Adverse Childhood Experiences and Adult Smoking, Nebraska, 2011

Introduction Smoking is a public health risk; the prevalence of smoking among adults in Nebraska is 18-4%. Studies indicate that maltreatment of children alters their brain development, possibly increasing risk for tobacco use. Previous studies have documented associations between childhood maltreatment and adult health behaviors, demonstrating the influence of adverse experiences on tobacco use. We examined prevalence and associations between adverse childhood experiences and smoking among Nebraskans. Methods We analyzed 2011 Nebraska Behavioral Risk Factor Surveillance System (Adverse Childhood Experience module) data, defining adverse childhood experience exposures as physical, sexual, and verbal abuse (ie, direct exposures), and household dysfunction associated with mental illness, substance abuse, divorce, domestic violence, and living with persons with incarceration histories (ie, environmental exposures). We estimated prevalence of exposures, taking into account the complex survey design. We used logistic regression with predicted margins to estimate adjusted relative risk for smoking by direct or environmental exposure. Results Approximately 51% of Nebraskans experienced 1 or more adverse childhood events; 7% experienced 5 or more. Prevalence of environmental exposures (42%) was significantly higher than that of direct exposures (31%). Prevalence of individual exposures ranged from 6% (incarceration of a household member) to 25% (verbal abuse). Adjusted relative risks of smoking for direct and environmental exposures were 1.5 and 1.8, respectively. Conclusion We present a new method of evaluating adverse childhood experience data. Prevalence of adverse childhood experiences is high among Nebraskans, and these exposures are associated with smoking. State-specific strategies to monitor adverse events among children and provide interventions might help to decrease the smoking rate in this population

Adverse Childhood Experiences and Adult Smoking, Nebraska, 2011

Introduction Smoking is a public health risk; the prevalence of smoking among adults in Nebraska is 18-4%. Studies indicate that maltreatment of children alters their brain development, possibly increasing risk for tobacco use. Previous studies have documented associations between childhood maltreatment and adult health behaviors, demonstrating the influence of adverse experiences on tobacco use. We examined prevalence and associations between adverse childhood experiences and smoking among Nebraskans. Methods We analyzed 2011 Nebraska Behavioral Risk Factor Surveillance System (Adverse Childhood Experience module) data, defining adverse childhood experience exposures as physical, sexual, and verbal abuse (ie, direct exposures), and household dysfunction associated with mental illness, substance abuse, divorce, domestic violence, and living with persons with incarceration histories (ie, environmental exposures). We estimated prevalence of exposures, taking into account the complex survey design. We used logistic regression with predicted margins to estimate adjusted relative risk for smoking by direct or environmental exposure. Results Approximately 51% of Nebraskans experienced 1 or more adverse childhood events; 7% experienced 5 or more. Prevalence of environmental exposures (42%) was significantly higher than that of direct exposures (31%). Prevalence of individual exposures ranged from 6% (incarceration of a household member) to 25% (verbal abuse). Adjusted relative risks of smoking for direct and environmental exposures were 1.5 and 1.8, respectively. Conclusion We present a new method of evaluating adverse childhood experience data. Prevalence of adverse childhood experiences is high among Nebraskans, and these exposures are associated with smoking. State-specific strategies to monitor adverse events among children and provide interventions might help to decrease the smoking rate in this population

Planetary science and exploration in the deep subsurface: results from the MINAR Program, Boulby Mine, UK

The subsurface exploration of other planetary bodies can be used to unravel their geological history and assess their habitability. On Mars in particular, present-day habitable conditions may be restricted to the subsurface. Using a deep subsurface mine, we carried out a program of extraterrestrial analog research – MINe Analog Research (MINAR). MINAR aims to carry out the scientific study of the deep subsurface and test instrumentation designed for planetary surface exploration by investigating deep subsurface geology, whilst establishing the potential this technology has to be transferred into the mining industry. An integrated multi-instrument suite was used to investigate samples of representative evaporite minerals from a subsurface Permian evaporite sequence, in particular to assess mineral and elemental variations which provide small-scale regions of enhanced habitability. The instruments used were the Panoramic Camera emulator, Close-Up Imager, Raman spectrometer, Small Planetary Linear Impulse Tool, Ultrasonic drill and handheld X-ray diffraction (XRD). We present science results from the analog research and show that these instruments can be used to investigate in situ the geological context and mineralogical variations of a deep subsurface environment, and thus habitability, from millimetre to metre scales. We also show that these instruments are complementary. For example, the identification of primary evaporite minerals such as NaCl and KCl, which are difficult to detect by portable Raman spectrometers, can be accomplished with XRD. By contrast, Raman is highly effective at locating and detecting mineral inclusions in primary evaporite minerals. MINAR demonstrates the effective use of a deep subsurface environment for planetary instrument development, understanding the habitability of extreme deep subsurface environments on Earth and other planetary bodies, and advancing the use of space technology in economic mining

Gene Transcription and Splicing of T-Type Channels Are Evolutionarily-Conserved Strategies for Regulating Channel Expression and Gating

T-type calcium channels operate within tightly regulated biophysical constraints for supporting rhythmic firing in the brain, heart and secretory organs of invertebrates and vertebrates. The snail T-type gene, LCav3 from Lymnaea stagnalis, possesses alternative, tandem donor splice sites enabling a choice of a large exon 8b (201 aa) or a short exon 25c (9 aa) in cytoplasmic linkers, similar to mammalian homologs. Inclusion of optional 25c exons in the III–IV linker of T-type channels speeds up kinetics and causes hyperpolarizing shifts in both activation and steady-state inactivation of macroscopic currents. The abundant variant lacking exon 25c is the workhorse of embryonic Cav3 channels, whose high density and right-shifted activation and availability curves are expected to increase pace-making and allow the channels to contribute more significantly to cellular excitation in prenatal tissue. Presence of brain-enriched, optional exon 8b conserved with mammalian Cav3.1 and encompassing the proximal half of the I–II linker, imparts a ∼50% reduction in total and surface-expressed LCav3 channel protein, which accounts for reduced whole-cell calcium currents of +8b variants in HEK cells. Evolutionarily conserved optional exons in cytoplasmic linkers of Cav3 channels regulate expression (exon 8b) and a battery of biophysical properties (exon 25c) for tuning specialized firing patterns in different tissues and throughout development

Chemoreceptor responsiveness at sea level does not predict the pulmonary pressure response to high altitude

The hypoxic ventilatory response (HVR) at sea level (SL) is moderately predictive of the change in pulmonary artery systolic pressure (PASP) to acute normobaric hypoxia. However, because of progressive changes in the chemoreflex control of breathing and acid-base balance at high altitude (HA), HVR at SL may not predict PASP at HA. We hypothesized that resting peripheral oxyhemoglobin saturation (SpO2) at HA would correlate better than HVR at SL to PASP at HA. In 20 participants at SL, we measured normobaric, isocapnic HVR (L/min·-%SpO2 -1) and resting PASP using echocardiography. Both resting SpO2 and PASP measures were repeated on day 2 (n=10), days 4-8 (n=12), and 2-3 weeks (n=8) after arrival at 5050m. These data were also collected at 5050m on life-long HA residents (Sherpa; n=21). Compared to SL, SpO2 decreased from 98.6 to 80.5% (P<0.001), while PASP increased from 21.7 to 34.0mmHg (P<0.001) after 2-3 weeks at 5050m. Isocapnic HVR at SL was not related to SpO2 or PASP at any time point at 5050m (all P>0.05). Sherpa had lower PASP (P<0.01) than lowlanders on days 4-8 despite similar SpO2. Upon correction for hematocrit, Sherpa PASP was not different from lowlanders at SL, but lower than lowlanders at all HA time points. At 5050m, whilst SpO2 was not related to PASP in lowlanders at any point (all R2=0.50), there was a weak relationship in the Sherpa (R2=0.16; P=0.07). We conclude that neither HVR at SL nor resting SpO2 at HA correlates with elevations in PASP at HA

Loss of Sex and Age Driven Differences in the Gut Microbiome Characterize Arthritis-Susceptible *0401 Mice but Not Arthritis-Resistant *0402 Mice

<div><h3>Background</h3><p>HLA-DRB1*0401 is associated with susceptibility, while HLA-DRB1*0402 is associated with resistance to developing rheumatoid arthritis (RA) and collagen-induced arthritis in humans and transgenic mice respectively. The influence of gut-joint axis has been suggested in RA, though not yet proven.</p> <h3>Methodology/Principal Findings</h3><p>We have used HLA transgenic mice carrying arthritis susceptible and -resistant HLA-DR genes to explore if genetic factors and their interaction with gut flora gut can be used to predict susceptibility to develop arthritis. Pyrosequencing of the 16S rRNA gene from the fecal microbiomes of DRB1*0401 and DRB1*0402 transgenic mice revealed that the guts of *0401 mice is dominated by a Clostridium-like bacterium, whereas the guts of *0402 mice are enriched for members of the <em>Porphyromonadaceae</em> family and <em>Bifidobacteria</em>. DRB1*0402 mice harbor a dynamic sex and age-influenced gut microbiome while DRB1*0401 mice did not show age and sex differences in gut microbiome even though they had altered gut permeability. Cytokine transcripts, measured by rtPCR, in jejuna showed differential TH17 regulatory network gene transcripts in *0401 and *0402 mice.</p> <h3>Conclusions/Significance</h3><p>We have demonstrated for the first time that HLA genes in association with the gut microbiome may determine the immune environment and that the gut microbiome might be a potential biomarker as well as contributor for susceptibility to arthritis. Identification of pathogenic commensal bacteria would provide new understanding of disease pathogenesis, thereby leading to novel approaches for therapy.</p> </div

A systematic review of cerebral microdialysis and outcomes in TBI: relationships to patient functional outcome, neurophysiologic measures, and tissue outcome

OBJECTIVE: To perform a systematic review on commonly measured cerebral microdialysis (CMD) analytes and their association to: (A) patient functional outcome, (B) neurophysiologic measures, and (C) tissue outcome; after moderate/severe TBI. The aim was to provide a foundation for next-generation CMD studies and build on existing pragmatic expert guidelines for CMD. METHODS: We searched MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to October 2016). Strength of evidence was adjudicated using GRADE. RESULTS: (A) Functional Outcome: 55 articles were included, assessing outcome as mortality or Glasgow Outcome Scale (GOS) at 3-6 months post-injury. Overall, there is GRADE C evidence to support an association between CMD glucose, glutamate, glycerol, lactate, and LPR to patient outcome at 3-6 months. (B) Neurophysiologic Measures: 59 articles were included. Overall, there currently exists GRADE C level of evidence supporting an association between elevated CMD measured mean LPR, glutamate and glycerol with elevated ICP and/or decreased CPP. In addition, there currently exists GRADE C evidence to support an association between elevated mean lactate:pyruvate ratio (LPR) and low PbtO2. Remaining CMD measures and physiologic outcomes displayed GRADE D or no evidence to support a relationship. (C) Tissue Outcome: four studies were included. Given the conflicting literature, the only conclusion that can be drawn is acute/subacute phase elevation of CMD measured LPR is associated with frontal lobe atrophy at 6 months. CONCLUSIONS: This systematic review replicates previously documented relationships between CMD and various outcome, which have driven clinical application of the technique. Evidence assessments do not address the application of CMD for exploring pathophysiology or titrating therapy in individual patients, and do not account for the modulatory effect of therapy on outcome, triggered at different CMD thresholds in individual centers. Our findings support clinical application of CMD and refinement of existing guidelines

Plasticity in the Human Gut Microbiome Defies Evolutionary Constraints

The gut microbiome of primates, including humans, is reported to closely follow host evolutionary history, with gut microbiome composition being specific to the genetic background of its primate host. However, the comparative models used to date have mainly included a limited set of closely related primates. To further understand the forces that shape the primate gut microbiome, with reference to human populations, we expanded the comparative analysis of variation among gut microbiome compositions and their primate hosts, including 9 different primate species and 4 human groups characterized by a diverse set of subsistence patterns (n = 448 samples). The results show that the taxonomic composition of the human gut microbiome, at the genus level, exhibits increased compositional plasticity. Specifically, we show unexpected similarities between African Old World monkeys that rely on eclectic foraging and human populations engaging in nonindustrial subsistence patterns; these similarities transcend host phylogenetic constraints. Thus, instead of following evolutionary trends that would make their microbiomes more similar to that of conspecifics or more phylogenetically similar apes, gut microbiome composition in humans from nonindustrial populations resembles that of generalist cercopithecine monkeys. We also document that wild cercopithecine monkeys with eclectic diets and humans following nonindustrial subsistence patterns harbor high gut microbiome diversity that is not only higher than that seen in humans engaging in industrialized lifestyles but also higher compared to wild primates that typically consume fiber-rich diets