FAP Radioligand Linker Optimization Improves Tumor Dose and Tumor-to-Healthy Organ Ratios in 4T1 Syngeneic Model.

Fibroblast activation protein (FAP) has attracted considerable attention as a possible target for the radiotherapy of solid tumors. Unfortunately, initial efforts to treat solid tumors with FAP-targeted radionuclides have yielded only modest clinical responses, suggesting that further improvements in the molecular design of FAP-targeted radiopharmaceutical therapies (RPT) are warranted. In this study, we report several advances on the previously described FAP6 radioligand that increase tumor retention and accelerate healthy tissue clearance. Seven FAP6 derivatives with different linkers or albumin binders were synthesized, radiolabeled, and investigated for their effects on binding and cellular uptake. The radioligands were then characterized in 4T1 tumor-bearing Balb/c mice using both single-photon emission computed tomography (SPECT) and ex vivo biodistribution analyses to identify the conjugate with the best tumor retention and tumor-to-healthy organ ratios. The results reveal an optimized FAP6 radioligand that exhibits efficacy and safety properties that potentially justify its translation into the clinic.

Determination of unbound platinum concentrations in human plasma using ultrafiltration and precipitation methods.

Quantification of the unbound portion of platinum (Pt) in human plasma is important for assessing the pharmacokinetics of the chemotherapeutic drug cisplatin. In this study, we sought to compare the recovery of unbound Pt using Nanosep® filters to 1) traditional filters (Centrifree®, Centrisart®, Amicon®) or trichloroacetic acid (TCA) protein precipitation, and 2) unbound, bound, and total Pt concentrations in clinical specimens. For the tested filters, the impact of 1) molecular weight cut-offs, 2) centrifugation force, and 3) total Pt concentration on Pt binding in human plasma was evaluated. Pt was quantified using inductively coupled-plasma mass spectrometry. In human plasma spiked with 0.9 µg/mL Pt, the percent of unbound Pt increased at higher centrifugation speeds. By comparison, the percent of unbound Pt was highest (42.1%) following TCA protein precipitation. When total Pt was ≤0.9 µg/mL, unbound Pt (∼20-30%) was consistent across filters. Conversely, when plasma was spiked with Pt exceeding 0.9 µg/mL, the percent of unbound Pt increased from 36.5 to 48% using ultrafiltration, compared to 63.4% to 79% with TCA precipitation. In patients receiving cisplatin-containing chemotherapy, the fraction of unbound Pt at concentrations exceeding 0.9 µg/mL ranged between 35 and 90%. Moreover, the unbound fraction of Pt in plasma correlated with the concentration of unbound (R2 = 0.738) and total Pt (R2 = 0.335). In summary, this study demonstrates that 1) the percent of unbound Pt is influenced by total and unbound Pt levels in vitro and in clinical specimens, and 2) ultrafiltration with Nanosep® filters is a feasible method for quantifying unbound Pt concentrations in human plasma.

Modeled impacts of bouillon fortification with micronutrients on child mortality in Senegal, Burkina Faso, and Nigeria.

Micronutrient interventions can reduce child mortality. By applying Micronutrient Intervention Modeling methods in Senegal, Burkina Faso, and Nigeria, we estimated the impacts of bouillon fortification on apparent dietary adequacy of vitamin A and zinc among children and folate among women. We then used the Lives Saved Tool to predict the impacts of bouillon fortification with ranges of vitamin A, zinc, and folic acid concentrations on lives saved among children 6-59 months of age. Fortification at 250 µg vitamin A/g and 120 µg folic acid/g was predicted to substantially reduce vitamin A- and folate-attributable deaths: 65% for vitamin A and 92% for folate (Senegal), 36% for vitamin A and 74% for folate (Burkina Faso), and >95% for both (Nigeria). Zinc fortification at 5 mg/g would avert 48% (Senegal), 31% (Burkina Faso), and 63% (Nigeria) of zinc-attributable deaths. The addition of all three nutrients at 30% of Codex nutrient reference values in 2.5 g bouillon was predicted to save an annual average of 293 child lives in Senegal (3.5% of deaths from all causes among children 6-59 months of age), 933 (2.1%) in Burkina Faso, and 18,362 (3.7%) in Nigeria. These results, along with evidence on program feasibility and costs, can help inform fortification program design discussions.

To close or not to close? Wound management in emergent colorectal surgery, an EAST multicenter prospective cohort study.

BACKGROUND: This study aimed to determine the clinical impact of wound management technique on surgical site infection (SSI), hospital length of stay (LOS), and mortality in emergent colorectal surgery. METHODS: A prospective observational study (2021-2023) of urgent or emergent colorectal surgery patients at 15 institutions was conducted. Pediatric patients and traumatic colorectal injuries were excluded. Patients were classified by wound closure technique: skin closed (SC), skin loosely closed (SLC), or skin open (SO). Primary outcomes were SSI, hospital LOS, and in-hospital mortality rates. Multivariable regression was used to assess the effect of wound closure on outcomes after controlling for demographics, patient characteristics, intensive care unit admission, vasopressor use, procedure details, and wound class. A priori power analysis indicated that 138 patients per group were required to detect a 10% difference in mortality rates. RESULTS: In total, 557 patients were included (SC, n = 262; SLC, n = 124; SO, n = 171). Statistically significant differences in body mass index, race/ethnicity, American Society of Anesthesiologist scores, EBL, intensive care unit admission, vasopressor therapy, procedure details, and wound class were observed across groups. Overall, average LOS was 16.9 ± 16.4 days, and rates of in-hospital mortality and SSI were 7.9% and 18.5%, respectively, with the lowest rates observed in the SC group. After risk adjustment, SO was associated with increased risk of mortality (OR, 3.003; p = 0.028) in comparison with the SC group. Skin loosely closed was associated with increased risk of superficial SSI (OR, 3.439; p = 0.014), after risk adjustment. CONCLUSION: When compared with the SC group, the SO group was associated with mortality but comparable when considering all other outcomes, while the SLC was associated with increased superficial SSI. Complete skin closure may be a viable wound management technique in emergent colorectal surgery. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Multi-center implementation of rapid whole genome sequencing provides additional evidence of its utility in the pediatric inpatient setting.

Objective: Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease. Study design: rWGS tests were ordered at eight hospitals between November 2017 and April 2020. Investigators completed a survey of demographic data, Human Phenotype Ontology (HPO) terms, test results and impacts of results on clinical care. Results: A total of 188 patients, on general hospital floors and intensive care unit (ICU) settings, underwent rWGS testing. Racial and ethnic characteristics of the tested infants were broadly representative of births in the country at large. 35% of infants received a diagnostic result in a median of 6 days. The most common HPO terms for tested infants indicated an abnormality of the nervous system, followed by the cardiovascular system, the digestive system, the respiratory system and the head and neck. Providers indicated a major change in clinical management because of rWGS for 32% of infants tested overall and 70% of those with a diagnostic result. Also, 7% of infants with a negative rWGS result and 23% with a variant of unknown significance (VUS) had a major change in management due to testing. Conclusions: Our study demonstrates that the implementation of rWGS is feasible across diverse institutions, and provides additional evidence to support the clinical utility of rWGS in a demographically representative sample of admitted infants and includes assessment of the clinical impact of uncertain rWGS results in addition to both positive and negative results.

A Potentially Versatile Enzyme Sensor Platform: Enzyme-Loaded, Tagged, Porous Polymeric Nanocapsules.

Enzymes are essential to life and indispensable in a wide range of industries (food, pharmaceutical, medical, biosensing, etc.); however, a significant shortcoming of these fragile biological catalysts is their poor stability. To address this challenge, a variety of immobilization methods have been described to enhance the enzyme's stability. These immobilization methods generally are specific to an individual enzyme or optimal for a particular application. The aim of this study is to explore the utility of porous, indicator moiety-tagged, polymeric nanocapsules (NCs) for the encapsulation of enzymes and measurement of the enzyme's substrate. As a model enzyme, glucose oxidase (GOx) is used. The GOx enzyme-loaded, fluorophore-tagged NCs were synthesized by using self-assembled surfactant vesicle templates. To show that the biological activity of GOx is preserved during entrapment, the rate of the GOx enzyme catalyzed reaction was measured. To evaluate the protective features of the porous NCs, the encapsulated GOx enzyme activity was followed in the presence of hydrolytic enzymes. During the encapsulation of GOx and the purification of the GOx-loaded NCs, the GOx activity decayed less than 10%, and up to 30% of the encapsulated GOx activity could be retained for 3-5 days in the presence of hydrolytic enzymes. In support of the potentially unique advantages of the enzyme-loaded NCs, as a proof-of-concept example, the fluorophore-tagged, GOx-loaded NCs were used for the determination of glucose in the concentration range between 18 and 162 mg/dL and for imaging the distribution of glucose concentration in imaging experiments.

Differences in Sleep EEG Coherence and Spindle Metrics in Toddlers With and Without Language Delay: A Prospective Observational Study.

Background: Sleep plays a crucial role in early language development, and sleep disturbances are common in children with neurodevelopmental disorders. Examining sleep microarchitecture in toddlers with and without language delays can offer key insights into neurophysiological abnormalities associated with atypical neurodevelopmental trajectories and potentially aid in early detection and intervention. Methods: Here, we investigated electroencephalogram (EEG) coherence and sleep spindles in 16 toddlers with language delay (LD) compared with a group of 39 typically developing (TD) toddlers. The sample was majority male (n = 34, 62%). Participants were aged 12-to-22 months at baseline, and 34 (LD, n=11; TD, n=23) participants were evaluated again at 36 months of age. Results: LD toddlers demonstrated increased EEG coherence compared to TD toddlers, with differences most prominent during slow-wave sleep. Within the LD group, lower expressive language skills were associated with higher coherence in REM sleep. Within the TD group, lower expressive language skills were associated with higher coherence in slow-wave sleep. Sleep spindle density, duration, and frequency changed between baseline and follow-up for both groups, with the LD group demonstrating a smaller magnitude of change than the TD group. The direction of change was frequency-dependent for both groups. Conclusions: These findings indicate that atypical sleep EEG connectivity and sleep spindle development can be detected in toddlers between 12 and 36 months and offers insights into neurophysiological mechanisms underlying the etiology of neurodevelopmental disorders. Trial registration: https://clinicaltrials.gov/study/NCT01339767; Registration date: 4/20/2011.

"not one size fits all" The challenges of measuring paediatric health-related quality of life and the potential role of digital ecological momentary assessment: a qualitative study.

PURPOSE: To explore the views of clinicians and researchers about the challenges of measuring health-related quality of life (HRQoL) in children (5-11 years) and to explore whether digital ecological momentary assessment (EMA) could enhance HRQoL measurement. METHODS: Semi-structured qualitative interviews with 18 professionals (10 academics/researchers, four clinicians, four with both professional backgrounds) experienced in child HRQoL measurement. We analysed data thematically. RESULTS: Theme One describes the uncertainty around conceptualising HRQoL for children and which domains to include; the greater immediacy and sensitivity of children's reflections on their HRQoL, leading to high variability of the construct; and the wide individual differences across childhood, incongruent with fixed HRQoL measures. Theme Two describes the challenges of proxy reporting, questioning whether proxies can meaningfully report a child's HRQoL and reflecting on discrepancies between child and proxy reporting. Theme Three covers the challenge of interpreting change in HRQoL over time; does a change in HRQoL reflect a change in health, or does this reflect developmental changes in how children report HRQoL. Theme Four discusses digital EMA for HRQoL data capture. In-the-moment, repeated measurement could provide rich data and address challenges of recall, ecological validity and variability; passive data could provide objective markers to supplement subjective responses; and technology could enable personalisation and child-centred design. However, participants also raised methodological, practical and ethical challenges of digital approaches. CONCLUSION: Digital EMA may address some of the challenges of HRQoL data collection with children. We conclude by discussing potential future research to explore and develop this approach.

Enhanced External Counterpulsation for the Treatment of Angina With Nonobstructive Coronary Artery Disease.

Angina and nonobstructive coronary artery disease (ANOCA) is associated with poor outcomes and limited treatment options. Enhanced external counterpulsation (EECP) is a noninvasive treatment that involves applying external inflatable cuffs to the lower extremities to increase blood flow during diastole, followed by deflation during systole. Although EECP is approved for treatment in patients with refractory angina due to obstructive coronary artery disease, its effectiveness in treating patients with ANOCA with refractory angina is limited to small studies. We assessed the efficacy of EECP treatment in patients with ANOCA (defined as ≤50% stenosis in any major epicardial vessels) with refractory anginaby measuring changes in Canadian Cardiovascular Society (CCS) angina class, 6-minute walk test, Duke Activity Status Index (DASI), Seattle Angina Questionnaire 7 (SAQ7), and weekly anginal episodes pre-EECP and post-EECP treatment. A total of 101 patients with ANOCA with CCS class III/IV angina completed a full course of EECP treatment at 2 large EECP centers. In 101 patients with ANOCA the mean age (SD) of 60.6 (11.3) years and 62.4% of the cohort were women. We found significant improvements post-EECP treatment in CCS angina class (mean (SD) 3.4 (0.5) to 2.4 (2.9), p <0.001), 6-minute walk test (median 1200 (IQR 972 to 1411) to 1358 (1170 to 1600), p <0.001), DASI (mean (SD) 15.2 (11.6) to 31.5 (16.3), p <0.001), SAQ7 (mean (DS) 36.2 (24.7) to 31.5 (16.3), p <0.001), and weekly anginal episodes (mean (SD) 5.3 (3.5) to 2.4 (2.9), p <0.001). After EECP treatment, 71 patients (70.3%) had an improvement of ≥1 CCS angina class, including 33 (32.7%) patients improving by ≥2 CCS classes. In conclusion, in patients with ANOCA, EECP therapy reduces CCS angina class and improves exercise tolerance and capacity; and should be considered a part of optimal medical therapy.

Congenital diaphragmatic hernia in siblings with PIGA-related congenital disorder of glycosylation.

There are over 150 proteins involved in glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, a class within the larger category of congenital disorders of glycosylation (CDG). Pathogenic variants identified in phosphatidylinositol glycan class A protein (PIGA) are associated with X-linked PIGA-CDG, a GPI-anchor defect. The disease has primarily been characterized by hypotonia, epilepsy, and global developmental delay; however, only 89 known cases are reported, so the phenotypic spectrum has likely not yet been fully delineated. Congenital diaphragmatic hernia (CDH) has been reported in patients with various GPI-anchor related defects but has only been described in one prior individual with PIGA-CDG. Here, we describe the second and third reported cases of CDH in two brothers with PIGA-CDG caused by a pathogenic missense variant in PIGA: c.355C > T, p.R119W. Chromosomal microarray and whole exome sequencing did not reveal another plausible explanation for the CDH. We relate our patients' clinical features to the single previously reported individual with CDH and PIGA-CDG. We then compare this case series with the subset of individuals with CDH and other GPI-anchor defects. These findings suggest that CDH should be considered in the phenotypic disease spectrum of PIGA-CDG.

Open Versus Laparoscopic Appendectomy: A Post Hoc Analysis of the EAST Appendicitis MUSTANG Study.

Background: We sought to understand which factors are associated with open appendectomy as final operative approach. We hypothesize that higher American Association for the Surgery of Trauma (AAST) Emergency General Surgery (EGS) grade is associated with open appendectomy. Patients and Methods: Post hoc analysis of the Eastern Association for the Surgery of Trauma (EAST) Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated and Gangrenous (MUSTANG) prospective appendicitis database was performed. All adults (age >18) undergoing appendectomy were stratified by final operative approach: laparoscopic or open appendectomy (including conversion from laparoscopic). Univariable analysis was performed to compare group characteristics and outcomes, and multivariable logistic regression was performed to identify demographic, clinical, or radiologic factors associated with open appendectomy. Results: A total of 3,019 cases were analyzed. One hundred seventy-five (5.8%) patients underwent open appendectomy, including 127 converted from laparoscopic to open. The median age was 37 (25) years and 53% were male. Compared with the laparoscopic group, open appendectomy patients had more comorbidities, higher proportion of symptoms greater than 96 hours, and higher AAST EGS grade. Moreover, on intraoperative findings, the open appendectomy group had a higher incidence of perforated and gangrenous appendicitis with purulent contamination, abscess/phlegmon, and purulent abdominal/pelvic fluid. On multivariable analysis controlling for comorbidities, clinical and imaging AAST grade, duration of symptoms, and intra-operative findings, only AAST Clinical Grade 5 appendicitis was independently associated with open appendectomy (odds ratio [OR], 5.63; 95% confidence interval [CI], 1.24-25.55; p = 0.025). Conclusions: In the setting of appendicitis, generalized peritonitis (AAST Clinical Grade 5) is independently associated with greater odds of open appendectomy.

Virtual Post-Intervention Speech and Language Assessment of Toddler and Preschool Participants in Babble Boot Camp.

PURPOSE: Babble Boot Camp (BBC) is a parent-implemented telepractice intervention for infants at risk for speech and language disorders. BBC uses a teach-model-coach-review approach, delivered through weekly 15-min virtual meetings with a speech-language pathologist. We discuss accommodations needed for successful virtual follow-up test administration and preliminary assessment outcomes for children with classic galactosemia (CG) and controls at age 2.5 years. METHOD: This clinical trial included 54 participants, 16 children with CG receiving BBC speech-language intervention from infancy, age 2 years, five children receiving sensorimotor intervention from infancy and changing to speech-language intervention at 15 months until 2 years of age, seven controls with CG, and 26 typically developing controls. The participants' language and articulation were assessed via telehealth at age 2.5 years. RESULTS: The Preschool Language Scale-Fifth Edition (PLS-5) was successfully administered with specific parent instruction and manipulatives assembled from the child's home. The GFTA-3 was successfully administered to all but three children who did not complete this assessment due to limited expressive vocabularies. Referrals for continued speech therapy based on PLS-5 and GFTA-3 scores were made for 16% of children who received BBC intervention from infancy as compared to 40% and 57% of children who began BBC at 15 months of age or did not receive BBC intervention, respectively. CONCLUSIONS: With extended time and accommodations from the standardized administration guidelines, virtual assessment of speech and language was possible. However, given the inherent challenges of testing very young children virtually, in-person assessment is recommended, when possible, for outcome measurements.

Posterior superior temporal cortex connectivity is related to social communication in toddlers.

The second year of life is a time when social communication skills typically develop, but this growth may be slower in toddlers with language delay. In the current study, we examined how brain functional connectivity is related to social communication abilities in a sample of 12-24 month-old toddlers including those with typical development (TD) and those with language delays (LD). We used an a-priori, seed-based approach to identify regions forming a functional network with the left posterior superior temporal cortex (LpSTC), a region associated with language and social communication in older children and adults. Social communication and language abilities were assessed using the Communication and Symbolic Behavior Scales (CSBS) and Mullen Scales of Early Learning. We found a significant association between concurrent CSBS scores and functional connectivity between the LpSTC and the right posterior superior temporal cortex (RpSTC), with greater connectivity between these regions associated with better social communication abilities. However, functional connectivity was not related to rate of change or language outcomes at 36 months of age. These data suggest an early marker of low communication abilities may be decreased connectivity between the left and right pSTC. Future longitudinal studies should test whether this neurobiological feature is predictive of later social or communication impairments.

Biomarkers of oxidative stress, diet and exercise distinguish soldiers selected and non-selected for special forces training.

INTRODUCTION: The metabolomic profiles of Soldiers entering the U.S. Special Forces Assessment and Selection course (SFAS) have not been evaluated. OBJECTIVES: To compare pre-SFAS blood metabolomes of Soldiers selected during SFAS versus those not selected, and explore the relationships between the metabolome, physical performance, and diet quality. METHODS: Fasted blood samples and food frequency questionnaires were collected from 761 Soldiers prior to entering SFAS to assess metabolomic profiles and diet quality, respectively. Physical performance was assessed throughout SFAS. RESULTS: Between-group differences (False Discovery Rate < 0.05) in 108 metabolites were detected. Selected candidates had higher levels of compounds within xenobiotic, pentose phosphate, and corticosteroid metabolic pathways, while non-selected candidates had higher levels of compounds potentially indicative of oxidative stress (i.e., sphingomyelins, acylcarnitines, glutathione, amino acids). Multiple compounds higher in non-selected versus selected candidates included: 1-carboxyethylphenylalanine; 4-hydroxy-nonenal-glutathione; α-hydroxyisocaproate; hexanoylcarnitine; sphingomyelin and were associated with lower diet quality and worse physical performance.  CONCLUSION: Candidates selected during SFAS had higher pre-SFAS levels of circulating metabolites that were associated with resistance to oxidative stress, higher physical performance and higher diet quality. In contrast, non-selected candidates had higher levels of metabolites potentially indicating elevated oxidative stress. These findings indicate that Soldiers who were selected for continued Special Forces training enter the SFAS course with metabolites associated with healthier diets and better physical performance. Additionally, the non-selected candidates had higher levels of metabolites that may indicate elevated oxidative stress, which could result from poor nutrition, non-functional overreaching/overtraining, or incomplete recovery from previous physical activity.

Sex differences in body composition and serum metabolome responses to sustained, physical training suggest enhanced fat oxidation in women compared with men.

Sex differences in energy metabolism during acute, submaximal exercise are well documented. Whether these sex differences influence metabolic and physiological responses to sustained, physically demanding activities is not well characterized. This study aimed to identify sex differences within changes in the serum metabolome in relation to changes in body composition, physical performance, and circulating markers of endocrine and metabolic status during a 17-day military training exercise. Blood was collected, and body composition and lower body power were measured before and after the training on 72 cadets (18 women). Total daily energy expenditure (TDEE) was assessed using doubly labeled water in a subset throughout. TDEE was greater in men (4,085 ± 482 kcal/d) than in women (2,982 ± 472 kcal/d, P < 0.001), but not after adjustment for dry lean mass (DLM). Men tended to lose more DLM than women (mean change [95% CI]: -0.2[-0.3, -0.1] vs. -0.0[-0.0, 0.0] kg, P = 0.063, Cohen's d = 0.50) and have greater reductions in lower body power (-244[-314, -174] vs. -130[-209, -51] W, P = 0.085, d = 0.49). Reductions in DLM and lower body power were correlated (r = 0.325, P = 0.006). Women demonstrated greater fat oxidation than men (Δfat mass/DLM: -0.20[-0.24, -0.17] vs. -0.15[-0.17, -0.13] kg, P = 0.012, d = 0.64). Metabolites within pathways of fatty acid, endocannabinoid, lysophospholipid, phosphatidylcholine, phosphatidylethanolamine, and plasmalogen metabolism increased in women relative to men. Independent of sex, changes in metabolites related to lipid metabolism were inversely associated with changes in body mass and positively associated with changes in endocrine and metabolic status. These data suggest that during sustained military training, women preferentially mobilize fat stores compared with men, which may be beneficial for mitigating loss of lean mass and lower body power.NEW & NOTEWORTHY Women preferentially mobilize fat stores compared with men in response to sustained, physically demanding military training, as evidenced by increased lipid metabolites and enhanced fat oxidation, which may be beneficial for mitigating loss of lean mass and lower body power.

Climate warming has direct and indirect effects on microbes associated with carbon cycling in northern lakes.

Northern lakes disproportionately influence the global carbon cycle, and may do so more in the future depending on how their microbial communities respond to climate warming. Microbial communities can change because of the direct effects of climate warming on their metabolism and the indirect effects of climate warming on groundwater connectivity from thawing of surrounding permafrost, especially at lower landscape positions. Here we used shotgun metagenomics to compare the taxonomic and functional gene composition of sediment microbes in 19 peatland lakes across a 1600-km permafrost transect in boreal western Canada. We found microbes responded differently to the loss of regional permafrost cover than to increases in local groundwater connectivity. These results suggest that both the direct and indirect effects of climate warming, which were respectively associated with loss of permafrost and subsequent changes in groundwater connectivity interact to change microbial composition and function. Archaeal methanogens and genes involved in all major methanogenesis pathways were more abundant in warmer regions with less permafrost, but higher groundwater connectivity partly offset these effects. Bacterial community composition and methanotrophy genes did not vary with regional permafrost cover, and the latter changed similarly to methanogenesis with groundwater connectivity. Finally, we found an increase in sugar utilization genes in regions with less permafrost, which may further fuel methanogenesis. These results provide the microbial mechanism for observed increases in methane emissions associated with loss of permafrost cover in this region and suggest that future emissions will primarily be controlled by archaeal methanogens over methanotrophic bacteria as northern lakes warm. Our study more generally suggests that future predictions of aquatic carbon cycling will be improved by considering how climate warming exerts both direct effects associated with regional-scale permafrost thaw and indirect effects associated with local hydrology.

Effectiveness of executive functioning training among heterogeneous adolescent samples: A systematic review.

The aim of the present systematic review was to discuss the reported efficacy of executive functioning training techniques among adolescents. A systematic review of the literature was conducted to retrieve and consolidate findings from articles evaluating executive functioning training techniques among adolescents. A total of 26 articles were located that examined the role of executive functioning training techniques among adolescents (age 10-19 years). Articles retrieved enabled comparison across psychiatric and medical diagnoses including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), as well as adolescents with physical health concerns. Results revealed that among typically developing adolescents, executive functioning training was non-significant or yielded small effect size improvements in executive functioning as measured by behavioral and neuroimaging tasks among 62.5% of studies reviewed. In contrast, in those with medical conditions, ASD, ADHD, and conduct disorder, all but two studies reviewed yielded a medium to large effect size, supporting the effectiveness of EF training. Future research is needed to identify the long-term efficacy of these treatments, as well as their generalizability to real-world conditions.

Effects of energy balance on cognitive performance, risk-taking, ambulatory vigilance and mood during simulated military sustained operations (SUSOPS).

Sustained operations (SUSOPS) require military personnel to conduct combat and training operations while experiencing physical and cognitive stress and limited sleep. These operations are often conducted in a state of negative energy balance and are associated with degraded cognitive performance and mood. Whether maintaining energy balance can mitigate these declines is unclear. This randomized crossover study assessed the effects of energy balance on cognitive performance, risk-taking propensity, ambulatory vigilance, and mood during a simulated 72-h SUSOPS. METHODS: Ten male Soldiers (mean ± SE; 22.4 ± 1.7 y; body weight 87.3 ± 1.1 kg) completed two, 72-h simulated SUSOPS in random order, separated by 7 days of recovery. Each SUSOPS elicited ∼4500 kcal/d total energy expenditure and restricted sleep to 4 h/night. During SUSOPS, participants consumed either an energy-balanced or restricted diet that induced a 43 ± 3% energy deficit. A cognitive test battery was administered each morning and evening to assess: vigilance, working memory, grammatical reasoning, risk-taking propensity, and mood. Real-time ambulatory vigilance was assessed each morning, evening, and night via a wrist-worn monitoring device. RESULTS: Participants exhibited heightened risk-taking propensity (p = 0.047) with lower self-reported self-control (p = 0.021) and fatigue (p = 0.013) during energy deficit compared to during energy balance. Vigilance accuracy (p < 0.001) and working memory (p = 0.040) performance decreased, and vigilance lapses increased (p < 0.001) during SUSOPS, but did not differ by diet. Percentage of correct responses to ambulatory vigilance stimuli varied during SUSOPS (p = 0.019) independent of diet, with generally poorer performance during the morning and night. Total mood disturbance (p = 0.001), fatigue (p < 0.001), tension (p = 0.003), and confusion (p = 0.036) increased whereas vigor decreased (p < 0.001) during SUSOPS, independent of diet. CONCLUSION: Prolonged physical activity combined with sleep restriction is associated with impaired vigilance, memory, and mood state. Under such conditions, maintaining energy balance prevents increased risk-taking and improves self-control, but does not improve other aspects of cognitive function or mood. Given the small sample in the present study, replication in a larger cohort is warranted.