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Muhammad Tariqus Salam,1 Sébastien Gélinas,1 Sébastien Desgent,2 Sandra Duss,2 Félix Bernier Turmel,1,3 Lionel Carmant,2 Mohamad Sawan,1 Dang Khoa Nguyen3 1Polystim Neurotechnologies Laboratory, Polytechnique Montréal, QC, Canada; 2Research Center, Sainte-Justine University Hospital Center (CHU Sainte-Justine), Université de Montréal, QC, Canada; 3Neurology Service, Department of Medicine, Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal (CHUM), QC, Canada Background: Intracranial electroencephalography (EEG) studies are widely used in the presurgical evaluation of drug-refractory patients with partial epilepsy. Because chronic implantation of intracranial electrodes carries a risk of infection, hemorrhage, and edema, it is best to limit the number of electrodes used without compromising the ability to localize the epileptogenic zone (EZ). There is always a risk that an intracranial study may fail to identify the EZ because of suboptimal coverage. We present a new subdural electrode design that will allow better sampling of suspected areas of epileptogenicity with lower risk to patients. Method: Impedance of the proposed electrodes was characterized in vitro using electrochemical impedance spectroscopy. The appearance of the novel electrodes on magnetic resonance imaging (MRI) was tested by placing the electrodes into a gel solution (0.9% NaCl with 14 g gelatin). In vivo neural recordings were performed in male Sprague Dawley rats. Performance comparisons were made using microelectrode recordings from rat cortex and subdural/depth recordings from epileptic patients. Histological examinations of rat brain after 3-week icEEG intracerebral electroencephalography (icEEG) recordings were performed. Results: The in vitro results showed minimum impedances for optimum choice of pure gold materials for electrode contacts and wire. Different attributes of the new electrodes were identified on MRI. The results of in vivo recordings demonstrated signal stability, 50% noise reduction, and up to 6 dB signal-to-noise ratio (SNR) improvement as compared to commercial electrodes. The wireless icEEG recording system demonstrated on average a 2% normalized root-mean-square (RMS) deviation. Following the long-term icEEG recording, brain histological results showed no abnormal tissue reaction in the underlying cortex. Conclusion: The proposed subdural electrode system features attributes that could potentially translate into better icEEG recordings and allow sampling of large of areas of epileptogenicity at lower risk to patients. Further validation for use in humans is required. Keywords: epilepsy, seizure, monitoring, surgery, electrodes

Exposure to bioaerosol allergens such as pollen can cause exacerbations of allergenic airway disease (AAD) in sensitive populations, and thus cause serious public health problems. Assessing these health impacts by linking the airborne pollen levels, concentrations of respirable allergenic material, and human allergenic response under current and future climate conditions is a key step toward developing preventive and adaptive actions. To that end, a regional-scale pollen emission and transport modeling framework was developed that treats allergenic pollens as non-reactive tracers within the coupled Weather Research and Forecasting Community Multiscale Air Quality (WRF/CMAQ) modeling system. The Simulator of the Timing and Magnitude of Pollen Season (STaMPS) model was used to generate a daily pollen pool that can then be emitted into the atmosphere by wind. The STaMPS is driven by species-specific meteorological (temperature and/or precipitation) threshold conditions and is designed to be flexible with respect to its representation of vegetation species and plant functional types (PFTs). The hourly pollen emission flux was parameterized by considering the pollen pool, friction velocity, and wind threshold values. The dry deposition velocity of each species of pollen was estimated based on pollen grain size and density. An evaluation of the pollen modeling framework was conducted for southern California (USA) for the period from March to June 2010. This period coincided with observations by the University of Southern California's Children's Health Study (CHS), which included O3, PM2.5, and pollen count, as well as measurements of exhaled nitric oxide in study participants. Two nesting domains with horizontal resolutions of 12 and 4 km were constructed, and six representative allergenic pollen genera were included: birch tree, walnut tree, mulberry tree, olive tree, oak tree, and brome grasses. Under the current parameterization scheme, the modeling framework tends to underestimate walnut and peak oak pollen concentrations, and tends to overestimate grass pollen concentrations. The model shows reasonable agreement with observed birch, olive, and mulberry tree pollen concentrations. Sensitivity studies suggest that the estimation of the pollen pool is a major source of uncertainty for simulated pollen concentrations. Achieving agreement between emission modeling and observed pattern of pollen releases is the key for successful pollen concentration simulations. © Author(s) 2014.

Rationale: Genetic variation in arginase (ARG) and nitric oxide synthase (NOS) has been associated with exhaled nitric oxide (FeNO) levels in children. Little is known about whether epigenetic variation in these genes modulates FeNO.Objectives: To evaluate whether DNA methylation in ARG and NOS genes is associated with FeNO.Methods: A subset of 940 participants in the Children's Health Study were selected for this study. Children were eligible if they had FeNO measurements and buccal cells collected on the same day. CpG loci located in the promoter regions of NOS1, NOS2A, NOS3, ARG1, and ARG2 genes were analyzed. Multiple loci in each gene were evaluated individually and averaged together. DNA methylation was measured using a bisulfite-polymerase chain reaction pyrosequencing assay. Linear regression models were used to investigate the association between DNA methylation and FeNO and whether associations differed by asthma status.Measurements and Main Results: DNA methylation in ARG2 was significantly associated with FeNO. A 1% increase in average DNA methylation of ARG2 was associated with a 2.3% decrease in FeNO (95% confidence interval, -4 to -0.6). This association was significantly larger in children with asthma (%diff = -8.7%) than in children with no asthma (%diff = -1.6%; p(int) = 0.01). Differences in FeNO by asthma status were also observed for ARG1 (%diff(asthma) = -4.4%; %diff(non-asthma) = 0.3%; p(int) = 0.02). DNA methylation in NOS genes was not associated with FeNO.Conclusions: DNA methylation in ARG1 and ARG2 is associated with FeNO in children with asthma and suggests a possible role for epigenetic regulation of nitric oxide production. [ABSTRACT FROM AUTHOR]

Rationale: The glutathione S-transferases (GSTs) are important detoxification enzymes.Objectives: To investigate effects of variants in GST mu genes on lung function and assess their interactions with tobacco smoke exposure.Methods: In this prospective study, 14,836 lung function measurements were collected from 2,108 children who participated in two Southern California cohorts. For each child, tagging single nucleotide polymorphisms in GSTM2, GSTM3, GSTM4, and GSTM5 loci were genotyped. Using principal components and haplotype analyses, the significance of each locus in relation to level and growth of FEV1, maximum midexpiratory flow rate (MMEF), and FVC was evaluated. Interactions between loci and tobacco smoke on lung function were also investigated.Measurements and Main Results: Variation in the GST mu family locus was associated with lower FEV1 (P = 0.01) and MMEF (0.04). Two haplotypes of GSTM2 were associated with FEV1 and MMEF, with effect estimates in opposite directions. One haplotype in GSTM3 showed a decrease in growth for MMEF (-164.9 ml/s) compared with individuals with other haplotypes. One haplotype in GSTM4 showed significantly decreased growth in FEV1 (-51.3 ml), MMEF (-69.1 ml/s), and FVC (-44.4 ml), compared with all other haplotypes. These results were consistent across two independent cohorts. Variation in GSTM2 was particularly important for FVC and FEV(1) among children whose mothers smoked during pregnancy.Conclusions: Genetic variation across the GST mu locus is associated with 8-year lung function growth. Children of mothers who smoked during pregnancy and had variation in GSTM2 had lower lung function growth. [ABSTRACT FROM AUTHOR]

Rationale: Transforming growth factor (TGF)-beta1 is involved in airway inflammation and remodeling, two key processes in asthma pathogenesis. Tobacco smoke and traffic emissions induce airway inflammation and modulate TGF-beta1 gene expression. We hypothesized that the effects of functional TGF-beta1 variants on asthma occurrence vary by these exposures.Objectives: We tested these hypotheses among 3,023 children who participated in the Children's Health Study.Methods: Tagging single-nucleotide polymorphisms rs4803457 C>T and C-509T (a functional promoter polymorphism) accounted for 94% of the haplotype diversity of the upstream region. Exposure to maternal smoking in utero was based on smoking by biological mother during pregnancy. Residential distance from nearest freeway was calculated based on residential address at study entry.Measurements and Main Results: Children with the -509TT genotype had a 1.8-fold increased risk of early persistent asthma (95% confidence interval [CI], 1.11-2.95). This association varied marginally significantly by in utero exposure to maternal smoking. Compared with children with the -509CC/CT genotype with no in utero exposure to maternal smoking, those with the -509TT genotype with such exposure had a 3.4-fold increased risk of early persistent asthma (95% CI, 1.46-7.80; interaction, P = 0.11). The association between TGF-beta1 C-509T and lifetime asthma varied by residential proximity to freeways (interaction P = 0.02). Children with the -509TT genotype living within 500 m of a freeway had over three-fold increased lifetime asthma risk (95% CI, 1.29-7.44) compared with children with CC/CT genotype living > 1500 m from a freeway.Conclusions: Children with the TGF-beta1 -509TT genotype are at increased risk of asthma when they are exposed to maternal smoking in utero or to traffic-related emissions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the associations of maternal and grandmaternal smoking before, during, and after pregnancy with childhood asthma. DESIGN, SETTING, AND PARTICIPANTS: We conducted a case-control study nested within the Children's Health Study in southern California. The case patients consisted of 338 children with asthma that had been diagnosed in the first 5 years of life, and 570 control subjects were countermatched on in utero exposure to maternal smoking within grade, sex, and community of residence. MEASUREMENTS: Detailed maternal and household smoking histories and other asthma risk factor information was obtained by telephone interview. RESULTS: The participation rates were 72.3% and 82.5%, respectively, for control subjects and case patients. In utero exposure to maternal smoking was associated with increased risk for asthma diagnosed in the first 5 years of life (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.0 to 2.3), and for persistent asthma (OR, 1.5; 95% CI, 1.0 to 2.3). The associations did not differ in children with early transient asthma compared to those with early persistent asthma. Relative to never-smokers, children whose mothers smoked throughout the pregnancy had an elevated risk of asthma in the first 5 years of life (OR, 1.6; 95% CI, 1.0 to 2.6). Children of mothers who quit smoking prior to the pregnancy showed no increased risk (OR, 0.9; 95% CI, 0.5 to 1.5). We were unable to assess the association of smoking cessation during pregnancy because very few mothers were reported to have done so (15%). Asthma risk did not increase in a monotonic pattern with smoking intensity during pregnancy. Postnatal secondhand smoke exposure was not independently associated with asthma. Grandmaternal smoking during the mother's fetal period was associated with increased asthma risk in her grandchildren (OR, 2.1; 95% CI, 1.4 to 3.2). CONCLUSIONS: Maternal and grandmaternal smoking during pregnancy may increase the risk of childhood asthma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Associations between single-nucleotide polymorphisms in the beta2-adrenergic receptor gene and asthma and wheeze have been inconsistent. Recent studies indicated that tobacco smoke affects beta2-adrenergic receptor gene expression and associations of beta2-adrenergic receptor gene variants with asthma in adults. We aimed to investigate the joint effects of in utero and childhood secondhand tobacco smoke exposure and 2 well-characterized functional single-nucleotide polymorphisms (Arg16Gly and Glu27Gln) of beta2-adrenergic receptor gene on asthma and wheezing in 3128 non-Hispanic and Hispanic white children of the Children's Health Study. METHODS: We fitted logistic regression models to estimate odds ratios and 95% confidence intervals for the independent and joint effects of these single-nucleotide polymorphisms and in utero and secondhand tobacco smoke exposure on asthma and wheeze outcomes. RESULTS: Exposures to in utero maternal smoking and secondhand tobacco smoke were associated with wheezing. Children who were homozygous for the Arg16 allele and were exposed to maternal smoking in utero were at a threefold increased risk for lifetime wheeze compared with children who were unexposed and had at least 1 Gly16 allele. We found similar joint effects of secondhand tobacco smoke and Arg16Gly with wheezing. The risk for lifetime, current, and nocturnal wheeze increased with the number of smokers at home among Arg16 homozygous children. The results were consistent in 2 cohorts of children recruited in 1993 and 1996. Diplotype-based analyses were consistent with the single-nucleotide polymorphism-specific results. No associations were found for Glu27Gln. CONCLUSIONS: Both in utero and childhood exposure to tobacco smoke were associated with an increased risk for wheeze in children, and the risks were greater for children with the Arg16Arg genotype or 2 copies of the Arg16-Gln27 diplotype. Exposures to smoking need to be taken into account when evaluating the effects of beta2-adrenergic receptor gene variants on respiratory health outcomes. [ABSTRACT FROM AUTHOR]

Background: Psychiatric illness during pregnancy is associated with adverse obstetric outcomes, but investigations into its impact on parenting capacity are limited. Child Protective Services (CPS) contact disproportionately impacts families marginalized by poverty, mental health disorders, and substance use disorders. Recently, there have been investigations into the significance of psychiatric illness and nonmental health-related factors that predict CPS custody arrangements., Objective: To identify clinical factors associated with newborns' custody under CPS for mothers with antenatal psychiatric hospitalization., Methods: We conducted a retrospective review of electronic medical records over a 10-year period (2012-2021) for patients who were pregnant during their inpatient psychiatric hospitalizations. We followed 81 patients (18 to 43 years old) who delivered within the hospital. The study endpoint was whether the newborn was placed under CPS custody. For the purposes of this study, psychiatric illness was categorized by the presence or absence of psychotic symptoms. We utilized logistic regressions to investigate the associations of these demographic and clinical factors with the study outcome of CPS custody., Results: For the entire study population, 64.2% of newborns had CPS custody arrangements. In multivariate analysis, after adjusting for potential confounders, patients with psychotic symptoms were at increased odds of having CPS custody arrangements (odds ratio = 8.43; 95% confidence interval 2.16-32.85) compared with patients without psychotic symptoms. Furthermore, multivariate analyses revealed that patients with a history of homelessness also had a higher risk (odds ratio = 6.59; 95% confidence interval: 1.24-35.13) of CPS custody arrangements for their newborns than those without a history of homelessness., Conclusions: The results of this study suggest that among pregnant and psychiatrically hospitalized patients, those with psychotic symptoms are significantly more likely to have CPS custody arrangements compared to those without psychotic symptoms. However, it is important to note that psychotic symptoms were not definitive for the inability to parent appropriately. In fact, nearly 25% of the study population who had psychotic symptoms were able to successfully transition home with their newborns as mothers. This emphasizes the importance of optimizing the management of psychotic symptoms, particularly among those who have children or plan to have children. The findings of this study also highlight the chronic impacts that those who have struggled with homelessness may experience, including parenting capacity after homelessness resolves., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Kratom ( Mitragyna speciosa ) use in the United States is becoming increasingly popular and its legal status varies widely from state to state. Multiple reports of adverse events associated with kratom use have ranged from liver injury, seizures, psychiatric disturbance, and rarely death., Methods: This study investigated coroner autopsy reports from Kern County in California for the year 2020 which included qualitative data on substances from blood toxicological reports. Of the 214 opioid-associated accidental overdoses reported, 4 subjects (1.9%) had mitragynine (kratom) exposure on the autopsy report and were included in the study. We reported available demographic information and comorbid substance findings from the associated autopsy reports., Results: All 4 individuals with mitragynine (kratom) toxicology had accidental opioid overdose deaths noted in autopsy reports. Each subject also had toxicology positive for at least one other substance. Fentanyl was found in 3 (75%) of the cases and suspected to be the primary contributor to opioid-related deaths in those cases. However, one fatality was without fentanyl, but instead had tested positive for benzodiazepines, cannabis, and other psychiatric medications., Discussion: The findings of this brief report provide insight into the role that mitragynine (kratom) may have in modulating risk of opioid-related deaths. The combined use of kratom with opioids such as fentanyl appears most likely to increase the risk of a fatal overdose, but it may also occur with other medications such as benzodiazepines and psychiatric medications. It is a serious concern that in the midst of the opioid overdose epidemic there is a growing presence of kratom use in the U.S. population with a largely unregulated status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Torrico, Patel, Nikolov, Salam, Padhy and Weinstein.)

Biomass fuel burning is a significant contributor of household fine particulate matter (PM 2.5 ) in the low to middle income countries (LMIC) and assessing PM 2.5 levels is essential to investigate exposure-related health effects such as pregnancy outcomes and acute lower respiratory infection in infants. However, measuring household PM 2.5 requires significant investments of labor, resources, and time, which limits the ability to conduct health effects studies. It is therefore imperative to leverage lower-cost measurement techniques to develop exposure models coupled with survey information about housing characteristics. Between April 2017 and March 2018, we continuously sampled PM 2.5 in three seasonal waves for approximately 48-h (range 46 to 52-h) in 74 rural and semi-urban households among the participants of the Bangladesh Cook Stove Pregnancy Cohort Study (CSPCS). Measurements were taken simultaneously in the kitchen, bedroom, and open space within the household. Structured questionnaires captured household-level information related to the sources of air pollution. With data from two waves, we fit multivariate mixed effect models to estimate 24-h average, cooking time average, daytime and nighttime average PM 2.5 in each of the household locations. Households using biomass cookstoves had significantly higher PM 2.5 concentrations than those using electricity/liquefied petroleum gas (626 μg/m 3 vs. 213 μg/m 3 ). Exposure model performances showed 10-fold cross validated R 2 ranging from 0.52 to 0.76 with excellent agreement in independent tests against measured PM 2.5 from the third wave of monitoring and ambient PM 2.5 from a separate satellite-based model (correlation coefficient, r = 0.82). Significant predictors of household PM 2.5 included ambient PM 2.5 , season, and types of fuel used for cooking. This study demonstrates that we can predict household PM 2.5 with moderate to high confidence using ambient PM 2.5 and household characteristics. Our results present a framework for estimating household PM 2.5 exposures in LMICs, which are often understudied and underrepresented due to resource limitations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Antibiotics are among the most important discoveries of the 20th century, having saved millions of lives from infectious diseases. Microbes have developed acquired antimicrobial resistance (AMR) to many drugs due to high selection pressure from increasing use and misuse of antibiotics over the years. The transmission and acquisition of AMR occur primarily via a human-human interface both within and outside of healthcare facilities. A huge number of interdependent factors related to healthcare and agriculture govern the development of AMR through various drug-resistance mechanisms. The emergence and spread of AMR from the unrestricted use of antimicrobials in livestock feed has been a major contributing factor. The prevalence of antimicrobial-resistant bacteria has attained an incongruous level worldwide and threatens global public health as a silent pandemic, necessitating urgent intervention. Therapeutic options of infections caused by antimicrobial-resistant bacteria are limited, resulting in significant morbidity and mortality with high financial impact. The paucity in discovery and supply of new novel antimicrobials to treat life-threatening infections by resistant pathogens stands in sharp contrast to demand. Immediate interventions to contain AMR include surveillance and monitoring, minimizing over-the-counter antibiotics and antibiotics in food animals, access to quality and affordable medicines, vaccines and diagnostics, and enforcement of legislation. An orchestrated collaborative action within and between multiple national and international organizations is required urgently, otherwise, a postantibiotic era can be a more real possibility than an apocalyptic fantasy for the 21st century. This narrative review highlights on this basis, mechanisms and factors in microbial resistance, and key strategies to combat antimicrobial resistance.

Background and Aims: Diabetic foot ulcer (DFU) is one of the most common but uncontrolled health issues of diabetic patients that needs more therapeutic considerations. This systematic review aims to study the current status of the etiological agents responsible for DFU, their frequency in some of the most occurring Asian countries, and their antibiotic resistance pattern based on available studies., Methods: Here, the literature survey was conducted on all the DFU studies with the records of etiological agents and conventional therapeutic treatment published until March 2021 using Medical Literature Analysis and Retrieval System Online (MEDLINE) and Web of Science Core Collection (WoSCC) database., Results: Overall, in our study, a total of 73 studies representing 12 Asian countries worldwide have been included. We found that the highest number of studies were reported from India (45%) followed by Pakistan (11%), China, Iran and others. 71% of recent studies reported DFU being attributed to poly-microbial infections while the dominant position was significantly secured by Gram- negative bacteria (77%, p = 0.34). Staphylococcus aureus was found to be the most prevalent isolate followed by Pseudomonas and then Escherichia coli (mean value - 22%, 17%, and 15% respectively). Antibiotic sensitivity pattern was determined based on availability in terms of median resistance (MR) and interquartile range (IQR) which showed the growing resistance developed by both Gram-positive and Gram-negative isolates. Gram positive pathogens were still reported as susceptible to vancomycin (MR 0%, IQR 0-22.8%), linezolid (MR 0%, IQR 0-15.53%) and imipenem (MR 11%, IQR 0-23.53%). Carbapenem genera, colistin, and amikacin were the most effective drugs against Gram-negative pathogens., Conclusion: The findings of this study highly recommend searching for alternative and complementary therapeutic regimens instead of prescribing conventional drugs blindly without investigating the progression of the stages of the ulcer, which may help reduce the medical and economic burden of this disease., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC). Published by Elsevier Ltd. All rights reserved.)

Purpose: The Cook Stove Pregnancy Cohort Study (CSPCS) was designed to assess the effects of biomass fuel use on household air pollution (HAP) as well as the effects of HAP (fine particulate matter, PM 2.5 ) on birth outcomes and acute lower respiratory infection (ALRI) among infants in Bangladesh., Participants: We recruited 903 women within 18 weeks of pregnancy from rural and semiurban areas of Bangladesh between November 2016 and March 2017. All women and their infants (N=831 pairs) were followed until 12 months after delivery and a subset have undergone respiratory and gut microbiota analysis., Methods: Questionnaires were administered to collect detailed sociodemographic, medical, nutritional and behavioural information on the mother-child dyads. Anthropometric measurements and biological samples were also collected, as well as household PM 2.5 concentrations., Findings to Date: Published work in this cohort showed detrimental effects of biomass fuel and health inequity on birth outcomes. Current analysis indicates high levels of household PM 2.5 being associated with cooking fuel type and infant ALRI. Lastly, we identified distinct gut and respiratory microbial communities at 6 months of age., Future Plans: This study provides an economical yet effective framework to conduct pregnancy cohort studies determining the health effects of adverse environmental exposures in low-resource countries. Future analyses in this cohort include assessing the effect of indoor PM 2.5 levels on (1) physical growth, (2) neurodevelopment, (3) age of first incidence and frequency of ALRI in infants and (4) the development of the respiratory and gut microbiome. Additional support has allowed us to investigate the effect of in utero exposure to metals on infant neurodevelopment in the first year of life., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Studies demonstrated associations between maternal exposure to household air pollution from cooking and increased risk of adverse birth outcomes in offspring; however, the modifying effect of socioeconomic status (SES) on this association has not been explored., Objectives: In a cohort of pregnant women with 800 single live births between 2016 and 2017 in rural and semi urban areas of Bangladesh, we tested the hypotheses that kitchen location and cooking fuel type affect birth outcomes (birth weight, low birth weight [LBW] and small for gestational age [SGA]) and these associations vary by SES., Methods: Demographic characteristics including SES, kitchen location and fuel type were assessed in prenatal visits. Neonatal anthropometric measurements were recorded within 72 h of births. We performed multivariable linear and logistic regressions adjusting for potential confounders to test the study hypotheses., Results: For newborns from households with indoor kitchens, adjusted mean birth weight was 65.13 g (95% confidence interval [CI]: -118.37, -11.90) lower and the odds of LBW and SGA were 58% (odds ratio [OR]:1.58, 95% CI: 1.12, 2.24) and 41% (OR: 1.41, 95% CI: 1.05, 1.92) higher compared to those born in households with outdoor kitchens. We found SES significantly modified the associations between kitchen location and birth outcomes in households using biomass fuels. Newborns from low SES households with indoor kitchens had 89 g lower birth weight and a higher odds of being born with LBW (OR: 2.08, 95% CI 1.23, 3.58), and SGA (OR: 1.70, 95% CI 1.06, 2.76) than those born in high SES households using outdoor kitchens., Conclusions: In areas with poor access or affordability to clean fuel such as in our study population, cooking in an outdoor kitchen can reduce the burden of LBW and SGA, particularly for low SES households. Promoting outdoor kitchens is a possible intervention strategy to mitigate adverse birth outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Febrile seizures (FS) are common, affecting 2-5% of children between the ages of 3 months and 6 years. Complex FS occur in 10% of patients with FS and are strongly associated with mesial temporal lobe epilepsy. Current research suggests that predisposing factors, such as genetic and anatomic abnormalities, may be necessary for complex FS to translate to mesial temporal lobe epilepsy. Sex hormones are known to influence seizure susceptibility and epileptogenesis, but whether sex-specific effects of early life stress play a role in epileptogenesis is unclear. Here, we investigate sex differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis following chronic stress and the underlying contributions of gonadal hormones to the susceptibility of hyperthermia-induced seizures (HS) in rat pups. Chronic stress consisted of daily injections of 40 mg/kg of corticosterone (CORT) subcutaneously from postnatal day (P) 1 to P9 in male and female rat pups followed by HS at P10. Body mass, plasma CORT levels, temperature threshold to HS, seizure characteristics, and electroencephalographic in vivo recordings were compared between CORT- and vehicle (VEH)-injected littermates during and after HS at P10. In juvenile rats (P18-P22), in vitro CA1 pyramidal cell recordings were recorded in males to investigate excitatory and inhibitory neuronal circuits. Results show that daily CORT injections increased basal plasma CORT levels before HS and significantly reduced weight gain and body temperature threshold of HS in both males and females. CORT also significantly lowered the generalized convulsions (GC) latency while increasing recovery time and the number of electrographic seizures (>10s), which had longer duration. Furthermore, sex-specific differences were found in response to chronic CORT injections. Compared to females, male pups had increased basal plasma CORT levels after HS, longer recovery time and a higher number of electrographic seizures (>10s), which also had longer duration. Sex-specific differences were also found at baseline conditions with lower latency to generalized convulsions and longer duration of electrographic seizures in males but not in females. In juvenile male rats, the amplitude of evoked excitatory postsynaptic potentials, as well as the amplitude of inhibitory postsynaptic currents, were significantly greater in CORT rats when compared to VEH littermates. These findings not only validate CORT injections as a stress model, but also show a sex difference in baseline conditions as well as a response to chronic CORT and an impact on seizure susceptibility, supporting a potential link between sustained early-life stress and complex FS. Overall, these effects also indicate a putatively less severe phenotype in female than male pups. Ultimately, studies investigating the biological underpinnings of sex differences as a determining factor in mental and neurologic problems are necessary to develop better diagnostic, preventative, and therapeutic approaches for all patients regardless of their sex., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has delivered one of the worst economic shocks in modern history and the hospitality sector has been severely affected. Since small businesses from the hospitality sector are known to be relatively more susceptible to the economic complications arising from a crisis, we explore the underlying factors and management practices that influence their continuity of operations as they continue to struggle with the on-going COVID-19 crisis in Pakistan. Using a phenomenological approach, in-depth interviews were conducted to comprehend the experiences of owners-managers. The findings show that government support, cordial relationships with stakeholders, self-determination of entrepreneurs and formal planning are the most crucial factors that shaped the immediate adjustments of operational activities in response to COVID-19. These resilient practices are hygiene concerns, increased promotion through social media, innovative marketing practices (e.g., revised offerings), operational cost-cutting and employee training to comply with changing standard operating procedures from the government and industry. The practical and theoretical implications are also discussed., (© 2021 Elsevier Ltd. All rights reserved.)

Background: Aripiprazole, a third-generation antipsychotic medication, has been used to treat a range of psychiatric disorders. According to the U.S. Food and Drug Administration's prescribing information, the most common adverse reactions in adult patients in clinical trials (≥10%) were nausea, vomiting, constipation, headache, dizziness, akathisia, anxiety, and insomnia. While hematological adverse effects may occur with aripiprazole, there is very limited information in the published literature on such adverse outcomes., Case Presentation: A 68-year-old Caucasian male with treatment resistant depression was hospitalized for suicidal ideation. The patient developed neutropenia after aripiprazole was introduced as an augmentation agent. The neutropenia was reversible with discontinuation of the medication., Conclusions: To our knowledge, we describe the first case report of suspected neutropenia-induced by aripiprazole use in a geriatric patient. While hematological adverse reactions are rare, we recommend adding CBC to the standard adverse systemic reaction monitoring of antipsychotic medications, particularly among the elderly.

Background: Maternal tobacco smoke exposure has been associated with altered DNA methylation. However, previous studies largely used methylation arrays, which cover a small fraction of CpGs, and focused on whole cord blood., Objectives: The current study examined the impact of in utero exposure to maternal tobacco smoke on the cord blood [Formula: see text] DNA methylome., Methods: The methylomes of 20 Hispanic white newborns ([Formula: see text] exposed to any maternal tobacco smoke in pregnancy; [Formula: see text] unexposed) from the Maternal and Child Health Study (MACHS) were profiled by whole-genome bisulfite sequencing (median coverage: [Formula: see text]). Statistical analyses were conducted using the Regression Analysis of Differential Methylation (RADMeth) program because it performs well on low-coverage data (minimizes false positives and negatives)., Results: We found that 10,381 CpGs were differentially methylated by tobacco smoke exposure [neighbor-adjusted p-values that are additionally corrected for multiple testing based on the Benjamini-Hochberg method for controlling the false discovery rate (FDR) [Formula: see text]]. From these CpGs, RADMeth identified 557 differentially methylated regions (DMRs) that were overrepresented ([Formula: see text]) in important regulatory regions, including enhancers. Of nine DMRs that could be queried in a reduced representation bisulfite sequencing (RRBS) study of adult [Formula: see text] cells ([Formula: see text] smokers; [Formula: see text] nonsmokers), four replicated ([Formula: see text]). Additionally, a CpG in the promoter of SLC7A8 (percent methylation difference: [Formula: see text] comparing exposed to unexposed) replicated ([Formula: see text]) in an EPIC (Illumina) array study of cord blood [Formula: see text] cells ([Formula: see text] exposed to sustained maternal tobacco smoke; [Formula: see text] unexposed) and in a study of adult [Formula: see text] cells across two platforms (EPIC: [Formula: see text] smokers; [Formula: see text] nonsmokers; 450K: [Formula: see text] smokers; [Formula: see text] nonsmokers)., Conclusions: Maternal tobacco smoke exposure in pregnancy is associated with cord blood [Formula: see text] DNA methylation in key regulatory regions, including enhancers. While we used a method that performs well on low-coverage data, we cannot exclude the possibility that some results may be false positives. However, we identified a differentially methylated CpG in amino acid transporter SLC7A8 that is highly reproducible, which may be sensitive to cigarette smoke in both cord blood and adult [Formula: see text] cells. https://doi.org/10.1289/EHP3398.

A hybrid 16-channel current-mode and the 8-channel optical implantable neurostimulating system is presented. The system generates arbitrary-waveform charge-balanced current-mode electrical pulses with an amplitude ranging from 50 [Formula: see text] to 10 mA. An impedance monitoring feedback loop is employed to automatically adjust the supply voltage, yielding a load-optimized power dissipation. The 8-channel optical stimulator drives an array of LEDs, each with a maximum of 25 mA current amplitude, and reuses the arbitrary-waveform generation function of the electrical stimulator. The LEDs are assembled within a custom-made 4×4 ECoG grid electrode array, enabling precise optical stimulation of neurons with a 300 [Formula: see text] pitch between the LEDs and simultaneous monitoring of the neural response by the ECoG electrode, at different distances of the stimulation site. The hybrid stimulation system is implemented on a mini-PCB, and receives power and stimulation commands inductively through a second board and a coil stacked on top of it. The entire system is sized at 3×2 . 5×1 cm 3 and weighs 7 grams. The system efficacy for electrical and optical stimulation is validated in-vivo using separate chronic and acute experiments.

Objective: Studies suggest that prenatal exposure to traffic-related air pollution (TRAP) may contribute to childhood obesity. While exact mechanisms for this association are unknown, circulating adipokines are hypothesized to contribute to early-life weight gain., Methods: The Maternal and Child Health Study birth cohort included 136 women from the Los Angeles County + University of Southern California Medical Center. This study estimated prenatal residential TRAP exposure and used linear regression analysis to examine associations between adipokines with TRAP exposure and infant weight change (birth to 6 months)., Results: A one standard deviation (1-SD: 2 ppb) increase in prenatal non-freeway nitrogen oxides was associated with 33% (P = 0.01) higher leptin and 9% higher high molecular weight adiponectin levels (P = 0.07) in cord blood. Leptin levels were 71% higher in mothers who lived <75 m than those living >300 m from major roadways (P = 0.03). A 1-SD (10 ng mL -1 ) increase in leptin was associated with a significant increase in infant weight change in female infants (0.62 kg, P = 0.02) but not male infants (0.11 kg, P = 0.48)., Conclusions: Higher TRAP exposures were associated with higher cord blood levels of leptin and high molecular weight adiponectin. These adipokines were associated with increased infant weight change in female infants, which may have implications for future obesity risk., (© 2017 World Obesity Federation.)

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

First, existing commercially available open-loop and closed-loop implantable neurostimulators are reviewed and compared in terms of their targeted application, physical size, system-level features, and performance as a medical device. Next, signal processing algorithms as the primary strength point of the closed-loop neurostimulators are reviewed, and various design and implementation requirements and trade-offs are discussed in details along with quantitative examples. The review results in a set of guidelines for algorithm selection and evaluation. Second, the implementation of an inductively-powered seizure-predicting microsystem for monitoring and treatment of intractable epilepsy is presented. The miniaturized system is comprised of two miniboards and a power receiver coil. The first board hosts a 24-channel neurostimulator system on chip fabricated in a [Formula: see text] CMOS technology and performs neural recording, on-chip digital signal processing, and electrical stimulation. The second board communicates recorded brain signals as well as signal processing results wirelessly. The multilayer flexible coil receives inductively-transmitted power. The system is sized at 2 × 2 × 0.7 [Formula: see text] and weighs 6 g. The approach is validated in the control of chronic seizures in vivo in freely moving rats.

Objective: Sudden unexplained death in epilepsy is the leading cause of death in young adult epilepsy patients, typically occurring during the early postictal period, presumably resulting from brainstem and cardiorespiratory dysfunction. We hypothesized that ictal discharges in the brainstem disrupt the cardiorespiratory network, causing mortality. To study this hypothesis, we chose an animal model comprising focal unilateral hippocampal injection of 4-aminopyridine (4-AP), which produced focal recurrent hippocampal seizures with secondary generalization in awake, behaving rats., Methods: We studied ictal and interictal intracranial electrographic activity (iEEG) in 23 rats implanted with a custom electrode array into the hippocampus, the contralateral cortex, and brainstem. The hippocampal electrodes contained a cannula to administer the potassium channel blocker and convulsant (4-AP). iEEG was recorded continuously before, during, and after seizures induced by 4-AP infusion into the hippocampus., Results: The control group (n = 5) was monitored for 2-3 months, and the weekly baseline iEEG recordings showed long-term stability. The low-dose group (1 μL 4-AP, 40 mm, n = 5) exhibited local electrographic seizures without spread to the contralateral cerebral cortex or brainstem. The high-dose group (5 μL 4-AP, 40 mm, n = 3) had several hippocampal electrographic seizures, which spread contralaterally and triggered brainstem discharges within 40 min, and were associated with violent motor seizures followed by dyspnea and respiratory arrest, with cortical and hippocampal iEEG flattening. The group that received high-dose 4-AP without brainstem implantation (n = 5) had similar seizure-related respiratory difficulties. Finally, five rats that received high-dose 4-AP without EEG recording also developed violent motor seizures with postictal respiratory arrest. Following visualized respiratory arrest in groups III, IV, and V, manual respiratory resuscitation was successful in five of 13 animals., Significance: These studies show that hippocampal seizure activity can spread or trigger brainstem epileptiform discharges that may cause mortality, possibly mediated by respiratory network dysfunction., (Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.)

Background: The fractional concentration of exhaled nitric oxide (FeNO) is a biomarker of airway inflammation that has proved to be useful in investigations of genetic and epigenetic airway susceptibility to ambient air pollutants. For example, susceptibility to airway inflammation from exposure to particulate matter with aerodynamic diameter < =2.5 μm (PM 2.5 ) varies by haplotypes and promoter region methylation in inducible nitric oxide synthase (iNOS encoded by NOS2). We hypothesized that PM2.5 susceptibility associated with these epigenetic and genetic variants may be greater in children with high FeNO from inflamed airways. In this study, we investigated genetic and epigenetic susceptibility to airborne particulate matter by examining whether the joint effects of PM2.5, NOS2 haplotypes and iNOS promoter methylation significantly vary across the distribution of FeNO in school children., Methods: The study included 940 school children in the southern California Children's Health Study who provided concurrent buccal samples and FeNO measurements. We used quantile regression to examine susceptibility by estimating the quantile-specific joint effects of PM 2.5 , NOS2 haplotype and methylation on FeNO., Results: We discovered striking differences in susceptibility to PM 2.5 in school children. The joint effects of short-term PM 2.5 exposure, NOS2 haplotypes and methylation across the FeNO distribution were significantly larger in the upper tail of the FeNO distribution, with little association in its lower tail, especially among children with asthma and Hispanic white children., Conclusion: School-aged children with higher FeNO have greater genetic and epigenetic susceptibility to PM 2.5 , highlighting the importance of investigating effects across the entire distribution of FeNO.

Rationale: Asthma and obesity often occur together in children. It is unknown whether asthma contributes to the childhood obesity epidemic., Objectives: We aimed to investigate the effects of asthma and asthma medication use on the development of childhood obesity., Methods: The primary analysis was conducted among 2,171 nonobese children who were 5-8 years of age at study enrollment in the Southern California Children's Health Study (CHS) and were followed for up to 10 years. A replication analysis was performed in an independent sample of 2,684 CHS children followed from a mean age of 9.7 to 17.8 years., Measurements and Main Results: Height and weight were measured annually to classify children into normal, overweight, and obese categories. Asthma status was ascertained by parent- or self-reported physician-diagnosed asthma. Cox proportional hazards models were fitted to assess associations of asthma history with obesity incidence during follow-up. We found that children with a diagnosis of asthma at cohort entry were at 51% increased risk of developing obesity during childhood and adolescence compared with children without asthma at baseline (hazard ratio, 1.51; 95% confidence interval, 1.08-2.10) after adjusting for confounders. Use of asthma rescue medications at cohort entry reduced the risk of developing obesity (hazard ratio, 0.57; 95% confidence interval, 0.33-0.96). In addition, the significant association between a history of asthma and an increased risk of developing obesity was replicated in an independent CHS sample., Conclusions: Children with asthma may be at higher risk of obesity. Asthma rescue medication use appeared to reduce obesity risk independent of physical activity.

First, existing sleep stage classifier sensors and algorithms are reviewed and compared in terms of classification accuracy, level of automation, implementation complexity, invasiveness, and targeted application. Next, the implementation of a miniature microsystem for low-latency automatic sleep stage classification in rodents is presented. The classification algorithm uses one EMG (electromyogram) and two EEG (electroencephalogram) signals as inputs in order to detect REM (rapid eye movement) sleep, and is optimized for low complexity and low power consumption. It is implemented in an on-board low-power FPGA connected to a multi-channel neural recording IC, to achieve low-latency (order of 1 ms or less) classification. Off-line experimental results using pre-recorded signals from nine mice show REM detection sensitivity and specificity of 81.69% and 93.86%, respectively, with the maximum latency of 39 [Formula: see text]. The device is designed to be used in a non-disruptive closed-loop REM sleep suppression microsystem, for future studies of the effects of REM sleep deprivation on memory consolidation.

We review integrated circuits for low-frequency noise and offset rejection as a motivation for the presented digitally-assisted neural amplifier design methodology. Conventional AC-coupled neural amplifiers inherently reject input DC offset but have key limitations in area, linearity, DC drift, and spectral accuracy. Their chopper stabilization reduces low-frequency intrinsic noise at the cost of degraded area, input impedance and design complexity. DC-coupled implementations with digital high-pass filtering yield improved area, linearity, drift, and spectral accuracy and are inherently suitable for simple chopper stabilization. As a design example, a 56-channel 0.13 [Formula: see text] CMOS intracranial EEG interface is presented. DC offset of up to ±50 mV is rejected by a digital low-pass filter and a 16-bit delta-sigma DAC feeding back into the folding node of a folded-cascode LNA with CMRR of 65 dB. A bank of seven column-parallel fully differential SAR ADCs with ENOB of 6.6 are shared among 56 channels resulting in 0.018 [Formula: see text] effective channel area. Compensation-free direct input chopping yields integrated input-referred noise of 4.2 μV rms over the bandwidth of 1 Hz to 1 kHz. The 8.7 [Formula: see text] chip dissipating 1.07 mW has been validated in vivo in online intracranial EEG monitoring in freely moving rats.

Extracellular potassium concentration, [K⁺] o , plays a fundamental role in the physiological functions of the brain. Studies investigating changes in [K⁺] o have predominantly relied upon glass capillary electrodes with K⁺-sensitive solution gradients for their measurements. However, such electrodes are unsuitable for taking spatio-temporal measurements and are limited by the surface area of their tips. We illustrate seizures invoked chemically and in optogenetically modified mice using blue light exposure while impedimetrically measuring the response. A sharp decrease of 1-2 mM in [K⁺] o before each spike has shown new physiological events not witnessed previously when measuring extracellular potassium concentrations during seizures in mice. We propose a novel approach that uses multichannel monolayer coated gold microelectrodes for in vivo spatio-temporal measurements of [K⁺] o in a mouse brain as an improvement to the conventional glass capillary electrode., Competing Interests: The authors declare no conflict of interest.

This paper presents a general methodology of inductive power delivery in wireless chronic rodent electrophysiology applications. The focus is on such systems design considerations under the following key constraints: maximum power delivery under the allowable specific absorption rate (SAR), low cost and spatial scalability. The methodology includes inductive coil design considerations within a low-frequency ferrite-core-free power transfer link which includes a scalable coil-array power transmitter floor and a single-coil implanted or worn power receiver. A specific design example is presented that includes the concept of low-SAR cellular single-transmitter-coil powering through dynamic tracking of a magnet-less receiver spatial location. The transmitter coil instantaneous supply current is monitored using a small number of low-cost electronic components. A drop in its value indicates the proximity of the receiver due to the reflected impedance of the latter. Only the transmitter coil nearest to the receiver is activated. Operating at the low frequency of 1.5 MHz, the inductive powering floor delivers a maximum of 15.9 W below the IEEE C95 SAR limit, which is over three times greater than that in other recently reported designs. The power transfer efficiency of 39% and 13% at the nominal and maximum distances of 8 cm and 11 cm, respectively, is maintained.

We assess and compare the effects of both closed-loop and open-loop neurostimulation of the rat hippocampus by means of a custom low-power programmable therapeutic neurostimulation device on the suppression of spontaneous seizures in a rodent model of epilepsy. Chronic seizures were induced by intraperitoneal kainic acid injection. Two bipolar electrodes were implanted into the CA1 regions of both hippocampi. The electrodes were connected to the custom-built programmable therapeutic neurostimulation device that can trigger an electrical stimulation either in a periodic manner or upon detection of the intracerebral electroencephalographic (icEEE) seizure onset. This device includes a microchip consisting of a 256-channel icEEG recording system and a 64-channel stimulator, and a programmable seizure detector implemented in a field-programmable gate array (FPGA). The neurostimulator was used to evaluate seizure suppression efficacy in ten epileptic rats for a total of 240 subject-days (5760 subject-hours). For this purpose, all rats were randomly divided into two groups: the no-stimulation group and the stimulation group. The no-stimulation group did not receive stimulation. The stimulation group received, first, closed-loop stimulation and, next, open-loop stimulation. The no-stimulation and stimulation groups had a similar seizure frequency baseline, averaging five seizures per day. Closed-loop stimulation reduced seizure frequency by 90% and open-loop stimulation reduced seizure frequency by 17%, both in the stimulation group as compared to the no-stimulation group.

Objective: Recent studies suggest that air pollution plays a role in type 2 diabetes (T2D) incidence and mortality. The underlying physiological mechanisms have yet to be established. We hypothesized that air pollution adversely affects insulin sensitivity and secretion and serum lipid levels., Research Design and Methods: Participants were selected from BetaGene (n = 1,023), a study of insulin resistance and pancreatic β-cell function in Mexican Americans. All participants underwent DXA and oral and intravenous glucose tolerance tests and completed dietary and physical activity questionnaires. Ambient air pollutant concentrations (NO2, O3, and PM2.5) for short- and long-term periods were assigned by spatial interpolation (maximum interpolation radius of 50 km) of data from air quality monitors. Traffic-related air pollution from freeways (TRAP) was estimated using the dispersion model as NOx. Variance component models were used to analyze individual and multiple air pollutant associations with metabolic traits., Results: Short-term (up to 58 days cumulative lagged averages) exposure to PM2.5 was associated with lower insulin sensitivity and HDL-to-LDL cholesterol ratio and higher fasting glucose and insulin, HOMA-IR, total cholesterol, and LDL cholesterol (LDL-C) (all P ≤ 0.036). Annual average PM2.5 was associated with higher fasting glucose, HOMA-IR, and LDL-C (P ≤ 0.043). The effects of short-term PM2.5 exposure on insulin sensitivity were largest among obese participants. No statistically significant associations were found between TRAP and metabolic outcomes., Conclusions: Exposure to ambient air pollutants adversely affects glucose tolerance, insulin sensitivity, and blood lipid concentrations. Our findings suggest that ambient air pollutants may contribute to the pathophysiology in the development of T2D and related sequelae., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Exhaled nitric oxide (FeNO), a biomarker of airway inflammation, predicts asthma risk in children. We previously found that the promoter haplotypes in inducible nitric oxide synthase (NOS2) and exposure to residential traffic independently influence FeNO level. Because NOS2 is inducible by environmental exposures such as traffic-related exposure, we tested the hypothesis that common NOS2 promoter haplotypes modulate the relationship between residential traffic-related exposure and FeNO level in children., Methods: In a cross-sectional population-based study, subjects (N = 2,457; 7-11 year-old) were Hispanic and non-Hispanic white children who participated in the Southern California Children's Health Study and had FeNO measurements. For residential traffic, lengths of local roads within circular buffers (50m, 100m and 200m radii around homes) around the subjects' homes were estimated using geographic information system (GIS) methods. We interrogated the two most common NOS2 promoter haplotypes that were found to affect FeNO level., Results: The relationship between local road lengths within 100m and 200m circular buffers and FeNO level varied significantly by one of the NOS2 promoter haplotypes (P-values for interaction between road length and NOS2 promoter haplotype = 0.02 and 0.03, respectively). In children who had ≤250m of local road lengths within 100m buffer around their homes, those with two copies of the haplotype had significantly lower FeNO (adjusted geometric mean = 11.74ppb; 95% confidence intervals (CI): 9.99 to 13.80) than those with no copies (adjusted geometric mean = 15.28ppb; 95% CI: 14.04 to 16.63) with statistically significant trend of lower FeNO level with increasing number of haplotype copy (P-value for trend = 0.002). In contrast, among children who had >250m of local road lengths within 100m buffer, FeNO level did not significantly differ by the haplotype copy-number (P-value for trend = 0.34). Similar interactive effects of this haplotype and local road lengths within 200m buffer on FeNO were also observed., Conclusions: Higher exposure from residential traffic nullifies the protective effect of one common NOS2 promoter haplotype on FeNO level. Regulation of traffic-related pollution may protect children's respiratory health.

Background: Asthma and rhinitis are common childhood health conditions. Being an understudied and rapidly growing population in the US, Hispanic children have a varying risk for these conditions that may result from sociocultural (including acculturative factors), exposure and genetic diversities. Hispanic populations have varying contributions from European, Amerindian and African ancestries. While previous literature separately reported associations between genetic ancestry and acculturation factors with asthma, whether Amerindian ancestry and acculturative factors have independent associations with development of early-life asthma and rhinitis in Hispanic children remains unknown. We hypothesized that genetic ancestry is an important determinant of early-life asthma and rhinitis occurrence in Hispanic children independent of sociodemographic, acculturation and environmental factors., Methods: Subjects were Hispanic children (5-7 years) who participated in the southern California Children's Health Study. Data from birth certificates and questionnaire provided information on acculturation, sociodemographic and environmental factors. Genetic ancestries (Amerindian, European, African and Asian) were estimated based on 233 ancestry informative markers. Asthma was defined by parental report of doctor-diagnosed asthma. Rhinitis was defined by parental report of a history of chronic sneezing or runny or blocked nose without a cold or flu. Sample sizes were 1,719 and 1,788 for investigating the role of genetic ancestry on asthma and rhinitis, respectively., Results: Children had major contributions from Amerindian and European ancestries. After accounting for potential confounders, per 25% increase in Amerindian ancestry was associated with 17.6% (95% confidence interval [CI]: 0.74-0.99) and 13.6% (95% CI: 0.79-0.98) lower odds of asthma and rhinitis, respectively. Acculturation was not associated with either outcome., Conclusions: Earlier work documented that Hispanic children with significant contribution from African ancestry are at increased asthma risk; however, in Hispanic children who have little contribution from African ancestry, Amerindian ancestry was independently associated with lower odds for development of early-childhood asthma and rhinitis.

Objective: To investigate the abortion of seizure generation using "minimal" intervention in hippocampi using two rat models of human temporal lobe epilepsy., Methods: The recording or stimulation electrodes were implanted into both hippocampi (CA1 area). Using the kainic acid (chronic: experiment duration 24 days) and the 4-aminopyridine (acute: experiment duration 2 h) models of paroxysms in rats, a real-time feedback stimulation paradigm was implemented, which triggered a short periodic electrical stimulus (5 Hz for 5 s) upon detecting a seizure precursor. Our seizure precursor detection algorithm relied on the monitoring of the real-time phase synchronization analysis, and detected/anticipated electrographic seizures as early as a few seconds to a few minutes before the behavioral and electrographic seizure onset, with a very low false-positive rate of the detection., Results: The baseline mean seizure frequencies were 5.39 seizures per day (chronic) and 13.2 seizures per hour (acute). The phase synchrony analysis detected 88% (434 of 494) of seizures with a mean false alarm of 0.67 per day (chronic) and 83% (86 of 104) of seizures with a mean false alarm of 0.47 per hour (acute). The feedback stimulation reduced the seizure frequencies to 0.41 seizures per day (chronic) and 2.4 seizures per hour (acute). Overall, the feedback stimulation paradigm reduced seizure frequency by a minimum of 80% to a maximum of 100% in 10 rats, with 83% of the animals rendered seizure-free., Significance: This approach represents a simple and efficient manner for stopping seizure development. Because of the short on-demand stimuli, few or no associated side effects are expected in clinical application in patients with epilepsy. Abnormal synchrony patterns are common features in epilepsy and other neurologic and psychiatric syndromes; therefore, this type of feedback stimulation paradigm could be a novel therapeutic modality for use in various neurologic and psychiatric disorders., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

While the fractional concentration of exhaled nitric oxide (FeNO) has proven useful in asthma research, its exact role in clinical care remains unclear, in part due to unexplained inter-subject heterogeneity. In this study, we assessed the hypothesis that the effects of determinants of the fractional concentration of exhaled nitric oxide (FeNO) vary with differing levels of FeNO. In a population-based cohort of 1542 school children aged 12-15 from the Southern California Children's Health Study, we used quantile regression to investigate if the relationships of asthma, socio-demographic and clinical covariates with FeNO vary across its distribution. Differences in FeNO between children with and without asthma increased steeply as FeNO increased (Estimated asthma effects (in ppb) at selected 20th, 50th and 80th percentiles of FeNO are 2.4, 6.3 and 22.2, respectively) but the difference was steeper with increasing FeNO in boys and in children with active rhinitis (p-values<0.01). Active rhinitis also showed significantly larger effects on FeNO at higher concentrations of FeNO (Estimated active rhinitis effects (in ppb) at selected 20th, 50th and 80th percentiles of FeNO are 2.1, 5.7 and 14.3, respectively). Boys and children of Asian descent had higher FeNO than girls and non-Hispanic whites; these differences were significantly larger in those with higher FeNO (p-values<0.01). In summary, application of quantile regression techniques provides new insights into the determinants of FeNO showing substantially varying effects in those with high versus low concentrations.