Sex differences and individual variability in the captive Jamaican fruit bat (Artibeus jamaicensis) intestinal microbiome and metabolome.

The intestinal microbiome plays an important role in mammalian health, disease, and immune function. In light of this function, recent studies have aimed to characterize the microbiomes of various bat species, which are noteworthy for their roles as reservoir hosts for several viruses known to be highly pathogenic in other mammals. Despite ongoing bat microbiome research, its role in immune function and disease, especially the effects of changes in the microbiome on host health, remains nebulous. Here, we describe a novel methodology to investigate the intestinal microbiome of captive Jamaican fruit bats (Artibeus jamaicensis). We observed a high degree of individual variation in addition to sex- and cohort-linked differences. The intestinal microbiome was correlated with intestinal metabolite composition, possibly contributing to differences in immune status. This work provides a basis for future infection and field studies to examine in detail the role of the intestinal microbiome in antiviral immunity.

Racial Disparities in Mental Health Disorders in Youth with Chronic Medical Conditions.

OBJECTIVE: To evaluate the association between race/ethnicity, poverty, and mental health in youth with chronic conditions. STUDY DESIGN: A cross-sectional comparative study was performed using the records of a tertiary care center from 2011 to 2015. INCLUSION CRITERIA: children aged 4-17 years with ≥1 hospitalization or emergency department visit. Exclusion criteria were those with arrhythmias or treatment with clonidine/benzodiazepines. The primary outcome variable was diagnosis or medication for anxiety, depression, or attention deficit hyperactivity disorder. The primary predictor variable was diagnosis of cystic fibrosis (CF), sickle cell disease (SCD), or congenital heart disease (CHD). RESULTS: We identified 112 313 patients, 0.2% with CF, 0.4% with SCD, and 1.0% with CHD. Patients with CF had the highest prevalence (23%) and odds (OR, 4.21; 95% CI, 3.07-5.77) of anxiety or depression, whereas patients with SCD had the lowest prevalence (7%) and odds (OR, 1.54; 95% CI, 1.11-2.14). Those with CHD had a prevalence of up to 17%, with 3-4 times higher odds of anxiety or depression (OR, 3.70; 95% CI, 2.98-4.61). All non-White participants were less likely to be diagnosed or treated for anxiety or depression and attention deficit hyperactivity disorder. Although poverty increased the probability of anxiety or depression in patients with CHD, this finding was not seen in patients with CF or SCD. CONCLUSIONS: Children with CF, SCD, and CHD are at increased risk of anxiety or depression; however non-White patients are likely being underdiagnosed and undertreated. Increased screening and recognition in minority children are needed to decrease disparities in mental health outcomes.

Insights into the Ultrafast Dynamics of CH2 OO and CH3 CHOO Following Excitation to the Bright 1 ππ* State: The Role of Singlet and Triplet States.

Criegee intermediates make up a class of molecules that are of significant atmospheric importance. Understanding their electronically excited states guides experimental detection and provides insight into whether solar photolysis plays a role in their removal from the troposphere. The latter is particularly important for large and functionalized Criegee intermediates. In this study, the excited state chemistry of two small Criegee intermediates, formaldehyde oxide (CH2 OO) and acetaldehyde oxide (CH3 CHOO), was modeled to compare their specific dynamics and mechanisms following excitation to the bright ππ* state and to assess the involvement of triplet states to the excited state decay process. Following excitation to the bright ππ* state, the photoexcited population exclusively evolves to form oxygen plus aldehyde products without the involvement of triplet states. This occurs despite the presence of a more thermodynamically stable triplet path and several singlet/triplet energy crossings at the Franck-Condon geometry and contrasts with the photodynamics of related systems such as acetaldehyde and acetone. This work sets the foundations to study Criegee intermediates with greater molecular complexity, wherein a bathochromic shift in the electron absorption profiles may ensure greater removal via solar photolysis.

Relationships Between Regional Cerebral Blood Flow and Neurocognitive Outcomes in Children and Adolescents With Congenital Heart Disease.

To identify regional cerebral blood flow (rCBF) alterations in children and adolescents with congenital heart disease (CHD) in relation to neurocognitive outcomes using a nonbiased data-driven approach. This is a prospective, observational study of children and adolescents with CHD without brain injury and healthy controls using pseudo-continuous arterial spin labeling (pCASL) MRI. Quantitative rCBF was compared between participants with CHD and healthy controls using a voxelwise data-driven method. Mediation analysis was then performed on a voxelwise basis, with the grouping variable as the independent variable, neurocognitive outcomes (from the NIH Toolbox Cognitive Battery) as the dependent variables, and rCBF as the mediator. After motion correction, a total of 80 studies were analyzable (27 for patients with CHD, 53 for controls). We found steeper age-related decline in rCBF among those with CHD compared to normal controls in the insula/ventromedial prefrontal regions (salience network) and the dorsal anterior cingulate and precuneus/posterior cingulate (default mode network), and posterior parietal/dorsolateral prefrontal (central executive network) (FWE-corrected P< 0.05). The reduced rCBF in the default mode/salience network was found to mediate poorer performance on an index of crystallized cognition from the NIH Toolbox Cognitive Battery in those with CHD compared to controls. In contrast, reduced rCBF in the central executive network/salience network mediated reduced deficits in fluid cognition among patients with CHD compared to controls. Regional cerebral blood flow alterations mediate domain-specific differences in cognitive performance in children and adolescents with CHD compared to healthy controls, independent of injury, and are likely related to brain and cognitive reserve mechanisms. Further research is needed to evaluate the potential of interventions in CHD targeting regional cerebral blood flow across lifespan.

Dribble Deficit Enables Measurement of Dribbling Speed Independent of Sprinting Speed in Collegiate, Male, Basketball Players.

ABSTRACT: Ramirez-Campillo, R, Gentil, P, Moran, J, Dalbo, VJ, and Scanlan, AT. Dribble Deficit enables measurement of dribbling speed independent of sprinting speed in collegiate, male, basketball players. J Strength Cond Res 35(7): 2040-2045, 2021-The aim of this study was to determine the relationships between sprinting and dribbling speed in basketball during linear and change-of-direction (COD) sprints using total dribbling time and Dribble Deficit. Collegiate, male, basketball players (n = 10; 21.0 ± 1.6 years) performed linear and COD sprints with and without dribbling a ball. Linear dribbling sprints were measured for the dominant and nondominant hands, whereas COD dribbling sprints involved bilateral use of hands. Dribble Deficit was determined as the difference between total time (second) during each dribbling trial and the equivalent nondribbling trial for linear and COD sprints. Simple linear regression analyses were performed during linear and COD sprints to determine the relationship (R) and shared variance (R2) between (a) sprinting times and total dribbling times and (b) sprinting times and Dribble Deficit. Large to very large, significant relationships were evident between linear sprinting and dribbling time for dominant (R = 0.86; R2 = 0.74, p = 0.001) and nondominant hands (R = 0.80; R2 = 0.65, p = 0.005). Trivial relationships were apparent between linear sprinting time and Dribble Deficit with dominant (R = 0.10; R2 = 0.01, p = 0.778) and nondominant hands (R = 0.03; R2 = 0.00, p = 0.940). A very large relationship was evident between COD sprinting and dribbling time (R = 0.91; R2 = 0.82, p < 0.001), whereas a trivial relationship was observed between COD sprinting time and COD Dribble Deficit (R = -0.23; R2 = 0.05, p = 0.530). Dribble Deficit eliminates the strong influence of sprinting speed on outcome measures typically seen when using tests predicated on total dribbling time. Consequently, Dribble Deficit may be of added use in basketball test batteries to measure dribbling speed across linear and multidirectional movement paths.

A Reevaluation of the Death of Vincent van Gogh: Suicide or Murder? The Need for a Definitive Autopsy.

Vincent van Gogh died on July 29, 1890, from an apparent gunshot wound to the belly sustained approximately 30 hours earlier on July 27. Although little is known how Vincent sustained his mortal wound, art historians have long believed that the death was the result of a suicide, a widely accepted "truth" for the mysterious death of the then unknown and now iconic artist. The basis and validity of this suicide narrative is still very hotly debated among van Gogh scholars to this day. We dug deeper into all the circumstantial evidence and testimonies to arrive at a comprehensive overview of the probability that it was likely impossible for Vincent to self-inflict his mortal wound.We used all the available circumstantial evidence related to the day Vincent van Gogh was wounded to present the information and conclusions as if we were before a judge as expert witnesses to answer the question: suicide or murder? If Vincent did not shoot himself in the belly (a red flag in and of itself), whoever inflicted that penetrating wound into his abdomen murdered him. In our study, results from firing the same model revolver that allegedly killed Vincent from various ranges (direct contact, intermediate, and distant) demonstrated within a reasonable degree of medical probability (greater than 50%) that it was not probable for Vincent van Gogh to shoot himself without a described powder burn.With little forensic evidence to rely on 130 years after the suspicious event, many have suggested a respectful exhumation and graveside autopsy utilizing 21 century techniques to bring resolve to this 19 century cold case. This crime, whether suicide or murder, has generated renewed interest and numerous questions surrounding the suspicious death of the most iconic artist of the 19th century. These missing forensic facts will remain buried with all the secrets Vincent took with him to his grave, unless a definitive autopsy is performed. What an autopsy could add to our forensic fact basis and understanding of this intriguing cold case is enormous and further delineated as the next step to answer these difficult, otherwise unanswerable questions and allow us to finally sign off on his death certificate with certainty.It is clearly impossible to definitively prove suicide or murder, but it is also impossible to disprove murder given the data and arguments offered in this analysis. A physician's opinion is based on the material available to him, and in this case, "our opinion as to the cause and manner of death is based on the limited amount of forensic information available. It is, therefore, our opinion, based on that limited information that in all medical probability, the cause of death is not a self-inflicted wound by Vincent van Gogh, and, thus, in all medical probability, a homicide."

The dynamics of large silicic systems from satellite remote sensing observations: the intriguing case of Domuyo volcano, Argentina.

Silicic magmatic systems are the most dangerous volcanoes on Earth, capable of large and catastrophic eruptions, yet their low eruptive frequency makes it challenging to interpret their short-term unrest. Here we present a decade-plus analysis that integrates, for the first time, time series of satellite interferometric synthetic aperture radar (InSAR) surface deformation and satellite thermal infrared edifice-scale surface warming at a large silicic system: Domuyo volcano, in Argentina. We find that deformation and warming are highly correlated, and depending on the sign and lag between the time series, either shallow sealing or magma influx could drive Domuyo's ongoing inflation (~ 0.15 m/year; from an InSAR-derived tabular source, ~ 11 × 8 × 1 km; ~ 6.5 km depth; ~ 0.037 km3/year volume-change rate) and warming (0.3-0.4 °C/year). This study shows the potential that combined satellite surface deformation and edifice-scale surface warming time series have on assessing the physical mechanisms of silicic volcanic systems and for constraining deterministic models.

Serological Evidence for Henipa-like and Filo-like Viruses in Trinidad Bats.

Bat-borne zoonotic pathogens belonging to the family Paramxyoviridae, including Nipah and Hendra viruses, and the family Filoviridae, including Ebola and Marburg viruses, can cause severe disease and high mortality rates on spillover into human populations. Surveillance efforts for henipaviruses and filoviruses have been largely restricted to the Old World; however, recent studies suggest a potentially broader distribution for henipaviruses and filoviruses than previously recognized. In the current study, we screened for henipaviruses and filoviruses in New World bats collected across 4 locations in Trinidad near the coast of Venezuela. Bat tissue samples were screened using previously established reverse-transcription polymerase chain reaction assays. Serum were screened using a multiplex immunoassay to detect antibodies reactive with the envelope glycoprotein of viruses in the genus Henipavirus and the family Filoviridae. Serum samples were also screened by means of enzyme-linked immunosorbent assay for antibodies reactive with Nipah G and F glycoproteins. Of 84 serum samples, 28 were reactive with ≥1 henipavirus glycoprotein by ≥1 serological method, and 6 serum samples were reactive against ≥1 filovirus glycoproteins. These data provide evidence of potential circulation of viruses related to the henipaviruses and filoviruses in New World bats.

Accumulation of trace elements in leatherback turtle (Dermochelys coriacea) eggs from the south-western Caribbean indicates potential health risks to consumers.

Trace metal and metalloid levels were measured in eggs of the NW Atlantic leatherback turtle (Dermochelys coriacea) from nesting grounds in the Bocas del Toro province, Panama, to infer exposure and associated risks to local communities. Samples were analyzed for a set of 26 essential and non-essential elements using inductively coupled plasma techniques. Median concentrations of Fe, Zn, As, Se and Sr in D. coriacea eggs were higher than previously reported for this species, which likely reflects differential contamination levels of specimens during foraging. The evaluation of non-carcinogenic human health risks from ingesting leatherback eggs has revealed potential deleterious effects due to high concentrations of As, Se and Sr for all examined age and gender groups, while Hg and Zn levels were above international standards for children. Hazard index (HI) values exceeded unity in all cases indicating serious health impacts related to possible additive effects of multiple metals co-occurring in the eggs. Our findings suggest that exposure to high (inorganic) As and Cr(VI) levels is associated with an increased carcinogenic risk, significantly exceeding the acceptable lifetime risk of 10-6 for both adults and children. Despite some limitations, such as unclear As and Cr speciation, our results demonstrated that the ingestion of D. coriacea eggs poses considerable health risks to local communities, and their consumption should not exceed 3.4 × 10-4 g (5.0 × 10-6 eggs) kg BW d-1. Resource managers and conservationists should focus their attention to human health effects as an alternative tool to address egg poaching and consumption.

Budget impact analysis of multiple varicella vaccination strategies: a Mexico perspective.

A number of live-attenuated varicella vaccines are produced globally that provide protection against the varicella zoster virus. In Mexico, varicella vaccination is not included in the national immunization program and is recommended for use only in high-risk subgroups. We developed a budget impact model to estimate the impact of universal childhood immunization against varicella on the national payer system in Mexico. A scenario of no varicella vaccination was compared to scenarios with vaccination with a single dose at 13 months of age, in alignment with the existing program of immunization with the measles-mumps-rubella vaccine. Nine different vaccination scenarios were envisioned, differing by vaccine type and by coverage. Varicella cases and treatment costs of each scenario were computed in a dynamic transmission model of varicella epidemiology, calibrated to the population of Mexico. Unit costs were based on Mexico sources or were from the literature. The results indicated that each of the three vaccine types increased vaccine acquisition and administration expenditures but produced overall cost savings in each of the first 10 years of the program, due to fewer cases and reduced varicella treatment costs. A highly effective vaccine at 95% coverage produced the greatest cost savings.

Crigler-Najjar Syndrome Type 1: Pathophysiology, Natural History, and Therapeutic Frontier.

BACKGROUND AND AIMS: We describe the pathophysiology, treatment, and outcome of Crigler-Najjar type 1 syndrome (CN1) in 28 UGT1A1 c.222C>A homozygotes followed for 520 aggregate patient-years. APPROACH AND RESULTS: Unbound ("free") bilirubin (Bf ) was measured in patient sera to characterize the binding of unconjugated bilirubin (BT ) to albumin (A) and validate their molar concentration ratio (BT /A) as an index of neurological risk. Two custom phototherapy systems were constructed from affordable materials to provide high irradiance in the outpatient setting; light dose was titrated to keep BT /A at least 30% below intravascular BT binding capacity (i.e., BT /A = 1.0). Categorical clinical outcomes were ascertained by chart review, and a measure (Lf ) was used to quantify liver fibrosis. Unbound bilirubin had a nonlinear relationship to BT (R2  = 0.71) and BT /A (R2  = 0.76), and Bf as a percentage of BT correlated inversely to the bilirubin-albumin equilibrium association binding constant (R2  = 0.69), which varied 10-fold among individuals. In newborns with CN1, unconjugated bilirubin increased 4.3 ± 1.1 mg/dL per day. Four (14%) neonates developed kernicterus between days 14 and 45 postnatal days of life; peak BT  ≥ 30 mg/dL and BT /A ≥ 1.0 mol:mol were equally predictive of perinatal brain injury (sensitivity 100%, specificity 93.3%, positive predictive value 88.0%), and starting phototherapy after age 13 days increased this risk 3.5-fold. Consistent phototherapy with 33-103 µW/cm2 •nm for 9.2 ± 1.1 hours/day kept BT and BT /A within safe limits throughout childhood, but BT increased 0.46 mg/dL per year to reach dangerous concentrations by 18 years of age. Liver transplantation (n = 17) normalized BT and eliminated phototherapy dependence. Liver explants showed fibrosis ranging from mild to severe. CONCLUSION: Seven decades after its discovery, CN1 remains a morbid and potentially fatal disorder.

Mercury bioaccumulation in tilefish from the northeastern Gulf of Mexico 2 years after the Deepwater Horizon oil spill: Insights from Hg, C, N and S stable isotopes.

Mercury (Hg) concentration in fish of the Gulf of the Mexico (GoM) is a major concern due to the importance of the GoM for U.S. fisheries. The Deepwater Horizon (DWH) oil spill in April 2010 in the northern GoM resulted in large amounts of oil and dispersant released to the water column, which potentially modified Hg bioaccumulation patterns in affected areas. We measured Hg species (methylmercury (MMHg) and inorganic Hg (IHg)) concentrations, and light (C, N and S) and Hg stable isotopes in muscle and liver tissues from tilefish (Lopholatilus chamaleonticeps) sampled in 2012 and 2013 along the shelf break of the northeastern GoM. Fish located close to the mouth of the Mississippi River (MR) and northwest of the DWH well-head (47 km) showed significantly lower Hg levels in muscle and liver than fish located further northeast of the DWH (>109 km), where 98% of tilefish had Hg levels in the muscle above US consumption advisory thresholds (50% for tilefish close to the DWH). Differences in light and Hg stable isotopes signatures were observed between these two areas, showing higher δ15N, and lower δ202Hg, Δ199Hg and δ34S in fish close to the DWH/MR. This suggests that suspended particles from the MR reduces Hg bioavailability at the base of the GoM food chains. This phenomenon can be locally enhanced by the DWH that resulted in increased particles in the water column as evidenced by the marine snow layer in the sediments. On the other hand, freshly deposited Hg associated with organic matter in more oligotrophic marine waters enhanced Hg bioaccumulation in local food webs. Comparing Hg isotopic composition in liver and muscle of fish indicates specific metabolic response in fish having accumulated high levels of MMHg.

Metal contents of marine turtle eggs (Chelonia mydas; Lepidochelys olivacea) from the tropical eastern pacific and the implications for human health.

Concentrations of eight elements were measured in Chelonia mydas and Lepidochelys olivacea eggs collected along the Pacific coast of Panama. Manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), and mercury (Hg) concentrations were similar to previous reports of these species from around the world, while lead (Pb) was lower than previous reports. Cd posed the highest health risk to people who regularly eat the eggs, with average consumption rates leading to target hazard quotients (THQ) of up to 0.35 ± 0.15. Our conclusions indicate that current turtle egg consumption in isolated, coastal Pacific communities may pose a health concern for young children, and that youth and young adults should limit their consumption of turtle eggs to reduce their total intake of nonessential metals.

Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis).

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the zoonotic potential of Betacoronaviruses. Investigations into the origin of MERS-CoV have focused on two potential reservoirs: bats and camels. Here, we investigated the role of bats as a potential reservoir for MERS-CoV. In vitro, the MERS-CoV spike glycoprotein interacted with Jamaican fruit bat (Artibeus jamaicensis) dipeptidyl peptidase 4 (DPP4) receptor and MERS-CoV replicated efficiently in Jamaican fruit bat cells, suggesting there is no restriction at the receptor or cellular level for MERS-CoV. To shed light on the intrinsic host-virus relationship, we inoculated 10 Jamaican fruit bats with MERS-CoV. Although all bats showed evidence of infection, none of the bats showed clinical signs of disease. Virus shedding was detected in the respiratory and intestinal tract for up to 9 days. MERS-CoV replicated transiently in the respiratory and, to a lesser extent, the intestinal tracts and internal organs; with limited histopathological changes observed only in the lungs. Analysis of the innate gene expression in the lungs showed a moderate, transient induction of expression. Our results indicate that MERS-CoV maintains the ability to replicate in bats without clinical signs of disease, supporting the general hypothesis of bats as ancestral reservoirs for MERS-CoV.

Altered Structural and Functional Connectivity in Late Preterm Preadolescence: An Anatomic Seed-Based Study of Resting State Networks Related to the Posteromedial and Lateral Parietal Cortex.

OBJECTIVE: Late preterm birth confers increased risk of developmental delay, academic difficulties and social deficits. The late third trimester may represent a critical period of development of neural networks including the default mode network (DMN), which is essential to normal cognition. Our objective is to identify functional and structural connectivity differences in the posteromedial cortex related to late preterm birth. METHODS: Thirty-eight preadolescents (ages 9-13; 19 born in the late preterm period (≥32 weeks gestational age) and 19 at term) without access to advanced neonatal care were recruited from a low socioeconomic status community in Brazil. Participants underwent neurocognitive testing, 3-dimensional T1-weighted imaging, diffusion-weighted imaging and resting state functional MRI (RS-fMRI). Seed-based probabilistic diffusion tractography and RS-fMRI analyses were performed using unilateral seeds within the posterior DMN (posterior cingulate cortex, precuneus) and lateral parietal DMN (superior marginal and angular gyri). RESULTS: Late preterm children demonstrated increased functional connectivity within the posterior default mode networks and increased anti-correlation with the central-executive network when seeded from the posteromedial cortex (PMC). Key differences were demonstrated between PMC components with increased anti-correlation with the salience network seen only with posterior cingulate cortex seeding but not with precuneus seeding. Probabilistic tractography showed increased streamlines within the right inferior longitudinal fasciculus and inferior fronto-occipital fasciculus within late preterm children while decreased intrahemispheric streamlines were also observed. No significant differences in neurocognitive testing were demonstrated between groups. CONCLUSION: Late preterm preadolescence is associated with altered functional connectivity from the PMC and lateral parietal cortex to known distributed functional cortical networks despite no significant executive neurocognitive differences. Selective increased structural connectivity was observed in the setting of decreased posterior interhemispheric connections. Future work is needed to determine if these findings represent a compensatory adaptation employing alternate neural circuitry or could reflect subtle pathology resulting in emotional processing deficits not seen with neurocognitive testing.

MRI evaluation and safety in the developing brain.

Magnetic resonance imaging (MRI) evaluation of the developing brain has dramatically increased over the last decade. Faster acquisitions and the development of advanced MRI sequences, such as magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), perfusion imaging, functional MR imaging (fMRI), and susceptibility-weighted imaging (SWI), as well as the use of higher magnetic field strengths has made MRI an invaluable tool for detailed evaluation of the developing brain. This article will provide an overview of the use and challenges associated with 1.5-T and 3-T static magnetic fields for evaluation of the developing brain. This review will also summarize the advantages, clinical challenges, and safety concerns specifically related to MRI in the fetus and newborn, including the implications of increased magnetic field strength, logistics related to transporting and monitoring of neonates during scanning, and sedation considerations, and a discussion of current technologies such as MRI conditional neonatal incubators and dedicated small-foot print neonatal intensive care unit (NICU) scanners.

Increasing opportunistic oral cancer screening examinations: findings from focus groups with general dentists in Puerto Rico.

This study aims to identify educational and training modalities that dentists in Puerto Rico (PR) believe will increase the quality and quantity of opportunistic oral cancer screening examinations (OCS) in dental offices on the island. The study was conducted in three phases: a systematic search of relevant literature, an expert review and consensus panel, and focus groups (FG) involving PR general dentists. To increase OCS by dentists in PR, the FG participants proposed a small group, hands-on OCS training, an integrated oral cancer course, and readily available videos, photographs, and computer simulations to further demonstrate OCS performance and facilitate differential diagnosis. OCS training requirements for licensure and re-licensure, improving OCS dentist-patient communication skills, and establishment of an oral lesion referral center were also viewed favorably. In conclusion, general dentists in our FGs believed the quality and quantity of OCS in Puerto Rico can be increased through the application of specific continuing education and training modalities.

Alterations of resting state networks and structural connectivity in relation to the prefrontal and anterior cingulate cortices in late prematurity.

Late preterm birth is increasingly recognized as a risk factor for cognitive and social deficits. The prefrontal cortex is particularly vulnerable to injury in late prematurity because of its protracted development and extensive cortical connections. Our study examined children born late preterm without access to advanced postnatal care to assess structural and functional connectivity related to the prefrontal cortex. Thirty-eight preadolescents [19 born late preterm (34-36 /7 weeks gestational age) and 19 at term] were recruited from a developing community in Brazil. Participants underwent neuropsychological testing. Individuals underwent three-dimensional T1-weighted, diffusion-weighted, and resting state functional MRI. Probabilistic tractography and functional connectivity analyses were carried out using unilateral seeds combining the medial prefrontal cortex and the anterior cingulate cortex. Late preterm children showed increased functional connectivity within regions of the default mode, salience, and central-executive networks from both right and left frontal cortex seeds. Decreased functional connectivity was observed within the right parahippocampal region from left frontal seeding. Probabilistic tractography showed a pattern of decreased streamlines in frontal white matter pathways and the corpus callosum, but also increased streamlines in the left orbitofrontal white matter and the right frontal white matter when seeded from the right. Late preterm children and term control children scored similarly on neuropsychological testing. Prefrontal cortical connectivity is altered in late prematurity, with hyperconnectivity observed in key resting state networks in the absence of neuropsychological deficits. Abnormal structural connectivity indicated by probabilistic tractography suggests subtle changes in white matter development, implying disruption of normal maturation during the late gestational period.

A genome-wide survey of CD4(+) lymphocyte regulatory genetic variants identifies novel asthma genes.

BACKGROUND: Genome-wide association studies have yet to identify the majority of genetic variants involved in asthma. We hypothesized that expression quantitative trait locus (eQTL) mapping can identify novel asthma genes by enabling prioritization of putative functional variants for association testing. OBJECTIVE: We evaluated 6706 cis-acting expression-associated variants (eSNPs) identified through a genome-wide eQTL survey of CD4(+) lymphocytes for association with asthma. METHODS: eSNPs were tested for association with asthma in 359 asthmatic patients and 846 control subjects from the Childhood Asthma Management Program, with verification by using family-based testing. Significant associations were tested for replication in 579 parent-child trios with asthma from Costa Rica. Further functional validation was performed by using formaldehyde-assisted isolation of regulatory elements (FAIRE) quantitative PCR and chromatin immunoprecipitation PCR in lung-derived epithelial cell lines (Beas-2B and A549) and Jurkat cells, a leukemia cell line derived from T lymphocytes. RESULTS: Cis-acting eSNPs demonstrated associations with asthma in both cohorts. We confirmed the previously reported association of ORMDL3/GSDMB variants with asthma (combined P = 2.9 × 10(-8)). Reproducible associations were also observed for eSNPs in 3 additional genes: fatty acid desaturase 2 (FADS2; P = .002), N-acetyl-α-D-galactosaminidase (NAGA; P = .0002), and Factor XIII, A1 (F13A1; P = .0001). Subsequently, we demonstrated that FADS2 mRNA is increased in CD4(+) lymphocytes in asthmatic patients and that the associated eSNPs reside within DNA segments with histone modifications that denote open chromatin status and confer enhancer activity. CONCLUSIONS: Our results demonstrate the utility of eQTL mapping in the identification of novel asthma genes and provide evidence for the importance of FADS2, NAGA, and F13A1 in the pathogenesis of asthma.