WNT2B Deficiency Causes Enhanced Susceptibility to Colitis Due to Increased Inflammatory Cytokine Production.

BACKGROUND & AIMS: Humans with WNT2B deficiency have severe intestinal disease, including significant inflammatory injury, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis. METHODS: We investigated the intestinal health of Wnt2b knock out (KO) mice. We assessed the baseline histology and health of the small intestine and colon, and the impact of inflammatory challenge using dextran sodium sulfate (DSS). We also evaluated human intestinal tissue. RESULTS: Mice with WNT2B deficiency had normal baseline histology but enhanced susceptibility to DSS colitis because of an increased early injury response. Although intestinal stem cells markers were decreased, epithelial proliferation was similar to control subjects. Wnt2b KO mice showed an enhanced inflammatory signature after DSS treatment. Wnt2b KO colon and human WNT2B-deficient organoids had increased levels of CXCR4 and IL6, and biopsy tissue from humans showed increased neutrophils. CONCLUSIONS: WNT2B is important for regulation of inflammation in the intestine. Absence of WNT2B leads to increased expression of inflammatory cytokines and increased susceptibility to gastrointestinal inflammation, particularly in the colon.

Longitudinal patterns of adversity from childhood to adolescence: Examining associations with mental health through emerging adulthood using a random-intercept latent transition analysis.

Childhood adversity can have detrimental impacts on life course mental and physical health. Timing, nature, severity, and chronicity of adversity are thought to explain much of the variability in health and developmental outcomes among exposed individuals. The current study seeks to characterize heterogeneity in adverse experiences over time at the individual, family, and neighborhood domains in a cohort of predominantly Black children (85% Black and 15% White, 46.2% girls, 67.2% free/reduced lunch in first grade), and to examine associations with mental health from sixth grade to age 26. Participants were part of a randomized universal preventive interventions trial in first grade with prospective follow-up through early adulthood. Separate models characterized heterogeneity in adversity in elementary, middle, and high schools. Changes in adversity over time and relationships with mental health (anxiety, depression, suicidal behaviors) were investigated using a random-intercept latent transition analysis (RI-LTA). We identified three-class solutions in early childhood, middle school, and high school. Generally, both a higher and a lower poly-adversity class were observed at each time point, with varying nature of adversity characterized by the third class. RI-LTA indicated prevalent within-individual changes in adverse exposure over time and differential associations with mental health and suicidal behaviors. Results suggest that treating adverse exposures as a static construct may limit the ability to characterize salient variation over time. Identifying complexity in adverse experiences and their relation to health and well-being is key for developing and implementing effective prevention and early intervention efforts to mitigate negative effects through the life course. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

G-CSF increases calprotectin expression, liver damage and neuroinflammation in a murine model of alcohol-induced ACLF.

Background and aims: Granulocyte colony-stimulating factor (G-CSF) has been proposed as a therapeutic option for patients with ACLF, however clinical outcomes are controversial. We aimed at dissecting the role of G-CSF in an alcohol-induced murine model of ACLF. Methods: ACLF was triggered by a single alcohol binge (5 g/kg) in a bile duct ligation (BDL) liver fibrosis model. A subgroup of mice received two G-CSF (200 µg/kg) or vehicle injections prior to acute decompensation with alcohol. Liver, blood and brain tissues were assessed. Results: Alcohol binge administered to BDL-fibrotic mice resulted in features of ACLF indicated by a significant increase in liver damage and systemic inflammation compared to BDL alone. G-CSF treatment in ACLF mice induced an increase in liver regeneration and neutrophil infiltration in the liver compared to vehicle-treated ACLF mice. Moreover, liver-infiltrating neutrophils in G-CSF-treated mice exhibited an activated phenotype indicated by increased expression of CXC motif chemokine receptor 2, leukotriene B4 receptor 1, and calprotectin. In the liver, G-CSF triggered increased oxidative stress, type I interferon response, extracellular matrix remodeling and inflammasome activation. Circulating IL-1ß was also increased after G-CSF treatment. In the cerebellum, G-CSF increased neutrophil infiltration and S100a8/9 expression, induced microglia proliferation and reactive astrocytes, which was accompanied by oxidative stress, and inflammasome activation compared to vehicle-treated ACLF mice. Conclusion: In our novel ACLF model triggered by alcohol binge that mimics ACLF pathophysiology, neutrophil infiltration and S100a8/9 expression in the liver and brain indicate increased tissue damage, accompanied by oxidative stress and inflammasome activation after G-CSF treatment.

Progress in elementary school reading linked to growth of cortical responses to familiar letter combinations within visual word forms.

Learning to read depends on the ability to extract precise details of letter combinations, which convey critical information that distinguishes tens of thousands of visual word forms. To support fluent reading skill, one crucial neural developmental process is one's brain sensitivity to statistical constraints inherent in combining letters into visual word forms. To test this idea in early readers, we tracked the impact of two years of schooling on within-subject longitudinal changes in cortical responses to three different properties of words: coarse tuning for print, and fine tuning to either familiar letter combinations within visual word forms or whole word representations. We then examined how each related to growth in reading skill. Three stimulus contrasts-words versus pseudofonts, words versus pseudowords, pseudowords versus nonwords-were presented while high-density EEG Steady-State Visual Evoked Potentials (SSVEPs, n = 31) were recorded. Internalization of abstract visual word form structures over two years of reading experience resulted in a near doubling of SSVEP amplitude, with increasing left lateralization. Longitudinal changes (decreases) in brain responses to such word form structural information were linked to the growth in reading skills, especially in rapid automatic naming of letters. No such changes were observed for whole word representation processing and coarse tuning for print. Collectively, these findings indicate that sensitivity to visual word form structure develops rapidly through exposure to print and is linked to growth in reading skill. RESEARCH HIGHLIGHTS: Longitudinal changes in cognitive responses to coarse print tuning, visual word from structure, and whole word representation were examined in early readers. Visual word form structure processing demonstrated striking patterns of growth with nearly doubled in EEG amplitude and increased left lateralization. Longitudinal changes (decreases) in brain responses to visual word form structural information were linked to the growth in rapid automatic naming for letters. No longitudinal changes were observed for whole word representation processing and coarse tuning for print.

Increasing Maternal Anxiety in the Pre- to Postpartum Transition Predicts Infant Feeding Practices and Beliefs.

OBJECTIVE: Anxiety symptoms increase for some mothers in the perinatal period. Little is known about how increasing anxiety relates to infant feeding beliefs or weight-for-length. We examined relationships between clinically meaningful increases in maternal anxiety symptoms and perceptions of infant feeding behaviors and weight-for-length. METHODS: Participants were 237 mothers with singleton pregnancies enrolled from obstetric care between 2015 and 2020 who completed the Infant Feeding Questionnaire (IFQ) at 6 months. Anxiety symptoms were measured during pregnancy (M = 24.6 weeks, SD = 6.3) and 6 weeks postpartum using the PROMIS-6A. Linear regression was used to test associations of prenatal, postpartum, or clinically meaningful increases in anxiety symptoms (ie, 3T-score increase) with two outcomes: IFQ (seven factors) and infant weight-for-length at age 6 months. RESULTS: Prenatal symptoms were unrelated to IFQ factors. Postpartum symptoms predicted IFQ factors related to worry, such as concern for infant undereating/becoming underweight (B = 0.012, P = .02). Increasing symptoms predicted worry-related concerns as well as concern for infant hunger (B = 0.60, P ≤ .01) and greater preference for feeding on a schedule (B = 0.65, P ≤ .01). In a model including both increasing symptoms and postpartum symptoms, increasing anxiety symptoms drove associations with IFQ factors (eg, preference for feeding on a schedule, (B = 0.81, P = .01). Anxiety was unrelated to infant weight-for-length at 6 months. CONCLUSIONS: Clinically meaningful increases in anxiety symptoms were associated with feeding beliefs related to worry. Increasing anxiety was a better predictor of feeding beliefs than the presence of pre- or postpartum symptoms alone. Mothers with increasing anxiety may benefit from support establishing health-promoting infant feeding practices.

miR-431 secreted by human vestibular schwannomas increases the mammalian inner ear's vulnerability to noise trauma.

Introduction: Vestibular schwannoma (VS) is an intracranial tumor that arises on the vestibular branch of cranial nerve VIII and typically presents with sensorineural hearing loss (SNHL). The mechanisms of this SNHL are postulated to involve alterations in the inner ear's microenvironment mediated by the genetic cargo of VS-secreted extracellular vesicles (EVs). We aimed to identify the EV cargo associated with poor hearing and determine whether its delivery caused hearing loss and cochlear damage in a mouse model in vivo. Methods: VS tissue was collected from routinely resected tumors of patients with good (VS-GH) or poor (VS-PH) pre-surgical hearing measured via pure-tone average and word recognition scores. Next-generation sequencing was performed on RNA isolated from cultured primary human VS cells and EVs from VS-conditioned media, stratified by patients' hearing ability. microRNA expression levels were compared between VS-PH and VS-GH samples to identify differentially expressed candidates for packaging into a synthetic adeno-associated viral vector (Anc80L65). Viral vectors containing candidate microRNA were infused to the semicircular canals of mice to evaluate the effects on hearing, including after noise exposure. Results: Differentially expressed microRNAs included hsa-miR-431-5p (enriched in VS-PH) and hsa-miR-192-5p (enriched in VS-GH). Newborn mice receiving intracochlear injection of viral vectors over-expressing hsa-miR-431-GFP, hsa-miR-192-GFP, or GFP only (control) had similar hearing 6 weeks post-injection. However, after acoustic trauma, the miR-431 group displayed significantly worse hearing, and greater loss of synaptic ribbons per inner hair cell in the acoustically traumatized cochlear region than the control group. Conclusion: Our results suggest that miR-431 contributes to VS-associated hearing loss following cochlear stress. Further investigation is needed to determine whether miR-431 is a potential therapeutic target for SNHL.

Chlamydia psittaci -Induced Reactive Infectious Mucocutaneous Eruption With Ocular Involvement.

INTRODUCTION: This report highlights a postinfectious mucocutaneous inflammatory response involving the ocular surface and adnexa after Chlamydophila psittaci exposure. CASE DESCRIPTION: A 35-year-old man presented after a prodrome of upper respiratory symptoms with rash and mucocutaneous blistering involving the ocular and oral mucosa, causing pseudomembranous conjunctivitis and corneal epithelial defects. Extensive inflammatory and infectious workup suggested recent C. psittaci infection. The patient was treated with doxycycline and supportive therapy, whereas the ocular surface was treated with lubrication and prophylactic antibiotics. In follow-up, he has retained excellent visual acuity but required scleral contact lenses to control ocular surface symptoms because of fibrotic changes of the marginal conjunctiva. DISCUSSION: Such blistering inflammation has most commonly been described after pediatric respiratory infections because of Mycoplasma pneumoniae with additional instances related to Chlamydia pneumoniae , Epstein-Barr virus, influenza B, and other stimuli . To the best of our knowledge, this is the first reported case of C. psittaci- induced reactive infectious mucocutaneous eruption (RIME). RIME is a rare parainfectious inflammatory condition with sequelae frequently involving the periocular mucosa. Although systemic and nonocular adverse outcomes in this condition tend to be self-limited, the impact on the ocular surface may be severe, and the consequences to vision may be ongoing, especially if not treated aggressively at the outset.

Using Epigenetic Clocks to Characterize Biological Aging in Studies of Children and Childhood Exposures: a Systematic Review.

Biological age, measured via epigenetic clocks, offers a unique and useful tool for prevention scientists to explore the short- and long-term implications of age deviations for health, development, and behavior. The use of epigenetic clocks in pediatric research is rapidly increasing, and there is a need to review the landscape of this work to understand the utility of these clocks for prevention scientists. We summarize the current state of the literature on the use of specific epigenetic clocks in childhood. Using systematic review methods, we identified studies published through February 2023 that used one of three epigenetic clocks as a measure of biological aging. These epigenetic clocks could either be used as a predictor of health outcomes or as a health outcome of interest. The database search identified 982 records, 908 of which were included in a title and abstract review. After full-text screening, 68 studies were eligible for inclusion. While findings were somewhat mixed, a majority of included studies found significant associations between the epigenetic clock used and the health outcome of interest or between an exposure and the epigenetic clock used. From these results, we propose the use of epigenetic clocks as a tool to understand how exposures impact biologic aging pathways and development in early life, as well as to monitor the effectiveness of preventive interventions that aim to reduce exposure and associated adverse health outcomes.

Surgical Management of Iris Bombe in Muscle-Eye-Brain Disease.

A 2-year-old girl with severe muscular dystrophy presented with unilateral eye pain and corneal clouding. She was found to have absent red reflex, hypotonia, cerebral hypoplasia, and iris bombe on ultrasound biomicroscopy, a feature not previously reported in this syndrome. She responded favorably to surgical management. Iris bombe can be a cause of glaucoma in muscle-eye-brain disease. This highlights the importance of incorporating ultrasound biomicroscopy into the diagnostic algorithm of muscle-eye-brain disease and other types of congenital syndromic glaucoma. [J Pediatr Ophthalmol Strabismus. 2023;60(4):e35-e37.].

Simulating Subject-Specific Aortic Hemodynamic Effects of Valvular Lesions in Rheumatic Heart Disease.

Rheumatic heart disease (RHD) is a neglected tropical disease despite the substantial global health burden. In this study, we aimed to develop a lower cost method of modeling aortic blood flow using subject-specific velocity profiles, aiding our understanding of RHD's consequences on the structure and function of the ascending aorta. Echocardiography and cardiovascular magnetic resonance (CMR) are often used for diagnosis, including valve dysfunction assessments. However, there is a need to further characterize aortic valve lesions to improve treatment options and timing for patients, while using accessible and affordable imaging strategies. Here, we simulated effects of RHD aortic valve lesions on the aorta using computational fluid dynamics (CFD). We hypothesized that inlet velocity distribution and wall shear stress (WSS) will differ between RHD and non-RHD individuals, as well as between subject-specific and standard Womersley velocity profiles. Phase-contrast CMR data from South Africa of six RHD subjects with aortic stenosis and/or regurgitation and six matched controls were used to estimate subject-specific velocity inlet profiles and the mean velocity for Womersley profiles. Our findings were twofold. First, we found WSS in subject-specific RHD was significantly higher (p < 0.05) than control subject simulations, while Womersley simulation groups did not differ. Second, evaluating spatial velocity differences (ΔSV) between simulation types revealed that simulations of RHD had significantly higher ΔSV than non-RHD (p < 0.05), these results highlight the need for implementing subject-specific input into RHD CFD, which we demonstrate how to accomplish through accessible methods.

WNT2B Deficiency Causes Increased Susceptibility to Colitis in Mice and Impairs Intestinal Epithelial Development in Humans.

Background and aims: WNT2B is a canonical Wnt ligand previously thought to be fully redundant with other Wnts in the intestinal epithelium. However, humans with WNT2B deficiency have severe intestinal disease, highlighting a critical role for WNT2B. We sought to understand how WNT2B contributes to intestinal homeostasis. Methods: We investigated the intestinal health of Wnt2b knock out (KO) mice. We assessed the impact of inflammatory challenge to the small intestine, using anti-CD3χ antibody, and to the colon, using dextran sodium sulfate (DSS). In addition, we generated human intestinal organoids (HIOs) from WNT2B-deficient human iPSCs for transcriptional and histological analyses. Results: Mice with WNT2B deficiency had significantly decreased Lgr5 expression in the small intestine and profoundly decreased expression in the colon, but normal baseline histology. The small intestinal response to anti-CD3χ antibody was similar in Wnt2b KO and wild type (WT) mice. In contrast, the colonic response to DSS in Wnt2b KO mice showed an accelerated rate of injury, featuring earlier immune cell infiltration and loss of differentiated epithelium compared to WT. WNT2B-deficient HIOs showed abnormal epithelial organization and an increased mesenchymal gene signature. Conclusion: WNT2B contributes to maintenance of the intestinal stem cell pool in mice and humans. WNT2B deficient mice, which do not have a developmental phenotype, show increased susceptibility to colonic injury but not small intestinal injury, potentially due to a higher reliance on WNT2B in the colon compared to the small intestine.WNT2B deficiency causes a developmental phenotype in human intestine with HIOs showing a decrease in their mesenchymal component and WNT2B-deficient patients showing epithelial disorganization. Data Transparency Statement: All RNA-Seq data will be available through online repository as indicated in Transcript profiling. Any other data will be made available upon request by emailing the study authors.

Appraisal of Pancreatic Lipase Inhibitory Potential of Ziziphus oenoplia (L.)Mill. Leaves by In Vitro and In Silico Approaches.

Pancreatic lipase is one of the crucial lipolytic enzymes of the gut that actively facilitates the digestion and absorption of the dietary triglycerides and cholesteryl esters. Although it has been deemed as one of the most reliable targets for the treatment of obesity and/or dyslipidemia, to date, orlistat is the only known FDA-approved, effective, oral pancreatic lipase inhibitor available for clinical use apart from the centrally acting antiobesity agents. However, it is known to be associated with adverse gastrointestinal and renal complications. In this study, we attempted to assess the antioxidant and porcine pancreatic lipase inhibitory potentials of Ziziphus oenoplia (L.)Mill. leaves through a systematic combination of in vitro and in silico approaches. Among the four different extracts including petroleum ether extract, ethyl acetate extract, ethanolic extract, and aqueous extract obtained through successive solvent extraction, the ethyl acetate extract has outperformed the other extracts and orderly displayed competent peroxide scavenging (IC50 value: 267.30 µg/mL) and porcine pancreatic lipase inhibitory (IC50 value: 444.44 µg/mL) potentials compared to the selected reference compounds: ascorbic acid (IC50 value: 251.50 µg/mL) and orlistat (IC50 value: 502.51 µg/mL) in the selected in vitro assay models. In addition, based on the molecular docking simulations of the six essential phytoconstituents of the leaves of Ziziphus oenoplia (L.)Mill. and their respective chemical analogues against the crystal structure of pancreatic lipase-colipase complex (PDB ID: 1LPB), four best-ranked molecules (PubChem CIDs: 15515703, 132582306, 11260294, and 44440845) have been proposed. Further, among these, the interaction potentials of the two top-ranked molecules (PubChem CIDs: 132582306 and 15515703) were analyzed through molecular dynamics (MD) simulations at a trajectory of 100 ns. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were theoretically predicted for all of the molecules using Swiss ADME and ADMET lab2.0. In conclusion, Ziziphus oenoplia (L.)Mill. leaves could become a prominent source for various potent bioactive compounds that may serve as prospective leads for the development of clinically cognizable pancreatic lipase inhibitors, provided their pharmacokinetic and in particular toxicity properties are thoroughly optimized.

What children do while they wait: The role of self-control strategies in delaying gratification.

Self-control plays an essential role in children's emotional and behavioral adjustment. A central behavioral indicator of self-control is the ability to delay gratification. Few studies have focused on understanding the heterogeneity of self-control behaviors that underlie children's ability to delay gratification. Therefore, we examined the role of spontaneous self-control behaviors (fidgeting, vocalizations, and anticipation/attentional focus toward a reward) in relation to 5-year old children's delay ability using Mischel's delay task (N = 144; Mage = 5.4 years, SD = 0.29). Latent mixture modeling was used to derive three distinct classes of self-control behaviors observed during the delay task: (1) Passive (low fidgeting, low vocalizations, but moderate anticipation), (2) Active (moderate fidgeting, moderate vocalizations, but high anticipation), and (3) Disruptive (high fidgeting, high vocalizations, and high anticipation). Children in the Passive class were more likely to delay the full task time compared with children in the Active class (odds ratio = 1.50, 95 % confidence interval = 1.28-1.81). There were no other differences in delay ability by self-control class. Children whose level of fidgeting and vocalizations matched their level of anticipation (i.e., Passive and Disruptive regulators) were able to delay more successfully than children who were mostly driven by anticipation (Active regulators). Some variation in children's delay ability and use of self-control strategies was explained by sociodemographic differences, specifically maternal age. Findings suggest probing processes underlying children's self-control to identify potential targets for intervention.

Fetal heart rate responses to maternal sleep-disordered breathing.

BACKGROUND: Maternal sleep-disordered breathing is associated with adverse pregnancy outcomes and is considered to be deleterious to the developing fetus. Maternal obesity potentiates sleep-disordered breathing, which, in turn, may contribute to the effect of maternal obesity on adverse fetal outcomes. However, only a few empirical studies have evaluated the contemporaneous effects of maternal sleep-disordered breathing events on fetal well-being. These events include apnea and hypopnea with accompanying desaturations in oxyhemoglobin. OBJECTIVE: This study aimed to reconcile contradictory findings on the associations between maternal apnea or hypopnea events and clinical indicators of fetal compromise. It also sought to broaden the knowledge base by examining the fetal heart rate and heart rate variability before, during, and after episodes of maternal apnea or hypopnea. To accomplish this, we employed overnight polysomnography, the gold standard for ascertaining maternal sleep-disordered breathing, and synchronized it with continuous fetal electrocardiography. STUDY DESIGN: A total of 84 pregnant women with obesity (body mass index >30 kg/m2) participated in laboratory-based polysomnography with digitized fetal electrocardiography recordings during or near 36 weeks of gestation. Sleep was recorded, on average, for 7 hours. Decelerations in fetal heart rate were identified. Fetal heart rate and heart rate variability were quantified before, during, and after each apnea or hypopnea event. Event-level intensity (desaturation magnitude, duration, and nadir O2 saturation level) and person-level characteristics based on the full overnight recording (apnea-hypopnea index, mean O2 saturation, and O2 saturation variability) were analyzed as potential moderators using linear mixed effects models. RESULTS: A total of 2936 sleep-disordered breathing events were identified, distributed among all but 2 participants. On average, participants exhibited 8.7 episodes of apnea or hypopnea per hour (mean desaturation duration, 19.1 seconds; mean O2 saturation nadir, 86.6% per episode); nearly half (n=39) of the participants met the criteria for obstructive sleep apnea. Only 45 of 2936 apnea or hypopnea events were followed by decelerations (1.5%). Conversely, most (n=333, 88%) of the 378 observed decelerations, including the prolonged ones, did not follow an apnea or a hypopnea event. Maternal sleep-disordered breathing burden, body mass index, and fetal sex were unrelated to the number of decelerations. Fetal heart rate variability increased during events of maternal apnea or hypopnea but returned to initial levels soon thereafter. There was a dose-response association between the size of the increase in fetal heart rate variability and the maternal apnea-hypopnea index, event duration, and desaturation depth. Longer desaturations were associated with a decreased likelihood of the variability returning to baseline levels after the event. The mean fetal heart rate did not change during episodes of maternal apnea or hypopnea. CONCLUSION: Episodes of maternal sleep apnea and hypopnea did not evoke decelerations in the fetal heart rate despite the predisposing risk factors that accompany maternal obesity. The significance of the modest transitory increase in fetal heart rate variability in response to apnea and hypopnea episodes is not clear but may reflect compensatory, delimited autonomic responses to momentarily adverse conditions. This study found no evidence that episodes of maternal sleep-disordered breathing pose an immediate threat, as reflected in fetal heart rate responses, to the near-term fetus.

Nephrotoxicity of Vancomycin in Combination With Beta-Lactam Agents: Ceftolozane-Tazobactam vs Piperacillin-Tazobactam.

BACKGROUND: Vancomycin (VAN)-associated acute kidney injury (AKI) is increased when VAN is combined with certain beta-lactams (BLs) such as piperacillin-tazobactam (TZP) but has not been evaluated with ceftolozane-tazobactam (C/T). Our aim was to investigate the AKI incidence of VAN in combination with C/T (VAN/C/T) compared with VAN in combination to TZP (VAN-TZP). METHODS: We conducted a multicenter, observational, comparative study across the United States. The primary analysis was a composite outcome of AKI and risk, injury, failure, loss, end stage renal disease; Acute Kidney Injury Network; or VAN-induced nephrotoxicity according to the consensus guidelines. Multivariable logistic regression analysis was conducted to adjust for confounding variables and stratified Kaplan-Meir analysis to assess the time to nephrotoxicity between the 2 groups. RESULTS: We included VAN/C/T (n = 90) and VAN-TZP (n = 284) at an enrollment ratio of 3:1. The primary outcome occurred in 12.2% vs 25.0% in the VAN-C/T and VAN-TZP groups, respectively (P = .011). After adjusting for confounding variables, VAN-TZP was associated with increased odds of AKI compared with VAN-C/T; with an adjusted odds ratio of 3.308 (95% confidence interval, 1.560-6.993). Results of the stratified Kaplan-Meir analysis with log-rank time-to-nephrotoxicity analysis indicate that time to AKI was significantly shorter among patients who received VAN-TZP (P = .004). Cox proportional hazards analysis demonstrated that TZP was consistent with the primary analysis (P = .001). CONCLUSIONS: Collectively, our results suggest that the AKI is not likely to be related to tazobactam but rather to piperacillin, which is a component in VAN-TZP but not in VAN-C/T.

Innate immune activation: Parallels in alcohol use disorder and Alzheimer's disease.

Alcohol use disorder is associated with systemic inflammation and organ dysfunction especially in the liver and the brain. For more than a decade, studies have highlighted alcohol abuse-mediated impairment of brain function and acceleration of neurodegeneration through inflammatory mechanisms that directly involve innate immune cells. Furthermore, recent studies indicate overlapping genetic risk factors between alcohol use and neurodegenerative disorders, specifically regarding the role of innate immunity in the pathomechanisms of both areas. Considering the pressing need for a better understanding of the relevance of alcohol abuse in dementia progression, here we summarize the molecular mechanisms of neuroinflammation observed in alcohol abuse and Alzheimer's disease, the most common cause of dementia. In addition, we highlight mechanisms that are already established in the field of Alzheimer's disease that may be relevant to explore in alcoholism to better understand alcohol mediated neurodegeneration and dementia, including the relevance of the liver-brain axis.

Solvents and Stabilization in Ionic Liquid Films.

We report the interfacial structures and chemical environments of ionic liquid films as a function of dilution with molecular solvents and over a range of film thicknesses (a few micrometers). Data from spectroscopic ellipsometry and infrared spectroscopy measurements show differences between films comprised of neat ionic liquids, as well as films comprised of ionic liquids diluted with two molecular solvents (water and acetonitrile). While the water-diluted IL films follow thickness trends predicted by the Landau-Levich model, neat IL and IL/MeCN films deviate significantly from predicted behaviors. Specifically, these film thicknesses are far greater than the predicted values, suggesting enhanced intermolecular interactions or other non-Newtonian behaviors not captured by the theory. We correlate film thicknesses with trends in the infrared intensity profiles across film thicknesses and IL-solvent dilution conditions and interpret the changes from expected behaviors as varying amounts of the film volume existing in isotropic (bulk) vs anisotropic (interfacial) states. The hydrogen bonding network of water-diluted ionic liquids is implicated in the agreement of this system with the Landau-Levich model's thickness predictions.

More than meets the eye: Examining physiological and behavioral regulation during delay of gratification task.

Children continually encounter situations where they must regulate impulsive responses to achieve a goal, requiring both self-control (SC) and delay of gratification. We examined concurrent behavioral SC strategies (fidgeting, vocalizations, anticipation) and physiological regulation (heart rate [HR], respiratory sinus arrhythmia [RSA]) in 126 children (M (SD) = 5.4 (0.29) years) during a standard delay of gratification task. Latent variable models derived latent SC classes and examined the moderating role of HR/RSA on SC and delay ability. Three classes of SC were identified: passive: low fidgeting and vocalizations, moderate anticipation; active: moderate fidgeting, low vocalizations, and high anticipation; and disruptive: moderate fidgeting, high vocalizations, and high anticipation. Children in the active class had the lowest odds of delaying full task time, compared to children in the passive (OR = 0.67, z = -5.25, p < .001) and disruptive classes (OR = 0.76, z = -2.03, p = .04). RSA changes during the task moderated the relationship between SC class and delay ability for children in the active class (aOR = 0.92, z = -3.1, p < .01). Within the group who struggled to delay gratification (active class), a subset exhibiting appropriate autonomic regulation was able to delay. The findings suggest probing congruency of observed behavioral and unobserved physiological regulation.

Moving up but not getting ahead: Family socioeconomic position in pregnancy, social mobility, and child cognitive development in the first seven years of life.

Objectives: Understanding when and how socioeconomic position (SEP) influences cognitive development is key to reducing population inequalities in health and achievement. The objective of this study was to determine the unique association between prenatal family SEP and child cognitive development, and to determine whether marked postnatal social mobility was associated with improvements in child cognitive performance to age 7. Methods: Data were from children enrolled in the US National Collaborative Perinatal Project (NCPP) (n = 28,761) during 1959-1965, a dataset large enough to observe marked mobility, which remains uncommon. Multivariable linear regression was used to examine the relationship between SEP (i.e., parental income, education, occupation) during gestation and cognitive performance at 8 months (Bayley Scales of Infant Development Mental Development Index) and at 7 years (Wechsler Intelligence Scale for Children). Results: Holding demographic and perinatal factors constant, family SEP during gestation was not associated with cognitive performance at 8 months (B = -0.03, 95% CI: -0.07-0.01) but was positively associated with performance at 7 years even after accounting for SEP at 7 years (B = 1.28, 95% CI: 1.11-1.45). Children whose families experienced the most extreme upward mobility (from the lowest to highest income quartile) showed a 12 percentile increase in cognitive performance in the first 7 years of life. Those with the most extreme downward mobility (from the highest to lowest income quartile) still experienced an 8 percentile increase in cognitive performance in this interval. Conclusions: The proportion of children in poverty today is similar to 1965 and intergenerational mobility has declined markedly. Prenatal SEP may contribute to inequalities in child cognitive performance that even extraordinary social mobility cannot erase. To optimize cognitive development across generations, current means-tested programs to support families with young children should be supplemented by universal approaches to ensure access to opportunity before young people become parents.

Measuring fetal heart rate and variability: Fetal cardiotocography versus electrocardiography.

Fetal heart rate variability is a key indicator of fetal neurodevelopment and well-being. Most studies have relied on Doppler-based fetal cardiotocography (fCTG) but recent technologies have made fetal electrocardiography (fECG) more widely available. We compared simultaneous recordings of fCTG and fECG in 131 fetuses twice during gestation (28 and 36 weeks) using a commercially available device (Monica AN24). Within-individual correlations for fetal heart rate values, based on averaged data during 50-min recordings, neared 1.0. Continuous and episodic measures of variability were also correlated, particularly at 36 weeks. Data collected during maternal polysomnography at 36 weeks were used to evaluate reliability of variability measures collected during the 50-min recording. Both fCTG- and fECG-derived measures of variability exhibited correspondence with variability during maternal presleep wakefulness and most sleep states. Results did not appreciably differ by data source or method used to calculate variability. fECG monitoring presented challenges, particularly at 28 weeks, when recordings with signal loss of ≤30% were available from only 27% of participants. Success rates improved to 84% at 36 weeks. fCTG was successful in over 90% of participants at each gestational age. Considerations in the selection of fECG versus fCTG in developmental research are discussed.