Adipokine Levels Are Altered by Shiftwork: A Preliminary Study

Shiftwork is often associated with metabolic diseases, and in the past few years, several cytokines have been postulated to contribute to various diseases, including insulin resistance. The aim of this study was to compare the concentrations of adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in samples of young adult men exposed to a fixed (i) night shift (n?=?9), working from 22:00 to 06:00?h; (ii) early morning shift (n?=?6), working from 06:00 to 14:00?h; and (iii) day shift (n?=?7), working from 08:00 to 17:00?h. The fixed night-shift and early-morning-shift samples were considered collectively as a shiftworker group given their work times. Blood samples were collected during the regular working day at 4-h intervals over the course of 24?h, thus totaling six samples. Morphological and physical activity parameters did not differ between the three groups. Total energy intake was lowest on the early morning shifts (p?<?.03). Both shiftworker groups ingested a significantly higher percentage of fat (p?<?.003) and a lower percentage of carbohydrate (p?<?.0005) than the day group. The early morning group had a lower mean 24-h level of adiponectin than the other two groups (p?=?.016), and both the early morning and night groups exhibited higher mean 24-h levels of TNF-α than the day group (p?=?.0001). The 24-h mean levels of IL-6 did not differ significantly between the groups (p?=?.147). None of the groups exhibited a significant circadian effect on adiponectin (p?=?.829), TNF-α (p?=?.779), or IL-6 (p?=?.979) levels. These results indicate that individuals who are enrolled in shiftwork are susceptible to alterations in the secretion of cytokines that are involved in insulin resistance and cardiovascular disease, both of which are known to affect this population. (Author correspondence: tmello@demello.net.br)     

国人汉语Stroop任务的大脑激活模式研究

目的:采用功能磁共振成像(functional MRI,fMRI)方法考察汉语Slroop任务大脑激活模式.方法:对8例正常汉族人进行了汉语Stroop色词任务实验测试,同时采用Siemens Sonata 1.5 T成像系统,采集其脑部的BOLD-fMRI数据,通过AFNI软件进行统计分析得到脑功能活动的图像,分析不同脑区的激活模式.结果:汉语Slroop任务主要激活双侧额中回、额下回、前扣带回和顶后区,双侧额上回、中央前回、基底节区和颞叶也有不同程度激活.结论:汉语Stroop任务有固定的大脑激活模式,是一种研究大脑高级认知的良好的神经心理学任务.     

Perception of Everyday Sounds: A Developmental Study of a Free Sorting Task

ObjectivesThe analysis of categorization of everyday sounds is a crucial aspect of the perception of our surrounding world. However, it constitutes a poorly explored domain in developmental studies. The aim of our study was to understand the nature and the logic of the construction of auditory cognitive categories for natural sounds during development. We have developed an original approach based on a free sorting task (FST). Indeed, categorization is fundamental for structuring the world and cognitive skills related to, without having any need of the use of language. Our project explored the ability of children to structure their acoustic world, and to investigate how such structuration matures during normal development. We hypothesized that age affects the listening strategy and the category decision, as well as the number and the content of individual categories.DesignEighty-two French children (6–9 years), 20 teenagers (12–13 years), and 24 young adults participated in the study. Perception and categorization of everyday sounds was assessed based on a FST composed of 18 different sounds belonging to three a priori categories: non-linguistic human vocalizations, environmental sounds, and musical instruments.ResultsChildren listened to the sounds more times than older participants, built significantly more classes than adults, and used a different strategy of classification. We can thus conclude that there is an age effect on how the participants accomplished the task. Analysis of the auditory categorization performed by 6-year-old children showed that this age constitutes a pivotal stage, in agreement with the progressive change from a non-logical reasoning based mainly on perceptive representations to the logical reasoning used by older children. In conclusion, our results suggest that the processing of auditory object categorization develops through different stages, while the intrinsic basis of the classification of sounds is already present in childhood.     

Genetic Variants of Angiotensin-Converting Enzyme Are Linked to Autism: A Case-Control Study

BackgroundAutism is a disease of complex nature with a significant genetic component. The importance of renin-angiotensin system (RAS) elements in cognition and behavior besides the interaction of angiotensin II (Ang II), the main product of angiotensin-converting enzyme (ACE), with neurotransmitters in CNS, especially dopamine, proposes the involvement of RAS in autism. Since the genetic architecture of autism has remained elusive, here we postulated that genetic variations in RAS are associated with autism.MethodsConsidering the relation between the three polymorphisms of ACE (I/D, rs4343 and rs4291) with the level of ACE activity, we have investigated this association with autism, in a case-control study. Genotype and allele frequencies of polymorphisms were determined in DNAs extracted from venous blood of 120 autistic patients and their age and sex-matched healthy controls, using polymerase chain reaction (PCR) and PCR–restriction fragment length polymorphism (PCR–RFLP) methods.ResultsThere were strong associations between both DD genotype of ACE I/D and the D allele, with autism (P = 0.006, OR = 2.9, 95% CI = 1.64–5.13 and P = 0.006, OR = 2.18, 95% CI = 1.37–3.48 respectively). Furthermore, a significant association between the G allele of rs4343 and autism was observed (P = 0.006, OR = 1.84, 95%CI = 1.26–2.67). Moreover, haplotype analysis revealed an association between DTG haplotype and autism (P = 0.008).ConclusionOur data suggests the involvement of RAS genetic diversity in increasing the risk of autism.     

Risky Drinking Patterns Are Being Continued into Pregnancy: A Prospective Cohort Study

Background

Risky patterns of alcohol use prior to pregnancy increase the risk of alcohol-exposed pregnancies and subsequent adverse outcomes. It is important to understand how consumption changes once women become pregnant.

Objective

The aim of this study was to describe the characteristics of women that partake in risky drinking patterns before pregnancy and to examine how these patterns change once they become pregnant.

Methods

A sample of 1577 women from the 1973–78 cohort of the Australian Longitudinal Study on Women’s Health were included if they first reported being pregnant in 2000, 2003, 2006, 2009 and reported risky drinking patterns prior to that pregnancy. Multinomial logistic regression was used to determine which risky drinking patterns were most likely to continue into pregnancy.

Results

When reporting risky drinking patterns prior to pregnancy only 6% of women reported weekly drinking only, whereas 46% reported binge drinking only and 48% reported both. Women in both binge categories were more likely to have experienced financial stress, not been partnered, smoked, used drugs, been nulliparous, experienced a violent relationship, and were less educated. Most women (46%) continued these risky drinking patterns into pregnancy, with 40% reducing these behaviors, and 14% completely ceasing alcohol consumption. Once pregnant, women who binged only prior to pregnancy were more likely to continue (55%) rather than reduce drinking (29%). Of the combined drinking group 61% continued to binge and 47% continued weekly drinking. Compared with the combined drinking group, binge only drinkers prior to pregnancy were less likely to reduce rather than continue their drinking once pregnant (OR = 0.37, 95% CI  =  0.29, 0.47).

Conclusions

Over a third of women continued risky drinking into pregnancy, especially binge drinking, suggesting a need to address alcohol consumption prior to pregnancy.     

A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

A_2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A_2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A_2AAR stimulation in a rat model of arthritis. We investigated A_2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A_2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A_2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A_2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A_2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A_2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A_2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A_2AARs in lymphocytes from RA patients. The effectiveness of A_2AAR stimulation in a rat model of arthritis supported the role of A_2AAR agonists as potential pharmacological treatment for RA.     

Incidental Findings on Brain MR Imaging in Older Community-Dwelling Subjects Are Common but Serious Medical Consequences Are Rare: A Cohort Study

Objectives

Incidental findings in neuroimaging occur in 3% of volunteers. Most data come from young subjects. Data on their occurrence in older subjects and their medical, lifestyle and financial consequences are lacking. We determined the prevalence and medical consequences of incidental findings found in community-dwelling older subjects on brain magnetic resonance imaging.

Design

Prospective cohort observational study.

Setting

Single centre study with input from secondary care.

Participants

Lothian Birth Cohort 1936, a study of cognitive ageing.

Main Outcome Measures

Incidental findings identified by two consultant neuroradiologists on structural brain magnetic resonance imaging at age 73 years; resulting medical referrals and interventions.

Primary and Secondary Outcome Measures

Prevalence of incidental findings by individual categories: neoplasms, cysts, vascular lesions, developmental, ear, nose or throat anomalies, by intra- and extracranial location; visual rating of white matter hyperintensities and brain atrophy.

Results

There were 281 incidental findings in 223 (32%) of 700 subjects, including 14 intra- or extracranial neoplasms (2%), 15 intracranial vascular anomalies (2%), and 137 infarcts or haemorrhages (20%). Additionally, 153 had moderate/severe deep white matter hyperintensities (22%) and 176 had cerebral atrophy at, or above, the upper limit of normal (25%) compared with a normative population template. The incidental findings were unrelated to white matter hyperintensities or atrophy; about a third of subjects had both incidental findings and moderate or severe WMH and a quarter had incidental findings and atrophy. The incidental findings resulted in one urgent and nine non-urgent referrals for further medical assessment, but ultimately in no new treatments.

Conclusions

In community-dwelling older subjects, incidental findings, including white matter hyperintensities and atrophy, were common. However, many findings were not of medical importance and, in this age group, most did not result in further assessment and none in change of treatment.     

Adherence and Uptake of Artemisinin-Based Combination Treatments for Uncomplicated Malaria: A Qualitative Study in Northern Ghana

BackgroundBased on the recommendations of the World Health Organization in 2004, Ghana changed her antimalarial drug policy from mono-therapy to Artemisinin-based Combination Therapy (ACTs). The country is currently using three first line drugs artesunate-amodiaquine, artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated malaria. Despite this policy, little or no qualitative studies have been conducted to establish the factors influencing adherence to the new treatment for malaria. This study explored factors influencing adherence to the use of ACTs in northern Ghana.MethodsThis was a qualitative study comprising forty (40) in-depth interviews with patients with malaria who visited selected public and private health facilities and received ACTs. Systematic sampling technique was used to select participants who were given ACTs for the interviews. Nvivo 9 software was used to code the data into themes for further analysis.ResultsThe study revealed very important differences in knowledge about ACTs. As expected, the less or illiterates could not mention the type of ACT they would prefer to use for treating their malaria. The educated ones had a good knowledge on ACTs and preferred artemether-lumefantrinee in treating their malaria. The reason was that the drug was good and it had minimal or no side effects. Individual attitudes toward the use of medications and the side effects associated with the use of these ACTs were found to be the main factors affecting adherence to the use of ACTs. Perceived cure of illness after the initial dose greatly affected adherence. Other factors such as forgetfulness and lack of information also influenced patient adherence to ACTs use.ConclusionIndividual knowledge, attitudes and behaviors greatly influence patients’ adherence to ACTs use. Since ACTs take a number of days to complete, continuous education by health professionals could improve on adherence to ACTs use by patients with malaria.     

Haplotypes in IL-8 Gene Are Associated to Age-Related Macular Degeneration: A Case-Control Study

Background

Age-related macular degeneration (AMD) is the main cause of blindness in the developed world. The etiology of AMD is multifactorial due to the interaction between genetic and environmental factors. IL-8 has a role in inflammation and angiogenesis; we report the genetic characterization of IL-8 allele architecture and evaluate the role of SNPs or haplotypes in the susceptibility to wet AMD, case-control study.

Methods

Case-control study including 721 AMD patients and 660 controls becoming from Italian population. Genotyping was carried out by Real Time-PCR. Differences in the frequencies were estimated by the chi-square test. Direct sequencing was carried out by capillary electrophoresis trough ABI3130xl.

Results

rs2227306 showed a p–value of 4.15*10⁻⁵ and an Odds Ratio (OR) for T allele of 1.39 [1.19–1.62]. After these positive results, we sequenced the entire IL-8 regulatory and coding regions of 60 patients and 30 controls stratified for their genotype at rs2227306. We defined two different haplotypes involving rs4073 (A/T), rs2227306 (C/T), rs2227346 (C/T) and rs1126647 (A/T): A-T-T-T (p-value: 2.08*10⁻⁹; OR: 1.68 [1.43–1.97]) and T-C-C-A (p-value: 7.07*10⁻¹¹; OR: 0.60 [0.51–0.70]). To further investigate a potential functional role of associated haplotypes, we performed an expression study on RNA extracted from whole blood of 75 donors to verify a possible direct correlation between haplotype and gene expression, failing to reveal significant differences.

Conclusions

These results suggest a possible secondary role of IL-8 gene in the development of the disease. This paper outlines the importance of association between inflammation and AMD. Moreover IL-8 is a new susceptibility genomic biomarker of AMD.     

Microstructural White Matter Tissue Characteristics Are Modulated by Homocysteine: A Diffusion Tensor Imaging Study

Homocysteine level can lead to adverse effects on the brain white matter through endothelial dysfunction, microstructural inflammation, and neurotoxin effects. Despite previously observed associations between elevated homocysteine and macroscopic structural brain changes, it is still unknown whether microstructural associations of homocysteine on brain tissue properties can be observed in healthy subjects with routine MRI. To this end, we investigated potential relationships between homocysteine levels and microstructural measures computed with diffusion tensor imaging (DTI) in a cohort of 338 healthy participants. Significant positive correlations were observed between homocysteine levels and diffusivity measures in the bilateral temporal WM, the brainstem, and the bilateral cerebellar peduncle. This is the first study demonstrating that DTI is sufficiently sensitive to relate microstructural WM properties to homocysteine levels in healthy subjects.     

Better Prognosis in Newborns with Trisomy 13 Who Received Intensive Treatments: A Retrospective Study of 16 Patients

Intensive treatment for newborns with trisomy 13 is controversial because of their lethal prognosis. We report the better life prognosis of patients with trisomy 13 who received intensive treatment. At our hospital, we provided an intensive management to such patients including resuscitation and surgical procedures as required. Herein, we present the results of a retrospective study (1989-2010) of 16 trisomy 13 cases who received an intensive treatment. None was diagnosed to have trisomy 13 before birth; 9 were delivered by C-section and oxygen was administered to all patients during postpartum resuscitation. Mechanical ventilation was used in 9 patients after tracheal intubation and tracheotomy was performed in 2 patients when withdrawing of extubation was difficult. Regarding prognosis, 9 patients died, 3 were referred to another hospital, and 4 were discharged from the hospital. Four and 7 patients died within 7 and 30 days after birth, respectively. Nine patients survived for >1 month, 7 for >180 days, and 5 for >3 years. Median survival for 16 patients was 733 days. The patients who received intensive treatments survived longer compared to the previous data. This study provides useful information concerning genetic counseling, especially from an ethical point of view, before providing intensive management to newborns with trisomy 13.     

Sharks: A Potential Source of Antiangiogenic Factors and Tumor Treatments

Since angiogenesis is a key feature of tumor growth, inhibiting this process is one way to treat cancer. Cartilage is a natural source of material with strong antiangiogenic activity. This report reviews knowledge of the anticancer properties of shark cartilage and clinical information on drugs such as neovastat and squalamine. Because their entire endoskeleton is composed of cartilage, sharks are thought to be an ideal source of angiogenic and tumor growth inhibitors. Shark cartilage extract has shown antiangiogenic and antitumor activities in animals and humans. The oral administration of cartilage extract was efficacious in reducing angiogenesis. Purified antiangiogenic factors from shark cartilage, such as U-995 and neovastat (AE-941), also showed antiangiogenic and antitumor activity. AE-941 is under phase III clinical investigation. Squalamine, a low molecular weight aminosterol, showed strong antitumor activity when combined with chemotherapeutic materials. The angiogenic tissue inhibitor of metalloprotease 3 (TIMP-3) and tumor suppressor protein (snm23) genes from shark cartilage were cloned and characterized.     

Task and Spatial Frequency Modulations of Object Processing: An EEG Study

Visual object processing may follow a coarse-to-fine sequence imposed by fast processing of low spatial frequencies (LSF) and slow processing of high spatial frequencies (HSF). Objects can be categorized at varying levels of specificity: the superordinate (e.g. animal), the basic (e.g. dog), or the subordinate (e.g. Border Collie). We tested whether superordinate and more specific categorization depend on different spatial frequency ranges, and whether any such dependencies might be revealed by or influence signals recorded using EEG. We used event-related potentials (ERPs) and time-frequency (TF) analysis to examine the time course of object processing while participants performed either a grammatical gender-classification task (which generally forces basic-level categorization) or a living/non-living judgement (superordinate categorization) on everyday, real-life objects. Objects were filtered to contain only HSF or LSF. We found a greater positivity and greater negativity for HSF than for LSF pictures in the P1 and N1 respectively, but no effects of task on either component. A later, fronto-central negativity (N350) was more negative in the gender-classification task than the superordinate categorization task, which may indicate that this component relates to semantic or syntactic processing. We found no significant effects of task or spatial frequency on evoked or total gamma band responses. Our results demonstrate early differences in processing of HSF and LSF content that were not modulated by categorization task, with later responses reflecting such higher-level cognitive factors.     

Low-Arousal Speech Noise Improves Performance in N-Back Task: An ERP Study

The relationship between noise and human performance is a crucial topic in ergonomic research. However, the brain dynamics of the emotional arousal effects of background noises are still unclear. The current study employed meaningless speech noises in the n-back working memory task to explore the changes of event-related potentials (ERPs) elicited by the noises with low arousal level vs. high arousal level. We found that the memory performance in low arousal condition were improved compared with the silent and the high arousal conditions; participants responded more quickly and had larger P2 and P3 amplitudes in low arousal condition while the performance and ERP components showed no significant difference between high arousal and silent conditions. These findings suggested that the emotional arousal dimension of background noises had a significant influence on human working memory performance, and that this effect was independent of the acoustic characteristics of noises (e.g., intensity) and the meaning of speech materials. The current findings improve our understanding of background noise effects on human performance and lay the ground for the investigation of patients with attention deficits.     

Neural Mechanisms Underlying the Cost of Task Switching: An ERP Study

Background

When switching from one task to a new one, reaction times are prolonged. This phenomenon is called switch cost (SC). Researchers have recently used several kinds of task-switching paradigms to uncover neural mechanisms underlying the SC. Task-set reconfiguration and passive dissipation of a previously relevant task-set have been reported to contribute to the cost of task switching.

Methodology/Principal Findings

An unpredictable cued task-switching paradigm was used, during which subjects were instructed to switch between a color and an orientation discrimination task. Electroencephalography (EEG) and behavioral measures were recorded in 14 subjects. Response-stimulus interval (RSI) and cue-stimulus interval (CSI) were manipulated with short and long intervals, respectively. Switch trials delayed reaction times (RTs) and increased error rates compared with repeat trials. The SC of RTs was smaller in the long CSI condition. For cue-locked waveforms, switch trials generated a larger parietal positive event-related potential (ERP), and a larger slow parietal positivity compared with repeat trials in the short and long CSI condition. Neural SC of cue-related ERP positivity was smaller in the long RSI condition. For stimulus-locked waveforms, a larger switch-related central negative ERP component was observed, and the neural SC of the ERP negativity was smaller in the long CSI. Results of standardized low resolution electromagnetic tomography (sLORETA) for both ERP positivity and negativity showed that switch trials evoked larger activation than repeat trials in dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC).

Conclusions/Significance

The results provide evidence that both RSI and CSI modulate the neural activities in the process of task-switching, but that these have a differential role during task-set reconfiguration and passive dissipation of a previously relevant task-set.     

Task Shifting Routine Inpatient Pediatric HIV Testing Improves Program Outcomes in Urban Malawi: A Retrospective Observational Study

Background

This study evaluated two models of routine HIV testing of hospitalized children in a high HIV-prevalence resource-constrained African setting. Both models incorporated “task shifting,” or the allocation of tasks to the least-costly, capable health worker.

Methods and Findings

Two models were piloted for three months each within the pediatric department of a referral hospital in Lilongwe, Malawi between January 1 and June 30, 2008. Model 1 utilized lay counselors for HIV testing instead of nurses and clinicians. Model 2 further shifted program flow and advocacy responsibilities from counselors to volunteer parents of HIV-infected children, called “patient escorts.” A retrospective review of data from 6318 hospitalized children offered HIV testing between January-December 2008 was conducted. The pilot quarters of Model 1 and Model 2 were compared, with Model 2 selected to continue after the pilot period. There was a 2-fold increase in patients offered HIV testing with Model 2 compared with Model 1 (43.1% vs 19.9%, p<0.001). Furthermore, patients in Model 2 were younger (17.3 vs 26.7 months, p<0.001) and tested sooner after admission (1.77 vs 2.44 days, p<0.001). There were no differences in test acceptance or enrollment rates into HIV care, and the program trends continued 6 months after the pilot period. Overall, 10244 HIV antibody tests (4779 maternal; 5465 child) and 453 DNA-PCR tests were completed, with 97.8% accepting testing. 19.6% of all mothers (n = 1112) and 8.5% of all children (n = 525) were HIV-infected. Furthermore, 6.5% of children were HIV-exposed (n = 405). Cumulatively, 72.9% (n = 678) of eligible children were evaluated in the hospital by a HIV-trained clinician, and 68.3% (n = 387) successfully enrolled into outpatient HIV care.

Conclusions/Significance

The strategy presented here, task shifting from lay counselors alone to lay counselors and patient escorts, greatly improved program outcomes while only marginally increasing operational costs. The wider implementation of this strategy could accelerate pediatric HIV care access in high-prevalence settings.