. Multi-center observational studies are warranted to confirm our observations.

Objective: L-theanine, a non-proteinic amino acid found in tea, is known to enhance attention particularly in high doses, with no reported adverse effects. We aimed to determine whether oral administration of L-theanine acutely enhances neurophysiological measures of selective attention in a dose-dependent manner. Methods: In a double-blind, placebo-controlled, counterbalanced, 4-way crossover study in a group of 27 healthy young adults, we compared the effects of 3 doses of L-theanine (100, 200 and 400 mg) with a placebo (distilled water) on latencies of amplitudes of attentive and pre-attentive cognitive event-related potentials (ERPs) recorded in an auditory stimulus discrimination task, before and 50 min after dosing. Results: Compared to the placebo, 400 mg of theanine showed a significant reduction in the latency of the parietal P3b ERP component ( p  < 0.05), whereas no significant changes were observed with lower doses. A subsequent exploratory regression showed that each 100-mg increase in dose reduces the P3b latency by 4 ms ( p  < 0.05). No dose-response effect was observed in P3b amplitude, pre-attentive ERP components or reaction time. Discussion: The findings indicate L-theanine can increase attentional processing of auditory information in a dose-dependent manner. The linear dose-response attentional effects we observed warrant further studies with higher doses of L-theanine.

Background and Aims: The often purported claim that coconut fat is beneficial for cardiovascular health and was disputed in several recent meta-analyses. However, the evidence on the effects of coconut fat intake on glycemic control remains equivocal. We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines to determine the effects of dietary coconut fats on markers of acute and long-term glycemic control., Methods and Results: PubMed, Scopus, ProQuest, and Web-of-Science databases were searched and the records were screened by three independent reviewers to identify interventional studies examining acute and long-term (i.e., >10 days) effects of coconut fat on glycemic control. DerSimonian-Laird random-effects meta-analyses were performed using the meta-package in R (4.0.2). Seven interventional studies on acute effects and 11 interventional studies on long-term effects of coconut fat were included. Meals with coconut fat acutely increased the incremental area under the curve (AUC) of glucose (p = 0.046) and decreased the incremental AUC of insulin (p = 0.037) vs. control meals. Long-term coconut fat intake increased HOMA-IR (p = 0.049), but did not significantly affect fasting glucose, insulin, or HOMA-β vs. control meals., Conclusions: Coconut fat in meals seems to be associated with a diminished postprandial insulin response, resulting in a subtle increase in the postprandial glycemic response. Long-term intake of coconut fat seems to increase insulin resistance, yet does not seem to be beneficial for long-term glycemic control. Thus, our results disprove the popular claim that coconut fat improves glycemic control., Registration: PROSPERO registry (CRD42020183450)., Competing Interests: Declaration of competing interest The authors have no potential conflicts of interest to declare pertinent to the content in the manuscript., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Frequency, microbiology, and outcomes of necrotizing soft tissue infections vary based on locoregional and environmental factors; however, there has been no global survey of these patterns. We performed a systematic review/meta-analysis on published reports of necrotizing soft tissue infections from across the globe., Methods: Peer-reviewed empirical studies examining rates of polymicrobial and monomicrobial necrotizing soft tissue infections with microbial isolation and overall mortality rate were extracted along with geographic location using PubMed, Scopus, ProQuest, and Web of Science. Random-effects meta-analyses and sensitivity analyses were performed, adjusting for publication bias. Meta-regression analyses examined moderator effects of risk factors., Results: One hundred and five studies (8,718 total patients) were included. Pooled prevalence of polymicrobial and monomicrobial infections were 53% and 37.9%, respectively. Truncal necrotizing soft tissue infections were commonly polymicrobial (P < .001), whereas monomicrobial infections prevailed in extremities (P = .008). Global prevalence of monomicrobial necrotizing soft tissue infections was observed to increase by 1.1% annually (P = .003). Staphylococcus aureus was the most common organism globally and in North America, Asia, the Middle East, and Africa, followed by Streptococcus pyogenes and Escherichia coli. Methicillin-resistant S. aureus accounted for 16% of necrotizing soft tissue infections globally. Overall mortality was 23.1%, observed to decline globally over the last decade (P = .020). No regional differences were noted for mortality., Conclusion: Although polymicrobial infections remain predominant worldwide, the incidence of monomicrobial infections is increasing. The observed decline in necrotizing soft tissue infection-related mortality is encouraging and may reflect advances in management, despite major variations in available healthcare resources globally., (Published by Elsevier Inc.)

Randomization is an important tool used to establish causal inferences in studies designed to further our understanding of questions related to obesity and nutrition. To take advantage of the inferences afforded by randomization, scientific standards must be upheld during the planning, execution, analysis, and reporting of such studies. We discuss ten errors in randomized experiments from real-world examples from the literature and outline best practices for their avoidance. These ten errors include: representing nonrandom allocation as random, failing to adequately conceal allocation, not accounting for changing allocation ratios, replacing subjects in nonrandom ways, failing to account for non-independence, drawing inferences by comparing statistical significance from within-group comparisons instead of between-groups, pooling data and breaking the randomized design, failing to account for missing data, failing to report sufficient information to understand study methods, and failing to frame the causal question as testing the randomized assignment per se. We hope that these examples will aid researchers, reviewers, journal editors, and other readers to endeavor to a high standard of scientific rigor in randomized experiments within obesity and nutrition research., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Visceral obesity may be a driving factor in nonalcoholic fatty liver disease (NAFLD) development. Previous studies have shown that the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), ameliorates obesity in high-fat (HF) fed male, C57Bl/6 mice at thermoneutral conditions, independent of uncoupling protein 1 (UCP1). Our goals herein were to investigate sex-dependent mechanisms of EPA in the livers of wild type (WT) and UCP1 knockout (KO) male and female mice fed a HF diet (45% kcal fat; WT-HF, KO-HF) with or without supplementation of 36 g/kg EPA (WT-EPA, KO-EPA). KO significantly increased body weight in males, with no significant reductions with EPA in the WT or KO groups. In females, there were no significant differences in body weight among KO groups and no effects of EPA. In males, liver TGs were significantly higher in the KO-HF group and reduced with EPA, which was not observed in females. Accordingly, gene and protein markers of mitochondrial oxidation, peroxisomal biogenesis and oxidation, as well as metabolic futile cycles were sex-dependently impacted by KO and EPA supplementation. These findings suggest a genotypic difference in response to dietary EPA supplementation on the livers of male and female mice with diet-induced obesity and housed at thermoneutrality.

We examined the acute effects of L-theanine, caffeine and their combination on sustained attention, inhibitory control and overall cognition in boys with attention deficit hyperactivity disorder (ADHD). L-Theanine (2.5 mg/kg), caffeine (2.0 mg/kg), their combination and a placebo were administered in a randomized four-way repeated-measures crossover with washout, to five boys (8-15 years) with ADHD. Functional magnetic resonance imaging (fMRI) was performed during a Go/NoGo task and a Stop-signal task ~ 1 h post-dose. NIH Cognition Toolbox was administered ~ 2 h post-dose. Treatment vs. placebo effects were examined in multi-level mixed-effects models. L-Theanine improved total cognition composite in NIH Cognition Toolbox (p = 0.040) vs. placebo. Caffeine worsened and L-theanine had a trend of worsening inhibitory control (i.e. increased Stop-signal reaction time; p = 0.031 and p = 0.053 respectively). L-Theanine-caffeine combination improved total cognition composite (p = 0.041), d-prime in the Go/NoGo task (p = 0.033) and showed a trend of improvement of inhibitory control (p = 0.080). L-Theanine-caffeine combination was associated with decreased task-related reactivity of a brain network associated with mind wandering (i.e. default mode network). L-Theanine-caffeine combination may be a potential therapeutic option for ADHD-associated impairments in sustained attention, inhibitory control and overall cognitive performance.

Emerging evidence from functional magnetic resonance imaging (fMRI) brain activation studies associated with dietary behavior reveals significant interaction of biological and behavioral mechanisms in response to visualized food stimuli. Because food intake is influenced by neurosensory stimulation and memory cues, personalized food images may be useful in prompting appropriate affective responses to food intake, which may subsequently lead to healthier eating behaviors. The current study used a cross-sectional mixed methods approach to explore neural responses and self-perceptions of eating behavior during review of personalized food images. A sample of college students (N = 16; 9 females; M age = 21.44) used cell-phone cameras and an online dietary tracking website to collect and report three days of diet. Within 2-3 weeks of completing dietary tracking activity, participants underwent an fMRI scan while reviewing recorded personal images and text descriptions of their diet. They also responded to three questions related to memory for the food items and future eating intentions. Post-scan interviews explored how participants felt after reviewing personal food images and the possible impact that such review might have on future food choices. Whole brain analyses suggested, compared to a written dietary record, that the visualization of personal images of diet evoked greater brain activation in memory regions (e.g., superior frontal gyrus) along with mediating emotion (e.g., thalamus, putamen, anterior cingulate cortex), imagery and executive functions (e.g., inferior orbitofrontal gyrus, fusiform, and parietal lobe). This study offers preliminary support for the use of personal food images to strengthen dietary monitoring., Competing Interests: Declaration of competing interest The authors have no disclosures or conflict of interest to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Regression to the mean (RTM) is a statistical phenomenon where initial measurements of a variable in a nonrandom sample at the extreme ends of a distribution tend to be closer to the mean upon a second measurement. Unfortunately, failing to account for the effects of RTM can lead to incorrect conclusions on the observed mean difference between the 2 repeated measurements in a nonrandom sample that is preferentially selected for deviating from the population mean of the measured variable in a particular direction. Study designs that are susceptible to misattributing RTM as intervention effects have been prevalent in nutrition and obesity research. This field often conducts secondary analyses of existing intervention data or evaluates intervention effects in those most at risk (i.e., those with observations at the extreme ends of a distribution)., Objectives: To provide best practices to avoid unsubstantiated conclusions as a result of ignoring RTM in nutrition and obesity research., Methods: We outlined best practices for identifying whether RTM is likely to be leading to biased inferences, using a flowchart that is available as a web-based app at https://dustyturner.shinyapps.io/DecisionTreeMeanRegression/. We also provided multiple methods to quantify the degree of RTM., Results: Investigators can adjust analyses to include the RTM effect, thereby plausibly removing its biasing influence on estimating the true intervention effect., Conclusions: The identification of RTM and implementation of proper statistical practices will help advance the field by improving scientific rigor and the accuracy of conclusions. This trial was registered at clinicaltrials.gov as NCT00427193., (Published by Oxford University Press on behalf of the American Society for Nutrition 2019.)

Objective: Identifying predictors of early weight loss may have value in predicting longer-term success in weight loss programmes. This study examined if weight history variables (ie, weight cycling history [WCH], age of onset of obesity [AOO]), and preintervention Three-Factor Eating Questionnaire (TFEQ) and Power of Food Scale (PFS) scores predicted weight loss (WL) and fat mass loss (FML) following a 3-week calorie restriction intervention., Methods: Thirty-two participants (19-60 y; body mass index [BMI] 30-39.9 kg/m 2 ) participated in a 3-week calorie restriction intervention (1120 kcal/d) as part of a larger clinical trial with 28 completers included in the current analyses. Preintervention WCH, AOO, TFEQ, and PFS subscale scores were collected, and WL and FML were measured. Multiple linear regression analyses were performed to predict WL and FML for relevant covariates in this study., Results: WCH, AOO, preintervention TFEQ subscale scores, and PFS subscale scores did not predict WL (all P s > .08) or FML ( P s > .06) except, PFS-food tasted scores significantly predicted WL ( r = -0.40, P = .03)., Conclusion: Although these variables were not robust predictors, results for at least the PFS suggest there may be value in further exploring this measure using larger sample sizes., Competing Interests: Corresponding author, Martin Binks, PhD, reports that the original data collection for this study was funded by Nestlé Health Science Inc. The funding agency was not involved in decisions related to the publication of outcomes. Dr Binks has also received honoraria in the past for presenting educational content on behalf of Nestlé Health Science Inc. Dr Binks further attests that this manuscript has neither been submitted for consideration nor been published elsewhere and represents an original work. The authors have no other potential conflicts of interest to declare., (© 2019 The Authors. Obesity Science & Practice published by John Wiley & Sons Ltd, World Obesity and The Obesity Society.)

Evidence on neurophysiological correlates of coexisting autism spectrum disorders (ASD) and overweight/obesity may elucidate mechanisms leading to the observed greater risk of obesity in children with ASD. An exploratory secondary data analysis was performed on resting state functional magnetic resonance imaging (rs-fMRI) data of children downloaded from the ABIDE Preprocessed database (n = 81). Children with isolated ASD showed hypo-connectivity between anterior and posterior default mode network (DMN) (p = 0.003; FWER). Children with coexisting ASD and overweight/obesity showed hyper-connectivity between anterior and posterior DMN (p = 0.015; FWER). More evidence is needed to confirm these contrasting rs-fMRI connectivity profiles and to explicate causal inferences regarding neurophysiological mechanisms associated with coexisting ASD and overweight/obesity.

Multiple studies have suggested that autism spectrum disorders seem to increase the risk of overweight and obesity. We examined the pooled prevalence and relative risk of developing overweight or obesity among children with autism spectrum disorders in a systematic review and meta-analysis. We searched PubMed, Scopus, ProQuest, and Web of Science databases and subsequently screened the records to identify studies that reported prevalence of overweight and/or obesity in children with ASD and matched groups of neurotypical children. DerSimonian-Laird random-effects meta-analyses were performed to examine pooled prevalence and relative risk of obesity in children with autism spectrum disorders using the "meta" package in R software. Among children with autism spectrum disorders, the prevalence of obesity was 22.2%. Children with ASD had a 41.1% greater risk (P = .018) of development of obesity. Non-Caucasian race, increasing age, female sex, and living in the United States emerged as positive moderators of the association between autism spectrum disorders and prevalence of overweight or obesity. Autism spectrum disorders seem to increase the risk of childhood obesity. Increased awareness of this association may allow the implementation of early interventions to reduce obesity and prevent potential deterioration of quality-of-life in this population., (© 2019 World Obesity Federation.)

Objective: To examine whether subscales of Food Craving Inventory (FCI) and Three-factor Eating Questionnaire (TFEQ) correlate with brain functional magnetic resonance imaging food-cue reactivity (fMRI-FCR) in the brain., Methods: Thirty-two male and female adults with obesity (19-60years; 30-39.9kg/m 2 ) participated in a 3-week dietary intervention (1120kcal/day from either 1) total meal replacement shakes, 2) portion-controlled typical food. FCI, TFEQ and fMRI-FCR were measured pre- and post-intervention. Correlations between pre-intervention fMRI-FCR and standardized pre-intervention FCI and TFEQ subscales; and also post- versus pre-intervention change in fMRI-FCR (ΔfMRI-FCR) and standardized changes in FCI and TFEQ subscales were examined at the whole brain level using tools in FMRIB Software Library., Results: Twenty-eight subjects completed the intervention. Pre-intervention high-fat food cravings (P=0.041) and fast-food cravings (P=0.017) were negatively correlated with fMRI-FCR of several brain regions that regulate executive control over ingestion (i.e. bilateral lateral frontal pole, dorsolateral prefrontal cortex and dorsal anterior cingulate cortex). Post- vs. pre-intervention change in sweet (P=0.012) and fast food cravings (P=0.004) were negatively correlated with ΔfMRI-FCR of bilateral lateral frontal pole, dorsolateral prefrontal cortex, inferior frontal gyrus (pars opercularis) and dorsal anterior cingulate cortex (i.e. brain regions that regulate executive control over ingestion). Negative correlations were also observed between the changes in sweet and fast food cravings and ΔfMRI-FCR of brain regions that regulate food reward (i.e. bilateral mid-anterior insula, right nucleus accumbens), motor readiness to ingest (i.e. bilateral precentral gyrus), internally focused attention (i.e. bilateral precuneus and posterior cingulate cortex) and visual object recognition (i.e. occipital pole, lateral occipital cortex and middle and inferior temporal cortices). Changes in cravings for starchy food (P=0.032) and overall food cravings (P=0.027) were also negatively correlated with ΔfMRI-FCR of brain regions involved in regulating internally focused attention and visual object recognition., Conclusions: In individuals with obesity, decreased food cravings seem to be reflective of increased fMRI-FCR of brain regions that regulate executive control over ingestion. Taken together, constructs measured by FCI seem to be reflective of neurophysiological processes underlying ingestive behavior and the changes in neurophysiological processes occurring during calorie restriction., Clinical Trials Registry Number: NCT02637271; the protocol is available at https://clinicaltrials.gov/ct2/show/NCT02637271., (Copyright © 2018 Elsevier Inc. All rights reserved.)

We considered 1) influence of self-reported hunger in behavioral and fMRI food-cue reactivity (fMRI-FCR) 2) optimal methods to model this. Adults (N = 32; 19-60 years; F = 21; BMI 30-39.9 kg/m 2 ) participated in an fMRI-FCR task that required rating 240 images of food and matched objects for 'appeal'. Hunger, satiety, thirst, fullness and emptiness were measured pre- and post-scan (visual analogue scales). Hunger, satiety, fullness and emptiness were combined to form a latent factor (appetite). Post-vs. pre-scores were compared using paired t-tests. In mixed-effects models, appeal/fMRI-FCR responses were regressed on image (i.e. food/objects), with random intercepts and slopes of image for functional runs nested within subjects. Each of hunger, satiety, thirst, fullness, emptiness and appetite were added as covariates in 4 forms (separate models): 1) change; 2) post- and pre-mean; 3) pre-; 4) change and pre-. Satiety decreased (Δ = -13.39, p = 0.001) and thirst increased (Δ = 11.78, p = 0.006) during the scan. Changes in other constructs were not significant (p's > 0.05). Including covariates did not influence food vs. object contrast of appeal ratings/fMRI-FCR. Significant image X covariate interactions were observed in some fMRI models. However, including these constructs did not improve the overall model fit. While some subjective, self-reported hunger, satiety and related constructs may be moderating fMRI-FCR, these constructs do not appear to be salient influences on appeal/fMRI-FCR in people with obesity undergoing fMRI., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: Calorie restriction via total meal replacement (TMR) results in greater reduction of food cravings compared to reduced-calorie typical diet (TD). Direct evidence of the impact of these interventions on human brain fMRI food-cue reactivity (fMRI-FCR) and functional connectivity is absent. We examined the effects of a 3-week 1120 kcal/d TMR intervention as compared to an iso-caloric TD intervention using an fMRI-FCR paradigm., Methods: Thirty-two male and female subjects with obesity (19-60 years; 30-39.9 kg/m 2 ) participated in a randomized two-group repeated measures dietary intervention study consisting of 1120 kcal/d from either 1) TMR (shakes), 2) TD (portion control). Pre-intervention and following the 3-week diet fMRI-FCR, functional connectivity, food cravings (Food Craving Inventory) and weight were considered., Results: Compared to TD, TMR showed increased fMRI-FCR of the bilateral dorsolateral prefrontal (dlPFC), orbitofrontal, anterior cingulate, primary motor and left insular cortices and bilateral nucleus accumbens regions in the post-intervention state relative to the pre-intervention state. Compared to TD, TMR was also associated with negative modulation of fMRI-FCR of the nucleus accumbens, orbitofrontal cortex and amygdala by dlPFC. Reduced body weight (4.87 kg, P < 0.001), body fat (2.19 kg, P = 0.004) and overall food cravings (0.41, P = 0.047) were seen in the TMR group. In the TD group reduced body weight (2.37 kg, P = 0.004) and body fat (1.64 kg, P = 0.002) were noted. Weight loss was significantly greater in TMR versus TD (2.50 kg, P = 0.007)., Conclusions: Greater weight loss and reduced cravings, coupled with stronger activations and potential negative modulation of the food reward related regions by the dlPFC during exposure to visual food cues is consistent with increased executive control in TMR vs. TD., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Oral intake of l-theanine and caffeine supplements is known to be associated with faster stimulus discrimination, possibly via improving attention to stimuli. We hypothesized that l-theanine and caffeine may be bringing about this beneficial effect by increasing attention-related neural resource allocation to target stimuli and decreasing deviation of neural resources to distractors. We used functional magnetic resonance imaging (fMRI) to test this hypothesis. Solutions of 200mg of l-theanine, 160mg of caffeine, their combination, or the vehicle (distilled water; placebo) were administered in a randomized 4-way crossover design to 9 healthy adult men. Sixty minutes after administration, a 20-minute fMRI scan was performed while the subjects performed a visual color stimulus discrimination task. l-Theanine and l-theanine-caffeine combination resulted in faster responses to targets compared with placebo (∆=27.8milliseconds, P=.018 and ∆=26.7milliseconds, P=.037, respectively). l-Theanine was associated with decreased fMRI responses to distractor stimuli in brain regions that regulate visual attention, suggesting that l-theanine may be decreasing neural resource allocation to process distractors, thus allowing to attend to targets more efficiently. l-Theanine-caffeine combination was associated with decreased fMRI responses to target stimuli as compared with distractors in several brain regions that typically show increased activation during mind wandering. Factorial analysis suggested that l-theanine and caffeine seem to have a synergistic action in decreasing mind wandering. Therefore, our hypothesis is that l-theanine and caffeine may be decreasing deviation of attention to distractors (including mind wandering); thus, enhancing attention to target stimuli was confirmed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Multiple studies have concluded that calorie restriction for at least 12 weeks is associated with reduced food cravings, while others have shown that calorie restriction may increase food cravings. We addressed this ambiguity in a systematic review and meta-analysis., Methods: We searched for studies conducted on subjects with obesity, implemented calorie restriction for at least 12 weeks and measured food cravings pre-intervention and post-intervention. Our final eight studies mostly used the Food Craving Inventory. Other comparable methods were converted to a similar scale. We used the duration ≥12 weeks, but closest to 16 weeks for studies with multiple follow-ups and performed DerSimonian-Laird random-effects meta-analyses using the 'metafor' package in r software., Results: Despite heterogeneity across studies, we observed reductions in pooled effects for overall food cravings (-0.246 [-0.490, -0.001]) as well as cravings for sweet (-0.410 [-0.626, -0.194]), high-fat (-0.190 [-0.343, -0.037]), starchy (-0.288 [-0.517, -0.058]) and fast food (-0.340 [-0.633, -0.048]) in the meta-analysis. Baseline body weight, type of intervention, duration, sample size and percentage of female subjects explained the heterogeneity., Conclusions: Calorie restriction is associated with reduced food cravings supporting a de-conditioning model of craving reductions. Our findings should ease the minds of clinicians concerned about increased cravings in patients undergoing calorie restriction interventions., (© 2017 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Objective: l-theanine is a constituent of tea which is claimed to enhance cognitive functions. We aimed to determine whether theanine and theanine-caffeine combination have acute positive effects on cognitive and neurophysiological measures of attention, compared to caffeine (a positive control) and a placebo in healthy individuals., Design: In a placebo-controlled, five-way crossover trial in 20 healthy male volunteers, we compared the effects of l-theanine (200 mg), caffeine (160 mg), their combination, black tea (one cup) and a placebo (distilled water) on cognitive (simple [SVRT] and recognition visual reaction time [RVRT]) and neurophysiological (event-related potentials [ERPs]) measures of attention. We also recorded visual (VEPs) and motor evoked potentials (MEPs) to examine any effects of treatments on peripheral visual and motor conduction, respectively., Results: Mean RVRT was significantly improved by theanine (P = 0.019), caffeine (P = 0.043), and theanine-caffeine combination (P = 0.001), but not by tea (P = 0.429) or placebo (P = 0.822). VEP or MEP latencies or SVRT did not show significant inter-treatment differences. Theanine (P = 0.001) and caffeine (P = 0.001) elicited significantly larger mean peak-to-peak N2-P300 ERP amplitudes than the placebo, whereas theanine-caffeine combination elicited a significantly larger mean N2-P300 amplitude than placebo (P < 0.001), theanine (P = 0.029) or caffeine (P = 0.005). No significant theanine × caffeine interaction was observed for RVRT or N2-P300 amplitude., Discussion: A dose of theanine equivalent of eight cups of back tea improves cognitive and neurophysiological measures of selective attention, to a degree that is comparable with that of caffeine. Theanine and caffeine seem to have additive effects on attention in high doses.

Human food intake is regulated by physiological energy homeostatic mechanisms and hedonic mechanisms. These are affected by both very short-term and longer-term calorie restriction (CR). To date, there are parallel discussions in the literature that fail to integrate across these disciplines and topics. First, much of the available neuroimaging research focusses on specific functional paradigms (e.g. reward, energy homeostasis). These paradigms often fail to consider more complex and inclusive models that examine how potential brain regions of interest interact to influence ingestion. Second, the paradigms used focus primarily on short-term CR (fasting) which has limited generalizability to clinical application. Finally, the behavioral literature, while frequently examining longer-term CR and related psychological constructs in the context of weight management (e.g. hedonic restraint, 'liking', 'wanting' and food craving), fails to adequately tie these phenomena to underlying neural mechanisms. The result is a less than complete picture of the brain's role in the complexity of the human experience of ingestion. This disconnect highlights a major limitation in the CR literature, where attempts are persistently made to exert behavioral control over ingestion, without fully understanding the complex bio behavioral systems involved. In this review we attempt to summarize all potential brain regions important for human ingestion, present a broad conceptual overview of the brain's multifaceted role in ingestive behavior, the human (psychological) experiences related to ingestion and to examine how these factors differ according to three forms of CR. These include short-term fasting, extended CR, and restrained eating. We aim to bring together the neuroimaging literature with the behavioral literature within a conceptual framework that may inform future translational research., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Creating a negative energy balance by decreasing caloric consumption and increasing physical activity is a common strategy used to treat obesity. A large number of review and original research papers have considered the role of physical activity in weight loss and maintenance. However, their conclusions are at times conflicting. In this review, we have critically evaluated the findings of systematic reviews and meta-analyses and supplemented their conclusions with recently published, high-quality clinical trials. We have eliminated studies that were methodologically flawed in an attempt to reduce the ambiguity in the literature. We further sought, through selective review of these publications, to isolate the effects of various types of exercise, independent of dietary interventions, to further clarify their independent contributions. Thus, our review describes (i) combined calorie restriction with physical activity interventions, (ii) physical activity interventions without calorie restriction and (iii) the role of physical activity on maintenance of weight loss. Through this critical examination of the literature, we have provided conclusions to address certain ambiguities regarding the role of physical activity in obesity treatment that will inform clinical practice. We have also identified several long-standing gaps in knowledge that will inform future research., (© 2016 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

We aimed to determine the effect of task-specific kinetic finger tremor, as indexed by surface electromyography (EMG), on the accuracy of a carrom stroke. Surface EMG of extensor digitorum communis muscle of the playing arm was recorded during rest, isometric contraction and stroke execution in 17 male carrom players with clinically observed finger tremor and 18 skill- and age-matched controls. Log-transformed power spectral densities (LogPSDs) of surface EMG activity (signifying tremor severity) at a 1-s pre-execution period correlated with angular error of the stroke. LogPSDs in 4-10 Hz range were higher in players with tremor than controls during pre-execution (P < 0.001), but not during the resting state (P = 0.067). Pre-execution tremor amplitude correlated with angular deviation (r = 0.45, P = 0.007). For the first time, we document a task-specific kinetic finger tremor in carrom players. This finger tremor during the immediate pre-execution phase appears to be a significant determinant of stroke accuracy.