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In a multicenter, randomized, placebo-controlled trial involving women at high risk for preterm preeclampsia, treatment with low-dose aspirin initiated at 11 to 14 weeks of gestation was associated with a lower incidence of this diagnosis.

Decreased success at work and educational attainment by adulthood are of concern for children with ADHD given their widely documented academic difficulties; however there are few studies that have examined this empirically and even fewer that have studied predictors and individual variability of these outcomes. The current study compares young adults with and without a childhood diagnosis of ADHD on educational and occupational outcomes and the predictors of these outcomes. Participants were from the Pittsburgh ADHD Longitudinal Study (PALS), a prospective study with yearly data collection. Significant group differences were found for nearly all variables such that educational and occupational attainment was lower for adults with compared to adults without histories of childhood ADHD. Despite the mean difference, educational functioning was wide-ranging. High school academic achievement significantly predicted enrollment in post-high school education and academic and disciplinary problems mediated the relationship between childhood ADHD and post-high school education. Interestingly, ADHD diagnosis and disciplinary problems negatively predicted occupational status while enrollment in post-high school education was a positive predictor. Job loss was positively predicted by a higher rate of academic problems and diagnosis of ADHD. This study supports the need for interventions that target the child and adolescent predictors of later educational and occupational outcomes in addition to continuing treatment of ADHD in young adulthood targeting developmentally appropriate milestones, such as completing post-high school education and gaining and maintaining stable employment.[PUBLICATION ABSTRACT]

Even after evidence-based treatment, Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with poor long-term outcomes. These outcomes may be partly explained by difficulties in peer functioning, which are common among children with ADHD and which do not respond optimally to standard ADHD treatments. We examined whether peer rejection and lack of dyadic friendships experienced by children with ADHD after treatment contribute to long-term emotional and behavioral problems and global impairment, and whether having a reciprocal friend buffers the negative effects of peer rejection. Children with Combined type ADHD (N=300) enrolled in the Multimodal Treatment Study of Children with ADHD (MTA) were followed for 8 years. Peer rejection and dyadic friendships were measured with sociometric assessments after the active treatment period (14 or 24 months after baseline; M ages 9.7 and 10.5 years, respectively). Outcomes included delinquency, depression, anxiety, substance use, and general impairment at 6 and 8 years after baseline (Mean ages 14.9 and 16.8 years, respectively). With inclusion of key covariates, including demographics, symptoms of ADHD, ODD, and CD, and level of the outcome variable at 24 months, peer rejection predicted cigarette smoking, delinquency, anxiety, and global impairment at 6 years and global impairment at 8 years after baseline. Having a reciprocal friend was not, however, uniquely predictive of any outcomes and did not reduce the negative effects of peer rejection. Evaluating and addressing peer rejection in treatment planning may be necessary to improve long-term outcomes in children with ADHD.[PUBLICATION ABSTRACT]

Background The goal of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) is to improve patient safety. The database has been used by hospitals across the United States to decrease the rate of adverse events and improve surgical outcomes, including dramatic decreases in 30-day mortality, morbidity, and complication rates. However, only a few orthopaedic surgical studies have employed the ACS NSQIP database, all of which have limited their analysis to either single orthopaedic procedures or reported rates of adverse events without considering the effect of patient characteristics and comorbidities. Question/purposes Our specific purposes included (1) investigating the most common orthopaedic procedures and 30-day adverse events, (2) analyzing the proportion of adverse events in the top 30 most frequently identified orthopaedic procedures, and (3) identifying patient characteristics and clinical risk factors for adverse events in patients undergoing hip fracture repair. Methods We used data from the ACS NSQIP database to identify a large prospective cohort of patients undergoing orthopaedic surgery procedures from 2005 to 2011 in more than 400 hospitals around the world. Outcome variables were separated into the following three categories: any complication, minor complication, and major complication. The rate of adverse events for the top 30 orthopaedic procedures was calculated. Bivariate and multivariate analyses were used to determine risk factors for each of the outcome variables for hip fracture repair. Results Of the 1,979,084 surgical patients identified in the database, 146,774 underwent orthopaedic procedures (7%). Of the 30 most common orthopaedic procedures, the top three were TKA, THA, and knee arthroscopy with meniscectomy, which together comprised 55% of patients (55,575 of 101,862). We identified 5368 complications within the top 30 orthopaedic procedures, representing a 5% complication rate. The minor and major complication rates were 3.1% (n = 3174) and 2.8% (n = 2880), respectively. The most common minor complication identified was urinary tract infection (n = 1534) and the most common major complication identified was death (n = 850). An American Society of Anesthesiologists class of 3 or higher was a consistent risk factor for all three categories of complications in patients undergoing hip fracture repair. Conclusions The ACS NSQIP database allows for evaluating current trends of adverse events in selected surgical specialties. However, variables specific to orthopaedic surgery, such as open versus closed injury, are needed to improve the quality of the results.

l -Lactate, traditionally considered a metabolic waste product, is increasingly recognized as an important intercellular energy currency in mammals. To enable investigations of the emerging roles of intercellular shuttling of l -lactate, we now report an intensiometric green fluorescent genetically encoded biosensor for extracellular l -lactate. This biosensor, designated eLACCO1.1, enables cellular resolution imaging of extracellular l -lactate in cultured mammalian cells and brain tissue. l -lactate is an important intercellular energy currency. Here the authors report a genetically encoded biosensor eLACCO1.1 to monitor extracellular l -lactate; they use eLACCO1.1 to image extracellular l -lactate in cultured mammalian cells and brain tissue.

This study compared the high school academic experience of adolescents with and without childhood ADHD using data from the Pittsburgh ADHD Longitudinal Study (PALS). Participants were 326 males with childhood ADHD and 213 demographically similar males without ADHD who were recruited at the start of the follow-up study. Data were collected yearly from parents, teachers and schools. The current study used assessment points at which the participants were currently in or had recently completed grades 9, 10, 11, and 12. Results indicated that adolescents with ADHD experienced significant academic impairment in high school relative to comparison adolescents, including lower overall and main academic subject grade point averages (GPA), lower levels of class placement (e.g. remedial vs. honors), and higher rates of course failure. In addition, teacher reports indicated that adolescents with ADHD completed and turned in a significantly lower percentage of assignments and were significantly less likely to be working up to their potential. Adolescents with ADHD were also significantly more likely to be absent or tardy during the academic year, and they were over eight times more likely than adolescents without ADHD to drop out of high school. These findings demonstrate that children with ADHD continue to experience severe academic impairment into high school. [PUBLICATION ABSTRACT]

Potassium ion (K + ) plays a critical role as an essential electrolyte in all biological systems. Genetically-encoded fluorescent K + biosensors are promising tools to further improve our understanding of K + -dependent processes under normal and pathological conditions. Here, we report the crystal structure of a previously reported genetically-encoded fluorescent K + biosensor, GINKO1, in the K + -bound state. Using structure-guided optimization and directed evolution, we have engineered an improved K + biosensor, designated GINKO2, with higher sensitivity and specificity. We have demonstrated the utility of GINKO2 for in vivo detection and imaging of K + dynamics in multiple model organisms, including bacteria, plants, and mice.

The hypothalamus senses the appetite-regulating hormones and also coordinates the metabolic function in alignment with the circadian rhythm. This alignment is essential to maintain the physiological conditions that prevent clinically important comorbidities, such as obesity or type-2 diabetes. However, a complete model of the hypothalamus that relates food intake with circadian rhythms and appetite hormones has not yet been developed. In this work, we present a computational model that accurately allows interpreting neural activity in terms of hormone regulation and sleep-wake cycles. We used a conductance-based model, which consists of a system of four differential equations that considers the ionotropic and metabotropic receptors, and the input currents from homeostatic hormones. We proposed a logistic function that fits available experimental data of insulin hormone concentration and added it into a short-term ghrelin model that served as an input to our dynamical system. Our results show a double oscillatory system, one synchronized by light-regulated sleep-wake cycles and the other by food-regulated feeding-fasting cycles. We have also found that meal timing frequency is highly relevant for the regulation of the hypothalamus neurons. We therefore present a mathematical model to explore the plausible link between the circadian rhythm and the endogenous food clock.

Table-top extreme ultraviolet (EUV) microscopy offers unique opportunities for label-free investigation of biological samples. Here, we demonstrate ptychographic EUV imaging of two dried, unstained model specimens: germlings of a fungus ( Aspergillus nidulans ), and bacteria ( Escherichia coli ) cells at 13.5 nm wavelength. We find that the EUV spectral region, which to date has not received much attention for biological imaging, offers sufficient penetration depths for the identification of intracellular features. By implementing a position-correlated ptychography approach, we demonstrate a millimeter-squared field of view enabled by infrared illumination combined with sub-60 nm spatial resolution achieved with EUV illumination on selected regions of interest. The strong element contrast at 13.5 nm wavelength enables the identification of the nanoscale material composition inside the specimens. Our work will advance and facilitate EUV imaging applications and enable further possibilities in life science.

Attention-deficit/hyperactivity disorder (ADHD) persists in older age and is postulated as a risk factor for cognitive impairment and Alzheimer’s Disease (AD). However, these findings rely primarily on electronic health records and can present biased estimates of disease prevalence. An obstacle to investigating age-related cognitive decline in ADHD is the absence of large-scale studies following patients with ADHD into older age. Alternatively, this study aimed to determine whether genetic liability for ADHD, as measured by a well-validated ADHD polygenic risk score (ADHD-PRS), is associated with cognitive decline and the development of AD pathophysiology in cognitively unimpaired (CU) older adults. We calculated a weighted ADHD-PRS in 212 CU individuals without a clinical diagnosis of ADHD (55–90 years). These individuals had baseline amyloid-β (Aβ) positron emission tomography, longitudinal cerebrospinal fluid (CSF) phosphorylated tau at threonine 181 (p-tau 181 ), magnetic resonance imaging, and cognitive assessments for up to 6 years. Linear mixed-effects models were used to test the association of ADHD-PRS with cognition and AD biomarkers. Higher ADHD-PRS was associated with greater cognitive decline over 6 years. The combined effect between high ADHD-PRS and brain Aβ deposition on cognitive deterioration was more significant than each individually. Additionally, higher ADHD-PRS was associated with increased CSF p-tau 181 levels and frontoparietal atrophy in CU Aβ-positive individuals. Our results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology. Findings were mostly observed in Aβ-positive individuals, suggesting that the genetic liability for ADHD increases susceptibility to the harmful effects of Aβ pathology.