Effects of Cognitive Behavioral Therapy on Insomnia of Maintenance Hemodialysis Patients

The objective of the study was to evaluate the effects of cognitive behavioral therapy [sleep-related behavior modification and progressive muscle relaxation on insomnia of maintenance hemodialysis (MHD) patients] on improving insomnia of MHD patients. 103 MHD patients complicated with insomnia were randomly assigned to treatment (n = 52) and control (n = 51) groups. The control group was treated with conventional hemodialysis, and the treatment group was additionally treated with cognitive behavioral therapy for 3 months (sleep-related behavior modification and progressive muscle relaxation). All cases were assessed by Symptom Checklist 90 (SCL-90) and Pittsburgh Sleep Quality Index (PSQI) before and 2, 4, 6, 8, 10, and 12 weeks after treatment. Fifty-one patients in the treatment group and 47 patients in the control group completed the experiments. After treatment, the total mean scores were (1.94 ± 0.50/2.29 ± 0.31); scores of somatization, depression, anxiety, hostility, and additional items were (1.87 ± 0.58/2.56 ± 0.26), (2.25 ± 0.80/2.79 ± 0.50), (1.79 ± 0.26/2.37 ± 0.34), (1.71 ± 0.46/2.25 ± 0.43), and (1.91 ± 0.67/2.26 ± 0.59) in SCL-90, respectively. The total scores for PSQI were (12.63 ± 2.27/16.40 ± 2.16); scores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, hypnotics, and daytime dysfunction which were (1.98 ± 0.76/2.57 ± 0.58), (1.75 ± 0.59/2.60 ± 0.50), (2.10 ± 0.50/2.62 ± 0.53), (2.06 ± 0.47/2.57 ± 0.54), (2.04 ± 0.69/2.45 ± 0.72), (1.02 ± 0.79/1.51 ± 0.98), and (1.69 ± 0.55/2.09 ± 0.58), respectively, were significantly lower in the treatment group compared with the control group. However, there were no significant differences in the scores of factors of obsessive–compulsive (2.26 ± 0.62/2.32 ± 0.38), interpersonal sensitivity (2.23 ± 0.64/2.43 ± 0.47), phobic anxiety (1.98 ± 0.62/2.01 ± 0.67), paranoid ideation (1.55 ± 0.43/1.69 ± 0.39), and psychoticism (1.57 ± 0.46/1.66 ± 0.49). The conclusion is that sleep-related behavior modification in combination with progressive muscle relaxation effectively improved the mental state and sleep quality of MHD patients with insomnia.     

Internet-Delivered Cognitive Behavioral Therapy to Treat Insomnia: A Systematic Review and Meta-Analysis

Background

Insomnia is of major public health importance. While cognitive behavioral therapy is beneficial, in-person treatment is often unavailable. We assessed the effectiveness of internet-delivered cognitive behavioral therapy for insomnia.

Objectives

The primary objectives were to determine whether online cognitive behavioral therapy for insomnia could improve sleep efficiency and reduce the severity of insomnia in adults. Secondary outcomes included sleep quality, total sleep time, time in bed, sleep onset latency, wake time after sleep onset, and number of nocturnal awakenings.

Data Sources

We searched PubMed/MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, PsycInfo, Cochrane Library, Embase, and the Web of Science for randomized trials.

Methods

Studies were eligible if they were randomized controlled trials in adults that reported application of cognitive behavioral therapy for insomnia via internet delivery. Mean differences in improvement in sleep measures were calculated using the Hartung-Knapp-Sidik-Jonkman method for random effects meta-analysis.

Results

We found 15 trials, all utilizing a pretest-posttest randomized control group design. Sleep efficiency was 72% at baseline and improved by 7.2% (95% CI: 5.1%, 9.3%; p<0.001) with internet-delivered cognitive behavioral therapy versus control. Internet-delivered cognitive behavioral therapy resulted in a decrease in the insomnia severity index by 4.3 points (95% CI: -7.1, -1.5; p = 0.017) compared to control. Total sleep time averaged 5.7 hours at baseline and increased by 20 minutes with internet-delivered therapy versus control (95% CI: 9, 31; p = 0.004). The severity of depression decreased by 2.3 points (95% CI: -2.9, -1.7; p = 0.013) in individuals who received internet-delivered cognitive behavioral therapy compared to control. Improvements in sleep efficiency, the insomnia severity index and depression scores with internet-delivered cognitive behavioral therapy were maintained from 4 to 48 weeks after post-treatment assessment. There were no statistically significant differences between sleep efficiency, total sleep time, and insomnia severity index for internet-delivered versus in-person therapy with a trained therapist.

Conclusion

In conclusion, internet-delivered cognitive behavioral therapy is effective in improving sleep in adults with insomnia. Efforts should be made to educate the public and expand access to this therapy. Registration Number, Prospero: CRD42015017622     

Dietary Mannoheptulose Does Not Significantly Alter Daily Energy Expenditure in Adult Labrador Retrievers

Mannoheptulose (MH), a sugar found in avocados that inhibits glycolysis in vitro, has been preliminarily investigated as a novel food ingredient for dogs. This study aimed to determine the effects of dietary MH, delivered as an extract of un-ripened avocado, on energy expenditure (EE) in healthy adult Labrador Retriever dogs (total of 12 dogs, 26.99 ± 0.634 kg, 4.9 ± 0.2 y). The study was a double-blind, cross-over with each dog receiving both dietary treatments, control (CON) and MH (400 mg/kg of diet; 6 mg/kg BW), in random order. Resting and post-prandial (10 h) EE and respiratory quotient (RQ) were determined by indirect calorimetry (d 42). The following day, body composition was assessed using dual X-ray absorptiometry. Continuous activity monitoring was conducted using an Atical® accelerometer (d 43–47). A vastus lateralis muscle biopsy was obtained prior to the morning meal (d 49) and 4 h after consumption of their meal (d 56) to determine the protein content and phosphorylation of 5'' adenosine monophosphate-activated protein kinase (AMPK). Diet did not affect body weight, resting EE or skeletal muscle AMPK phosphorylation. Dogs fed MH had significantly lower post-prandial RQ (p = 0.02) and ratio of fat to lean body mass (p = 0.02). Physical activity during light time periods (but not dark) was lower in dogs fed MH (p < 0.05) during weekends, but not on weekdays. These results suggest that MH affects energy balance of adult dogs, but that these effects are not dose dependent and not due to physical activity.     

Inhibition of CaMKII Does Not Attenuate Cardiac Hypertrophy in Mice with Dysfunctional Ryanodine Receptor

In cardiac muscle, the release of calcium ions from the sarcoplasmic reticulum through ryanodine receptor ion channels (RyR2s) leads to muscle contraction. RyR2 is negatively regulated by calmodulin (CaM) and by phosphorylation of Ca²⁺/CaM-dependent protein kinase II (CaMKII). Substitution of three amino acid residues in the CaM binding domain of RyR2 (RyR2-W3587A/L3591D/F3603A, RyR2^ADA) impairs inhibition of RyR2 by CaM and results in cardiac hypertrophy and early death of mice carrying the RyR2^ADA mutation. To test the cellular function of CaMKII in cardiac hypertrophy, mutant mice were crossed with mice expressing the CaMKII inhibitory AC3-I peptide or the control AC3-C peptide in the myocardium. Inhibition of CaMKII by AC3-I modestly reduced CaMKII-dependent phosphorylation of RyR2 at Ser-2815 and markedly reduced CaMKII-dependent phosphorylation of SERCA2a regulatory subunit phospholamban at Thr-17. However the average life span and heart-to-body weight ratio of Ryr2^ADA/ADA mice expressing the inhibitory peptide were not altered compared to control mice. In Ryr2^ADA/ADA homozygous mice, AC3-I did not alter cardiac morphology, enhance cardiac function, improve sarcoplasmic reticulum Ca²⁺ handling, or suppress the expression of genes implicated in cardiac remodeling. The results suggest that CaMKII was not required for the rapid development of cardiac hypertrophy in Ryr2^ADA/ADA mice.     

Conjugated Linoleic Acid Does Not Improve Insulin Tolerance in Mice*

Objective: To determine if the addition or removal of dietary conjugated linoleic acid (CLA) would alter insulin tolerances in mice from two genetic lines. Research Methods and Procedures: High metabolic rate (MH) and low metabolic rate (ML) mice were assigned to consume 1) a control diet ad libitum, 2) a control diet at a restricted intake, or 3) a diet containing 1% CLA ad libitum. After 9 weeks, an insulin tolerance test was conducted, and a portion of the mice were killed. All remaining mice consumed the control diet ad libitum. Insulin tolerance tests were conducted 11 and 32 days after the diet change, and mice were killed 3 days after each test. Body fatness, fat pad weights, and serum insulin concentrations of mice were determined at each time‐point. Two follow‐up experiments were also conducted. Results: Restricted mice had insulin sensitivities not different than control mice. CLA‐fed MH mice in experiment 1 were resistant (p < 0.001) to insulin on each day measured. CLA‐fed ML mice were slightly resistant (p = 0.08) to exogenous insulin on day 0 of recovery and not different from control mice on day 11 or 32. Glucose response to insulin in MH mice fed CLA in experiments 2 or 3 did not differ from control mice. Discussion: Mice fed CLA did not have improved insulin tolerances compared with control mice. In some cases, dietary CLA may cause insulin resistance. MH mice seem more sensitive to CLA than ML mice.     

Docosahexaenoic Acid Supplementation Does Not Improve Western Diet-Induced Cardiomyopathy in Rats

Obesity increases risk for cardiomyopathy in the absence of hypertension, diabetes or ischemia. The fatty acid milieu, modulated by diet, may modify myocardial structure and function, lending partial explanation for the array of cardiomyopathic phenotypy. We sought to identify gross, cellular and ultrastructural myocardial changes associated with Western diet intake, and subsequent modification with docosahexaenoic acid (DHA) supplementation. Wistar and Sprague-Dawley (SD) rats received 1 of 3 diets: control (CON); Western (WES); Western + DHA (WES+DHA). After 12 weeks of treatment, echocardiography was performed and myocardial adiponectin, fatty acids, collagen, area occupied by lipid and myocytes, and ultrastructure were determined. Strain effects included higher serum adiponectin in Wistar rats, and differences in myocardial fatty acid composition. Diet effects were evident in that both WES and WES+DHA feeding were associated with similarly increased left ventricular (LV) diastolic cranial wall thickness (LVW_cr/d) and decreased diastolic internal diameter (LVID_d), compared to CON. Unexpectedly, WES+DHA feeding was associated additionally with increased thickness of the LV cranial wall during systole (LVW_cr/s) and the caudal wall during diastole (LVW_ca/d) compared to CON; this was observed concomitantly with increased serum and myocardial adiponectin. Diastolic dysfunction was present in WES+DHA rats compared to both WES and CON. Myocyte cross sectional area (CSA) was greater in WES compared to CON rats. In both fat-fed groups, transmission electron microscopy (TEM) revealed myofibril degeneration, disorganized mitochondrial cristae, lipid inclusions and vacuolation. In the absence of hypertension and whole body insulin resistance, WES+DHA intake was associated with more global LV thickening and with diastolic dysfunction, compared to WES feeding alone. Myocyte hypertrophy, possibly related to subcellular injury, is an early change that may contribute to gross hypertrophy. Strain differences in adipokines and myocardial fatty acid accretion may underlie heterogeneous data from rodent studies.     

Red Light Stimulates Feeding Motivation in Fish but Does Not Improve Growth

Nile tilapia fish were individually reared under similar light levels for 8 weeks under five colored light spectra (maximum wavelength absorbance): white (full light spectrum), blue (∼452 nm), green (∼516 nm), yellow (∼520 nm) or red (∼628 nm). The effects of light on feeding, latency to begin feeding, growth and feed conversion were measured during the last 4 weeks of the study (i.e., after acclimation). We found that red light stimulates feeding, as in humans, most likely by affecting central control centers, but the extra feeding is not converted into growth.     

Sleep Deprivation in the Dark Period Does Not Impair Memory in OF1 Mice

There is increasing evidence that sleep facilitates memory acquisition and consolidation. Moreover, the sleep-wake history preceding memory acquisition and retention as well as circadian timing may be important. We showed previously that sleep deprivation (SD) following learning in OF1 mice impaired their performance on an object recognition task. The learning task was scheduled at the end of the 12 h dark period and the test 24 h later. To investigate the influence of the prominent circadian sleep-wake distribution typical for rodents, we now scheduled the learning task at the beginning of the dark period. Wakefulness following immediately after the learning task was attained either by gentle interference (SD; n?=?20) or by spontaneous wheel running (RW; n?=?20). Two control groups were used: one had no RW throughout the experiment (n?=?23), while the other group's wheel was blocked immediately after acquisition (n?=?16), thereby preventing its use until testing. Recognition memory, defined as the difference in exploration of a novel and of familiar objects, was assessed 24 h later during the test phase. Motor activity and RW use were continuously recorded. Remarkably, performance on the object recognition task was not influenced by the protocols; the waking period following acquisition did not impair memory, independent of the method inducing wakefulness (i.e., sleep deprivation or spontaneous running). Thus, all groups explored the novel object significantly longer than the familiar ones during the test phase. Interestingly, neither the amount of rest lost during the SD interventions nor the amount of rest preceding acquisition influenced performance. However, the total amount of rest obtained by the control and SD mice subjected to acquisition at “dark offset” correlated positively (r?=?0.66) with memory at test, while no such relationship occurred in the corresponding groups tested at dark onset. Neither the amount of running nor intermediate rest correlated with performance at test in the RW group. We conclude that interfering with sleep during the dark period does not affect object recognition memory consolidation.     

Hepatitis B Virus Infection Does Not Significantly Influence Plasmodium Parasite Density in Asymptomatic Infections in Ghanaian Transfusion Recipients

Background

Areas endemic for malaria and Hepatitis B virus (HBV) infection largely overlap geographically. A recent study has suggested the existence of an interaction between the two pathogens in symptomatic co-infected individuals on the South-American continent. We examined this issue in a hyperendemic area for both pathogens in sub-Saharan Africa.

Methodology and Findings

Pre-transfusion samples from a retrospective cohort of 154 blood transfusion recipients were screened for both serological and molecular markers of HBV and Plasmodium genomes using species-specific nested PCR and quantitative real-time PCR. Thirty-seven individuals met exclusion criteria and were subsequently eliminated from further analysis. Of 117 participants, 90% of recipients exhibited evidence of exposure to HBV, 42% with HBsAg and/or HBV DNA and 48% anti-HBc reactive without detectable HBV DNA. Plasmodium genome prevalence by NAT was 50%. Parasitemic individuals were significantly younger than non-parasitemic individuals (P = 0.04). Parasitemia level was not significantly lower in individuals with HBV DNA positive infections compared to those with HBV DNA negative exposures. HBV DNA load was not significantly different in parasitemic and non-parasitemic individuals.

Conclusion

The data presented suggests that, in sub-Saharan Africa, asymptomatic co-infections with these two ubiquitous pathogens do not appear to significantly affect each other and evolve independently.     

Ingestion of Broccoli Sprouts Does Not Improve Endothelial Function in Humans with Hypertension

Ingestion of glucosinolates has previously been reported to improve endothelial function in spontaneously hypertensive rats, possibly because of an increase in NO availability in the endothelium due to an attenuation of oxidative stress; in our study we tried to see if this also would be the case in humans suffering from essential hypertension.

Methods

40 hypertensive individuals without diabetes and with normal levels of cholesterol were examined. The participants were randomized either to ingest 10 g dried broccoli sprouts, a natural donor of glucosinolates with high in vitro antioxidative potential, for a 4 week period or to continue their ordinary diet and act as controls. Blood pressure, endothelial function measured by flow mediated dilation (FMD) and blood samples were obtained from the participants every other week and the content of glucosinolates was measured before and after the study. Measurements were blinded to treatment allocation.

Results

In the interventional group overall FMD increased from 4% to 5.8% in the interventional group whereas in the control group FMD was stable (4% at baseline and 3.9% at the end of the study). The change in FMD in the interventional group was mainly due to a marked change in FMD in two participants while the other participants did not have marked changes in FMD. The observed differences were not statistically significant. Likewise significant changes in blood pressure or blood samples were not detected between or within groups. Diastolic blood pressure stayed essentially unchanged in both groups, while the systolic blood pressure showed a small non significant decrease (9 mm Hg) in the interventional group from a value of 153 mm Hg at start.

Conclusion

Daily ingestion of 10 g dried broccoli sprouts does not improve endothelial function in the presence of hypertension in humans.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00252018","term_id":"NCT00252018"}}NCT00252018     

Dim Light at Night Does Not Disrupt Timing or Quality of Sleep in Mice

Artificial nighttime illumination has recently become commonplace throughout the world; however, in common with other animals, humans have not evolved in the ecological context of chronic light at night. With prevailing evidence linking the circadian, endocrine, immune, and metabolic systems, understanding these relationships is important to understanding the etiology and progression of several diseases. To eliminate the covariate of sleep disruption in light at night studies, researchers often use nocturnal animals. However, the assumption that light at night does not affect sleep in nocturnal animals remains unspecified. To test the effects of light at night on sleep, we maintained Swiss-Webster mice in standard light/dark (LD) or dim light at night (DLAN) conditions for 8–10 wks and then measured electroencephalogram (EEG) and electromyogram (EMG) biopotentials via wireless telemetry over the course of two consecutive days to determine differences in sleep timing and homeostasis. Results show no statistical differences in total percent time, number of episodes, maximum or average episode durations in wake, slow-wave sleep (SWS), or rapid eye movement (REM) sleep. No differences were evident in SWS delta power, an index of sleep drive, between groups. Mice kept in DLAN conditions showed a relative increase in REM sleep during the first few hours after the dark/light transition. Both groups displayed normal 24-h circadian rhythms as measured by voluntary running wheel activity. Groups did not differ in body mass, but a marked negative correlation of body mass with percent time spent awake and a positive correlation of body mass with time spent in SWS was evident. Elevated body mass was also associated with shorter maximum wake episode durations, indicating heavier animals had more trouble remaining in the wake vigilance state for extended periods of time. Body mass did not correlate with activity levels, nor did activity levels correlate with time spent in different sleep states. These data indicate that heavier animals tend to sleep more, potentially contributing to further weight gain. We conclude that chronic DLAN exposure does not significantly affect sleep timing or homeostasis in mice, supporting the use of dim light with nocturnal rodents in chronobiology research to eliminate the possible covariate of sleep disruption.     

Long-Term Cognitive and Behavioral Outcomes following Resolution of Sleep Disordered Breathing in Preschool Children

This study aimed to determine the long term effects of resolution of SDB in preschool children, either following treatment or spontaneous recovery, on cognition and behavior. Children diagnosed with SDB at 3-5y (N = 35) and non-snoring controls (N = 25), underwent repeat polysomnography (PSG) and cognitive and behavioral assessment 3 years following a baseline study. At follow-up, children with SDB were grouped into Resolved and Unresolved. Resolution was defined as: obstructive apnea hypopnea index (OAHI) ≤1 event/h; no snoring detected on PSG; and no parental report of habitual snoring. 57% (20/35) of children with SDB received treatment, with SDB resolving in 60% (12/20). 43% (15/35) were untreated, of whom 40% (6/15) had spontaneous resolution of SDB. Cognitive reduced between baseline and follow-up, however this was not related to persistent disease, with no difference in cognitive outcomes between Resolved, Unresolved or Control groups. Behavioral functioning remained significantly worse in children originally diagnosed with SDB compared to control children, regardless of resolution. Change in OAHI did not predict cognitive or behavioral outcomes, however a reduction in nocturnal arousals, irrespective of full resolution, was associated with improvement in attention and aggressive behavior. These results suggest that resolution of SDB in preschool children has little effect on cognitive or behavioral outcomes over the long term. The association between sleep fragmentation and behavior appears independent of SDB, however may be moderated by concomitant SDB. This challenges the assumption that treatment of SDB will ameliorate associated cognitive and behavioural deficits and supports the possibility of a SDB phenotype.     

A Soluble Activin Receptor Type IIB Does Not Improve Blood Glucose in Streptozotocin-Treated Mice

Type 1 diabetes mellitus (T1DM), or insulin dependent DM, is accompanied by decreased muscle mass. The growth factor myostatin (MSTN) is a negative regulator of muscle growth, and a loss of MSTN signaling has been shown to increase muscle mass and prevent the development of obesity, insulin resistance and lipodystrophic diabetes in mice. The effects of MSTN inhibition in a T1DM model on muscle mass and blood glucose are unknown. We asked whether MSTN inhibition would increase muscle mass and decrease hyperglycemia in mice treated with streptozotocin (STZ) to destroy pancreatic beta cells. After diabetes developed, mice were treated with a soluble MSTN/activin receptor fused to Fc (ACVR2B:Fc). ACVR2B:Fc increased body weight and muscle mass compared to vehicle treated mice. Unexpectedly, ACVR2B:Fc reproducibly exacerbated hyperglycemia within approximately one week of administration. ACVR2B:Fc treatment also elevated serum levels of the glucocorticoid corticosterone. These results suggest that although MSTN/activin inhibitors increased muscle mass, they may be counterproductive in improving health in patients with T1DM.     

Consistent Strategy Updating in Spatial and Non-Spatial Behavioral Experiments Does Not Promote Cooperation in Social Networks

The presence of costly cooperation between otherwise selfish actors is not trivial. A prominent mechanism that promotes cooperation is spatial population structure. However, recent experiments with human subjects report substantially lower level of cooperation then predicted by theoretical models. We analyze the data of such an experiment in which a total of 400 players play a Prisoner''s Dilemma on a square lattice in two treatments, either interacting via a fixed square lattice (15 independent groups) or with a population structure changing after each interaction (10 independent groups). We analyze the statistics of individual decisions and infer in which way they can be matched with the typical models of evolutionary game theorists. We find no difference in the strategy updating between the two treatments. However, the strategy updates are distinct from the most popular models which lead to the promotion of cooperation as shown by computer simulations of the strategy updating. This suggests that the promotion of cooperation by population structure is not as straightforward in humans as often envisioned in theoretical models.     

Enhanced Mitochondrial Superoxide Scavenging Does Not Improve Muscle Insulin Action in the High Fat-Fed Mouse

Improving mitochondrial oxidant scavenging may be a viable strategy for the treatment of insulin resistance and diabetes. Mice overexpressing the mitochondrial matrix isoform of superoxide dismutase (sod2^tg mice) and/or transgenically expressing catalase within the mitochondrial matrix (mcat^tg mice) have increased scavenging of O₂˙ˉ and H₂O₂, respectively. Furthermore, muscle insulin action is partially preserved in high fat (HF)-fed mcat^tg mice. The goal of the current study was to test the hypothesis that increased O₂˙ˉ scavenging alone or in combination with increased H₂O₂ scavenging (mtAO mice) enhances in vivo muscle insulin action in the HF-fed mouse. Insulin action was examined in conscious, unrestrained and unstressed wild type (WT), sod2^tg, mcat^tg and mtAO mice using hyperinsulinemic-euglycemic clamps (insulin clamps) combined with radioactive glucose tracers following sixteen weeks of normal chow or HF (60% calories from fat) feeding. Glucose infusion rates, whole body glucose disappearance, and muscle glucose uptake during the insulin clamp were similar in chow- and HF-fed WT and sod2^tg mice. Consistent with our previous work, HF-fed mcat^tg mice had improved muscle insulin action, however, an additive effect was not seen in mtAO mice. Insulin-stimulated Akt phosphorylation in muscle from clamped mice was consistent with glucose flux measurements. These results demonstrate that increased O₂˙ˉ scavenging does not improve muscle insulin action in the HF-fed mouse alone or when coupled to increased H₂O₂ scavenging.     

Anti-Retroviral Therapy Decreases but Does Not Normalize Indoleamine 2,3-Dioxygenase Activity in HIV-Infected Patients

Background

Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established.

Methods

We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14).

Results

Among 76 participants, higher baseline IDO activity was associated with lower CD4⁺ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4⁺ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity.

Conclusions

IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.     

Modeling Systematic Change in Stopover Duration Does Not Improve Bias in Trends Estimated from Migration Counts

The use of counts of unmarked migrating animals to monitor long term population trends assumes independence of daily counts and a constant rate of detection. However, migratory stopovers often last days or weeks, violating the assumption of count independence. Further, a systematic change in stopover duration will result in a change in the probability of detecting individuals once, but also in the probability of detecting individuals on more than one sampling occasion. We tested how variation in stopover duration influenced accuracy and precision of population trends by simulating migration count data with known constant rate of population change and by allowing daily probability of survival (an index of stopover duration) to remain constant, or to vary randomly, cyclically, or increase linearly over time by various levels. Using simulated datasets with a systematic increase in stopover duration, we also tested whether any resulting bias in population trend could be reduced by modeling the underlying source of variation in detection, or by subsampling data to every three or five days to reduce the incidence of recounting. Mean bias in population trend did not differ significantly from zero when stopover duration remained constant or varied randomly over time, but bias and the detection of false trends increased significantly with a systematic increase in stopover duration. Importantly, an increase in stopover duration over time resulted in a compounding effect on counts due to the increased probability of detection and of recounting on subsequent sampling occasions. Under this scenario, bias in population trend could not be modeled using a covariate for stopover duration alone. Rather, to improve inference drawn about long term population change using counts of unmarked migrants, analyses must include a covariate for stopover duration, as well as incorporate sampling modifications (e.g., subsampling) to reduce the probability that individuals will be detected on more than one occasion.     

Long-Term Monensin Supplementation Does Not Significantly Affect the Quantity or Diversity of Methanogens in the Rumen of the Lactating Dairy Cow

A long-term monensin supplementation trial involving lactating dairy cattle was conducted to determine the effect of monensin on the quantity and diversity of rumen methanogens in vivo. Fourteen cows were paired on the basis of days in milk and parity and allocated to one of two treatment groups, receiving (i) a control total mixed ration (TMR) or (ii) a TMR with 24 mg of monensin premix/kg of diet dry matter. Rumen fluid was obtained using an ororuminal probe on day −15 (baseline) and days 20, 90, and 180 following treatment. Throughout the 6-month experiment, the quantity of rumen methanogens was not significantly affected by monensin supplementation, as measured by quantitative real-time PCR. The diversity of the rumen methanogen population was investigated using denaturing gradient gel electrophoresis (DGGE) and 16S rRNA clone gene libraries. DGGE analysis at each sampling point indicated that the molecular diversity of rumen methanogens from monensin-treated cattle was not significantly different from that of rumen methanogens from control cattle. 16S rRNA gene libraries were constructed from samples obtained from the rumen fluids of five cows, with a total of 166 clones examined. Eleven unique 16S rRNA sequences or phylotypes were identified, five of which have not been recognized previously. The majority of clones (98.2%) belonged to the genus Methanobrevibacter, with all libraries containing Methanobrevibacter strains M6 and SM9 and a novel phylotype, UG3322.2. Overall, long-term monensin supplementation was not found to significantly alter the quantity or diversity of methanogens in the rumens of lactating dairy cattle in the present study.     

Reducing the Standard Deviation in Multiple-Assay Experiments Where the Variation Matters but the Absolute Value Does Not

When the value of a quantity for a number of systems (cells, molecules, people, chunks of metal, DNA vectors, so on) is measured and the aim is to replicate the whole set again for different trials or assays, despite the efforts for a near-equal design, scientists might often obtain quite different measurements. As a consequence, some systems’ averages present standard deviations that are too large to render statistically significant results. This work presents a novel correction method of a very low mathematical and numerical complexity that can reduce the standard deviation of such results and increase their statistical significance. Two conditions are to be met: the inter-system variations of matter while its absolute value does not, and a similar tendency in the values of must be present in the different assays (or in other words, the results corresponding to different assays must present a high linear correlation). We demonstrate the improvements this method offers with a cell biology experiment, but it can definitely be applied to any problem that conforms to the described structure and requirements and in any quantitative scientific field that deals with data subject to uncertainty.     

Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs.