Central Executive and Default Mode Networks: An Appraisal of Executive Function and Social Skill Brain-Behavior Correlates in Youth with Autism Spectrum Disorder.

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.

The effectiveness of botulinum toxin for chronic tension-type headache prophylaxis: A systematic review and meta-analysis.

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).

Association Between Autism Spectrum Disorders and Cardiometabolic Diseases: A Systematic Review and Meta-analysis.

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.

Dose-response effect of L-theanine on psychomotor speed, sustained attention, and inhibitory control: a double-blind, placebo-controlled, crossover study.

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.

Regional Variations in Microbiology and Outcomes of Necrotizing Soft Tissue Infections: A Systematic Review and Meta-Analysis.

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.

L-theanine improves neurophysiological measures of attention in a dose-dependent manner: a double-blind, placebo-controlled, crossover study.

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.

Effects of consumption of coconut oil or coconut on glycemic control and insulin sensitivity: A systematic review and meta-analysis of interventional trials.

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-ß 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).

Sex-Dependent Effects of Eicosapentaenoic Acid on Hepatic Steatosis in UCP1 Knockout Mice.

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.

Global patterns of necrotizing soft tissue infections: A systematic review and meta-analysis.

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.

Errors in the implementation, analysis, and reporting of randomization within obesity and nutrition research: a guide to their avoidance.

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.

Effects of L-theanine-caffeine combination on sustained attention and inhibitory control among children with ADHD: a proof-of-concept neuroimaging RCT.

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.

Psychological and weight history variables as predictors of short-term weight and body fat mass loss.

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/m2) 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 Ps > .08) or FML (Ps > .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.

Best (but oft-forgotten) practices: identifying and accounting for regression to the mean in nutrition and obesity research.

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.

Brain activation and affective judgements in response to personal dietary images: An fMRI preliminary study.

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.

The risk of overweight and obesity in children with autism spectrum disorders: A systematic review and meta-analysis.

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.

Effects of Overweight or Obesity on Brain Resting State Functional Connectivity of Children with Autism Spectrum Disorder.

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.