The Association between Cognition and Academic Performance in Ugandan Children Surviving Malaria with Neurological Involvement

Background

The contribution of different cognitive abilities to academic performance in children surviving cerebral insult can guide the choice of interventions to improve cognitive and academic outcomes. This study''s objective was to identify which cognitive abilities are associated with academic performance in children after malaria with neurological involvement.

Methods

62 Ugandan children with a history of malaria with neurological involvement were assessed for cognitive ability (working memory, reasoning, learning, visual spatial skills, attention) and academic performance (reading, spelling, arithmetic) three months after the illness. Linear regressions were fit for each academic score with the five cognitive outcomes entered as predictors. Adjusters in the analysis were age, sex, education, nutrition, and home environment. Exploratory factor analysis (EFA) and structural equation models (SEM) were used to determine the nature of the association between cognition and academic performance. Predictive residual sum of squares was used to determine which combination of cognitive scores was needed to predict academic performance.

Results

In regressions of a single academic score on all five cognitive outcomes and adjusters, only Working Memory was associated with Reading (coefficient estimate = 0.36, 95% confidence interval = 0.10 to 0.63, p<0.01) and Spelling (0.46, 0.13 to 0.78, p<0.01), Visual Spatial Skills was associated with Arithmetic (0.15, 0.03 to 0.26, p<0.05), and Learning was associated with Reading (0.06, 0.00 to 0.11, p<0.05). One latent cognitive factor was identified using EFA. The SEM found a strong association between this latent cognitive ability and each academic performance measure (P<0.0001). Working memory, visual spatial ability and learning were the best predictors of academic performance.

Conclusion

Academic performance is strongly associated with the latent variable labelled “cognitive ability” which captures most of the variation in the individual specific cognitive outcome measures. Working memory, visual spatial skills, and learning together stood out as the best combination to predict academic performance.     

Apathy, but not depression, reflects inefficient cognitive strategies in Parkinson's disease

Background

The relationship between apathy, depression and cognitive impairment in Parkinson''s disease (PD) is still controversial. The objective of this study is to investigate whether apathy and depression are associated with inefficient cognitive strategies in PD.

Methods

In this prospective clinical cohort study conducted in a university-based clinical and research movement disorders center we studied 48 PD patients. Based on clinical evaluation, they were classified in two groups: PD with apathy (PD-A group, n = 23) and PD without apathy (PD-NA group, n = 25). Patients received clinical and neuropsychological evaluations. The clinical evaluation included: Apathy Evaluation Scale-patient version, Hamilton Depression Rating Scale-17 items, the Unified Parkinson''s Disease Rating Scale and the Hoehn and Yahr staging system; the neuropsychological evaluation explored speed information processing, attention, working memory, executive function, learning abilities and memory, which included several measures of recall (immediate free, short delay free, long delay free and cued, and total recall).

Findings

PD-A and PD-NA groups did not differ in age, disease duration, treatment, and motor condition, but differed in recall (p<0.001) and executive tasks (p<0.001). Immediate free recall had the highest predictive value for apathy (F =  10.94; p = 0.002). Depression and apathy had a weak correlation (Pearson index  = 0.3; p<0.07), with three items of the depression scale correlating with apathy (Pearson index between .3 and.4; p<0.04). The depressed and non-depressed PD patients within the non-apathetic group did not differ.

Conclusion

Apathy, but not depression, is associated with deficit in implementing efficient cognitive strategies. As the implementation of efficient strategies relies on the fronto-striatal circuit, we conclude that apathy, unlike depression, is an early expression of executive impairment in PD.     

IMPLEMENTATION OF 12-HOUR SHIFTS IN A BRAZILIAN PETROCHEMICAL PLANT: IMPACT ON SLEEP AND ALERTNESS

A recent worldwide trend in chemical and petrochemical industries is to extend the duration of shifts. Optimization of the labor force to reduce costs is one reason to increase the length of working time in a shift. Implementation of 12h shifts is a controversial decision for managers and scientists. Literature reviews show alertness is lower during the nighttime hours, and sleep duration is reduced and worse during the daytime. The main objective of this study was to evaluate the impacts of 12h shifts on alertness and sleep. To evaluate the duration and quality of sleep and alertness during work, 22 male shift workers on a continuous rotating schedule at a petrochemical plant completed activity logs and estimated alertness using analog 10-cm scales for 30 consecutive days, three times (at 2h, 6h, and 10h of the shift) every work shift. Statistical tests (analysis of variance [ANOVA] and Tukey) were performed to detect differences between workdays and off days. The shift schedule was 2 days/3 nights/4 off days, followed by 3 days/2 nights/5 off days, followed by 2 days/2 nights/5 off days. Sleep duration varied significantly (p <. 001) among the work shifts and off days. Comparing work nights, the shortest mean sleep occurred after the second night (mean = 311.4 minutes, SD = 101.7 minutes), followed by the third night (mean = 335.3 minutes, SD = 151.2 minutes). All but one shift (sleep after the first work night) were significantly different from sleep after the first 2 workdays (p <. 002). Tukey tests showed no significant differences in sleep quality between workdays and nights, with the exception of sleep after the third day compared to sleep after night shifts. However, significant differences were detected between off days and work nights (p <. 01). ANOVA analysis showed borderline differences among perceived alertness during day shifts (p =. 073) and significant differences among the hours of theshifts(p =. 0005), especially when comparing the 2nd hour of the first day with the 10th hour of all the day shifts. There were no significant differences in perceived alertness during night work among the first, second, and third nights (p =. 573), but there were significant differences comparing the times (2nd, 6th, 10th hour) of the night shifts (p ≤. 001). The evaluation of sleep (duration and quality) and level of alertness have been extensively used in the literature as indicators of possible performance decrements at work. The results of this study show poorer sleep after and significantly decreased alertness during night work. Shifts of 12h are usually implemented for technical and economic reasons. These results point out the necessity of a careful trade-off between the financial and technical gains longer shifts might bring and the possible losses due to incidents or accidents from performance decrements during work. (Chronobiology International, 17(4), 521–537, 2000)     

Postoperative deterioration in health related quality of life as predictor for survival in patients with glioblastoma: a prospective study

Background

Studies indicate that acquired deficits negatively affect patients'' self-reported health related quality of life (HRQOL) and survival, but the impact of HRQOL deterioration after surgery on survival has not been explored.

Objective

Assess if change in HRQOL after surgery is a predictor for survival in patients with glioblastoma.

Methods

Sixty-one patients with glioblastoma were included. The majority of patients (n = 56, 91.8%) were operated using a neuronavigation system which utilizes 3D preoperative MRI and updated intraoperative 3D ultrasound volumes to guide resection. HRQOL was assessed using EuroQol 5D (EQ-5D), a generic instrument. HRQOL data were collected 1–3 days preoperatively and after 6 weeks. The mean change in EQ-5D index was −0.05 (95% CI −0.15–0.05) 6 weeks after surgery (p = 0.285). There were 30 patients (49.2%) reporting deterioration 6 weeks after surgery. In a Cox multivariate survival analysis we evaluated deterioration in HRQOL after surgery together with established risk factors (age, preoperative condition, radiotherapy, temozolomide and extent of resection).

Results

There were significant independent associations between survival and use of temozolomide (HR 0.30, p = 0.019), radiotherapy (HR 0.26, p = 0.030), and deterioration in HRQOL after surgery (HR 2.02, p = 0.045). Inclusion of surgically acquired deficits in the model did not alter the conclusion.

Conclusion

Early deterioration in HRQOL after surgery is independently and markedly associated with impaired survival in patients with glioblastoma. Deterioration in patient reported HRQOL after surgery is a meaningful outcome in surgical neuro-oncology, as the measure reflects both the burden of symptoms and treatment hazards and is linked to overall survival.     

Implementation of 12-hour shifts in a Brazilian petrochemical plant: impact on sleep and alertness

A recent worldwide trend in chemical and petrochemical industries is to extend the duration of shifts. Optimization of the labor force to reduce costs is one reason to increase the length of working time in a shift. Implementation of 12h shifts is a controversial decision for managers and scientists. Literature reviews show alertness is lower during the nighttime hours, and sleep duration is reduced and worse during the daytime. The main objective of this study was to evaluate the impacts of 12h shifts on alertness and sleep. To evaluate the duration and quality of sleep and alertness during work, 22 male shift workers on a continuous rotating schedule at a petrochemical plant completed activity logs and estimated alertness using analog 10-cm scales for 30 consecutive days, three times (at 2h, 6h, and 10h of the shift) every work shift. Statistical tests (analysis of variance [ANOVA] and Tukey) were performed to detect differences between workdays and off days. The shift schedule was 2 days/3 nights/4 off days, followed by 3 days/2 nights/5 off days, followed by 2 days/2 nights/5 off days. Sleep duration varied significantly (p < .001) among the work shifts and off days. Comparing work nights, the shortest mean sleep occurred after the second night (mean = 311.4 minutes, SD = 101.7 minutes), followed by the third night (mean = 335.3 minutes, SD = 151.2 minutes). All but one shift (sleep after the first work night) were significantly different from sleep after the first 2 workdays (p < .002). Tukey tests showed no significant differences in sleep quality between workdays and nights, with the exception of sleep after the third day compared to sleep after night shifts. However, significant differences were detected between off days and work nights (p < .01). ANOVA analysis showed borderline differences among perceived alertness during day shifts (p = .073) and significant differences among the hours of the shifts (p = .0005), especially when comparing the 2nd hour of the first day with the 10th hour of all the day shifts. There were no significant differences in perceived alertness during night work among the first, second, and third nights (p = .573), but there were significant differences comparing the times (2nd, 6th, 10th hour) of the night shifts (p < .001). The evaluation of sleep (duration and quality) and level of alertness have been extensively used in the literature as indicators of possible performance decrements at work. The results of this study show poorer sleep after and significantly decreased alertness during night work. Shifts of 12h are usually implemented for technical and economic reasons. These results point out the necessity of a careful trade-off between the financial and technical gains longer shifts might bring and the possible losses due to incidents or accidents from performance decrements during work.     

A randomized controlled trial of interventions to impede date palm sap contamination by bats to prevent nipah virus transmission in bangladesh

Background

Drinking raw date palm sap is a risk factor for human Nipah virus (NiV) infection. Fruit bats, the natural reservoir of NiV, commonly contaminate raw sap with saliva by licking date palm’s sap producing surface. We evaluated four types of physical barriers that may prevent bats from contacting sap.

Methods

During 2009, we used a crossover design and randomly selected 20 date palm sap producing trees and observed each tree for 2 nights: one night with a bamboo skirt intervention applied and one night without the intervention. During 2010, we selected 120 trees and randomly assigned four types of interventions to 15 trees each: bamboo, dhoincha (local plant), jute stick and polythene skirts covering the shaved part, sap stream, tap and collection pot. We enrolled the remaining 60 trees as controls. We used motion sensor activated infrared cameras to examine bat contact with sap.

Results

During 2009 bats contacted date palm sap in 85% of observation nights when no intervention was used compared with 35% of nights when the intervention was used [p<0.001]. Bats were able to contact the sap when the skirt did not entirely cover the sap producing surface. Therefore, in 2010 we requested the sap harvesters to use larger skirts. During 2010 bats contacted date palm sap [2% vs. 83%, p<0.001] less frequently in trees protected with skirts compared to control trees. No bats contacted sap in trees with bamboo (p<0.001 compared to control), dhoincha skirt (p<0.001) or polythene covering (p<0.001), but bats did contact sap during one night (7%) with the jute stick skirt (p<0.001).

Conclusion

Bamboo, dhoincha, jute stick and polythene skirts covering the sap producing areas of a tree effectively prevented bat-sap contact. Community interventions should promote applying these skirts to prevent occasional Nipah spillovers to human.     

On-Call Duty Effects on Sleep-State Physiological Stability in Male Medical Interns

Background

On-call duty among medical interns is characterized by sleep deprivation and stressful working conditions, both of which alter cardiac autonomic modulation. We hypothesized that sleep stability decreased in medical interns during on-call duty. We used cardiopulmonary-coupling (CPC) analysis to test our hypothesis.

Methods

We used electrocardiogram (ECG)-based CPC analysis to quantify physiological parameters of sleep stability in 13 medical interns during on-call and on-call duty-free periods. There were ten 33.5-h on-call duty shifts per month for interns, each followed by 2 on-call duty-free days, over 3 months. Measurements during sleep were collected before, during, and after an on-call shift. Measurements were repeated 3 months later during an on-call duty-free period.

Results

The medical interns had significantly reduced stable sleep, and displayed increased latency to the first epoch of stable sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights. Interns also had significantly increased rapid-eye-movement (REM) sleep during the on-call night shift, compared to the pre-call and on-call duty-free nights.

Conclusion

Medical interns suffer disrupted sleep stability and continuity during on-call night shifts. The ECG-based CPC analysis provides a straightforward means to quantify sleep quality and stability in medical staff performing shift work under stressful conditions.     

Time Course of Neurobehavioral Alertness During Extended Wakefulness in Morning- and Evening-Type Healthy Sleepers

The aim of the study was to evaluate the influence of chronotype (morning-type versus evening-type) living in a fixed sleep-wake schedule different from one's preferred sleep schedules on the time course of neurobehavioral performance during controlled extended wakefulness. The authors studied 9 morning-type and 9 evening-type healthy male subjects (21.4?±?1.9 yrs). Before the experiment, all participants underwent a fixed sleep-wake schedule mimicking a regular working day (bedtime: 23:30?h; wake time: 07:30?h). Then, following two nights in the laboratory, both chronotypes underwent a 36-h constant routine, performing a cognitive test of sustained attention every hour. Core body temperature, salivary melatonin secretion, objective alertness (maintenance of wakefulness test), and subjective sleepiness (visual analog scale) were also assessed. Evening-types expressed a higher level of subjective sleepiness than morning types, whereas their objective levels of alertness were not different. Cognitive performance in the lapse domain remained stable during the normal waking day and then declined during the biological night, with a similar time course for both chronotypes. Evening types maintained optimal alertness (i.e., 10% fastest reaction time) throughout the night, whereas morning types did not. For both chronotypes, the circadian performance profile was correlated with the circadian subjective somnolence profile and was slightly phase-delayed with melatonin secretion. Circadian performance was less correlated with circadian core body temperature. Lapse domain was phase-delayed with body temperature (2–4?h), whereas optimal alertness was slightly phase-delayed with body temperature (1?h). These results indicate evening types living in a fixed sleep-wake schedule mimicking a regular working day (different from their preferred sleep schedules) express higher subjective sleepiness but can maintain the same level of objective alertness during a normal waking day as morning types. Furthermore, evening types were found to maintain optimal alertness throughout their nighttime, whereas morning types could not. The authors suggest that evening-type subjects have a higher voluntary engagement of wake-maintenance mechanisms during extended wakefulness due to adaptation of their sleep-wake schedule to social constraints. (Author correspondence: jack.taillard@gmail.com)     

Time course of neurobehavioral alertness during extended wakefulness in morning- and evening-type healthy sleepers

The aim of the study was to evaluate the influence of chronotype (morning-type versus evening-type) living in a fixed sleep-wake schedule different from one's preferred sleep schedules on the time course of neurobehavioral performance during controlled extended wakefulness. The authors studied 9 morning-type and 9 evening-type healthy male subjects (21.4 ± 1.9 yrs). Before the experiment, all participants underwent a fixed sleep-wake schedule mimicking a regular working day (bedtime: 23:30 h; wake time: 07:30 h). Then, following two nights in the laboratory, both chronotypes underwent a 36-h constant routine, performing a cognitive test of sustained attention every hour. Core body temperature, salivary melatonin secretion, objective alertness (maintenance of wakefulness test), and subjective sleepiness (visual analog scale) were also assessed. Evening-types expressed a higher level of subjective sleepiness than morning types, whereas their objective levels of alertness were not different. Cognitive performance in the lapse domain remained stable during the normal waking day and then declined during the biological night, with a similar time course for both chronotypes. Evening types maintained optimal alertness (i.e., 10% fastest reaction time) throughout the night, whereas morning types did not. For both chronotypes, the circadian performance profile was correlated with the circadian subjective somnolence profile and was slightly phase-delayed with melatonin secretion. Circadian performance was less correlated with circadian core body temperature. Lapse domain was phase-delayed with body temperature (2-4 h), whereas optimal alertness was slightly phase-delayed with body temperature (1 h). These results indicate evening types living in a fixed sleep-wake schedule mimicking a regular working day (different from their preferred sleep schedules) express higher subjective sleepiness but can maintain the same level of objective alertness during a normal waking day as morning types. Furthermore, evening types were found to maintain optimal alertness throughout their nighttime, whereas morning types could not. The authors suggest that evening-type subjects have a higher voluntary engagement of wake-maintenance mechanisms during extended wakefulness due to adaptation of their sleep-wake schedule to social constraints.     

Liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance

Introduction

Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients.

Methods

Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi''s classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses.

Results

Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056).

Conclusions

In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity.     

Sociodemographic and disease correlates of body image distress among patients with systemic sclerosis

Background

Body image concerns are infrequently studied in systemic sclerosis (SSc), even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.

Methods

SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.

Results

A total of 489 SSc patients (432 female, 57 male) were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively), as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively). Greater social discomfort was robustly associated with younger age (−0.017, p<0.001) and upper-body telangiectasias (0.32, p = 0.021). Dissatisfaction with appearance was associated with hand contractures (0.07, p = 0.036).

Conclusion

This study found that dissatisfaction with appearance and social discomfort were associated with numerous disfiguring characteristics of SSc, in addition to age. These results underline that there are multiple factors contributing to body image distress in SSc, as well as the need to attend to both disease and social contexts in understanding the impact of disfigurement among patients.     

Sleep Extension Improves Neurocognitive Functions in Chronically Sleep-Deprived Obese Individuals

Background

Sleep deprivation and obesity, are associated with neurocognitive impairments. Effects of sleep deprivation and obesity on cognition are unknown, and the cognitive long-term effects of improvement of sleep have not been prospectively assessed in short sleeping, obese individuals.

Objective

To characterize neurocognitive functions and assess its reversibility.

Design

Prospective cohort study.

Setting

Tertiary Referral Research Clinical Center.

Patients

A cohort of 121 short-sleeping (<6.5 h/night) obese (BMI 30–55 kg/m²) men and pre-menopausal women.

Intervention

Sleep extension (468±88 days) with life-style modifications.

Measurements

Neurocognitive functions, sleep quality and sleep duration.

Results

At baseline, 44% of the individuals had an impaired global deficit score (t-score 0–39). Impaired global deficit score was associated with worse subjective sleep quality (p = 0.02), and lower urinary dopamine levels (p = 0.001). Memory was impaired in 33%; attention in 35%; motor skills in 42%; and executive function in 51% of individuals. At the final evaluation (N = 74), subjective sleep quality improved by 24% (p<0.001), self-reported sleep duration increased by 11% by questionnaires (p<0.001) and by 4% by diaries (p = 0.04), and daytime sleepiness tended to improve (p = 0.10). Global cognitive function and attention improved by 7% and 10%, respectively (both p = 0.001), and memory and executive functions tended to improve (p = 0.07 and p = 0.06). Serum cortisol increased by 17% (p = 0.02). In a multivariate mixed model, subjective sleep quality and sleep efficiency, urinary free cortisol and dopamine and plasma total ghrelin accounted for 1/5 of the variability in global cognitive function.

Limitations

Drop-out rate.

Conclusions

Chronically sleep-deprived obese individuals exhibit substantial neurocognitive deficits that are partially reversible upon improvement of sleep in a non-pharmacological way. These findings have clinical implications for large segments of the US population.

Trail registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00261898","term_id":"NCT00261898"}}NCT00261898. NIDDK protocol 06-DK-0036     

Reduced exercise tolerance and pulmonary capillary recruitment with remote secondhand smoke exposure

Rationale

Flight attendants who worked on commercial aircraft before the smoking ban in flights (pre-ban FAs) were exposed to high levels of secondhand smoke (SHS). We previously showed never-smoking pre-ban FAs to have reduced diffusing capacity (Dco) at rest.

Methods

To determine whether pre-ban FAs increase their Dco and pulmonary blood flow () during exercise, we administered a symptom-limited supine-posture progressively increasing cycle exercise test to determine the maximum work (watts) and oxygen uptake () achieved by FAs. After 30 min rest, we then measured Dco and at 20, 40, 60, and 80 percent of maximum observed work.

Results

The FAs with abnormal resting Dco achieved a lower level of maximum predicted work and compared to those with normal resting Dco (mean±SEM; 88.7±2.9 vs. 102.5±3.1%predicted ; p = 0.001). Exercise limitation was associated with the FAs'' FEV₁ (r = 0.33; p = 0.003). The Dco increased less with exercise in those with abnormal resting Dco (mean±SEM: 1.36±0.16 vs. 1.90±0.16 ml/min/mmHg per 20% increase in predicted watts; p = 0.020), and amongst all FAs, the increase with exercise seemed to be incrementally lower in those with lower resting Dco. Exercise-induced increase in was not different in the two groups. However, the FAs with abnormal resting Dco had less augmentation of their Dco with increase in during exercise (mean±SEM: 0.93±0.06 vs. 1.47±0.09 ml/min/mmHg per L/min; p<0.0001). The Dco during exercise was inversely associated with years of exposure to SHS in those FAs with ≥10 years of pre-ban experience (r = −0.32; p = 0.032).

Conclusions

This cohort of never-smoking FAs with SHS exposure showed exercise limitation based on their resting Dco. Those with lower resting Dco had reduced pulmonary capillary recruitment. Exposure to SHS in the aircraft cabin seemed to be a predictor for lower Dco during exercise.     

Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants

Background

The importance of maternal dietary choline for fetal neural development and later cognitive function has been well-documented in experimental studies. Although choline is an essential dietary nutrient for humans, evidence that low maternal choline in pregnancy impacts neurodevelopment in human infants is lacking. We determined potential associations between maternal plasma free choline and its metabolites betaine and dimethylglycine in pregnancy and infant neurodevelopment at 18 months of age.

Methodology

This was a prospective study of healthy pregnant women and their full-term, single birth infants. Maternal blood was collected at 16 and 36 weeks of gestation and infant neurodevelopment was assessed at 18 months of age for 154 mother-infant pairs. Maternal plasma choline, betaine, dimethylglycine, methionine, homocysteine, cysteine, total B12, holotranscobalamin and folate were quantified. Infant neurodevelopment was evaluated using the Bayley Scales of Infant Development–III. Multivariate regression, adjusting for covariates that impact development, was used to determine the associations between maternal plasma choline, betaine and dimethylglycine and infant neurodevelopment.

Results

The maternal plasma free choline at 16 and 36 weeks gestation was median (interquartile range) 6.70 (5.78–8.03) and 9.40 (8.10–11.3) µmol/L, respectively. Estimated choline intakes were (mean ±SD) 383±98.6 mg/day, and lower than the recommended 450 mg/day. Betaine intakes were 142±70.2 mg/day. Significant positive associations were found between infant cognitive test scores and maternal plasma free choline (B = 6.054, SE = 2.283, p = 0.009) and betaine (B = 7.350, SE = 1.933, p = 0.0002) at 16 weeks of gestation. Maternal folate, total B12, or holotranscobalamin were not related to infant development.

Conclusion

We show that choline status in the first half of pregnancy is associated with cognitive development among healthy term gestation infants. More work is needed on the potential limitation of choline or betaine in the diets of pregnant women.     

Non-Visual Effects of Light on Melatonin,Alertness and Cognitive Performance: Can Blue-Enriched Light Keep Us Alert?

Background

Light exposure can cascade numerous effects on the human circadian process via the non-imaging forming system, whose spectral relevance is highest in the short-wavelength range. Here we investigated if commercially available compact fluorescent lamps with different colour temperatures can impact on alertness and cognitive performance.

Methods

Sixteen healthy young men were studied in a balanced cross-over design with light exposure of 3 different light settings (compact fluorescent lamps with light of 40 lux at 6500K and at 2500K and incandescent lamps of 40 lux at 3000K) during 2 h in the evening.

Results

Exposure to light at 6500K induced greater melatonin suppression, together with enhanced subjective alertness, well-being and visual comfort. With respect to cognitive performance, light at 6500K led to significantly faster reaction times in tasks associated with sustained attention (Psychomotor Vigilance and GO/NOGO Task), but not in tasks associated with executive function (Paced Visual Serial Addition Task). This cognitive improvement was strongly related with attenuated salivary melatonin levels, particularly for the light condition at 6500K.

Conclusions

Our findings suggest that the sensitivity of the human alerting and cognitive response to polychromatic light at levels as low as 40 lux, is blue-shifted relative to the three-cone visual photopic system. Thus, the selection of commercially available compact fluorescent lights with different colour temperatures significantly impacts on circadian physiology and cognitive performance at home and in the workplace.     

Reduced metabolism in brain "control networks" following cocaine-cues exposure in female cocaine abusers

Objective

Gender differences in vulnerability for cocaine addiction have been reported. Though the mechanisms are not understood, here we hypothesize that gender differences in reactivity to conditioned-cues, which contributes to relapse, are involved.

Method

To test this we compared brain metabolism (using PET and ¹⁸FDG) between female (n = 10) and male (n = 16) active cocaine abusers when they watched a neutral video (nature scenes) versus a cocaine-cues video.

Results

Self-reports of craving increased with the cocaine-cue video but responses did not differ between genders. In contrast, changes in whole brain metabolism with cocaine-cues differed by gender (p<0.05); females significantly decreased metabolism (−8.6%±10) whereas males tended to increase it (+5.5%±18). SPM analysis (Cocaine-cues vs Neutral) in females revealed decreases in frontal, cingulate and parietal cortices, thalamus and midbrain (p<0.001) whereas males showed increases in right inferior frontal gyrus (BA 44/45) (only at p<0.005). The gender-cue interaction showed greater decrements with Cocaine-cues in females than males (p<0.001) in frontal (BA 8, 9, 10), anterior cingulate (BA 24, 32), posterior cingulate (BA 23, 31), inferior parietal (BA 40) and thalamus (dorsomedial nucleus).

Conclusions

Females showed greater brain reactivity to cocaine-cues than males but no differences in craving, suggesting that there may be gender differences in response to cues that are not linked with craving but could affect subsequent drug use. Specifically deactivation of brain regions from “control networks” (prefrontal, cingulate, inferior parietal, thalamus) in females could increase their vulnerability to relapse since it would interfere with executive function (cognitive inhibition). This highlights the importance of gender tailored interventions for cocaine addiction.     

Women born preterm or with inappropriate weight for gestational age are at risk of subsequent gestational diabetes and pre-eclampsia

Introduction

Low birthweight, which can be caused by inappropriate intrauterine growth or prematurity, is associated with development of gestational diabetes mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects of prematurity and inappropriate intrauterine growth remain uncertain.

Methods

Through nation-wide registries we identified all Danish mothers in the years 1989–2007. Two separate cohorts consisting mothers born 1974–1977 (n = 84219) and 1978–1981 (n = 32376) were studied, due to different methods of registering birthweight and gestational age in the two periods. Data was linked with information on GDM, pre-eclampsia and education.

Results

In a multivariate logistic regression model the odds of developing GDM was increased by 5–7% for each week the mother was born before term (p = 0.018 for 1974–1977, p = 0.048 for 1978–1981), while the odds were increased by 13–17% for each standard deviation (SD) reduction in birthweight for gestational age for those who were small or normal for gestational age (p<0.0001 and p = 0.035) and increased by 118–122% for each SD increase above the normal range (p<0.0001 and p = 0.024). The odds of pre-eclampsia was increased by 3–5% for each week the mother was born before term (p = 0.064 and p = 0.04), while the odds were increased 11–12% for each SD reduction in birthweight for gestational age (p<0.0001 and p = 0.0002).

Conclusion

In this cohort of young Danish mothers, being born premature or with increasingly low birthweight for gestational age was associated with an increased risk of GDM and pre-eclampsia in adulthood, while increasingly high birthweight for gestational age was associated with an increased risk of GDM and a decreased risk of pre-eclampsia. Inappropriate weight for gestational age was a more important risk factor than prematurity.     

Common genetic variation in the SERPINF1 locus determines overall adiposity, obesity-related insulin resistance, and circulating leptin levels

Objective

Pigment epithelium-derived factor (PEDF) belongs to the serpin family of peptidase inhibitors (serpin F1) and is among the most abundant glycoproteins secreted by adipocytes. In vitro and mouse in vivo data revealed PEDF as a candidate mediator of obesity-induced insulin resistance. Therefore, we assessed whether common genetic variation within the SERPINF1 locus contributes to adipose tissue-related prediabetic phenotypes in humans.

Subjects/Methods

A population of 1,974 White European individuals at increased risk for type 2 diabetes was characterized by an oral glucose tolerance test with glucose and insulin measurements (1,409 leptin measurements) and genotyped for five tagging SNPs covering 100% of common genetic variation (minor allele frequency ≥0.05) in the SERPINF1 locus. In addition, a subgroup of 486 subjects underwent a hyperinsulinaemic-euglycaemic clamp and a subgroup of 340 magnetic resonance imaging (MRI) and spectroscopy (MRS).

Results

After adjustment for gender and age and Bonferroni correction for the number of SNPs tested, SNP rs12603825 revealed significant association with MRI-derived total adipose tissue mass (p = 0.0094) and fasting leptin concentrations (p = 0.0035) as well as nominal associations with bioelectrical impedance-derived percentage of body fat (p = 0.0182) and clamp-derived insulin sensitivity (p = 0.0251). The association with insulin sensitivity was completely abolished by additional adjustment for body fat (p = 0.8). Moreover, the fat mass-increasing allele of SNP rs12603825 was significantly associated with elevated fasting PEDF concentrations (p = 0.0436), and the PEDF levels were robustly and positively associated with all body fat parameters measured and with fasting leptin concentrations (p<0.0001, all).

Conclusion

In humans at increased risk for type 2 diabetes, a functional common genetic variant in the gene locus encoding PEDF contributes to overall body adiposity, obesity-related insulin resistance, and circulating leptin levels.     

Shift work is not associated with high blood pressure or prevalence of hypertension

Background

Working mostly at night has been suggested to be associated with upset of chronobiological rhythms and high blood pressure, but the evidence from epidemiological studies is weak.

Methods

In a cross-sectional survey, we evaluated the association between shift work and blood pressure, pre-hypertension and hypertension. In total, 493 nurses, nurse technicians and assistants, were selected at random in a large general hospital setting. Hypertension was diagnosed by the mean of four automatic blood pressure readings ≥140/90 mmHg or use of blood pressure lowering agents, and pre-hypertension by systolic blood pressure ≥120–139 or diastolic blood pressure ≥80–89 mmHg. Risk factors for hypertension were evaluated by a standardized questionnaire and anthropometric measurements. The association between the shift of work and blood pressure, pre-hypertension and hypertension was explored using univariate and multivariate analyses that controlled for risk factors for hypertension by covariance analysis and modified Poisson regression.

Results

The mean age of the participants was 34.3±9.4 years and 88.2% were women. Night shift workers were older, more frequently married or divorced, and less educated. The prevalence of hypertension in the whole sample was 16%, and 28% had pre-hypertension. Blood pressure (after adjustment for confounding) was not different in day and night shift workers. The prevalence of hypertension and pre-hypertension by shift work was not different in the univariate analysis and after adjustment for confounding (all risk ratios  = 1.0).

Conclusion

Night shift work did not increase blood pressure and was not associated with hypertension or pre-hypertension in nursing personnel working in a large general hospital.     

Postoperative Chemoradiotherapy versus Postoperative Chemotherapy for Completely Resected Gastric Cancer with D2 Lymphadenectomy: A Meta-Analysis

Background

Both chemoradiotherapy and chemotherapy are used in postoperative adjuvant therapy for resected gastric cancer. However, it is controversial whether chemoradiotherapy or chemotherapy is the optimal strategy for patients with gastric cancer after D2 lymphadenectomy. The present meta-analysis aims to provide more evidence on the relative benefits of adjuvant therapies in this setting.

Methods

We conducted a systematic review of randomized controlled trials, extracted time-to-event data using Tierney methods (when not reported), and performed meta-analysis to obtain the relative hazards of adjuvant chemoradiotherapy to chemotherapy on efficacy and toxicities.

Results

A total of 895 patients from 3 randomized controlled trials were identified for this meta-analysis. All patients were from Asian countries. Our results showed that postoperative chemoradiotherapy significantly improved locoregional recurrence-free survival [LRRFS: hazard ratio (HR) = 0.53, 95% CI = 0.32–0.87, p = 0.01] and disease-free survival (DFS: HR = 0.72, 95% CI = 0.59–0.89, p = 0.002); however, the improvement of distant metastasis recurrence-free survival (DMRFS: HR = 0.86; 95% CI = 0.66–1.11, p = 0.25) and overall survival (OS: HR = 0.79, 95% CI = 0.61–1.03, p = 0.08) were non-significant. The main grade 3 or 4 toxicities were equivalent between the two groups.

Conclusion

In non-selected Asian patients with resected gastric cancer who underwent D2 lymphadenectomy, postoperative chemoradiotherapy improved LRRFS and DFS but might not improve OS compared to postoperative chemotherapy.