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Impaired glycaemic control is a major risk factor for developing type 2 diabetes (T2D), a worldwide health epidemic intrinsically linked to diet and obesity. Whey proteins (WP) are increasingly popular supplements that are a rich source of branched-chain amino acids (BCAA), essential for muscle protein synthesis and metabolic regulation. In humans, fasting plasma concentrations of BCAA are maintained around 350 µM but become chronically elevated by 10-25% in persons with T2D. Little is known about whether BCAA from WP impacts circulating BCAA concentrations and contributes to this phenomenon. This narrative review used a systematic search approach with relevant keywords to identify evidence from randomised controlled trials in normoglycaemic humans and those with insulin resistance or T2D, on the effects of WP intake on plasma BCAA and glycaemic control. This review is, to the authors’ knowledge, the first to specifically examine the effects of WP intake on plasma BCAA concentrations in relation to glycaemic control. Whilst the majority of acute studies identified (n=6) reported that WP consumption between 10 to 50 g significantly elevates postprandial BCAA and insulin responses (as evidenced by peak concentration and/or area under the curve), evidence from chronic studies (n=3) report inconsistent findings on the impact of 9 to 51g of WP per day on fasting BCAA and glycaemic control (e.g., fasting glucose and insulin, insulin clearance). Findings from this literature review highlight the need for further studies that investigate the relationship between WP consumption with BCAA and glycaemic control, and to determine underlying mechanisms of action.
Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.
Artificial intelligence (AI) has the potential to enhance clinical decision-making, including in infectious diseases. By improving antimicrobial resistance prediction and optimizing antibiotic prescriptions, these technologies may support treatment strategies and address critical gaps in healthcare. This study evaluates the effectiveness of AI in guiding appropriate antibiotic prescriptions for infectious diseases through a systematic literature review.
Methods:
We conducted a systematic review of studies evaluating AI (machine learning or large language models) used for guidance on prescribing appropriate antibiotics in infectious disease cases. Searches were performed in PubMed, CINAHL, Embase, Scopus, Web of Science, and Google Scholar for articles published up to October 25, 2024. Inclusion criteria focused on studies assessing the performance of AI in clinical practice, with outcomes related to antimicrobial management and decision-making.
Results:
Seventeen studies used machine learning as part of clinical decision support systems (CDSS). They improved prediction of antimicrobial resistance and optimized antimicrobial use. Six studies focused on large language models to guide antimicrobial therapy; they had higher prescribing error rates, patient safety risks, and needed precise prompts to ensure accurate responses.
Conclusions:
AI, particularly machine learning integrated into CDSS, holds promise in enhancing clinical decision-making and improving antimicrobial management. However, large language models currently lack the reliability required for complex clinical applications. The indispensable role of infectious disease specialists remains critical for ensuring accurate, personalized, and safe treatment strategies. Rigorous validation and regular updates are essential before the successful integration of AI into clinical practice.
Transcranial direct current stimulation (tDCS) is a promising treatment for major depressive disorder (MDD). This study evaluated its antidepressant and cognitive effects as a safe, effective, home-based therapy for MDD.
Methods
This double-blind, sham-controlled, randomized trial divided participants into low-intensity (1 mA, n = 47), high-intensity (2 mA, n = 49), and sham (n = 45) groups, receiving 42 daily tDCS sessions, including weekends and holidays, targeting the dorsolateral prefrontal cortex for 30 minutes. Assessments were conducted at baseline and weeks 2, 4, and 6. The primary outcome was cognitive improvement assessed by changes in total accuracy on the 2-back test from baseline to week 6. Secondary outcomes included changes in depressive symptoms (HAM-D), anxiety (HAM-A), and quality of life (QLES). Adverse events were monitored. This trial was registered with ClinicalTrials.gov (NCT04709952).
Results
In the tDCS study, of 141 participants (102 [72.3%] women; mean age 35.7 years, standard deviation 12.7), 95 completed the trial. Mean changes in the total accuracy scores from baseline to week 6 were compared across the three groups using an F-test. Linear mixed-effects models examined the interaction of group and time. Results showed no significant differences among groups in cognitive or depressive outcomes at week 6. Active groups experienced more mild adverse events compared to sham but had similar rates of severe adverse events and dropout.
Conclusions
Home-based tDCS for MDD demonstrated no evidence of effectiveness but was safe and well-tolerated. Further research is needed to address the technical limitations, evaluate broader cognitive functions, and extend durations to evaluate its therapeutic potential.
Objectives: Studies in PD have traditionally focused on motor features, however, interest in non-motor manifestations has increased resulting in improved knowledge regarding the prognosis of the disease. Although several studies have explored the incidence of dementia in PD cohorts, these studies have been conducted mainly in reference centers in high-income countries (HIC). In this study we aimed to analyze the prevalence of cognitive impairment in people with parkinsonism and PD and its association with incident dementia in a population- based study, of elderly from six Latin American countries.
Methods: This report consists of the analysis of data from a follow-up of 12,865 elderly people aged 65 years or older, carried out by 10/66 Dementia Research Group. Residents of urban and rural areas, from six low and middle- income countries (Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico and Peru). Exposures include parkinsonism and PD defined according to the UK Parkinson’s Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main exposure and dementia was measured through the dementia diagnosis algorithm from 10/66 DRG.
Results: At baseline, the overall prevalence of cognitive impairment was 14% (n = 1,581), in people with parkinsonism and PD, it was of 30.0% and 26.2%, respectively. Parkinsonism and PD were individually associated with prevalent and incident dementia after controlling for age, sex, and education. The pooled odds ratios from a fixed-effects meta-analysis were 2.2 (95% CI: 1.9 – 2.6) for parkinsonism and 1.9 (95% CI: 1.4 – 2.4) for PD. Regarding incident dementia, the pooled sub-Hazard ratio estimated using a competing risk model was 1.5 (95% CI: 1.2 –1.9) for parkinsonism and 1.5 (95% CI: 1.0 – 2.2) forPD.
Conclusions: Parkinsonism and PD were associated cross-sectionally with the presence of cognitive impairment, and prospectively with incident dementia in elderly people in the community population of Latin America studied. Systematic screening for cognitive impairment and dementia with valid tools in PD patients may help with earlier detection of those at highest risk for adverse outcomes. Identifying modifiable risk factors could potentially lead to efficient interventions even in advanced stages of PD.
Background: Limited knowledge exists about the association between Parkinsonism or Parkinson’s disease (PD) and cognitive impairment and dementia in Latin America.
Objectives: The study aimed to determine the cross-sectional and prospective associations between Parkinsonism and PD with cognitive impairment and dementia in a large multi-country cohort in Latin America.
Methods: The 10/66 is a prospective, observational cohort study. This population-based cohort study was based in six Latin American countries: Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico, and Peru. The study includes 12,865 participants from six countries, including residents aged 65 years and living in urban and rural catchment areas. Exposures included diagnosed Parkinsonism and PD defined according to the United Kingdom Parkinson’s Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main outcome measure for cross-sectional analysis and dementia was used to measure the prospective association with the exposures. Logistic regression models were used to explore the association between Parkinsonism/PD with cognitive impairment at baseline. Competing risk models were used to assess the prospective association between Parkinsonism/PD with incident dementia accounting for competing risk of mortality. Individual country analyses were combined via fixed-effect meta-analysis.
Results: At baseline, the prevalence of cognitive impairment in people with Parkinsonism and PD was 30% and 26.2%, respectively. Parkinsonism (OR 2.2 (95%CI 1.9 – 2.6)) and PD (1.9 (95%CI 1.4 – 2.4)) were individually associated with baseline and incident cognitive impairment after accounting for age, sex, and education, after pooling. In competing risk models, the pooled sub- hazard ratios for dementia in the fixed effect metanalysis were 1.5 (95%CI 1.2 – 1.9) for parkinsonism and 1.5 (95%CI 1.0 – 2.2) for PD.
Conclusions: Parkinsonism and PD were cross-sectionally associated with cognitive impairment and prospectively associated with incident dementia in Latin America. Routine screening for cognitive impairment and dementia with validated tools in PD patients may aid earlier detection of those at greater risk ofadverseoutcomes.
Similar to adults with posttraumatic stress disorder, children with early life adversity show bias in memory for negative emotional stimuli. However, it is not well understood how childhood adversity impacts mechanisms underlying emotional memory. N = 56 children (8–14 years, 48% female) reported on adverse experiences including potentially traumatic events and underwent fMRI while attending to emotionally pleasant, neutral, or negative images. Post-scan, participants completed a cued recall test to assess memory for these images. Emotional difference-in-memory (DM) scores were computed by subtracting negative or positive from neutral recall performance. All children showed enhancing effects of emotion on recall, with no effect of trauma load. However, children with less trauma showed a larger emotional DM for both positive and negative stimuli when amygdala or anterior hippocampal activity was higher. In contrast, highly trauma-exposed children demonstrated a lower emotional DM with greater amygdala or hippocampal activity. This suggested that alternative neural mechanisms might support emotional enhancement of encoding in children with greater trauma load. Whole-brain analyses revealed that right fusiform activity during encoding positively correlated with both trauma load and successful later recall of positive images. Therefore, highly trauma-exposed children may use alternative, potentially adaptive neural pathways via the ventral visual stream to encode positive emotional events.
GX is a code designed to solve the nonlinear gyrokinetic system for low-frequency turbulence in magnetized plasmas, particularly tokamaks and stellarators. In GX, our primary motivation and target is a fast gyrokinetic solver that can be used for fusion reactor design and optimization along with wide-ranging physics exploration. This has led to several code and algorithm design decisions, specifically chosen to prioritize time to solution. First, we have used a discretization algorithm that is pseudospectral in the entire phase space, including a Laguerre–Hermite pseudospectral formulation of velocity space, which allows for smooth interpolation between coarse gyrofluid-like resolutions and finer conventional gyrokinetic resolutions and efficient evaluation of a model collision operator. Additionally, we have built GX to natively target graphics processors (GPUs), which are among the fastest computational platforms available today. Finally, we have taken advantage of the reactor-relevant limit of small $\rho _*$ by using the radially local flux-tube approach. In this paper we present details about the gyrokinetic system and the numerical algorithms used in GX to solve the system. We then present several numerical benchmarks against established gyrokinetic codes in both tokamak and stellarator magnetic geometries to verify that GX correctly simulates gyrokinetic turbulence in the small $\rho _*$ limit. Moreover, we show that the convergence properties of the Laguerre–Hermite spectral velocity formulation are quite favourable for nonlinear problems of interest. Coupled with GPU acceleration, which we also investigate with scaling studies, this enables GX to be able to produce useful turbulence simulations in minutes on one (or a few) GPUs and higher fidelity results in a few hours using several GPUs. GX is open-source software that is ready for fusion reactor design studies.
Background: Data on antimicrobial use at the national level is crucial to establish domestic antimicrobial stewardship policies and enable medical institutions to benchmark against each other. This study aimed to analyze antimicrobial use in Korean hospitals. Methods: We investigated the antimicrobials prescribed in Korean hospitals between 2018 and 2021, using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. Results: Out of more than 1,900 hospitals, PCHs and TCHs represented the largest and lowest percentage of hospitals, respectively. The most frequently prescribed antimicrobial in 2021 was piperacillin/β-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial class according to the KONAS classification was ‘broad-spectrum antibacterial agents predominantly used for community-acquired infections’ in TCHs and SCHs, and 'narrow spectrum beta-lactam agents' in PCH. Total consumption of antimicrobials has decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and from 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period, but not in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, while use of reserve antimicrobials has decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs, it has increased from 0.7 to 0.8 DOT/1,000 patient-days in PCHs. Conclusion: This study confirms that antimicrobial use differs by hospital type in Korea. Recent increases of use of antimicrobials, including reserve antimicrobials, in PCHs reflect the challenges that must be addressed.
Accordingly, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) working committee, composed of domestic experts, developed Korea’s first KMAP-BP in 2002 and later in 2006, 2010, and 2010. A revised version of KMAP-BP was announced every four years four times in 2014 and 2018.6-10). The treatment strategy considering the safety and tolerability of KMAP-BP 2022 was developed by collecting opinions from domestic bipolar disorder experts.
Objectives
Safety and tolerability of drugs are very important factors in the treatment of bipolar disorder. An expert opinion survey was conducted on treatment strategies in various special clinical situations, such as significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling.
Methods
A written survey about treatment strategies related to safety and tolerability was prepared and focused on significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling. Ninety-three experts of the review committee completed the survey.
Results
In the case of weight gain occurring during drug treatment, it was preferred to replace it with a drug that caused less weight gain, such as lamotrigine, aripiprazole, or ziprasidone. If there was a significant weight gain due to the treatment drug, it was preferred to intervene as soon as possible. In the case of hyperprolactinemia, it was selected to change the medication and discontinue it for benign rash caused by lamotrigine. In improving drug adherence, the preference for long-acting injections increased. Antipsychotics can be used with great caution in pregnant or reproductive women.
Conclusions
Treatment strategies in various clinical situations related to safety and tolerability in drug treatment for bipolar disorder were described. It is hoped that it will be useful in practical clinical situations.
Mental healthcare services that address a variety of primary complaints which are highly related to maladaptive personality traits among the general population are important to prevent developing psychiatric disorders.
Objectives
This study aimed to examine the effectiveness of a digital mental health service (named “Mindling”) that focuses on maladaptive personality traits in the general population.
Methods
Participants were recruited through a South Korean community website and screened for adults between the ages of 18 and 60 in terms of personality traits such as perfectionism, low self-esteem, social isolation, or anxiety. Participants were allocated to four intervention programs (Riggy, Pleaser, Shelly, and Jumpy) based on their screening results and were randomly assigned to digital treatment and waitlist groups. Each intervention program was conducted online for 10 weeks. The primary outcomes were all measured by self-report questionnaires; in addition to stress levels, each program included measures of perfectionism (Riggy), low self-esteem (Pleaser), loneliness (Shelly), and anxiety (Jumpy). The secondary outcomes included self-efficacy, depression, and other psychological states. All participants completed pre-treatment (baseline), intervention (week 5), and post-treatment (week 10) assessments, and the treatment group completed a separate follow-up assessment (week 14).
Results
In the treatment group, 70.05% of the participants completed the full course of the digital intervention. The mean scores for each primary outcome measure and some secondary outcome measures were significantly different between baseline and post-treatment in the treatment group for the Total, Riggy, Pleaser, Shelly, and Jumpy programs, but these differences were not observed in the waitlist group. In addition, mean differences between the treatment and waitlist groups at post-treatment assessment were significant for all primary outcome measures and some secondary outcome measures. Specifically, the levels of stress (Total program), perfectionism (Riggy), loneliness (Shelly), and anxiety (Jumpy) were significantly lower in the treatment group, while self-esteem (Pleaser) was higher. In addition, the mean differences between post-treatment and follow-up assessment data were not statistically significant for all primary outcome measures and nearly all secondary outcome measures.
Conclusions
This study validated the effectiveness of the digital intervention program targeting maladaptive personality traits and suggested its sustainable effects.
Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.
A new magnetic mirror machine named KAIMIR (KAIST mirror) has been designed and constructed at the Korea Advanced Institute of Science and Technology (KAIST) to study mirror plasma physics and simulate the boundary regions of magnetic fusion plasmas such as in a tokamak. The purpose of this paper is to introduce the characteristics and initial experimental results of KAIMIR. The cylindrical vacuum chamber has a length of 2.48 m and a diameter of 0.5 m and consists of three sub-chambers, namely the source, centre and expander chambers. A magnetic mirror configuration is achieved by electromagnetic coils with a maximum magnetic field strength of 0.4 T at the mirror nozzles and 0.1 T at the centre. The source plasma is generated by a plasma washer gun installed in the source chamber with a pulse forming network system. The typical discharge time is ~12 ms with a ~6 ms (1–7 ms) steady period. Initial results show that the on-axis electron density at the centre is 1019–20 m−3 and the electron temperature is 4–7 eV. Two parameters were varied in this initial phase, the source power and the mirror ratio, which is the ratio of highest to lowest magnetic field strength in the mirror-confined region. We observed that the increase of the electron density was mitigated for a source power above 0.2 MW. It was also found that the electron density increases almost linearly with the mirror ratio. Accordingly, the stored electron energy was also linearly proportional to the mirror ratio, similar to the scaling of the gas dynamic trap.
The COVID-19 pandemic significantly disrupted schools and learning formats. Children with epilepsy are at-risk for generalized academic difficulties. We investigated the potential impact of COVID-19 on learning in those with epilepsy by comparing achievement on well-established academic measures among school-age children with epilepsy referred prior to the COVID-19 pandemic and those referred during the COVID-19 pandemic.
Participants and Methods:
This study included 466 children [52% male, predominately White (76%), MAge=10.75 years] enrolled in the Pediatric Epilepsy Research Consortium Epilepsy (PERC) Surgery database project who were referred for surgery and seen for neuropsychological testing. Patients were divided into two groups based on a proxy measure of pandemic timing completed by PERC research staff at each site (i.e., “were there any changes to typical in-person administration [of the evaluation] due to COVID?”). 31% of the sample (N = 144) were identified as having testing during the pandemic (i.e., “yes” response), while 69% were identified as having testing done pre-pandemic (i.e., “no” response). Of the 31% who answered yes, 99% of administration changes pertained to in-person testing or other changes, with 1% indicating remote testing. Academic achievement was assessed by performance measures (i.e., word reading, reading comprehension, spelling, math calculations, and math word problems) across several different tests. T-tests compared the two groups on each academic domain. Subsequent analyses examined potential differences in academic achievement among age cohorts that approximately matched grade level [i.e., grade school (ages 5-10), middle school (ages 11-14), and high school (ages 15-18)].
Results:
No significant differences were found between children who underwent an evaluation before the pandemic compared to those assessed during the pandemic based on age norms across academic achievement subtests (all p’s > .34). Similarly, there were no significant differences among age cohorts. The average performance for each age cohort generally fell in the low average range across academic skills. Performance inconsistently varied between age cohorts. The youngest cohort (ages 5-10) scored lower than the other cohorts for sight-word reading, whereas this cohort scored higher than the middle cohort (ages 11-14) for math word problems and reading comprehension. There were no significant differences between the two pandemic groups on demographic variables, intellectual functioning, or epilepsy variables (i.e., age of onset, number of seizure medications, seizure frequency).
Conclusions:
Academic functioning was generally equivalent between children with epilepsy who underwent academic testing as part of a pre-surgical evaluation prior to the pandemic compared to those who received testing during the pandemic. Additionally, academic functioning did not significantly differ between age cohorts. Children with epilepsy may have entered the pandemic with effective academic supports and/or were accustomed to school disruptions given their seizure history. Replication is needed as findings are based on a proxy measure of pandemic timing and the extent to which children experienced in-person, remote, and hybrid learning is unknown. Children tested a year into the pandemic, after receiving instruction through varying educational methods, may score differently than those tested earlier. Future research can address these gaps. Although it is encouraging that academic functioning was not disproportionately impacted during the pandemic in this sample, children with epilepsy are at-risk for generalized academic difficulties and continued monitoring of academic functioning is necessary.
The stria terminalis (ST) is a white matter tract with connections to limbic and autonomic brain structures that is implicated in affective functioning. Recent works suggests that ST functional integrity and connectivity is associated with faster responses to emotional cues (Dzafic et al., 2019) and may be influenced by environmental factors including socioeconomic status (SES) and childhood adversity (Banihashemi et al., 2020). The role of the ST in the experience of more daily affective experiences, such as depressive symptoms, remains unexplored. Therefore, the present study examined the role of the ST and SES, as assessed by household income, in the relationship between age and depressive symptoms in typically developing children and adolescents.
Participants and Methods:
Participants include 64 typically developing children and adolescents age 8-21 (Mage=13.27, SD=3.15) who participated in an ongoing study of development of neurocognitive and social-cognitive skills. Participants completed imaging on a 3Tesla MR Siemens PRISMA scanner. Tractography was executed via ENIGMA tract-based spatial statistics to quantify WM integrity and provided values for mean fractional anisotropy (mFA) of the ST. Depressive symptoms were measured with the Behavior Assessment Scale for Children-Third Edition (BASC-3) parent report scale, and annual family income was obtained per parent report. Mediation and moderation analyses were conducted using Process version 4.1 (Hayes, 2022) in SPSS version 28. As depression symptoms are often higher in early adolescence than later, we examined the indirect effect of age on depressive symptoms through ST mFA and evaluated this relationship at different levels of family income.
Results:
Age was associated with lower levels of depressive symptoms (b=-.98, t=-2.18, p<.05), whereas greater right ST mFA was associated with higher levels of depressive symptoms (b=42.05, t=2.50, p<.05). Right ST mFA explained significant variance in the relationship between age and parent-reported depression (ab=.13, 95% CI [.02, .29]). The conditional indirect effect of family income was significant for children with annual family incomes between 25-50k (effect=.16, 95% CI [.01, .38]) and 75-100k (effect=.13, 95% CI [.001, .31]), but not for 100k+ (effect=.11, 95% CI [-.05, .33]).
Conclusions:
The present study revealed a significant, positive relationship between white matter integrity in the right ST and parent-reported depressive symptoms in healthy children and young adults. Finding extend on prior work implicating the ST in threat responsivity (Dzafic et al., 2019). Moreover,results suggest the role of the ST in the relationship between age and depression depends on level of family income, such that ST mFA explains more variance at lower income levels, and is no longer significant for children from families with income greater than 100k. These findings support the notion that environmental stressors (such as lower family income) may strengthen ST pathways via activity-dependent plasticity and repeated, coordinated activation (Rinaman et al., 2011). Future studies should examine these brain-behavior associations, as they may replicate in a larger sample, with more nuanced indicators of environmental stress.
The Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database Project is a multisite collaborative that includes neuropsychological evaluations of children presenting for epilepsy surgery. There is some evidence for specific neuropsychological phenotypes within epilepsy (Hermann et al, 2016); however, this is less clear in pediatric patients. As a first step, we applied an empirically-based subtyping approach to determine if there were specific profiles using indices from the Wechsler scales [Verbal IQ (VIQ), Nonverbal IQ (NVIQ), Processing Speed Index (PSI), Working Memory Index (WMI)]. We hypothesized that there would be at least four profiles that are distinguished by slow processing speed and poor working memory as well as profiles with significant differences between verbal and nonverbal reasoning abilities.
Participants and Methods:
Our study included 372 children (M=12.1 years SD=4.1; 77.4% White; 48% male) who completed an age-appropriate Wechsler measure, enough to render at least two index scores. Epilepsy characteristics included 84.4% with focal epilepsy (evenly distributed between left and right focus) and 13.5% with generalized or mixed seizure types; mean age of onset = 6.7 years, SD = 4.5; seizure frequency ranged from daily to less than monthly; 53% had structural etiology; 71% had an abnormal MRI; and mean number of antiseizure medications was two. Latent profile analysis was used to identify discrete underlying cognitive profiles based on intellectual functioning. Demographic and epilepsy characteristics were compared among profiles.
Results:
Based on class enumeration procedures, a 3-cluster solution provided the best fit for the data, with profiles characterized by generally Average, Low Average, or Below Average functioning. 32.8% were in the Average profile with mean index scores ranging from 91.7-103.2; 47.6% were in the Low Average profile with mean index ranging from 80.7 to 84.5; and 19.6% were in the Below Average profile with mean index scores ranging from 55.0-63.1. Across all profiles, the lowest mean score was the PSI, followed by WMI. VIQ and NVIQ represented relatively higher scores for all three profiles. Mean discrepancy between indices within a profile was as large as 11.5 IQ points. No demographics or epilepsy characteristics were significantly different across cognitive phenotypes.
Conclusions:
Latent cognitive phenotypes in a pediatric presurgical cohort were differentiated by general level of functioning; however, across profiles, processing speed was consistently the lowest index followed by working memory. These findings across phenotypes suggest a common relative weakness which may result from a global effect of antiseizure medications and/or the widespread impact of seizures on neural networks even in a largely focal epilepsy cohort; similar to adult studies with temporal lobe epilepsy (Hermann et al, 2007). Future work will use latent profile analysis to examine phenotypes across other domains relevant to pediatric epilepsy including attention, naming, motor, and memory functioning. These findings are in line with collaborative efforts towards cognitive phenotyping which is the aim of our PERC Epilepsy Surgery Database Project that has already established one of the largest pediatric epilepsy surgery cohorts.
Children with epilepsy are at greater risk of lower academic achievement than their typically developing peers (Reilly and Neville, 2015). Demographic, social, and neuropsychological factors, such as executive functioning (EF), mediate this relation. While research emphasizes the importance of EF skills for academic achievement among typically developing children (e.g., Best et al., 2011; Spiegel et al., 2021) less is known among children with epilepsy (Ng et al., 2020). The purpose of this study is to examine the influence of EF skills on academic achievement in a nationwide sample of children with epilepsy.
Participants and Methods:
Participants included 427 children with epilepsy (52% male; MAge= 10.71), enrolled in the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database who had been referred for surgery and underwent neuropsychological testing. Academic achievement was assessed by performance measures (word reading, reading comprehension, spelling, and calculation and word-based mathematics) and parent-rating measures (Adaptive Behavior Assessment System (ABAS) Functional Academics and Child Behavior Checklist (CBCL) School Performance). EF was assessed by verbal fluency measures, sequencing, and planning measures from the Delis Kaplan Executive Function System (DKEFS), NEPSY, and Tower of London test. Rating-based measures of EF included the 'Attention Problems’ subscale from the CBCL and 'Cognitive Regulation’ index from the Behavior Rating Inventory of Executive Function (BRIEF-2). Partial correlations assessed associations between EF predictors and academic achievement, controlling for fullscale IQ (FSIQ; A composite across intelligence tests). Significant predictors of each academic skill or rating were entered into a two-step regression that included FSIQ, demographics, and seizure variables (age of onset, current medications) in the first step with EF predictors in the second step.
Results:
Although zero-order correlations were significant between EF predictors and academic achievement (.29 < r’s < .63 for performance; -.63 < r’s < -.50 for rating measures), partial correlations controlling for FSIQ showed fewer significant relations. For performance-based EF, only letter fluency (DKEFS Letter Fluency) and cognitive flexibility (DKEFS Trails Condition 4) demonstrated significant associations with performance-based academic achievement (r’s > .29). Regression models for performance-based academic achievement indicated that letter fluency (ß = .22, p = .017) and CBCL attention problems (ß = -.21, p =.002) were significant predictors of sight-word reading. Only letter fluency (ß = .23, p =.006) was significant for math calculation. CBCL Attention Problems were a significant predictor of spelling performance (ß = -.21, p = .009) and reading comprehension (ß = -.18, p =.039). CBCL Attention Problems (ß = -.38, p <.001 for ABAS; ß = -.34, p =.002 for CBCL School) and BRIEF-2 Cognitive Regulation difficulties (ß = -.46, p < .001 for ABAS; ß = -.46, p =.013 for CBCL School) were significant predictors of parent-rated ABAS Functional Academics and CBCL School Performance.
Conclusions:
Among a national pediatric epilepsy dataset, performance-based and ratings-based measures of EF predicted performance academic achievement, whereas only ratings-based EF predicted parent-rated academic achievement, due at least in part to shared method variance. These findings suggest that interventions that increase cognitive regulation, reduce symptoms of attention dysfunction, and promote self-generative, flexible thinking, may promote academic achievement among children with epilepsy.
Pediatric patients with frontal lobe epilepsy (FLE) have higher rates of attention deficit hyperactivity disorder (ADHD), as well as executive functioning (EF) and fine motor (FM) challenges. Relations between these constructs have been established in youth with ADHD and are supported by FM and EF skill involvement in frontal-subcortical systems. Still, they are not well understood in pediatric FLE. We hypothesized that poorer FM performance would be related to greater executive dysfunction and ADHD symptomatology in this group.
Participants and Methods:
47 children and adolescents with FLE (AgeM=12.47, SD=5.18; IQM=84.07; SD=17.56; Age of Seizure OnsetM=6.85, SD=4.64; right-handed: n=34; left-handed: n=10; Unclear: n=3) were enrolled in the Pediatric Epilepsy Research Consortium dataset as part of their phase I epilepsy surgical evaluation. Participants were selected if they had unifocal FLE and completed the Lafayette Grooved Pegboard (GP). Seizure lateralization (left-sided: n=19; right-sided: n=26; bilateral: n=2) and localization were established via data (e.g., EEG, MRI) presented at a multidisciplinary team case conference. Patients completed neuropsychological measures of FM, attention, and EF. Parents also completed questionnaires inquiring about their child’s everyday EF and ADHD symptomatology. Correlational analyses were conducted to examine FM, EF, and ADHD relations.
Results:
Dominant hand (DH) manual dexterity (GP) was related to parent-reported EF (Behavior Rating Inventory of Executive Function, Second Edition [BRIEF-2]-Global Executive Composite [GEC]: r(15) =-.70, p<.01, d=1.96). While not statistically significant, medium to large effect sizes were found for GP DH and parent-reported inattention (Behavior Assessment System for Children, Third Edition [BASC-3]-Attention Problems: r(12)=-.39, p=.17, d=.85) and hyperactivity/impulsivity (BASC-3-Hyperactivity: r(11)= -.44, p=.13, d=.98), as well as performance-based attention (Conners Continuous Performance Test, Third Edition -Omission Errors: r(12)=-.35, p=.22, d=.41), working memory (Wechsler Intelligence Scale for Children - Fifth Edition [WISC-V]-Digit Span [DS]: r(19)=.38, p=.09, d=.82) and cognitive flexibility (Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Category Switching: r(13)=.46, p=.08, d=1.04); this suggests that these relations may exist but that our study was underpowered to detect them. Non-dominant hand (NDH) manual dexterity was related to performance-based working memory (WISC-V-DS: r(19)=.50, p<.01, d=1.12) and cognitive flexibility (D-KEFS-Trails Making Test Number-Letter Switching: r(17)=.64, p<.01, d=1.67). Again, while underpowered, medium to large effect sizes were found for GP NDH and parent-reported EF (BRIEF-2 GEC: r(15) =-.45, p=.07, d=1.01) and performance-based phonemic fluency (D-KEFS-Letter Fluency: r(13)=.31, p=.20, d=.65).
Conclusions:
Our findings suggest that FM, EF, and ADHD are related in youth with FLE; however, these relations appear to vary by skill and hand. We posit that our findings are due in part to the frontal-cerebellar networks given their anatomic proximity between frontal motor areas and the dorsolateral prefrontal cortex - as well as their shared functional involvement in these networks. Future studies should evaluate the predictive validity of initial FM skills for later executive dysfunction and ADHD symptomatology in FLE. If such relations emerge, contributions of early FM interventions on EF development should be examined. Further replication of these findings with a larger sample is warranted.
This meta-analysis aimed to consolidate existing data from randomised controlled trials on hypoplastic left heart syndrome.
Methods:
Hypoplastic left heart syndrome specific randomised controlled trials published between January 2005 and September 2021 in MEDLINE, EMBASE, and Cochrane databases were included. Regardless of clinical outcomes, we included all randomised controlled trials about hypoplastic left heart syndrome and categorised them according to their results. Two reviewers independently assessed for eligibility, relevance, and data extraction. The primary outcome was mortality after Norwood surgery. Study quality and heterogeneity were assessed. A random-effects model was used for analysis.
Results:
Of the 33 included randomised controlled trials, 21 compared right ventricle-to-pulmonary artery shunt and modified Blalock–Taussig-Thomas shunt during the Norwood procedure, and 12 regarded medication, surgical strategy, cardiopulmonary bypass tactics, and ICU management. Survival rates up to 1 year were superior in the right ventricle-to-pulmonary artery shunt group; this difference began to disappear at 3 years and remained unchanged until 6 years. The right ventricle-to-pulmonary artery shunt group had a significantly higher reintervention rate from the interstage to the 6-year follow-up period. Right ventricular function was better in the modified Blalock–Taussig-Thomas shunt group 1–3 years after the Norwood procedure, but its superiority diminished in the 6-year follow-up. Randomised controlled trials regarding medical treatment, surgical strategy during cardiopulmonary bypass, and ICU management yielded insignificant results.
Conclusions:
Although right ventricle-to-pulmonary artery shunt appeared to be superior in the early period, the two shunts applied during the Norwood procedure demonstrated comparable long-term prognosis despite high reintervention rates in right ventricle-to-pulmonary artery shunt due to pulmonary artery stenosis. For medical/perioperative management of hypoplastic left heart syndrome, further randomised controlled trials are needed to deliver specific evidence-based recommendations.
Self-compassion (SC) describes an emotionally positive attitude extended toward ourselves when we suffer, consisting of three main components; self-kindness, common humanity, and mindfulness (Germer & Neff, 2013). SC entails being warm and understanding towards ourselves when encountering pain or personal shortcomings, rather than ignoring them or flagellating ourselves with self-criticism. SC also involves recognizing that suffering and failure are part of the shared human experience rather than isolating. In addition, SC requires taking a mindful approach to one’s feelings and thoughts, without judgment of them.
Objectives
Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing depression and anxiety in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied.
Methods
Magnetic resonance imaging data were acquired from 71 healthy participants with measured levels of SC and its six subscales. Mirroring network as WM regions of interest were analyzed using tract-based spatial statistics (TBSS). After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed.
Results
We found that self-compassion scale (SCS) total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores of SCS were also negatively correlated with FA values of the same regions. The FA values of SLF related to SC were found to be negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy.
Conclusions
Our findings suggest that levels of SC and its self-kindness and mindfulness components may be negatively associated with DMN-related WM microstructures in healthy individuals. These less WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies.