The MCP-4/MCP-1 ratio in plasma is a candidate circadian biomarker for chronic post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is psychiatric disease, which can occur following exposure to traumatic events. PTSD may be acute or chronic, and can have a waxing and waning course of symptoms. It has been hypothesized that proinflammatory cytokines and chemokines in the cerebrospinal fluid (CSF) or plasma might be mediators of the psychophysiological mechanisms relating a history of trauma exposure to changes in behavior and mental health disorders, and medical morbidity. Here we test the cytokine/chemokine hypothesis for PTSD by examining levels of 17 classical cytokines and chemokines in CSF, sampled at 0900 hours, and in plasma sampled hourly for 24 h. The PTSD and healthy control patients are from the NIMH Chronic PTSD and healthy control cohort, initially described by Bonne et al. (2011), in which the PTSD patients have relatively low comorbidity for major depressive disorder (MDD), drug or alcohol use. We find that in plasma, but not CSF, the bivariate MCP4 (CCL13)/ MCP1(CCL2) ratio is ca. twofold elevated in PTSD patients compared with healthy controls. The MCP-4/MCP-1 ratio is invariant over circadian time, and is independent of gender, body mass index or the age at which the trauma was suffered. By contrast, MIP-1ß is a candidate biomarker for PTSD only in females, whereas TARC is a candidate biomarker for PTSD only in males. It remains to be discovered whether these disease-specific differences in circadian expression for these specific immune signaling molecules are biomarkers, surrogates, or drivers for PTSD, or whether any of these analytes could contribute to therapy.

Anthropometric trends from 1997 to 2012 in infants born at ⩽28 weeks' gestation or less.

OBJECTIVE: Postnatal growth failure is common after preterm birth, in particular for infants born at ⩽28 weeks' gestation, but it is unknown if growth-to-term equivalent age has improved over the years as neonatal intensive care in general, and infant nutrition in particular, have improved. The objective of the study was to evaluate anthropometric trends at NICU discharge for infants born at ⩽28 weeks' gestation using a large national database. STUDY DESIGN: Analysis of growth in weight, length, head circumference and body mass index (kg m2) in 23 005 infants born in 1997 to 2012 who survived to neonatal intensive care unit discharge at ⩽41 weeks' postmenstrual age. RESULTS: Discharge weight, length, head circumference and body mass index were converted to Z-scores using a reference database, and growth trends over the 16 years were summarized. Discharge results also were summarized for common neonatal morbidities, including chronic lung disease. Gestational age at birth and postmenstrual age at discharge were similar across the 16 years. Discharge weight, length and head circumference Z-scores were all below the median, but head circumference Z-scores consistently were closer to the median than were weight and length. In 1997 compared with 2012, the weight Z-score improved from -1.5 to -0.6; the length Z-score increased the least, from -1.68 to just -1.16; the head circumference Z-score improved from -0.68 to -0.30; and the body mass index Z-score increased from -0.66 to 0.19. Percent small-for-gestational age at birth was stable across the years at 8.4 to 9.3%, and the frequency of postnatal growth failure at discharge improved from 55.4% in 1997 to 19.6% in 2012. CONCLUSIONS: Growth-to-discharge progressively improved from 1997 to 2012, but Z-scores remained below the reference median for weight, length and head circumference. Length Z-scores were consistently significantly less than for weight, and body mass index Z-scores have been above the reference median since 2002. Prospective studies are needed to quantify anthropometric trends in relation to body composition and to current nutritional strategies.

A longitudinal study of serum insulin and insulin resistance as predictors of weight and body fat gain in African American and Caucasian children.

BACKGROUND: The influence of insulin and insulin resistance (IR) on children's weight and fat gain is unclear. OBJECTIVE: To evaluate insulin and IR as predictors of weight and body fat gain in children at high risk for adult obesity. We hypothesized that baseline IR would be positively associated with follow-up body mass index (BMI) and fat mass. SUBJECTS/METHODS: Two hundred and forty-nine healthy African American and Caucasian children aged 6-12 years at high risk for adult obesity because of early-onset childhood overweight and/or parental overweight were followed for up to 15 years with repeated BMI and fat mass measurements. We examined baseline serum insulin and homeostasis model of assessment-IR (HOMA-IR) as predictors of follow-up BMI Z-score and fat mass by dual-energy X-ray absorptiometry in mixed model longitudinal analyses accounting for baseline body composition, pubertal stage, sociodemographic factors and follow-up interval. RESULTS: At baseline, 39% were obese (BMI⩾95th percentile for age/sex). Data from 1335 annual visits were examined. Children were followed for an average of 7.2±4.3 years, with a maximum follow-up of 15 years. After accounting for covariates, neither baseline insulin nor HOMA-IR was significantly associated with follow-up BMI (Ps>0.26), BMIz score (Ps>0.22), fat mass (Ps>0.78) or fat mass percentage (Ps>0.71). In all models, baseline BMI (P<0.0001), body fat mass (P<0.0001) and percentage of fat (P<0.001) were strong positive predictors for change in BMI and fat mass. In models restricted to children without obesity at baseline, some but not all models had significant interaction terms between body adiposity and insulinemia/HOMA-IR that suggested less gain in mass among those with greater insulin or IR. The opposite was found in some models restricted to children with obesity at baseline. CONCLUSIONS: In middle childhood, BMI and fat mass, but not insulin or IR, are strong predictors of children's gains in BMI and fat mass during adolescence.

An evaluation of the completeness and accuracy of active tuberculosis reporting in the United States military.

SETTING: Despite the low incidence of tuberculosis (TB) in the United States military, there is uncertainty in the overall reporting and estimates of incidence. OBJECTIVE: To assess TB reporting in the active component US military. DESIGN: TB notification in the US military was compared with three other data sources: laboratory, hospitalization and pharmacy records. Sensitivity and positive predictive value were estimated for all data sources using a gold standard of either a reportable medical event (RME) reported as confirmed or a positive laboratory result for Mycobacterium tuberculosis. Uncorrected and capture-recapture (CR) methods were used to estimate underreporting and completeness of data sources. RESULTS: Completeness of reporting of pulmonary TB cases was estimated as 72.4% uncorrected or 58.3% with CR. Even after correction for possible underreporting, the incidence of active pulmonary TB was only 0.87 per 100,000 person-years between 2004 and 2006. CONCLUSION: The rate of active TB in the US military is low. Like civilian surveillance, US military RME surveillance may substantially underreport TB incidence rates. Expanding surveillance to include data sources such as hospitalizations and pharmacy records will increase the number of TB diagnoses at the cost of including many false-positives.

Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial.

OBJECTIVE: To determine if modafinil can improve fatigue in patients with post-polio syndrome. METHODS: We used a randomized, placebo-controlled crossover trial. Intervention with modafinil (400 mg/day) and placebo occurred over 6-week periods. Primary endpoint (fatigue) was assessed using the Fatigue Severity Scale as the main outcome measure. Other measures included the Visual Analog Scale for Fatigue and the Fatigue Impact Scale. Secondary endpoint (health-related quality of life) was assessed using the 36-Item Short-Form. Analysis of variance for repeated measures was applied to assess treatment, period, and carryover effects. RESULTS: Thirty-six patients were randomized, 33 of whom (mean age: 61 years) completed required interventions. Treatment with modafinil was safe and well-tolerated. After adjusting for periods and order effects, no difference was observed between treatments. CONCLUSION: Based on the utilized measures of outcome modafinil was not superior to placebo in alleviating fatigue or improving quality of life in the studied post-polio syndrome population.

Electrical amygdala kindling in alcohol-withdrawal kindled rats.

Repeated alcohol withdrawal has been shown to kindle seizure activity. The purpose of the present investigation was to study electrical amygdala kindling in rats previously exposed to alcohol-withdrawal kindling. In three independent experiments, male Wistar rats were subjected to multiple episodes each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. In the first experiment, the alcohol-withdrawal kindled animals were divided into two groups depending on whether spontaneous alcohol-withdrawal seizures were observed in episodes 10-13. In the second and third experiments, the alcohol-withdrawal kindled animals were compared to a group in which alcohol-withdrawal kindling was prevented by diazepam treatment during the withdrawal reactions in order to discriminate between the effect of withdrawal and intoxication. Electrical kindling was initiated 28-35 days after the last alcohol dose by exposing the animals to daily electrical stimulations of the right amygdala. The results showed that amygdala kindling was facilitated in alcohol-withdrawal kindled animals which showed spontaneous withdrawal seizure activity, compared with animals exposed to multiple episodes of alcohol withdrawal which did not develop withdrawal seizures or with animals exposed to a single episode of alcohol intoxication. When compared to the control group, the alcohol-withdrawal kindled group with seizures also kindled at a faster rate, but the difference did not reach statistical significance and therefore the results must be regarded as preliminary at present.

Serotonin1A receptor autoradiography during alcohol-withdrawal kindling.

A series of autoradiography experiments were conducted in order to test the theory that the serotonin (5-HT) receptor subtype 5-HT(1a) is involved in alcohol-withdrawal kindled convulsive behaviour. Alcohol-withdrawal kindling was performed by subjecting male Wistar rats to multiple episodes consisting of 2 days of alcohol intoxication and 5 days of alcohol withdrawal. In the first episode alcohol intoxication led to focal downregulation of [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) binding sites in septum and subregions of frontal cortex, hippocampus, and entorhinal cortex. This alcohol-induced response was blunted in both alcohol-withdrawal kindled animals and in animals exposed to repeated alcohol dependence in which the previous withdrawal reactions were blocked by diazepam administration. A paradoxical upregulation of [3H]-8-OH-DPAT binding sites was found in septum and subregions of frontal cortex, hippocampus, and entorhinal cortex in control animals which were fed isocalorically with the alcohol-withdrawal kindled animals and subsequently exposed to 2 days of alcohol intoxication. It was concluded that the alterations in the alcohol induced 5-HT(1a) receptor regulation after multiple episodes of alcohol dependence were not caused by alcohol-withdrawal kindling processes per se, but were due to both alcohol specific and alcohol non-specific effects.

No loss of somatostatin-immunoreactive neurons in the hippocampal dentate hilus of alcohol-withdrawal-kindled rats.

The neuropeptide somatostatin has been suggested to play a role in seizure genesis, electrical kindling and the neurotoxic effects of alcohol. The purpose of the present experiment was to study somatostatin-immunoreactive (SS-IR) neurons in hippocampus during alcohol-withdrawal kindling. Alcohol-withdrawal kindling was performed by subjecting male Wistar rats to seven weekly episodes consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. Then the kindled animals (multiple withdrawal group) and a single withdrawal group, which was fed isocalorically with the kindled animals during episodes 1-7, were exposed to 4 days of severe alcohol intoxication (episode 8). During the following withdrawal, the seizure activity was observed 9-15 h after last alcohol dose, in order to subdivide the animals from these two groups into groups with and without seizures. Subsequently, SS-IR neurons were visualized immunocytochemically and counted in the hilus of the dentate gyrus (hippocampus). The number of SS-IR neurons per unit area of the hilus was neither affected by a single nor by multiple episodes of alcohol withdrawal. We therefore concluded that a loss of these neurons is not involved in the development of alcohol-withdrawal-kindled seizures.