Heart rate dynamics and asymmetry during sympathetic activity stimulation and post-stimulation recovery in ski mountaineers-a pilot exploratory study.

There is a lack of studies on non-linear heart rate (HR) variability in athletes. We aimed to assess the usefulness of short-term HR dynamics and asymmetry parameters to evaluate the neural modulation of cardiac activity based on non-stationary RR interval series by studying their changes during sympathetic nervous system activity stimulation (isometric handgrip test) and post-stimulation recovery in professional ski mountaineers. The correlation between the changes in the parameters and the respiratory rate (RespRate) and also the duration of the career was analyzed. Short-term (5 min) and ultra-short-term (1 min) rates of patterns with no variations (0V), number of acceleration runs of length 1 (AR1), and short-term Porta's Index were greater, whereas Guzik's Index (GI) was smaller during sympathetic stimulation compared to rest. GI increased and the number of AR1 decreased during recovery. Greater increases in GI and RMSSD were associated with greater decreases in RespRate during recovery. Greater increases in RespRate from rest to short-term sympathetic stimulation were associated with greater increases in 0V (Max-min method) and AR1 but also with greater decreases in decelerations of short-term variance and accelerations and decelerations of long-term variance. Greater increases in 0V (Max-min method) and number of AR1 during sympathetic stimulation were associated with a shorter career duration. Greater decreases in these parameters during recovery were associated with a longer career duration. Changes in measures of HR dynamics and asymmetry, calculated based on short-term non-stationary RRi time series induced by sympathetic stimulation and post-stimulation recovery, reflected sympathovagal shift and were associated with condition-related alterations in RespRate and career duration in athletes who practice ski mountaineering.

Aerobic Capacity in Relation to Selected Elements of Body Posture.

BACKGROUND: In the 21st century, with the rapid development of many human life areas, physical activity should be prevalent in health maintenance and promotion. Body posture is a motor habit characteristic of every individual. Its correctness depends on numerous aspects, e.g., physical activity, age, mental state, or eating habits. There are numerous reports in the literature on the impact of physical activity on body posture, correct foot arch development, and the level of aerobic capacity in children and adolescents, but there is a noticeable lack of assessments of these characteristics and their correlations in adults. AIM: To evaluate aerobic capacity in males and females in relation to selected body posture elements. METHODS: The study involved 45 females and 46 males aged 20-21 years. The inclusion criteria involved declared good health and no contraindications. Selected somatic traits, body posture, and physical capacity indicators were determined. RESULTS: Physical capacity shows a significant relationship with body mass in both sexes (female: r = -0.346; p = 0.020; male: r = -0.321; p = 0.030). A significant correlation was observed between aerobic capacity and lean body mass in females (r = -0.428; p = 0.003) and body mass (r = -0.461; p = 0.001) and body fat percentage in males (r = -0.443; p = 0.002). A significant correlation was demonstrated between maximal oxygen uptake and Clarke's angle (r = -0.300; p = 0.045) in females, between maximal oxygen uptake and the loaded area of the right foot (r = -0.247; p = 0.098) in the male group, and between maximal oxygen uptake and spine lateral deviation (r = 0.352; p = 0.018) in females. There was no dimorphism between body posture elements and physical capacity except for the level of foot longitudinal arches, feet loading surface, spine lateral deviation, and the range of spine mobility in the sagittal and frontal planes. Aerobic capacity significantly influenced lean body mass (ß = -0.379; p = 0.007) and spine deviation from the anatomical axis in the frontal plane in females (ß = 0.287; p = 0.039) and body fat percentage in males (ß = -0.443; p = 0.002). CONCLUSIONS: Selected body posture elements demonstrate relationships with physical capacity in both sexes. The results should find wide practical applications, e.g., in promoting a comprehensive assessment of body posture and physical capacity as determinants of health maintenance.

A data-driven quality-score system for rating drug products and its implications for the health care industry.

The quality of drug products in the United States has been a matter of growing concern. Buyers and payers of pharmaceuticals have limited insight into measures of drug-product quality. Therefore, a quality-score system driven by data collection is proposed to differentiate between the qualities of drug products produced by different manufacturers. The quality scores derived using this proposed system would be based upon public regulatory data and independently-derived chemical data. A workflow for integrating the system into procurement decisions within health care organizations is also suggested. The implementation of such a quality-score system would benefit health care organizations by including the consideration of the quality of products while also considering price as a part of the drug procurement process. Such a system would also benefit the U.S. health care industry by bringing accountability and transparency into the drug supply chain and incentivizing manufacturers to place an increased emphasis on the quality and safety of their drug products.

Association of exposure to ambient particulate matter with maternal thyroid function in early pregnancy.

BACKGROUND: It is known that maternal thyroid dysfunction during early pregnancy can cause adverse pregnancy complications and birth outcomes. This study was designed to examine the association between ambient particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) and particulate matter with aerodynamic diameters ≤10 µm (PM10) exposure and maternal thyroid function during early pregnancy. METHODS: This study was based on data from a birth cohort study of 921 pregnant women in China. We estimated associations between ambient PM2.5 and PM10 exposure during the first trimester of pregnancy (estimated with land-use regression models) and maternal thyroid hormone concentrations (free thyroxine (FT4), free tri-iodothyronine (FT3), and thyroid-stimulating hormone (TSH)) collected between weeks 10 and 17 of gestation using linear regression models adjusting for potential confounders. Ambient PM2.5 and PM10 concentrations were modeled per interquartile range (IQR) increment and as tertiles based on the distribution of the exposure levels. RESULTS: An IQR increment (68 µg/m3) in PM2.5 exposure was associated with a significant decrease in maternal FT4 levels (ß = -0.60, 95% CI: -1.07, -0.12); and a significant decrease in FT4/FT3 ratio (ß = -0.13, 95% CI: -0.25, -0.02). Further analyses showed that, relative to the lowest tertile, women in both the middle and highest tertiles of PM2.5 had significantly lower concentrations of maternal FT4 and FT4/FT3 ratio. No significant associations were found between PM2.5 and FT3 or TSH levels. PM10 exposure was not significantly associated with maternal thyroid function. CONCLUSIONS: Our study suggested that higher ambient PM2.5, not PM10, exposed during the first trimester of pregnancy were associated with a significant decrease in maternal serum FT4 concentrations and FT4/FT3 ratio. Studies in populations with different exposure levels are needed to replicate our study results.

Changes in blood rheological properties and biochemical markers after participation in the XTERRA Poland triathlon competition.

The importance of physical activity in preventing chronic cardiovascular and metabolic diseases and the role of exercise as an adjunct therapy are widely recognized. Triathlon is a typically endurance discipline. Prolonged and intensive exercise is known to cause changes in blood rheological properties and biochemical markers; sometimes athletes participating in strenuous competitions need medical attention. To understand the phenomena occurring in the body in such situations, we decided to study participants' biomarkers after the XTERRA Poland 2017 triathlon competition. The study involved 10 triathletes. The XTERRA Poland 2017 event comprised 1500-m swimming, 36-km cycling, and 10-km mountain running. Blood samples were collected 2 days before, immediately after, and 16 h after the competition. Immediately after the race, white blood cells count, platelets, and uric acid levels were significantly (P < 0.001) increased; haematocrit, Na+, Cl-, and IgA were decreased. On the following day, Na+, Cl-, and C-reactive protein levels were significantly (P < 0.001) increased; white blood cells count, red blood cells count, haemoglobin, haematocrit, mean corpuscular volume, platelets, IgG, and IgA were decreased. Assessing rheological parameters such as erythrocyte deformability and aggregation is useful for monitoring adverse effects of intensive and exhaustive exercise. The study illustrates the change in blood rheological properties and biochemical markers after intensive physical effort. Despite these differences, the indicators were within the reference range for the general population, which may demonstrate normal body function in the studied triathletes.

Test-Retest Reliability of Handgrip Strength Measurement in Children and Preadolescents.

The reliability of handgrip strength (HGS) measurement has been confirmed in adults but has been sparsely addressed in pediatric populations. The aims of this study are twofold: to determine whether sex, age and/or hand-dominance influence the test-retest differences and to establish the reliability level of the HGS measurement in typical developing pediatric participants. A total of 338 participants aged 7-13 years were tested using a digital handgrip strength (HGS) dynamometer (Jamar Plus+ Dynamometer) by the same rater on two testing trials separated by a one-day interval between sessions. The HGS testing was conducted according to the American Society of Hand Therapists recommendations. Relative and absolute reliability statistics were calculated. Age influenced the test-retest difference of the HGS measurement as children compared to preadolescents had lower intraclass correlation coefficients (0.95 vs. 0.98), standard error of measurement (SEM) (0.74 vs. 0.78 kg), smallest detectable difference (SDD) (2.05 vs. 2.16 kg) and higher values of the percentage value of SEM (5.48 vs. 3.44%), normalized SDD (15.52 vs. 9.61%) and a mean difference between the test and retest values (0.50 vs. 0.02 kg) for the dominant hand. The results indicate that the protocol using the Jamar digital handgrip dynamometer is a reliable instrument to measure HGS in participants aged 7-13 years with typical development. Clinicians and researchers therefore can have confidence in determining the minimally clinical effect for HGS.

Ability to Reach Low-Income Smokers Enrolled in a Randomised Controlled Trial Varies with Time of Month.

INTRODUCTION: Because of financial pressures, low-income individuals sometimes run out of cellphone service towards the end of the month. AIMS: To determine if the time of month affects ability to reach low-income smokers by telephone. METHODS: We reviewed data from a completed trial in the United States of emergency department (ED)-initiated tobacco dependence treatment for low-income smokers at a busy, academic ED in an urban community. We recorded the date of each one-month follow-up call, and divided each month into four time blocks: Week 1, Week 2, Week 3, and Week 4. RESULTS: A total of 2,049 phone calls were made to reach 769 participants. Of these calls, 677 (33%) resulted in contact; 88% of all participants were contacted. Using generalised estimating equations with Week 4 as reference, the odds of a successful contact at Weeks 1, 2, and 3 were, respectively, 1.52 (95% CI 1.18, 1.96), 1.30 (95% CI 1.01, 1.66), and 1.37 (95% CI 1.07, 1.76). CONCLUSIONS: Study participants became progressively difficult to reach. This result may reflect low-income smokers' decreased rates of active telephone service later in the month and suggests a mechanism to improve follow-up rates in future studies of low-income populations.

Successful Tobacco Dependence Treatment in Low-Income Emergency Department Patients: A Randomized Trial.

STUDY OBJECTIVE: Tobacco use is common among emergency department (ED) patients, many of whom have low income. Our objective is to study the efficacy of an intervention incorporating motivational interviewing, nicotine replacement, and quitline referral for adult smokers in an ED. METHODS: This was a 2-arm randomized clinical trial conducted from October 2010 to December 2012 in a northeastern urban US ED with 90,000 visits per year. Eligible subjects were aged 18 years or older, smoked, and were self-pay or had Medicaid insurance. Intervention subjects received a motivational interview by a trained research assistant, 6 weeks' worth of nicotine patches and gum initiated in the ED, a faxed referral to the state smokers' quitline, a booster call, and a brochure. Control subjects received the brochure, which provided quitline information. The primary outcome was biochemically confirmed tobacco abstinence at 3 months. Secondary endpoints included quitline use. RESULTS: Of 778 enrolled subjects, 774 (99.5%) were alive at 3 months. The prevalence of biochemically confirmed abstinence was 12.2% (47/386) in the intervention arm versus 4.9% (19/388) in the control arm, for a difference in quit rates of 7.3% (95% confidence interval 3.2% to 11.5%). In multivariable logistic modeling controlling for age, sex, and race or ethnicity, study subjects remained more likely to be abstinent than controls (odds ratio 2.72; 95% confidence interval 1.55 to 4.75). CONCLUSION: An intensive intervention improved tobacco abstinence rates in low-income ED smokers. Because approximately 20 million smokers, many of whom have low income, visit US EDs annually, these results suggest that ED-initiated treatment may be an effective technique to treat this group of smokers.

Selection of the treatment effect for sample size determination in a superiority clinical trial using a hybrid classical and Bayesian procedure.

Specification of the treatment effect that a clinical trial is designed to detect (θA) plays a critical role in sample size and power calculations. However, no formal method exists for using prior information to guide the choice of θA. This paper presents a hybrid classical and Bayesian procedure for choosing an estimate of the treatment effect to be detected in a clinical trial that formally integrates prior information into this aspect of trial design. The value of θA is found that equates the pre-specified frequentist power and the conditional expected power of the trial. The conditional expected power averages the traditional frequentist power curve using the conditional prior distribution of the true unknown treatment effect θ as the averaging weight. The Bayesian prior distribution summarizes current knowledge of both the magnitude of the treatment effect and the strength of the prior information through the assumed spread of the distribution. By using a hybrid classical and Bayesian approach, we are able to formally integrate prior information on the uncertainty and variability of the treatment effect into the design of the study, mitigating the risk that the power calculation will be overly optimistic while maintaining a frequentist framework for the final analysis. The value of θA found using this method may be written as a function of the prior mean µ0 and standard deviation τ0, with a unique relationship for a given ratio of µ0/τ0. Results are presented for Normal, Uniform, and Gamma priors for θ.

Comparison of Drug Approvals in Europe Versus the United States: An Analysis of Discrepancies Between Drug Products Reviewed by EMA and FDA.

BACKGROUND: Regulators from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) do not always agree on interpretation of data for a drug's safety and efficacy. METHODS AND RESULTS: The authors compared all new molecular entities approved or rejected in a 5-year period from 2007 to 2011, identified where FDA and EMA reviews resulted in different regulatory decisions, and explored potential mechanisms for the discrepancies. Thirteen entities were associated with different regulatory decisions, and 2 drugs were withdrawn from their respective markets in 2010: one from the US (Mylotarg; gemtuzumab ozogamicin) and the other in Europe (Thelin; sitaxentan sodium). CONCLUSIONS: There are relatively few cases where FDA and EMA substantively differ with regard to product approvals and market withdrawals. It is likely that the scientific and cultural differences between FDA and EMA will continue to diminish over time, because these two agencies increasingly work together as pharmaceutical product development increasingly becomes a global endeavor.

How do perceptions about cessation outcomes moderate the effectiveness of a gain-framed smoking cessation telephone counseling intervention?

The distinction between prevention and detection behaviors provides a useful guideline for appropriately framing health messages in terms of gains or losses. However, this guideline assumes that everyone perceives the outcomes associated with a behavior in a consistent manner, as prevention or detection. Individuals' perceptions of a behavior vary, and so the effects of framed messages may be optimized by considering individuals' perceptions rather than the prevention or detection function of the behavior. The authors tested this message-framing paradigm in a secondary analysis of data from a trial evaluating gain-framed smoking cessation counseling delivered through a state quitline (Toll et al., 2010 ). Smokers (N = 2,032) who called a state quitline received either gain-framed or standard care messages. Smokers' beliefs about the positive consequences of stopping smoking (outcome expectancies) were evaluated at baseline. Smoking status and self-efficacy were assessed at 3 months. Outcome expectancies moderated the framing effects among men but not among women. Men in the gain-framed counseling condition who had positive outcome expectancies were more likely to quit and had more confidence in their ability to quit or to remain abstinent than men who were uncertain of the positive outcome of smoking cessation. Among men, self-efficacy mediated the moderated framing effects of the intervention on quit status. These findings suggest that it may be useful to consider sex and individual differences in outcome expectancies when delivering gain-framed smoking cessation messages in the context of a state quitline.

Preterm birth results in alterations in neural connectivity at age 16 years.

Very low birth weight preterm (PT) children are at high risk for brain injury. Employing diffusion tensor imaging (DTI), we tested the hypothesis that PT adolescents would demonstrate microstructural white matter disorganization relative to term controls at 16 years of age. Forty-four PT subjects (600-1250 g birth weight) without neonatal brain injury and 41 term controls were evaluated at age 16 years with DTI, the Wechsler Intelligence Scale for Children-III (WISC), the Peabody Picture Vocabulary Test-Revised (PPVT), and the Comprehensive Test of Phonological Processing (CTOPP). PT subjects scored lower than term subjects on WISC full scale (p=0.003), verbal (p=0.043), and performance IQ tests (p=0.001), as well as CTOPP phonological awareness (p=0.004), but scored comparably to term subjects on PPVT and CTOPP Rapid Naming tests. PT subjects had lower fractional anisotropy (FA) values in multiple regions including bilateral uncinate fasciculi (left: p=0.01; right: p=0.004), bilateral external capsules (left: p<0.001; right: p<0.001), the splenium of the corpus callosum (p=0.008), and white matter serving the inferior frontal gyrus bilaterally (left: p<0.001; right: p=0.011). FA values in both the left and right uncinate fasciculi correlated with PPVT scores (a semantic language task) in the PT subjects (left: r=0.314, p=0.038; right: r=0.336, p=0.026). FA values in the left and right arcuate fasciculi correlated with CTOPP Rapid Naming scores (a phonologic task) in the PT subjects (left: r=0.424, p=0.004; right: r=0.301, p=0.047). These data support for the first time that dual pathways underlying language function are present in PT adolescents. The striking bilateral dorsal correlations for the PT group suggest that prematurely born subjects rely more heavily on the right hemisphere than typically developing adults for performance of phonological language tasks. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.

Nicotine dependence as a moderator of a quitline-based message framing intervention.

High nicotine dependence is a reliable predictor of difficulty quitting smoking and remaining smoke-free. Evidence also suggests that the effectiveness of various smoking cessation treatments may vary by nicotine dependence level. Nicotine dependence, as assessed by Heaviness of Smoking Index baseline total scores, was evaluated as a potential moderator of a message-framing intervention provided through the New York State Smokers' Quitline (free telephone based service). Smokers were exposed to either gain-framed (n=810) or standard-care (n=1222) counseling and printed materials. Those smoking 10 or more cigarettes per day and medically eligible were also offered a free 2-week supply of nicotine patches, gum, or lozenge. Smokers were contacted for follow-up interviews at 3 months by an independent survey group. There was no interaction of nicotine dependence scores and message condition on the likelihood of achieving 7-day point prevalence smoking abstinence at the 3-month follow-up contact. Among continuing smokers at the 3-month follow-up, smokers who reported higher nicotine dependence scores were more likely to report smoking more cigarettes per day and this effect was greater in response to standard-care messages than gain-framed messages. Smokers with higher dependence scores who received standard-care messages also were less likely to report use of nicotine medications compared with less dependent smokers, while there was no difference in those who received gain-framed messages. These findings lend support to prior research demonstrating nicotine dependence heterogeneity in response to message framing interventions and suggest that gain-framed messages may result in less variable smoking outcomes than standard-care messages.

Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial.

BACKGROUND: Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting. METHODS: Smokers (N=172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date. RESULTS: The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43). CONCLUSIONS: For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.

Sample size for post-marketing safety studies based on historical controls.

PURPOSE: As part of a drug's entire life cycle, post-marketing studies are an important part in the identification of rare, serious adverse events. Recently, the US Food and Drug Administration (FDA) has begun to implement new post-marketing safety mandates as a consequence of increased emphasis on safety. The purpose of this research is to provide exact sample size formula for the proposed hybrid design, based on a two-group cohort study with incorporation of historical external data. METHODS: Exact sample size formula based on the Poisson distribution is developed, because the detection of rare events is our outcome of interest. Performance of exact method is compared to its approximate large-sample theory counterpart. RESULTS: The proposed hybrid design requires a smaller sample size compared to the standard, two-group prospective study design. In addition, the exact method reduces the number of subjects required in the treatment group by up to 30% compared to the approximate method for the study scenarios examined. CONCLUSIONS: The proposed hybrid design satisfies the advantages and rationale of the two-group design with smaller sample sizes generally required.

Functional connectivity to a right hemisphere language center in prematurely born adolescents.

Prematurely born children are at increased risk for language deficits at school age and beyond, but the neurobiological basis of these findings remains poorly understood. Thirty-one PT adolescents (600-1250g birth weight) and 36 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children-III (WISC-III), the Peabody Picture Vocabulary Test-Revised (PPVT-R), the Comprehensive Test of Phonological Processing (CTOPP) and the Test of Word Reading Efficiency (TOWRE) at 16years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. PT subjects scored significantly lower on all components of the WISC-III (p<0.05) compared to term subjects, but there was no significant difference in PPVT-R scores between the groups. Functional connectivity (fcMRI) between Wernicke's area (left BA 22) and the right supramarginal gyrus (BA 40) was increased in preterm subjects relative to term controls (p=0.03), and the strength of this connection was inversely related to performance on both the PPVT-R (R(2)=0.553, p=0.002), and the verbal comprehension index (R(2)=0.439, p=0.019). Preterm adolescents engage a dorsal right hemisphere region for language at age 16years. Those with the greatest cognitive deficits demonstrate increasing reliance on this alternate pathway.

GABAA-benzodiazepine receptor availability in smokers and nonsmokers: relationship to subsyndromal anxiety and depression.

Many smokers experience subsyndromal anxiety symptoms while smoking and during acute abstinence, which may contribute to relapse. We hypothesized that cortical gamma aminobutyric acid(A)-benzodiazepine receptor (GABA(A)-BZR) availability in smokers and nonsmokers might be related to the expression of subsyndromal anxiety, depressive, and pain symptoms. Cortical GABA(A)-BZRs were imaged in 15 smokers (8 men and 7 women), and 15 healthy age and sex-matched nonsmokers, and 4 abstinent tobacco smokers (3 men; 1 woman) using [(123)I]iomazenil and single photon emission computed tomography (SPECT). Anxiety and depressive symptoms were measured using the Spielberger's State-Trait Anxiety Index (STAI) and the Center for Epidemiology Scale for Depressive Symptoms (CES-D). The cold pressor task was administered to assess pain tolerance and sensitivity. The relationship between cortical GABA(A)-BZR availability, smoking status, and subsyndromal depression and anxiety symptoms, as well as pain tolerance and sensitivity, were evaluated. Surprisingly, there were no statistically significant differences in overall GABA(A)-BZR availability between smokers and nonsmokers or between active and abstinent smokers; however, cortical GABA(A)-BZR availability negatively correlated with subsyndromal state anxiety symptoms in nonsmokers but not in smokers. In nonsmokers, the correlation was seen across many brain areas with state anxiety [parietal (r = -0.47, P = 0.03), frontal (r = -0.46, P = 0.03), anterior cingulate (r = -0.47, P = 0.04), temporal (r = -0.47, P = 0.03), occipital (r = -0.43, P = 0.05) cortices, and cerebellum (r = -0.46, P = 0.04)], trait anxiety [parietal (r = -0.72, P = 0.02), frontal (r = -0.72, P = 0.02), and occipital (r = -0.65, P = 0.04) cortices] and depressive symptoms [parietal (r = -0.68; P = 0.02), frontal (r = -0.65; P = 0.03), anterior cingulate (r = -0.61; P = 0.04), and temporal (r = -0.66; P = 0.02) cortices]. The finding that a similar relationship between GABA(A)-BZR availability and anxiety symptoms was not observed in smokers suggests that there is a difference in GABA(A)-BZR function, but not number, in smokers. Thus, while subsyndromal anxiety and depressive symptoms in nonsmokers may be determined in part by GABA(A)-BZR availability, smoking disrupts this relationship. Aberrant regulation of GABA(A)-BZR function in vulnerable smokers may explain why some smokers experience subsyndromal anxiety and depression.

Alterations in neural connectivity in preterm children at school age.

Converging data suggest recovery from injury in the preterm brain. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that cerebral connectivity involving Wernicke's area and other important cortical language regions would differ between preterm (PT) and term (T) control school age children during performance of an auditory language task. Fifty-four PT children (600-1250 g birth weight) and 24 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children - III (WISC-III), the Peabody Individual Achievement Test - Revised (PIAT-R) and the Peabody Picture Vocabulary Test - Revised (PPVT-R) at 8 years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. We found that PT subjects scored significantly lower on all components of the WISC-III (p<0.009), the PIAT-R Reading Comprehension test (p=0.013), and the PPVT-R (p=0.001) compared to term subjects. Connectivity analyses revealed significantly stronger neural circuits in PT children between Wernicke's area and the right inferior frontal gyrus (R IFG, Broca's area homologue) and both the left and the right supramarginal gyri (SMG) components of the inferior parietal lobules (p

Incidence, prevalence, and clinical significance of abnormal hematologic indices in compensated cirrhosis.

BACKGROUND & AIMS: Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance. METHODS: We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, < or =13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, < or =4000/mm3), or thrombocytopenia (platelet counts, < or =150,000/mm3). The primary end points were death or transplant surgery. RESULTS: Most subjects had thrombocytopenia at baseline. Kaplan-Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5-53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1-49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child-Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = -0.35, P < .0001; white blood cell count, r = -0.31, P < .0001). CONCLUSIONS: Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality.