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The degree of chromatic adaptation of midget ganglion cells of the parvocellular (PC) pathway was studied by measuring long-(L) to middle-wavelength (M) cone weighting at different mean chromaticities in the mid-photopic range. Cone weighting was measured using a protocol involving changing the relative phase of modulated lights, which provided an estimate independent of the level of maintained activity. The degree of adaptation at 2500 td was found to be less than complete (i.e., sub-Weberian), with the M- and L-cone contributions having slopes averaging 0.89 rather than 1.0. This is broadly consistent with the degree of light adaptation present in this cell class. The changes in maintained activity following a step change in chromaticity took tens of seconds to return toward a baseline level, but changes in cone weighting appeared much faster. [ABSTRACT FROM AUTHOR]

The development of accurate predictions for a new drug's absorption, distribution, metabolism, and excretion profiles in the early stages of drug development is crucial due to high candidate failure rates. The absence of comprehensive, standardised, and updated pharmacokinetic (PK) repositories limits pre-clinical predictions and often requires searching through the scientific literature for PK parameter estimates from similar compounds. While text mining offers promising advancements in automatic PK parameter extraction, accurate Named Entity Recognition (NER) of PK terms remains a bottleneck due to limited resources. This work addresses this gap by introducing novel corpora and language models specifically designed for effective NER of PK parameters. Leveraging active learning approaches, we developed an annotated corpus containing over 4000 entity mentions found across the PK literature on PubMed. To identify the most effective model for PK NER, we fine-tuned and evaluated different NER architectures on our corpus. Fine-tuning BioBERT exhibited the best results, achieving a strict F 1 score of 90.37% in recognising PK parameter mentions, significantly outperforming heuristic approaches and models trained on existing corpora. To accelerate the development of end-to-end PK information extraction pipelines and improve pre-clinical PK predictions, the PK NER models and the labelled corpus were released open source at https://github.com/PKPDAI/PKNER ., (© 2024. The Author(s).)

Prenatal alcohol exposure and fetal alcohol spectrum disorders (FASDs) remain critical public health issues. Alcohol use in pregnancy is a leading preventable cause of birth defects, developmental disabilities, and learning disabilities. Alcohol screening and brief intervention (SBI) is effective at reducing excessive alcohol use. However, this clinical preventive service remains critically underutilized in primary care. In 2014, the Centers for Disease Control and Prevention called for the creation of FASD Champion programs to promote clinician education about FASDs. Six professional health organizations and groups providing reproductive and child health services set out to create FASD Champion programs. The American College of Obstetricians and Gynecologists FASDs Prevention Program was created to focus on reducing alcohol-exposed pregnancies. The American Academy of Pediatrics' Champion program maintains the goal of improving health outcomes for children with FASDs by improving pediatricians' diagnostic capacity. The American Academy of Family Physicians has prioritized training family physician champions to improve the delivery of alcohol SBI among adult patients. The University of Alaska Anchorage has partnered with the National Association of Nurse Practitioners in Women's Health, the American College of Nurse-Midwives, and the Association of Women's Health, Obstetric, and Neonatal Nurses to assure advanced practice registered nurses and midwives have the knowledge and skills to prevent alcohol-exposed pregnancies and FASDs. The American Association of Medical Assistants has prioritized expanding the knowledge and skills of medical assistants related to promoting alcohol-free pregnancies. Finally, the Champions program at the University of Texas at Austin was established to train health social workers in alcohol SBI. Through the advocacy, education, and mission of these 6 health sectors in collaboration with national organizations and educational institutions, the evidence-based approach of alcohol SBI is being disseminated throughout the United States to reduce the harmful effects of prenatal alcohol exposure., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The chikungunya virus (CHIKV) is a member of the genus Alphavirus, family Togaviridae. CHIKV causes an acute systemic febrile condition, accompanied by severe polyarthralgia, intense muscle pain, and maculopapular exanthema, which may still occur in many patients. In rare cases, unusual symptoms may occur, eventually worsening the condition and resulting in a fatal outcome. It is a single-stranded, non-segmented RNA virus with a genome of approximately 11,805 nucleotides that organises a genetic and molecular chain that encodes non-structural proteins (nsP1, nsP2, nsP3, nsP4) and structural proteins (E3, E2, 6K, and E1). The fundamental role of immune response in the evolution of the disease is known. Understanding the role of immune response in the pathogenesis of CHIKV infection is challenging. In this context, innate and adaptive immune responses establish a connective interface that induces the production of various mediators that modulate the strategy of inhibiting viral replication. However, the immune escape articulated by the virus indicates that the action of pro-and anti-inflammatory cytokines contributes to the worsening of the disease and potentiates tissue damage with joint involvement. In this review, we discuss the role of the primary pro-and anti-inflammatory cytokines in the immunopathological processes of chikungunya fever., (© 2023 John Wiley & Sons Ltd.)

Arboviruses, such as yellow fever virus (YFV), dengue virus (DENV), and chikungunya virus (CHIKV), present wide global dissemination and a pathogenic profile developed in infected individuals, from non-specific clinical conditions to severe forms, characterised by the promotion of significant lesions in different organs of the harbourer, culminating in multiple organ dysfunction. An analytical cross-sectional study was carried out via the histopathological analysis of 70 samples of liver patients, collected between 2000 and 2017, with confirmed laboratory diagnoses, who died due to infection and complications due to yellow fever (YF), dengue fever (DF), and chikungunya fever (CF), to characterise, quantify, and compare the patterns of histopathological alterations in the liver between the samples. Of the histopathological findings in the human liver samples, there was a significant difference between the control and infection groups, with a predominance of alterations in the midzonal area of the three cases analysed. Hepatic involvement in cases of YF showed a greater intensity of histopathological changes. Among the alterations evaluated, cell swelling, microvesicular steatosis, and apoptosis were classified according to the degree of tissue damage from severe to very severe. Pathological abnormalities associated with YFV, DENV, and CHIKV infections showed a predominance of changes in the midzonal area. We also noted that, among the arboviruses studied, liver involvement in cases of YFV infection was more intense., Competing Interests: The authors declare no conflicts of interest.

Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis and pneumonia in children under one year and a leading cause of infant hospitalization. Palivizumab was approved by the FDA in 1998 as RSV immunoprophylaxis to prevent severe RSV disease in children with specific health conditions and those born at <35 weeks gestational age (wGA). This study compared RSV-related hospitalization (RSVH) and RSVH characteristics in very preterm (<29 wGA) and term (>37 wGA) infants. Using the MarketScan Commercial and Multi-State Medicaid administrative claims databases, infants born between 7/1/2003 and 6/30/2020 were identified and classified as very preterm or term. Infants with evidence of health conditions, such as congenital heart disease and cystic fibrosis, were excluded. During 2003-2020 RSV seasons (November to March), claims incurred by infants while they were <12 months old were evaluated for outpatient administration of palivizumab and RSVH. The study included 40,123 very preterm infants and 4,421,942 term infants. Rate of RSVH in very preterm infants ranged 1.5-3.8 per 100 infant-seasons in commercially insured infants and 3.5-8.4 in Medicaid insured infants and were inversely related to wGA at birth. Relative risk of RSVH in very preterm was 3-4 times higher, and ICU admissions and mechanical ventilation were more common during RSVH in very preterm infants relative to term infants. However, these outcomes were less common or less severe in very preterm infants who received outpatient palivizumab administration, despite evidence of higher baseline risk of RSVH in these infants.

Tephra is a unique volcanic product with an unparalleled role in understanding past eruptions, long-term behavior of volcanoes, and the effects of volcanism on climate and the environment. Tephra deposits also provide spatially widespread, high-resolution time-stratigraphic markers across a range of sedimentary settings and thus are used in numerous disciplines (e.g., volcanology, climate science, archaeology). Nonetheless, the study of tephra deposits is challenged by a lack of standardization that inhibits data integration across geographic regions and disciplines. We present comprehensive recommendations for tephra data gathering and reporting that were developed by the tephra science community to guide future investigators and to ensure that sufficient data are gathered for interoperability. Recommendations include standardized field and laboratory data collection, reporting and correlation guidance. These are organized as tabulated lists of key metadata with their definition and purpose. They are system independent and usable for template, tool, and database development. This standardized framework promotes consistent documentation and archiving, fosters interdisciplinary communication, and improves effectiveness of data sharing among diverse communities of researchers., (© 2022. USGS Volcano Science Center.)

In this section, we present Interdisciplinary Guidelines and Recommendations for Neonatal Intensive Care Unit (NICU) Discharge Preparation and Transition Planning. The foundation for these guidelines and recommendations is based on existing literature, practice, available policy statements, and expert opinions. These guidelines and recommendations are divided into the following sections: Basic Information, Anticipatory Guidance, Family and Home Needs Assessment, Transfer and Coordination of Care, and Other Important Considerations. Each section includes brief introductory comments, followed by the text of the guidelines and recommendations in table format. After each table, there may be further details or descriptions that support a guideline or recommendation. Our goal was to create recommendations that are both general and adaptable while also being specific and actionable. Each NICU's implementation of this guidance will be dependent on the unique makeup and skills of their team, as well as the availability of local programs and resources. The recommendations based only on expert opinion could be topics for future research., (© 2022. The Author(s).)

The National Perinatal Association (NPA) coordinated a multidisciplinary work group to develop guidelines and recommendations for Neonatal Intensive Care Unit (NICU) discharge preparation and thus the transition from NICU to home for infants admitted to the NICU and their families. In this section, we explore the concepts of NICU discharge readiness as well as transition planning and preparation. We describe the process that was used to develop the guidelines and recommendations as well as the timeline for the work. NPA hopes that the readers will find the Interdisciplinary Guidelines and Recommendations for NICU Discharge Preparation and Transition Planning to be beneficial, useful, and pertinent., (© 2022. The Author(s).)

Background: A successful transition from the neonatal intensive care unit (NICU) to home is aided by a comprehensive discharge planning program that keeps families involved and engaged with the discharge preparation process., Purpose: To compare the assessment of parental NICU discharge preparedness with parental satisfaction with the NICU discharge preparation., Methods: Families were surveyed 4 to 6 weeks after NICU discharge, and those selecting "very prepared" were considered "satisfied" with their discharge preparation. On discharge day, families were considered "prepared" for discharge based on their overall level of preparedness and their nurse's rating of them on a discharge readiness assessment tool., Results: In total, 1104 families (60%) reported being both "satisfied" and "prepared"; 293 families (16%) were "satisfied" but not "prepared"; 297 families (16%) were not "satisfied" but were "prepared"; and 134 families (7%) were neither "satisfied" nor "prepared." Compared with families that were both "satisfied" and "prepared," families that were neither "satisfied" nor "prepared" were more likely to be raising the infant alone, of Black race, and to have sicker infants., Implications for Practice: Some families are at a higher risk and merit more consideration during NICU discharge planning. Assess the discharge readiness of all families prior to discharge. Those at an increased risk may benefit from more discharge education and training, specifically for single mothers, those with limited resources, or others considered at high risk., Competing Interests: The authors have no conflicts of interest or competing interests., (Copyright © 2021 by The National Association of Neonatal Nurses.)

Background: Microglia are active modulators of Alzheimer's disease but their role in relation to amyloid plaques and synaptic changes due to rising amyloid beta is unclear. We add novel findings concerning these relationships and investigate which of our previously reported results from transgenic mice can be validated in knock-in mice, in which overexpression and other artefacts of transgenic technology are avoided., Methods: App NL-F and App NL-G-F knock-in mice expressing humanised amyloid beta with mutations in App that cause familial Alzheimer's disease were compared to wild type mice throughout life. In vitro approaches were used to understand microglial alterations at the genetic and protein levels and synaptic function and plasticity in CA1 hippocampal neurones, each in relationship to both age and stage of amyloid beta pathology. The contribution of microglia to neuronal function was further investigated by ablating microglia with CSF1R inhibitor PLX5622., Results: Both App knock-in lines showed increased glutamate release probability prior to detection of plaques. Consistent with results in transgenic mice, this persisted throughout life in App NL-F mice but was not evident in App NL-G-F with sparse plaques. Unlike transgenic mice, loss of spontaneous excitatory activity only occurred at the latest stages, while no change could be detected in spontaneous inhibitory synaptic transmission or magnitude of long-term potentiation. Also, in contrast to transgenic mice, the microglial response in both App knock-in lines was delayed until a moderate plaque load developed. Surviving PLX5266-depleted microglia tended to be CD68-positive. Partial microglial ablation led to aged but not young wild type animals mimicking the increased glutamate release probability in App knock-ins and exacerbated the App knock-in phenotype. Complete ablation was less effective in altering synaptic function, while neither treatment altered plaque load., Conclusions: Increased glutamate release probability is similar across knock-in and transgenic mouse models of Alzheimer's disease, likely reflecting acute physiological effects of soluble amyloid beta. Microglia respond later to increased amyloid beta levels by proliferating and upregulating Cd68 and Trem2. Partial depletion of microglia suggests that, in wild type mice, alteration of surviving phagocytic microglia, rather than microglial loss, drives age-dependent effects on glutamate release that become exacerbated in Alzheimer's disease., (© 2021. The Author(s).)

Neonatal intensive care unit (NICU) discharge readiness is the primary caregivers' masterful attainment of technical care skills and knowledge, emotional comfort and confidence with infant care by the time of discharge. NICU discharge preparation is the process of facilitating discharge readiness. Discharge preparation is the process with discharge readiness as the goal. Our previous work described the importance of NICU discharge readiness and strategies for discharge preparation from an American medical system perspective. NICU discharge planning is, however, of international relevance as challenges in relation to hospital discharge are a recurring global theme. In this manuscript, we conceptualise NICU discharge preparation with international perspective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

The nature and timing of the shift from the Late Middle Paleolithic (LMP) to the Early Upper Paleolithic (EUP) varied geographically, temporally, and substantively across the Near East and Eurasia; however, the result of this process was the archaeological disappearance of Middle Paleolithic technologies across the length and breadth of their geographic distribution. Ortvale Klde rockshelter (Republic of Georgia) contains the most detailed LMP-EUP archaeological sequence in the Caucasus, an environmentally and topographically diverse region situated between southwest Asia and Europe. Tephrochronological investigations at the site reveal volcanic ash (tephra) from various volcanic sources and provide a tephrostratigraphy for the site that will facilitate future correlations in the region. We correlate one of the cryptotephra layers to the large, caldera-forming Nemrut Formation eruption (30,000 years ago) from Nemrut volcano in Turkey. We integrate this tephrochronological constraint with new radiocarbon dates and published ages in an OxCal Bayesian age model to produce a revised chronology for the site. This model increases the ages for the end of the LMP (∼47.5-44.2 ka cal BP) and appearance of the EUP (∼46.7-43.6 ka cal BP) at Ortvale Klde, which are earlier than those currently reported for other sites in the Caucasus but similar to estimates for specific sites in southwest Asia and eastern Europe. These data, coupled with archaeological, stratigraphic, and taphonomic observations, suggest that at Ortvale Klde, (1) the appearance of EUP technologies of bone and stone has no technological roots in the preceding LMP, (2) a LMP population vacuum likely preceded the appearance of these EUP technologies, and (3) the systematic combination of tephra correlations and absolute dating chronologies promises to substantially improve our inter-regional understanding of this critical time interval of human evolution and the potential interconnectedness of hominins at different sites., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The Tierra Blanca Joven (TBJ) eruption from Ilopango volcano deposited thick ash over much of El Salvador when it was inhabited by the Maya, and rendered all areas within at least 80 km of the volcano uninhabitable for years to decades after the eruption. Nonetheless, the more widespread environmental and climatic impacts of this large eruption are not well known because the eruption magnitude and date are not well constrained. In this multifaceted study we have resolved the date of the eruption to 431 ± 2 CE by identifying the ash layer in a well-dated, high-resolution Greenland ice-core record that is >7,000 km from Ilopango; and calculated that between 37 and 82 km 3 of magma was dispersed from an eruption coignimbrite column that rose to ∼45 km by modeling the deposit thickness using state-of-the-art tephra dispersal methods. Sulfate records from an array of ice cores suggest stratospheric injection of 14 ± 2 Tg S associated with the TBJ eruption, exceeding those of the historic eruption of Pinatubo in 1991. Based on these estimates it is likely that the TBJ eruption produced a cooling of around 0.5 °C for a few years after the eruption. The modeled dispersal and higher sulfate concentrations recorded in Antarctic ice cores imply that the cooling would have been more pronounced in the Southern Hemisphere. The new date confirms the eruption occurred within the Early Classic phase when Maya expanded across Central America., Competing Interests: The authors declare no competing interest.

We as a couple spent 50 years working in visual psychophysics of color vision, temporal vision, and luminance adaptation. We sought collaborations with ophthalmologists, anatomists, physiologists, physicists, and psychologists, aiming to relate visual psychophysics to the underlying physiology of the primate retina. This review describes our journey and reflections in exploring the visual system.

Early exposure to stress and adversity can have both immediate and lasting effects on physical and psychological health. Critical periods have been identified in infancy, during which the presence or absence of experiences can alter developmental trajectories. There are multiple explanations for how exposure to psychosocial stress, before conception or early in life, has an impact on later increased risk for developmental delays, mental health, and chronic metabolic diseases. Through both epidemiologic and animal models, the mechanisms by which experiences are transmitted across generations are being identified. Because psychosocial stress has multiple components that can act as stress mediators, a comprehensive understanding of the complex interactions between multiple adverse or beneficial experiences and their ultimate effects on health is essential to best identify interventions that will improve health and outcomes. This review outlines what is known about the biology, transfer, and effects of psychosocial stress and early life adversity from the perinatal period to adulthood. This information can be used to identify potential areas in which clinicians in neonatal medicine could intervene to improve outcomes., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: Discharge readiness is a key determinant of outcomes for families in the NICU. Since 2003, using a broad set of outcome and process measures, we have conducted an ongoing quality improvement initiative to improve the discharge preparation process in our NICU and readiness of families being discharged from the NICU., Methods: Iterative improvements to the discharge preparation process were made by a multidisciplinary committee. Discharge readiness was measured by using a parental and nurse survey for all families discharged from our NICU. Primary outcome measures included parental self-assessment of discharge readiness and nurse assessment of the family's emotional and technical discharge readiness. Secondary outcome measures included assessment of specific technical skills and emotional factors. Process measures included nursing familiarity with family at discharge. Improvement over time was analyzed by using statistical process control charts., Results: Significant improvement was seen in all primary outcome measures. Family self-assessment of discharge readiness increased from 85.1% to 89.1%; nurse assessment of the family's emotional discharge readiness increased from 81.2% to 90.5%, and technical discharge readiness increased from 81.4% to 87.7%. Several secondary outcome measures revealed significant improvement, whereas most remained stable. Nurse familiarity with the family at discharge increased over time., Conclusions: Quality improvement methodology can be used to measure and improve discharge readiness of families with an infant in the NICU. This model can provide the necessary framework for a structured approach to systematically evaluating and improving the discharge preparation process in a NICU., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

This study aimed to investigate the presence of norovirus (NoV) in recreational waters of four estuarine beaches located in Mosqueiro Island, Belém city, Brazilian Amazon, during two years of monitoring (2012 and 2013). NoV particles were concentrated on filtering membrane by the adsorption-elution method and detected by semi-nested RT-PCR (reverse transcription polymerase chain reaction) and sequencing. NoV positivity was observed in 37.5% (39/104) of the surface water samples, with genogroup GI (69.2%) occurring at a higher frequency than GII (25.7%), with a cocirculation of both genogroups in two samples (5.1%). This virus was detected in all sampling points analyzed, showing the highest detection rate at the Paraíso Beach (46.2%). Statistically, there was a dependence relationship between tide levels and positive detection, with a higher frequency at high tide (46.7%) than at low tide (25%) periods. Months with the highest detection rates (April 2012 and April/May 2013) were preceded by periods of higher precipitation (March 2012 and February/March 2013). Phylogenetic analysis showed the circulation of the old pandemic variant (GII.4-US&#95;95-96) and GI.8. The NoV detection demonstrated viral contamination on the beaches and evidenced the health risk to bathers, mainly through recreational activities such as bathing, and highlighted the importance of including enteric viruses research in the recreational water quality monitoring.

Over the last two decades, the prevalence of substance use among women of childbearing age has risen dramatically in the United States making substance use during pregnancy a significant public health concern. This article offers a general overview of the epidemiology of perinatal substance use focusing primarily on the United States but when available international trends will be presented as well., (© 2019 Published by Elsevier Ltd.)

The leishmaniases are diseases that affect millions of people across the world, in particular visceral leishmaniasis (VL) which is fatal unless treated. Current standard of care for VL suffers from multiple issues and there is a limited pipeline of new candidate drugs. As such, there is a clear unmet medical need to identify new treatments. This paper describes the optimization of a phenotypic hit against Leishmania donovani, the major causative organism of VL. The key challenges were to balance solubility and metabolic stability while maintaining potency. Herein, strategies to address these shortcomings and enhance efficacy are discussed, culminating in the discovery of preclinical development candidate GSK3186899/DDD853651 (1) for VL.

Fluidic soft sensors have been widely used in wearable devices for human motion capturing. However, thus far, the biocompatibility of the conductive liquid, the linearity of the sensing signal, and the hysteresis between the loading and release processes have limited the sensing quality as well as the applications of these sensors. In this paper, silicone based strain and force sensors composed of a novel biocompatible conductive liquid (potassium iodide and glycerol solution) are introduced. The strain sensors exhibit negligible hysteresis up to 5 Hz, with a gauge factor of 2.2 at 1 Hz. The force sensors feature a novel multi-functional layered structure, with micro-cylinder-filled channels to achieve high linearity, low hysteresis (5.3% hysteresis at 1 Hz), and good sensitivity (100% resistance increase at a 5 N load). The sensors' gauge factors are stable at various temperatures and humidity levels. These bio-compatible, low hysteresis, and high linearity sensors are promising for safe and reliable diagnostic devices, wearable motion capture, and compliant human-computer interfaces.

Objective: We compared the Neonatal Intensive Care Unit discharge preparedness of families with and without Limited English Proficiency (LEP)., Study Design: We performed a retrospective analysis of discharged families. Each family's discharge preparation was self-assessed on the day of discharge, and the discharging nurse assessed the family's overall emotional and technical discharge preparedness all on 9-point Likert scales. Families were considered not prepared for discharge if they rated themselves or the nurse rated their preparedness as <7 on the Likert scale., Results: Among 1307 discharged families, 90 had LEP. The odds of being prepared for discharge were the same for both groups (aOR = 0.62, 95% CI: 0.27-1.41; p = 0.258). In multivariable analyses, families with LEP were less likely to be prepared with technical baby care skills (aOR = 0.32, 95% CI: 0.13-0.81)., Conclusion: Families with LEP are at higher risk and may require special attention when preparing for NICU discharge.

Background: Plant foods may stimulate intestinal secretion through chemicals designed to deter herbivores, including lactucins in lettuce and rhein in rhubarb. This may increase ileostomy output and induce diarrhoea in people with intact bowels., Objective: We aimed to determine the effect of food on intestinal water content using Magnetic Resonance Imaging (MRI)., Design: A three period crossover trial of isocaloric meals in adults without bowel disorders. Meals: 2 slices white bread with 10 g butter; 300 g rhubarb with 60 mL lactose free cream; 300 g lettuce with 30 mL mayonnaise., Primary Outcome: Area under curve (AUC) small bowel water content (SBWC) using MRI., Secondary Outcomes: ascending colon water content; T1 relaxation time of ascending colon (T1AC); gastric volume; visual analogue scales of bloating and satiety (0-100). MRI analysts were blinded. Scanned fasting and hourly to 180 min postprandial. Symptoms scored half-hourly., Results: 9 female and 6 male subjects completed the study. AUC SBWC fell after bread but rose after lettuce and even more after rhubarb, difference from baseline being (Bread AUC -5662 (1209) ml.min vs Lettuce 3194 (1574) ml.min and Rhubarb 10586 (1629) ml.min (P < 0.01). Rhubarb induced a rise in T1AC but differences at 3 hours were not significant (P = 0.06). Gastric volume at T = 0 significantly was higher for both lettuce and rhubarb (571 ± 92 and 558 ± 89 mls) respectively compared to bread (314 ± 108 mls) (p < 0.0001). Symptom scores were higher for lettuce > rhubarb > bread., Conclusion: Lettuce and rhubarb meals increased intestinal water content, demonstrating how different foods can alter ileal flow and stool consistency., (© 2018 American Society for Parenteral and Enteral Nutrition.)

The coordination environment of Cm(iii) bound at the Fe(iii) binding sites of transferrin was investigated using a combined experimental and theoretical approach. Complexation studies with two hTf/2N single point mutants, Y95F (Tyr → Phe) and H249A (His → Ala) were performed. The substitution of Tyr 95 by the non-complexing Phe prevents Cm(iii) from forming of a strong, multidentate complex with the mutant. In contrast, with the H249A mutant Cm(iii) complexation at the binding site still occurs although a slightly higher pH is required to form the complex. This elucidates that His plays a minor role and is not a key ligand like Tyr 95. MD/DFT calculations of Cm(iii) bound at the N-terminal binding site provide further structural information. All coordinating groups present in the Fe(iii) transferrin complex are also found for Cm(iii), i.e. Asp 63, Tyr 95, Tyr 188 and His 249. Additionally, two water molecules, one monodentate and one bidentate carbonate ion complete the coordination environment. This structure of the Cm(iii) hTf/2N complex is confirmed by vibronic sideband spectroscopy which allows an identification of the directly coordinating groups. The results underline an involvement of Asp 63, Tyr 95, Tyr 188 and His 249 as well as carbonate in Cm(iii) coordination at the transferrin Fe(iii) binding site.

Fetal alcohol spectrum disorder (FASD) is an umbrella term used to describe preventable birth defects and intellectual and/or developmental disabilities resulting from prenatal alcohol exposure. The American Academy of Pediatrics has a previous clinical report in which diagnostic criteria for a child with an FASD are discussed and tools to assist pediatricians with its management can be found. This clinical report is intended to foster pediatrician awareness of approaches for screening for prenatal alcohol exposure in clinical practice, to guide management of a child with an FASD after the diagnosis is made, and to summarize available resources for FASD management., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

This study examined the impact of parent-child attunement of morning cortisol on parenting and child outcomes in dyads with and without parental depression. Participants included 142 parent-child dyads (3-5 years-old) who provided morning cortisol samples at Wave 1, and 98 dyads returned for the 3-year follow-up at Wave 2. Results indicated that for parents with a history of depression and for female children, stronger attunement predicted increases in parental hostility from Wave 1 to Wave 2. For females only, stronger attunement was related to children's depressive symptoms at Wave 1 and Wave 2. Stronger attunement was also associated with increases in children's depressive symptoms from Wave 1 to Wave 2, poorer psychosocial functioning at Wave 1, and ADHD symptoms at Wave 2. Findings highlight attunement as an important biological process related to parenting and child outcomes and suggest it may play a role in the intergenerational transmission of depression risk., (© 2018 Wiley Periodicals, Inc.)

Little research has examined the processes underlying children's persistent sleep problems and links with later psychopathology. The current study examined the stability of parent-child sleep interactions as assessed with the parent-reported Parent-Child Sleep Interactions Scale (PSIS) and examined whether sleep interactions in preschool-age children predict sleep problems and psychiatric symptoms later in childhood. Participants included 108 preschool-age children (50% female) and their parents. Parents completed the PSIS when children were 3-5 years (T1) and again when they were 6-9 years (T2). The PSIS includes three subscales-Sleep Reinforcement (reassurance of child sleep behaviors), Sleep Conflict (parent-child conflict at bedtime), Sleep Dependence (difficulty going to sleep without parent)-and a total score. Higher scores indicate more problematic bedtime interactions. Children's sleep problems and psychiatric symptoms at T1 and T2 were assessed with a clinical interview. PSIS scores were moderately stable from T1 to T2, and the factor structure of the PSIS remained relatively consistent over time. Higher total PSIS scores at T1 predicted increases in children's sleep problems at T2. Higher PSIS Sleep Conflict scores at T1 predicted increases in oppositional defiant disorder symptoms at T2. Children with more sleep problems and higher PSIS Sleep Reinforcement scores at T1 showed increases in attention deficit/hyperactivity disorder, depressive, and anxiety symptoms at T2. These findings provide evidence for the predictive validity of the PSIS and highlight the importance of early parent-child sleep interactions in the development of sleep and psychiatric symptoms in childhood. Parent-child sleep interactions may serve as a useful target for interventions.

N-Myristoyltransferase (NMT) represents a promising drug target within the parasitic protozoa Trypanosoma brucei (T. brucei), the causative agent for human African trypanosomiasis (HAT) or sleeping sickness. We have previously validated T. brucei NMT as a promising druggable target for the treatment of HAT in both stages 1 and 2 of the disease. We report on the use of the previously reported DDD85646 (1) as a starting point for the design of a class of potent, brain penetrant inhibitors of T. brucei NMT.

Recent fate-mapping studies and gene-expression profiles suggest that commonly used protocols to generate bone marrow-derived cultured dendritic cells yield a heterogeneous mixture, including some CD11c hi cells that may not have a bona fide counterpart in vivo. In this study, we provide further evidence of the discordance between ex vivo-isolated and in vitro-cultured CD11c + cells by analyzing an additional phenotype, the ability to support cytosolic growth of the facultative intracellular bacterial pathogen Listeria monocytogenes Two days after foodborne infection of mice with GFP-expressing L. monocytogenes , a small percentage of CD103 neg and CD103 + conventional dendritic cells (cDC) in the intestinal lamina propria and mesenteric lymph nodes were GFP + However, in vitro infection of the same subsets of cells harvested from naive mice resulted in inefficient invasion by the bacteria (<0.1% of the inoculum). The few intracellular bacteria detected survived for only a few hours. In contrast, cultured CD103 neg CD11c + cells induced by GM-CSF readily supported exponential growth of L. monocytogenes Flt3 ligand-induced cultures yielded CD103 + CD11c + cells that more closely resembled cDC, with only a modest level of L. monocytogenes replication. For both culture protocols, the longer the cells were maintained in vitro, the more readily they supported intracellular growth. The results of this study suggest that cDC are not a niche for intracellular growth of L. monocytogenes during intestinal infection of mice., (Copyright © 2017 by The American Association of Immunologists, Inc.)

This study examined the moderating role of parental hostility on the associations between parental depression and the cortisol awakening response (CAR) and morning cortisol levels of both parents and children. 148 parents and 148 preschool-aged children provided salivary cortisol samples at waking, 30 and 45 min post-waking on two consecutive days. Parental depression was assessed using a clinical interview, and parental hostility was assessed using an observational parent-child interaction task. Results indicated that the combination of parental lifetime depression and high parental hostility was associated with lower morning cortisol levels in both parents and children. This interactive effect was present in children regardless of their exposure to parental depression. In addition, the combination of higher levels of parents' current depressive symptoms and parental hostility was associated with lower parent CAR. Lastly, parents' and children's lower morning cortisol levels were associated with parent-reported child externalizing symptoms. Findings demonstrate that parents and children have similar stress system functioning related to parental depression and the parenting context, as well as children's behavioral problems, which may play a role in the intergenerational transmission of risk for psychopathology., (© 2017 Wiley Periodicals, Inc.)

Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, is the most common cause of cardiac-related deaths in endemic regions of Latin America. There is an urgent need for new safer treatments because current standard therapeutic options, benznidazole and nifurtimox, have significant side effects and are only effective in the acute phase of the infection with limited efficacy in the chronic phase. Phenotypic high content screening against the intracellular parasite in infected VERO cells was used to identify a novel hit series of 5-amino-1,2,3-triazole-4-carboxamides (ATC). Optimization of the ATC series gave improvements in potency, aqueous solubility, and metabolic stability, which combined to give significant improvements in oral exposure. Mitigation of a potential Ames and hERG liability ultimately led to two promising compounds, one of which demonstrated significant suppression of parasite burden in a mouse model of Chagas' disease.

This study examined biological concordance between parent and child morning cortisol and whether parent and child-level risk factors for depression moderated this association. Participants included 136 parents and their preschool-aged children. Parents and children obtained salivary cortisol samples at waking, and 30 and 45min post-waking across two days to assess the cortisol awakening response. Parental lifetime depression was assessed using a clinical interview and child temperamental negative emotionality (NE) and positive emotionality (PE) were assessed using an observational laboratory-based assessment. Results indicated significant parent-child concordance between both average cortisol levels and cortisol fluctuations across waking. Greater concordance was observed for dyads with parents with a lifetime history of depression and with children high in NE and PE. These parent- and child-level moderators were associated with different indices of concordance. Findings highlight the need to examine the role of parent and child risk factors for depression on parent-child adrenocortical concordance., (Copyright © 2017 Elsevier B.V. All rights reserved.)